WO2016014954A1

WO2016014954A1 - Tandem z-selective metathesis / dihydroxylation

Info

Publication number: WO2016014954A1
Application number: PCT/US2015/042013
Authority: WO
Inventors: Robert H. Grubbs; Peter K. DORNAN; Zachary K. WICKENS
Original assignee: California Institute of Technology
Current assignee: California Institute of Technology
Priority date: 2014-07-25
Filing date: 2015-07-24
Publication date: 2016-01-28
Anticipated expiration: 2017-01-25

Abstract

This invention relates generally to C-H activated ruthenium olefin metathesis catalyst compounds and the use of such catalysts in tandem Z-selective cross-metathesis /stereospecific dihydroxylation. The invention discloses an assisted tandem catalysis procedure for the Z-selective cross-metathesis / dihydroxylation of terminal olefins, containing electron withdrawing groups at the allylic position, to yield anti-diols. Ruthenium catalyzes both transformations, and the Z-selectivity observed in the cross- metathesis is translated to anti'-selectivity via the stereospecific dihydroxylation. Densely functionalized anti-diols with four contiguous heteroatom substituted carbon atoms can be synthesized from simple allyl alcohol and allyl amine derivatives.

Description

International PCT Patent Application For:

TANDEM Z-SELECTIVE METATHESIS / DIHYDROXYLATION

By Inventors:

Robert H. Grubbs, Peter K. Dornan, and Zachary K. Wickens

TANDEM Z-SELECTIVE METATHESIS / DIHYDROXYLATION By Inventors: Robert H. Grubbs, Peter K. Dornan, and Zachary K. Wickens CROSS REFERENCE TO RELATED APPLICATIONS [001] The present application claims the benefit of U.S. Provisional Patent Application No. 62/149,214, filed April 17, 2015, of U.S. Provisional Patent Application No. 62/117,351, filed February 17, 2015, of U.S. Provisional Patent Application No. 62/029,743, filed July 28, 2014, and of U.S. Provisional Patent Application No. 62/029,318, filed July 25, 2014, which are each incorporated herein by reference in their entirety. STATEMENT OF FEDERAL SUPPORT [002] This invention was made with government support under GM031332 awarded by the National Institutes of Health, under CHE1212767 awarded by the National Science Foundation and under N00014- 14-1-0650 awarded by the Office of Naval Research. The government has certain rights in the invention. TECHNICAL FIELD

[003] This invention relates generally to C-H activated ruthenium olefin metathesis catalyst compounds and the use of such catalysts in the metathesis of olefins and olefin compounds, such as, in the use of such catalysts in Z-selective olefin metathesis reactions, such as tandem Z-selective cross- metathesis / stereospecific dihydroxylation. The invention has utility in the fields of catalysis, organic synthesis, and industrial and fine chemicals chemistry. BACKGROUND

[004] Highly functionalized and stereochemically complex motifs are attractive targets in synthesis due to their diverse molecular interactions in therapeutic and other specialty applications. Efficient synthesis of densely functionalized targets from simple starting materials is thus an important challenge. Assisted tandem catalysis, where coupled catalytic processes are effected by a single catalyst, can significantly increase molecular complexity using a single multitasking catalyst (D. E. Fogg, E. N. dos Santos, Coord. Chem. Rev. 2004, 248, 2365–2379). [005] Ruthenium metathesis catalysts have frequently been used in tandem reactions since the C–C bond formation step in olefin metathesis can be coupled to a structural elaboration step which introduces additional functionality. For metathesis-hydrogenation, see: a) J. Louie, C. W. Bielawski, R. H. Grubbs, J. Am. Chem. Soc. 2001, 123, 11312–11313; b) K. D. Camm, N. Martinez Castro, Y. Liu, P. Czechura, J. L. Snelgrove, D. E. Fogg, J. Am. Chem. Soc. 2007, 129, 4168–4169; For metathesis-olefin isomerization, see: c) A. E. Sutton, B. A. Seigal, D. F. Finnegan, M. L. Snapper, J. Am. Chem. Soc. 2002, 124, 13390– 13391; d) B. Schmidt, Eur. J. Org. Chem. 2003, 816–819; For metathesis-atom transfer radical cyclization, see: e) B. Schmidt, M. Pohler, J. Organomet. Chem. 2005, 690, 5552–5555; f) B. A. Seigal, C. Fajardo, M. L. Snapper, J. Am. Chem. Soc. 2005, 127, 16329–16332; For metathesis-cyclopropanation, see: g) B. G. Kim, M. L. Snapper, J. Am. Chem. Soc. 2006, 128, 52–53; For metathesis-oxidation, see: h) H. Kato, T. Ishigame, N. Oshima, N. Hoshiya, K. Shimawaki, M. Arisawa, S. Shuto, Adv. Synth. Catal. 2011, 353, 2676–2680; i) B. Schmidt, S. Krehl, Chem. Commun. 2011, 47, 5879–5881; j) B. Schmidt, S. Krehl, S. Hauke, J. Org. Chem. 2013, 78, 5427–5435; For metathesis dihydroxylation, see: k) S. Beligny, S. Eibauer, S. Maechling, S. Blechert, Angew. Chem. Int. Ed. 2006, 45, 1900–1903; l) A. A. Scholte, M. H. An, M. L. Snapper, Org. Lett. 2006, 8, 4759–4762; m) N. M. Neisius, B. Plietker, J. Org. Chem. 2008, 73, 3218–3227. In 2006, Blechert (see S. Beligny, S. Eibauer, S. Maechling, S. Blechert, Angew. Chem. Int. Ed. 2006, 45, 1900–1903) and Snapper (see A. A. Scholte, M. H. An, M. L. Snapper, Org. Lett. 2006, 8, 4759–4762) demonstrated that cross-metathesis using second generation catalysts Ru-1 or Ru-2 (Scheme 1) followed by Ru-catalyzed dihydroxylation in the presence of NaIO4 as an oxidant led to the corresponding diol (Scheme 2).

Scheme 1. Second generation (Ru-1 and Ru-2) and cyclometalated (Ru-3 and Ru-4) ruthenium alkylidene complexes

[006] In the case of

. , . , . , S. Blechert, Angew. Chem. Int. Ed. 2006, 45, 1900–1903) and Snapper’s (see A. A. Scholte, M. H. An, M. L. Snapper, Org. Lett. 2006, 8, 4759–4762) synthesis of syn-diols, the dihydroxylation step is highly stereospecific, and thus diol diastereoselectivity is determined by olefin geometry. Since the metathesis occurs under thermodynamic (i.e., substrate) control, primarily E olefins were produced, leading to predominantly syn- diol products.

Scheme 2. Tandem metathesis–dihydroxylation

[007] Thus anti-diols (see for representative examples of anti 1,2-diol synthesis: a) H. C. Kolb, M. S. VanNieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483–2547; b) H. C. Brown, G. Narla, J. Org. Chem. 1995, 60, 4686–4687; c) A. B. Northrup, D. W. C. MacMillan, Science 2004, 305, 1752–1755; d) S. M. Lim, N. Hill, A. G. Myers, J. Am. Chem. Soc. 2009, 131, 5763–5765; e) S. B. Han, H. Han, M. J. Krische, J. Am. Chem. Soc. 2010, 132, 1760–1761; f) D. Kim, J. S. Lee, S. B. Kong, H. Han, Angew. Chem. Int. Ed. 2013, 52, 4203–4206), which are important motifs in natural products as well as intermediates in synthesis, are inaccessible by these methods. If a catalyst controlled cross-metathesis could be coupled to a dihydroxylation, then anti-diols with predictable and high levels of diastereoselectivity could be accessed. Using this multitasking approach, simple allyl alcohol and allyl amine derivatives could be transformed into valuable densely functionalized products in a catalyst controlled fashion.

[008] 1,2-Diols are a common structural motif found in numerous classes of natural products, including carbohydrates and polyketides, as well as chiral ligands. Stereospecific dihydroxylation is a powerful method to access stereodefined diols from olefins (H. C. Kolb, M. S. Van Nieuwenhze, K. B. Sharpless, Chem. Rev. 1994, 94, 2483–2547; C. J. R. Bataille, T. J. Donohoe, Chem. Soc. Rev. 2010, 40, 114–128). However, the diastereopurity of the resulting diol is largely dependent on the geometrical purity of the olefin substrate. The synthesis of Z-olefins (which lead to anti 1,2-diols by dihydroxylation) in high geometrical purity is a difficult challenge (S. Shahane, C. Bruneau, C. Fischmeister, ChemCatChem 2013, 5, 3436–3459).

[009] Recently, the discovery of highly Z-selective ruthenium-based olefin metathesis catalysts has been reported, of which Ru-4, also referred to in the art as Ad-DIPP-NO₃ (see Scheme 3), is currently the most selective (K. Endo, R. H. Grubbs, J. Am. Chem. Soc. 2011, 133, 8525–8527; B. K. Keitz, K. Endo, P. R. Patel, M. B. Herbert, R. H. Grubbs, J. Am. Chem. Soc. 2012, 134, 693–699; L. E. Rosebrugh, M. B. Herbert, V. M. Marx, B. K. Keitz, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 1276–1279). Given the ability of oxygenated ruthenium species to catalyze olefin dihydroxylation, it was sought to develop a tandem Z-selective cross-metathesis / stereospecific dihydroxylation. Herein, initial results towards the goal of developing this multitasking catalyst protocol are disclosed.

Scheme 3.

[0010] Discovering tandem catalytic sequences is an attractive goal since more than one reaction may be performed with the same catalyst, and intermediates do not need to be isolated. Several tandem processes involving olefin metathesis have been developed, including metathesis-hydrogenation (J. Louie, C. W. Bielawski, R. H. Grubbs, J. Am. Chem. Soc. 2001, 123, 11312–11313; K. D. Camm, N. Martinez Castro, Y. Liu, P. Czechura, J. L. Snelgrove, D. E. Fogg, J. Am. Chem. Soc. 2007, 129, 4168– 4169), metathesis-olefin isomerization (A. E. Sutton, B. A. Seigal, D. F. Finnegan, M. L. Snapper, J. Am. Chem. Soc. 2002, 124, 13390–13391; B. Schmidt, Eur. J. Org. Chem. 2003, 2003, 816–819), metathesis- atom transfer radical cyclization (B. Schmidt, M. Pohler, J. Organomet. Chem. 2005, 690, 5552–5555; B. A. Seigal, C. Fajardo, M. L. Snapper, J. Am. Chem. Soc. 2005, 127, 16329–16332), enyne metathesis- cyclopropanation (B. G. Kim, M. L. Snapper, J. Am. Chem. Soc. 2006, 128, 52–53), metathesis-oxidation (H. Kato, T. Ishigame, N. Oshima, N. Hoshiya, K. Shimawaki, M. Arisawa, S. Shuto, Adv. Synth. Catal. 2011, 353, 2676–2680; B. Schmidt, S. Krehl, Chem. Commun. 2011, 47, 5879–5881; B. Schmidt, S. Krehl, S. Hauke, J. Org. Chem. 2013, 78, 5427–5435), and metathesis-dihydroxylation (S. Beligny, S. Eibauer, S. Maechling, S. Blechert, Angew. Chem. Int. Ed. 2006, 45, 1900–1903; A. A. Scholte, M. H. An, M. L. Snapper, Org. Lett. 2006, 8, 4759–4762; N. M. Neisius, B. J. Plietker, Org. Chem. 2008, 73, 3218–3227). In 1981, Sharpless developed catalytic biphasic conditions in order to generate RuO4 in situ from RuCl3 and stoichiometric NaIO4 in CCl4/MeCN/H2O (P. H. J. Carlsen, T. Katsuki, V. S. Martin, K. B. Sharpless, J. Org. Chem. 1981, 46, 3936–3938).

[0011] The use of acetonitrile was critical to achieving high activity. It was proposed that nitriles can stabilize low-valent catalytic intermediates and prevent the formation of insoluble ruthenium carboxylates. Sharpless applied these conditions to several types of oxidations, including the oxidative cleavage of olefins to carboxylic acids. Subsequently, Shing demonstrated that the oxidation of olefins can be stopped at the diol by careful control of the reaction conditions (T. K. M. Shing, V. W.-F. Tai, E. K. Tam, W. Angew. Chem. Int. Ed. Engl. 1994, 33, 2312–2313). They used a 3:3:1 mixture of ethyl acetate : MeCN : H₂O and 1.5 eq NaIO₄ at 0°C and stopped the reaction after 3 minutes. With this protocol, which was termed“flash dihydroxylation,” good yields of diols were obtained, with small amounts of overoxidation. Plietker found that addition of strong Brønsted acid, such as H₂SO₄ (B. Plietker, M. Niggemann, Org. Lett. 2003, 5, 3353–3356) or soft Lewis acids such as CeCl₃ (B. Plietker, M. Niggemann, J. Org. Chem. 2005, 70, 2402–2405) greatly accelerate the dihydroxylation, and enable catalyst loadings as low as 0.5 mol%. It is hypothesized that the acid facilitates hydrolysis of the ruthenate ester.

[0012] Blechert developed the first tandem metathesis-dihyroxylation, employing a variation of Plietker’s oxidation conditions with YbCl₃ (S. Beligny, S. Eibauer, S. Maechling, S. Blechert, Angew. Chem. Int. Ed. 2006, 45, 1900–1903). In this report the authors examined RCM- dihyroxylation, as well as three examples of cross-metathesis / dihydroxylation. Snapper and co-workers subsequently reported a similar tandem process for RCM-dihydroxylation and cross-metathesis / dihydroxylation (A. A. Scholte, M. H. An, M. L. Snapper, Org. Lett. 2006, 8, 4759–4762). In this case, Plietker’s oxidation conditions with CeCl3 were used. The cross-metathesis products led to syn-diol products, due to the stereospecific nature of the ruthenium dihydroxylation. Plietker has developed a chiral auxiliary directed diastereoselective cross-metathesis / dihydroxylation that also leads to syn-diols (N. M.Neisius, B. Plietker, J. Org. Chem. 2008, 73, 3218–3227).

[0013] Significant progress has been made in the development of Z-selective olefin metathesis catalysts using Ru (see K. Endo, R. H. Grubbs, J. Am. Chem. Soc. 2011, 133, 8525–8527; B. K. Keitz, K. Endo, P. R. Patel, M. B. Herbert, R. H. Grubbs, J. Am. Chem. Soc. 2012, 134, 693–699; L. E. Rosebrugh, M. B. Herbert, V. M. Marx, B. K. Keitz, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 1276–1279; S. M. Bronner, M. B. Herbert, P. R. Patel, V. M. Marx, R. H. Grubbs, Chem. Sci. 2014, 5, 4091–4098; M. J. Koh, R. K. M. Khan, S. Torker, M. Yu, M. S. Mikus, A. H. Hoveyda, Nature 2015, 517, 181–186), Mo, (see S. J. Malcolmson, S. J. Meek, E. S. Sattely, R. R. Schrock, A. H. Hoveyda, Nature 2008, 456, 933– 937; M. M. Flook, A. J. Jiang, R. R. Schrock, P. Müller, A. H. Hoveyda, J. Am. Chem. Soc. 2009, 131, 7962–7963; A. J. Jiang, Y. Zhao, R. R. Schrock, A. H. Hoveyda, J. Am. Chem. Soc. 2009, 131, 16630– 16631) and W (see D. V. Peryshkov, R. R. Schrock, M. K. Takase, P. Müller, A. H. Hoveyda, J. Am. Chem. Soc. 2011, 133, 20754–20757) alkylidene complexes. Highly Z-selective cyclometalated Ru complexes (Ru-3 and Ru-4, Scheme 1) have been investigated for diverse applications (for examples of Z-selective cross-metathesis, see: a) B. K. Keitz, K. Endo, M. B. Herbert, R. H. Grubbs, J. Am. Chem. Soc. 2011, 133, 9686–9688; For examples of ROMP, see: b) B. K. Keitz, A. Fedorov, R. H. Grubbs, J. Am. Chem. Soc. 2012, 134, 2040–2043; c) L. E. Rosebrugh, V. M. Marx, B. K. Keitz, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 10032–10035; For examples of enantioselective catalysis, see: d) J. Hartung, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 10183–10185; e) J. Hartung, P. K. Dornan, R. H. Grubbs, J. Am. Chem. Soc. 2014, 136, 13029–13037; For examples of macrocyclizations, see: f) V. M. Marx, M. B. Herbert, B. K. Keitz, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 94–97), and feature an NHC ligand that is chelated to the metal via an additional Ru–C bond. Diisopropylphenyl substituted Ru-4 was found to achieve up to 7400 turnovers in a homodimerization reaction, with >95% Z-selectivity (see L. E. Rosebrugh, M. B. Herbert, V. M. Marx, B. K. Keitz, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 1276– 1279). Computational studies suggest that a steric and electronic preference for a side-bound metallacyclobutane intermediate forces all substituents of the metallacycle to point in one direction, leading to Z-olefins (see P. Liu, X. Xu, X. Dong, B. K. Keitz, M. B. Herbert, R. H. Grubbs, K. N. Houk, J. Am. Chem. Soc. 2012, 134, 1464–1467; H. Miyazaki, M. B. Herbert, P. Liu, X. Dong, X. Xu, B. K. Keitz, T. Ung, G. Mkrtumyan, K. N. Houk, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 5848–5858). However, these complexes have not been demonstrated to be viable for tandem catalysis, despite the potential to significantly increase the molecular complexity with high stereocontrol in single-pot sequence.

[0014] It is proposed that cyclometalated complexes would be able to catalyze the dihydroxylation of olefins if conditions could be identified to generate a suitably oxidized ruthenium species (see S. Beligny, S. Eibauer, S. Maechling, S. Blechert, Angew. Chem. Int. Ed. 2006, 45, 1900–1903; A. A. Scholte, M. H. An, M. L. Snapper, Org. Lett. 2006, 8, 4759–4762; N. M. Neisius, B. Plietker, J. Org. Chem. 2008, 73, 3218–3227). It was anticipated that under acidic aqueous oxidizing conditions the adamantyl C–Ru bond would be cleaved, generating a species similar to that generated in dihydroxylation with Ru-2 (see S. Beligny, S. Eibauer, S. Maechling, S. Blechert, Angew. Chem. Int. Ed. 2006, 45, 1900–1903). Furthermore, it was proposed that catalyst controlled Z-selectivity in cross-metathesis with Ru-3 or Ru- 4 would be translated into high anti-selectivity via a stereospecific pathway. Herein, the successful development of a tandem Z-selective metathesis– dihydroxylation is disclosed, as well as preliminary mechanistic studies which shed light on catalyst inhibition pathways.

[0015] Despite the advances achieved in the art, a continuing need therefore exists for further improvements in the areas of tandem Z-selective cross-metathesis / stereospecific dihydroxylation. BRIEF SUMMARY OF THE DISCLOSURE

[0016] The invention is directed to addressing one or more of the aforementioned concerns and relates to tandem Z-selective cross-metathesis / stereospecific dihydroxylation. More particularly, the invention relates to C-H activated ruthenium olefin metathesis catalyst compounds and the use of such catalysts in tandem Z-selective cross-metathesis /stereospecific dihydroxylation.

[0017] In one embodiment the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross- metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[0018] In another embodiment, the invention provides an assisted tandem catalysis procedure for the Z-selective cross-metathesis / dihydroxylation of terminal olefins, containing electron withdrawing groups at the allylic position, to yield anti-diols. Ruthenium catalyzes both transformations, and the Z- selectivity observed in the cross-metathesis is translated to anti-selectivity via the stereospecific dihydroxylation. Densely functionalized anti-diols with four contiguous heteroatom substituted carbon atoms can be synthesized from simple allyl alcohol and allyl amine derivatives.

[0019] In another embodiment the invention, provides a C-H activated catalyst compound composed of a Group 8 transition metal complex and a chelating ligand structure formed from the metal center M, a neutral electron donor ligand L¹, and a 2-electron anionic donor bridging moiety Q*. A general structure of catalyst compounds according to the invention is shown below:

wherein,

M is a Group 8 transition metal (e.g., Ru or Os); X¹ is an anionic ligand;

L¹ is a neutral two electron ligand, where L¹ may connect with R²;

R¹ and R² are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups, and wherein R¹ may connect with R² and/or L¹;

Q* is a 2-electron anionic donor bridging moiety (e.g., alkyl, aryl, carboxylate, alkoxy, aryloxy, or sulfonate, etc.);

Q is a linker, typically a hydrocarbylene linker, including substituted hydrocarbylene, heteroatom-containing hydrocarbylene, and substituted heteroatom-containing hydrocarbylene linkers, wherein two or more substituents on adjacent atoms within Q may also be linked to form an additional cyclic structure, which may be similarly substituted to provide a fused polycyclic structure of two to about five cyclic groups. Q is often, although again not necessarily, a two-atom linkage or a three-atom linkage;

X is an atom selected from C, N, O, S, and P. Since O and S are divalent, n is necessarily zero when X is O or S. Similarly, when X is N or P, then n is 1, and when X is C, then n is 2; and

R³ and R⁴ are independently selected from hydrocarbyl, substituted hydrocarbyl, heteroatom- containing hydrocarbyl, and substituted heteroatom-containing, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), heteroatom-containing hydrocarbyl (e.g., heteroatom-containing C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂- C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), and substituted heteroatom-containing hydrocarbyl (e.g., substituted heteroatom-containing C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅- C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), and functional groups.

[0020] By using the C-H activated catalyst compounds of the invention, tandem Z-selective cross- metathesis / stereospecific dihydroxylation methods to prepare compounds comprising anti-1 ,2-diols, were discovered. DETAILED DESCRIPTION OF THE DISCLOSURE

[0021] The invention is directed to a stereoselective synthesis of anti-1,2-diols, developed using a multitasking Ru-catalyst in an assisted tandem catalysis protocol. A cyclometalated ruthenium complex catalyses first a Z-selective cross-metathesis of two terminal olefins followed by a stereospecific dihydroxylation. Both steps are catalyzed by Ru, as the Ru-complex is converted to a dihydroxylation catalyst upon addition of NaIO4 (Scheme 4) and the stereocontrol of the cross-metathesis is translated via high stereospecificity in the dihydroxylation step to diastereoselectivity for the 1,2-anti-diol. Scheme 4. Z-selective catalysts lead to anti-diols

[0022] In another aspect, the invention provides an assisted tandem catalysis procedure for the Z- selective cross-metathesis / dihydroxylation of terminal olefins to yield anti-diols. Ruthenium catalyzes both transformations, and the Z-selectivity observed in the cross-metathesis is translated to anti- selectivity via the stereospecific dihydroxylation. Densely functionalized anti-diols with four contiguous heteroatom substituted carbon atoms can be synthesized from simple allyl alcohol and allyl amine derivatives. The behaviour of the in situ generated Ru-based oxidation catalyst was probed with unfunctionalized electron rich alkenes, and these were found to inhibit dihydroxylation. Further studies are ongoing to elucidate details of the reaction mechanism. It is envisioned that this methodology will have applications in target oriented synthesis involving anti-diols, and the mechanistic insights will help to uncover further applications of cyclometalated ruthenium alkylidene catalysts.

[0023] In a further aspect, the invention provides a tandem Z-selective metathesis / dihydroxylation reaction, which is effective for substrates containing electron withdrawing groups at the allylic position. [0024] A variety of olefins were transformed into valuable highly functionalized and stereodefined molecules. Mechanistic experiments are performed to probe the nature of the oxidation step and catalyst inhibition pathways. These experiments point the way to more broadly applicable tandem catalytic transformations. It has been demonstrated that Z-selective catalysts lead to anti-diols in a catalyst controlled fashion via the Z-olefin. The tandem Z-selective metathesis– dihydroxylation reaction

[0025] The homodimerization– dihydroxylation of allyl butyrate was examined in order to determine the effect of catalyst and reaction conditions on selectivity (Table 1). The metathesis step was performed under static vacuum conditions, in order to keep the concentration of ethylene in solution low. Shing’s conditions of NaIO₄ in 3:3:1 EtOAc:MeCN:H₂O (see T. K. M. Shing, V. W.-F. Tai, E. K. W. Tam, Angew. Chem. Int. Ed. Engl. 1994, 33, 2312–2313; T. K. M. Shing, E. K. W. Tam, V. W.-F. Tai, I. H. F. Chung, Q. Jiang, Chem.– Eur. J. 1996, 2, 50–57) were used for the dihydroxylation step. Strong Brønsted acids, such as H₂SO₄ (see B. Plietker, M. Niggemann, Org. Lett. 2003, 5, 3353–3356) or Lewis acids such as CeCl₃ (see B. Plietker, M. Niggemann, J. Org. Chem. 2005, 70, 2402–2405) have been demonstrated to accelerate dihydroxylation. It has been proposed that acids facilitate hydrolysis of a ruthenate ester intermediate. Second generation Ru-complex Ru-2, which is expected to operate under thermodynamic control of olefin geometry, generated the syn diol product with 8:1 selectivity (entry 1). Use of cyclometalated mesityl substituted Ru-3 and diisopropylphenyl substituted Ru-4 generated the desired product 6a in 56% and 68% yield, respectively, with only trace quantities of the syn diol by-product (entries 2 and 3). This anti-selectivity can be attributed to the high Z-selectivity of these catalysts typically observed in cross-metathesis (see L. E. Rosebrugh, M. B. Herbert, V. M. Marx, B. K. Keitz, R. H. Grubbs, J. Am. Chem. Soc. 2013, 135, 1276–1279; B. L. Quigley, R. H. Grubbs, Chem. Sci. 2013, 5, 501–506).

[0026] Achieving high activity and Z-selectivity has been found to depend strongly on the removal of ethylene from solution. Performing the metathesis under static vacuum was critical, as the yield was diminished to 49% when the metathesis step was performed at 1 atm (entry 4), presumably a larger concentration of ethylene in solution results in slower productive metathesis and more secondary metathesis processes. The use of additives, such as nBu₄NCl during dihydroxylation, or the use of ethyl vinyl ether to quench the metathesis reaction, did not improve the yield (entries 5 and 6). Performing the dihydroxylation in the absence of a Lewis acid co-catalyst still resulted in productive dihydroxylation, albeit in only 31% yield (entry 9). Other acids, such as H₂SO₄ and YbCl₃, were also less effective than CeCl3, producing 6a in 56 and 61% yield respectively (entries 10 and 11).

Table 1. Effect of catalyst, additives and conditions on the tandem Z-selective metathesis–

dihydroxylation reaction.

E

ntr Ru Acid Chan es from Yield 6a Yield

[a] Determined by integration of the crude ¹H NMR spectrum using mesitylene as an internal standard. Note: For Table 1, entry 6, ethyl vinyl ether (0.2 mmol, 18.6 μL) was added after the metathesis step, and the mixture was stirred for 20 minutes at ambient temperature. Subsequently, the volatiles were removed and the mixture was dissolved in ethyl acetate to add to the oxidation mixture. The Z-selective homodimerization– dihydroxylation reaction

[0027] With optimized conditions in hand, the scope of the Z-selective homodimerization – dihydroxylation, was next examined. A wide variety of densely functionalized, stereodefined anti-diol could be prepared from comparatively simple starting materials (Table 2). Esters, carbonates, carbamates, and amine derivatives were all well tolerated, generating the resulting anti-diol in up to 72% yield. The molecular structure of 6c was determined by X-ray crystallography, supporting the anti- stereochemistry. In addition to probing the overall tandem process, the independent metathesis step was also monitored in each case to ensure high Z-selectivity (in all cases, over 90% Z-selectivity was obtained), since only the homodimerization of allyl acetate has been explored previously with these chelated catalysts (see B. K. Keitz, K. Endo, P. R. Patel, M. B. Herbert, R. H. Grubbs, J. Am. Chem. Soc. 2012, 134, 693–699).

Table 2. Tandem Z-selective homodimerization– dihydroxylation of allyl substituted terminal olefins

Entry R Product Yield (%)

OCOnPr

[a] Using 1 mol% catalyst in an open vial in the glove box The Z-selective heterocross-metathesis / dihydroxylation

[0028] Achieving unsymmetrical substitution patterns via heterocross-metathesis / dihydroxylation is an appealing target, particularly if differentially protected products can be obtained. Z-selective heterocross-metathesis can be achieved by using an excess of one of the olefin partners (see B. L. Quigley, R. H. Grubbs, Chem. Sci. 2013, 5, 501–506; J. S. Cannon, R. H. Grubbs, Angew. Chem. Int. Ed. 2013, 52, 9001–9004). Tosyl and Cbz protected allyl amine were used as coupling partners with allyl butyrate or allyl benzoate (Table 3), generating the corresponding substituted amino triols in up to 63% yield. Such orthogonally protected products are valuable building blocks for target oriented synthesis. Table 3. Z-selective heterocross-metathesis / dihydroxylation of allyl substituted terminal olefins

E^ntry _R ¹ _R ² _Product Yield (%)

4

[0029] Next, the tandem methodology on gram scale in order to probe scalability of the process was examined. Allyl benzoate was subjected to cross-metathesis with 0.5 mol% catalyst Ru-4 in an open vial in an inert atmosphere glove box, followed by dihydroxylation using the standard conditions outside the glove box (Scheme 5). Isolation of the target diol was conveniently achieved without the need for column chromatography: trituration of the crude reaction mixture with ether provided 6c in 66% yield.

Scheme 5. Gram scale tandem Z-selective metathesis– dihydroxylation

[0030 xperiments

were performed. Firstly, Z-2-butenyl 1,4-diacetate 3 was subjected to the standard dihydroxylation conditions in the presence or absence of Ru-catalyst Ru-4 (Scheme 6). Without Ru-4, no conversion was observed, indicating that Ru is a catalyst for both the metathesis and dihydroxylation steps, and therefore this tandem transformation is indeed an example of assisted tandem catalysis (see D. E. Fogg, E. N. dos Santos, Coord. Chem. Rev. 2004, 248, 2365–2379). In the presence of Ru-4 (1 mol%), anti-diol 2 was generated as a single diastereomer, thus confirming the stereospecificity of the dihydroxylation. Scheme 6. Control experiment indicates that ruthenium is required in the dihydroxylation

[0031] Next, the relative reactivity of electron neutral and electron deficient internal olefins toward dihydroxylation with Ru-4 was investigated (Scheme 7). Z-4-butene 11 was subjected to the standard dihydroxylation conditions with Ru-4 (1 mol%) and no diol was observed. Furthermore, when a 1:1 mixture of 11 and Z-2-butenyl 1,4-diacetate 3 was subjected to the same conditions, no diol from either alkene was observed. Since 3 is successfully dihydroxylated when it is the only substrate present (see Scheme 8), this result indicates that 11 is not only unreactive, but also inhibits dihydroxylation of 3. It was proposed that formation of a stable ruthenate ester from a [3+2] cycloaddition between 11 and a Ru bis-oxo species, sequesters the ruthenium catalyst, making it unavailable for catalysis of dihydroxylation of 3. Hydrolysis of osmate esters is known to be a slow step in the osmium catalyzed dihydroxylation of certain olefins (see K. B. Sharpless, W. Amberg, Y. L. Bennani, G. A. Crispino, J. Hartung, K. S. Jeong, H. L. Kwong, K. Morikawa, Z. M. Wang, J. Org. Chem. 1992, 57, 2768–2771; M. H. Junttila, O. E. O. Hormi, J. Org. Chem. 2007, 72, 2956–2961). The allylic functional groups could either be acting as electron withdrawing groups to render the Ru center more electrophilic, or as directing groups. For directed dihydroxylation, see: T. J. Donohoe, Synlett 2002, 1223-1232.

Scheme 7. A) Ruthenium catalyst Ru-4 is required for dihydroxylation. B) Z-4-octene 11 is unreactive in dihydroxylation. C) 11 inhibits the dihydroxylation of 3. Oxidation conditions: NaIO₄ (2 eq), CeCl₃

(10 mol%), EtOAc:MeCN:H₂O (3:3:1), 20 min, 0 °C.

Schem

1 inhitibs the dihydroxylation of cis-butenyldiacetate 3.

[0032] tene 11 inhibits dihydroxylation, it was anticipated that cross-metathesis /

dihydroxylation between 1-pentene 12 and allyl benzoate 5c could be challenging, due to concomitant generation of 11 under the kinetically controlled conditions. Indeed, under the standard conditions this tandem reaction failed to produce any diol (Scheme 9A). In order to probe the inherent reactivity of the hetero cross-metathesis intermediate in the absence of inhibitory by-products, the tandem sequence with removal of volatiles in vacuo was performed prior to addition of the reagents for dihydroxylation. Pleasingly, diol 13 was produced in 33% yield under unoptimized conditions (Scheme 9B). Therefore removal of 4-octene and residual 1-pentene lead to restoration of the dihydroxylation activity, albeit with slightly lower efficiency. Z-olefins with functionality at only one of the allylic positions are inherently still reactive with catalyst Ru-4. Some olefin intermediate remained after the 20 minute oxidation, resulting in low yield. Therefore, dihydroxylation to give diol 13 is likely slower than formation of 6c. This result points the way to further expand the substrate scope of tandem metathesis– dihydroxylation. Scheme 9. Cross-metathesis / dihydroxylation of allyl benzoate and 1-pentene under standard conditions (A) and with removal of volatile intermediates prior to the oxidation step (B).

[0033] In one embodiment of the present invention, allyl acetate 1 was subjected to cross-metathesis conditions under static vacuum, and then the reaction mixture was added to a mixture of NaIO4 and CeCl₃ in MeCN:EtOAc:H₂O (3:3:1). The anti diol 2 was isolated in 60% yield, and spectroscopic data was consistent with literature values (T. K. M. Shing, E. K. W.Tam, V. W.-F. Tai, I. H. F. Chung, Q. Jiang, Chem.– Eur. J. 1996, 2, 50–57), thus confirming the anti-stereochemistry.

[0034] As a control experiment, Z-alkene 3 was subjected to the oxidation conditions in the absence of ruthenium. No oxidation was observed, which supports the multitasking role of the ruthenium catalyst.

[0035] In one embodiment of the present invention, N-tosyl allyl amine 4 was also a competent substrate, undergoing homodimerization and dihydroxylation to give 5 in 66% yield.

[0036] In one embodiment of the present invention, cross-metathesis is possible if an excess of one of the alkene partners is used. N-tosyl allyl amine 4 was subjected to cross-metathesis with an excess of allyl butyrate 6 (5 eq). The resulting diol 7 was isolated after dihydroxylation in 63% yield.

[0037] In one embodiment of the present invention, olefins that lack an electron withdrawing group at the allylic position can undergo Z-selective metathesis, but do not undergo dihydroxylation.

However, if RuCl3 is added during the oxidation, the dihydroxylation will occur. Terminal olefin 8 was successfully converted to diol 9 using this procedure. This result indicates that the ruthenium species generated upon subjecting the Ru-4 catalyst to the oxidation conditions is not the same as the species generated with RuCl3 under the same oxidation conditions.

[0038] In one embodiment of the present invention terminal olefin 8 was homodimerized and then subjected to oxidation conditions in the presence of diacetate 3. Interestingly, neither olefin is dihydroxylated in this case. Considering that diacetate 3 is a competent dihydroxylation substrate under these conditions, this result indicates that olefin 10 is not only unreactive towards but actually inhibits catalytic dihydroxylation. It was hypothesized that a stable ruthenate ester is formed with olefin 10, thus sequestering the catalytic species.

Terminology and Definitions

[0039] Unless otherwise indicated, the invention is not limited to specific reactants, substituents, catalysts, reaction conditions, or the like, as such may vary. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not to be interpreted as being limiting.

[0040] As used in the specification and the appended claims, the singular forms“a,”“an,” and“the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “an Į -olefin” includes a single Į -olefin as well as a combination or mixture of two or more Į -olefins, reference to“a substituent” encompasses a single substituent as well as two or more substituents, and the like.

[0041] As used in the specification and the appended claims, the terms“for example,”“for instance,”“such as,” or“including” are meant to introduce examples that further clarify more general subject matter. Unless otherwise specified, these examples are provided only as an aid for understanding the invention, and are not meant to be limiting in any fashion.

[0042] In this specification and in the claims that follow, reference will be made to a number of terms, which shall be defined to have the following meanings:

[0043] The term“alkyl” as used herein refers to a linear, branched, or cyclic saturated hydrocarbon group typically although not necessarily containing 1 to about 24 carbon atoms, preferably 1 to about 12 carbon atoms, such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, t-butyl, octyl, decyl, and the like, as well as cycloalkyl groups such as cyclopentyl, cyclohexyl and the like. Generally, although again not necessarily, alkyl groups herein contain 1 to about 12 carbon atoms. The term“lower alkyl” intends an alkyl group of 1 to 6 carbon atoms, and the specific term“cycloalkyl” intends a cyclic alkyl group, typically having 4 to 8, preferably 5 to 7, carbon atoms. The term“substituted alkyl” refers to alkyl substituted with one or more substituent groups, and the terms“heteroatom-containing alkyl” and “heteroalkyl” refer to alkyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms“alkyl” and“lower alkyl” include linear, branched, cyclic, unsubstituted, substituted, and/or heteroatom-containing alkyl and lower alkyl, respectively.

[0044] The term“alkylene” as used herein refers to a difunctional linear, branched, or cyclic alkyl group, where“alkyl” is as defined above.

[0045] The term“alkenyl” as used herein refers to a linear, branched, or cyclic hydrocarbon group of 2 to about 24 carbon atoms containing at least one double bond, such as ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, octenyl, decenyl, tetradecenyl, hexadecenyl, eicosenyl, tetracosenyl, and the like. Preferred alkenyl groups herein contain 2 to about 12 carbon atoms. The term“lower alkenyl” intends an alkenyl group of 2 to 6 carbon atoms, and the specific term“cycloalkenyl” intends a cyclic alkenyl group, preferably having 5 to 8 carbon atoms. The term“substituted alkenyl” refers to alkenyl substituted with one or more substituent groups, and the terms“heteroatom-containing alkenyl” and“heteroalkenyl” refer to alkenyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms“alkenyl” and“lower alkenyl” include linear, branched, cyclic, unsubstituted, substituted, and/or heteroatom-containing alkenyl and lower alkenyl, respectively.

[0046] The term“alkenylene” as used herein refers to a difunctional linear, branched, or cyclic alkenyl group, where“alkenyl” is as defined above.

[0047] The term“alkynyl” as used herein refers to a linear or branched hydrocarbon group of 2 to about 24 carbon atoms containing at least one triple bond, such as ethynyl, n-propynyl, and the like. Preferred alkynyl groups herein contain 2 to about 12 carbon atoms. The term“lower alkynyl” intends an alkynyl group of 2 to 6 carbon atoms. The term“substituted alkynyl” refers to alkynyl substituted with one or more substituent groups, and the terms“heteroatom-containing alkynyl” and

“heteroalkynyl” refer to alkynyl in which at least one carbon atom is replaced with a heteroatom. If not otherwise indicated, the terms“alkynyl” and“lower alkynyl” include linear, branched, unsubstituted, substituted, and/or heteroatom-containing alkynyl and lower alkynyl, respectively.

[0048] The term“alkoxy” as used herein intends an alkyl group bound through a single, terminal ether linkage; that is, an“alkoxy” group may be represented as -O-alkyl where alkyl is as defined above. A“lower alkoxy” group intends an alkoxy group containing 1 to 6 carbon atoms. Analogously, “alkenyloxy” and“lower alkenyloxy” respectively refer to an alkenyl and lower alkenyl group bound through a single, terminal ether linkage, and“alkynyloxy” and“lower alkynyloxy” respectively refer to an alkynyl and lower alkynyl group bound through a single, terminal ether linkage.

[0049] The term“aryl” as used herein, and unless otherwise specified, refers to an aromatic substituent containing a single aromatic ring or multiple aromatic rings that are fused together, directly linked, or indirectly linked (such that the different aromatic rings are bound to a common group such as a methylene or ethylene moiety). Preferred aryl groups contain 5 to 24 carbon atoms, and particularly preferred aryl groups contain 5 to 14 carbon atoms. Exemplary aryl groups contain one aromatic ring or two fused or linked aromatic rings, e.g., phenyl, naphthyl, biphenyl, diphenylether, diphenylamine, benzophenone, and the like.“Substituted aryl” refers to an aryl moiety substituted with one or more substituent groups, and the terms“heteroatom-containing aryl” and“heteroaryl” refer to aryl substituents in which at least one carbon atom is replaced with a heteroatom, as will be described in further detail infra.

[0050] The term“aryloxy” as used herein refers to an aryl group bound through a single, terminal ether linkage, wherein“aryl” is as defined above. An“aryloxy” group may be represented as -O-aryl where aryl is as defined above. Preferred aryloxy groups contain 5 to 24 carbon atoms, and particularly preferred aryloxy groups contain 5 to 14 carbon atoms. Examples of aryloxy groups include, without limitation, phenoxy, o-halo-phenoxy, m-halo-phenoxy, p-halo-phenoxy, o-methoxy-phenoxy, m- methoxy-phenoxy, p-methoxy-phenoxy, 2,4-dimethoxy-phenoxy, 3,4,5-trimethoxy-phenoxy, and the like.

[0051] The term“alkaryl” refers to an aryl group with an alkyl substituent, and the term“aralkyl” refers to an alkyl group with an aryl substituent, wherein“aryl” and“alkyl” are as defined above.

Preferred alkaryl and aralkyl groups contain 6 to 24 carbon atoms, and particularly preferred alkaryl and aralkyl groups contain 6 to 16 carbon atoms. Alkaryl groups include, for example, p-methylphenyl, 2,4- dimethylphenyl, p-cyclohexylphenyl, 2,7-dimethylnaphthyl, 7-cyclooctylnaphthyl, 3-ethyl-cyclopenta- 1,4-diene, and the like. Examples of aralkyl groups include, without limitation, benzyl, 2-phenyl-ethyl, 3-phenyl-propyl, 4-phenyl-butyl, 5-phenyl-pentyl, 4-phenylcyclohexyl, 4-benzylcyclohexyl, 4- phenylcyclohexylmethyl, 4-benzylcyclohexylmethyl, and the like. The terms“alkaryloxy” and “aralkyloxy” refer to substituents of the formula -OR wherein R is alkaryl or aralkyl, respectively, as just defined.

[0052] The term“acyl” refers to substituents having the formula -(CO)-alkyl, -(CO)-aryl, or -(CO)- aralkyl, and the term“acyloxy” refers to substituents having the formula -O(CO)-alkyl, -O(CO)-aryl,or - O(CO)-aralkyl, wherein“alkyl,”“aryl,” and“aralkyl” are as defined above.

[0053] The terms“cyclic” and“ring” refer to alicyclic or aromatic groups that may or may not be substituted and/or heteroatom containing, and that may be monocyclic, bicyclic, or polycyclic. The term“alicyclic” is used in the conventional sense to refer to an aliphatic cyclic moiety, as opposed to an aromatic cyclic moiety, and may be monocyclic, bicyclic, or polycyclic.

[0054] The terms“halo” and“halogen” and“halide” are used in the conventional sense to refer to a chloro, bromo, fluoro, or iodo substituent.

[0055] “Hydrocarbyl” refers to univalent hydrocarbyl radicals containing 1 to about 30 carbon atoms, preferably 1 to about 24 carbon atoms, most preferably 1 to about 12 carbon atoms, including linear, branched, cyclic, saturated, and unsaturated species, such as alkyl groups, alkenyl groups, aryl groups, and the like. The term“lower hydrocarbyl” intends a hydrocarbyl group of 1 to 6 carbon atoms, preferably 1 to 4 carbon atoms, and the term“hydrocarbylene” intends a divalent hydrocarbyl moiety containing 1 to about 30 carbon atoms, preferably 1 to about 24 carbon atoms, most preferably 1 to about 12 carbon atoms, including linear, branched, cyclic, saturated and unsaturated species. The term “lower hydrocarbylene” intends a hydrocarbylene group of 1 to 6 carbon atoms.“Substituted hydrocarbyl” refers to hydrocarbyl substituted with one or more substituent groups, and the terms “heteroatom-containing hydrocarbyl” and“heterohydrocarbyl” refer to hydrocarbyl in which at least one carbon atom is replaced with a heteroatom. Similarly,“substituted hydrocarbylene” refers to hydrocarbylene substituted with one or more substituent groups, and the terms“heteroatom-containing hydrocarbylene” and heterohydrocarbylene” refer to hydrocarbylene in which at least one carbon atom is replaced with a heteroatom. Unless otherwise indicated, the term“hydrocarbyl” and

“hydrocarbylene” are to be interpreted as including substituted and/or heteroatom-containing

hydrocarbyl and hydrocarbylene moieties, respectively. [0056] The term“heteroatom-containing” as in a“heteroatom-containing hydrocarbyl group” refers to a hydrocarbon molecule or a hydrocarbyl molecular fragment in which one or more carbon atoms is replaced with an atom other than carbon, e.g., nitrogen, oxygen, sulfur, phosphorus or silicon, typically nitrogen, oxygen or sulfur. Similarly, the term“heteroalkyl” refers to an alkyl substituent that is heteroatom-containing, the term“heterocyclic” refers to a cyclic substituent that is heteroatom- containing, the terms“heteroaryl” and“heteroaromatic” respectively refer to“aryl” and“aromatic” substituents that are heteroatom-containing, and the like. It should be noted that a“heterocyclic” group or compound may or may not be aromatic, and further that“heterocycles” may be monocyclic, bicyclic, or polycyclic as described above with respect to the term“aryl.” Examples of heteroalkyl groups include alkoxyaryl, alkylsulfanyl-substituted alkyl, N-alkylated amino alkyl, and the like. Examples of heteroaryl substituents include pyrrolyl, pyrrolidinyl, pyridinyl, quinolinyl, indolyl, pyrimidinyl, imidazolyl, 1,2,4-triazolyl, tetrazolyl, etc., and examples of heteroatom-containing alicyclic groups are pyrrolidino, morpholino, piperazino, piperidino, etc.

[0057] By“substituted” as in“substituted hydrocarbyl,”“substituted alkyl,”“substituted aryl,” and the like, as alluded to in some of the aforementioned definitions, is meant that in the hydrocarbyl, alkyl, aryl, or other moiety, at least one hydrogen atom bound to a carbon (or other) atom is replaced with one or more non-hydrogen substituents. Examples of such substituents include, without limitation:

functional groups referred to herein as“Fn,” such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₂-C₂₄ alkenyloxy, C₂-C₂₄ alkynyloxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂- C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂- C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (-COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)- NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)₂), mono-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)₂), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH2), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH2), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (- (CO)-H), thioformyl (-(CS)-H), amino (-NH₂), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁-C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted amino (- NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)2), C₂-C₂₄ alkylamido (-NH-(CO)- alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino

(-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (-CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), nitro (-NO₂), nitroso (-NO), sulfo (-SO₂-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S- aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO₂-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO₂-N(H) alkyl), C₁-C₂₄

dialkylaminosulfonyl (-SO2-N(alkyl)2), C₅-C₂₄ arylsulfonyl (-SO2-aryl), boryl (-BH2), borono (- B(OH)2), boronato (-B(OR)2 where R includes without limitation alkyl or other hydrocarbyl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), and phosphino (-PH2); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁2 alkyl, more preferably C₁-C₆ alkyl), C₂-C₂₄ alkenyl (preferably C₂-C₁2 alkenyl, more preferably C₂-C₆ alkenyl), C₂-C₂₄ alkynyl (preferably C₂-C₁₂ alkynyl, more preferably C₂-C₆ alkynyl), C₅-C₂₄ aryl (preferably C₅-C₁₄ aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl).

[0058] By“functionalized” as in“functionalized hydrocarbyl,”“functionalized alkyl,”

“functionalized olefin,”“functionalized cyclic olefin,” and the like, is meant that in the hydrocarbyl, alkyl, olefin, cyclic olefin, or other moiety, at least one hydrogen atom bound to a carbon (or other) atom is replaced with one or more functional groups such as those described hereinabove. The term “functional group” is meant to include any functional species that is suitable for the uses described herein.

[0059] The term“nil” as used herein, means nonexistent or absent. [0060] In addition, the aforementioned functional groups may, if a particular group permits, be further substituted with one or more additional functional groups or with one or more hydrocarbyl moieties such as those specifically enumerated above. Analogously, the above-mentioned hydrocarbyl moieties may be further substituted with one or more functional groups or additional hydrocarbyl moieties such as those specifically enumerated.

[0061] The terms“1,2-diol” and“vicinal diol” are used interchangeably herein, and are intended to have the same meaning.

[0062] The term“internal olefin” as used herein means an olefin wherein each of the olefinic carbons is substituted by at least one non-hydrogen substituent. The internal olefin may be di- substituted, tri-substituted, or tetra-substituted. The“internal olefin” may have an E-configuration or a Z-configuration.

[0063] The term“terminal olefin” as used herein means an olefin wherein one of the olefinic carbons is substituted by at least one non-hydrogen substituent. The terminal olefin may be di- substituted or mono-substituted.

[0064] The term“reactant internal olefin” as used herein means an internal olefin (i.e., an internal C=C double bond) present in an olefin compound used in a cross-metathesis reaction with another olefin compound to form a cross-metathesis product. The“reactant internal olefin” may be di-substituted, tri- substituted, or tetra-substituted. The“reactant internal olefin” may have an E-configuration or a Z- configuration.

[0065] The term“reactant terminal olefin” as used herein means a terminal olefin (i.e., a terminal C=C double bond) present in an olefin compound used in a cross-metathesis reaction with another olefin compound.

[0066] The term“cross-metathesis product” as used herein means at least one olefin product formed as a result of a cross-metathesis reaction between a first olefin reactant and a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction, wherein the first olefin reactant and the second olefin reactant may be the same or different, and wherein the at least one olefin product comprises an internal C=C double bond. The internal C=C double bond may be di-substituted, tri-substituted, or tetra-substituted, and the internal C=C double bond may have an E-configuration or a Z-configuration, preferably a Z-configuration. In one embodiment the“cross- metathesis product” is at least one olefin product comprising an internal C=C double bond, wherein the internal C=C double bond is di-substituted, and the internal C=C double bond has a Z-configuration.

[0067] The term“product internal olefin” as used herein means an internal olefin (i.e., an internal C=C double bond) present in a cross-metathesis product formed by a cross-metathesis reaction, wherein each of the olefinic carbons of the internal olefin is substituted by at least one non-hydrogen substituent. The“product internal olefin” may be di-substituted, tri-substituted, or tetra-substituted. The“product internal olefin” may have an E-configuration or a Z-configuration. Preferably the“product internal olefin” has a Z-configuration. In one embodiment, the“product internal olefin” is di-substituted. In one embodiment, the“product internal olefin” has a Z-configuration and is di-substituted.

[0068] The term“ruthenium species” as used herein refers to RuCl₃ as a hydrate but also to anhydrous RuCl₃, RuO₄, or Ruthenium salts such as Ru(III)(acetylacetonate), RuI₃, Dichloro(p- cymene)ruthenium(II) dimer Ru(O) precursors, such as triruthenium dodecacarbonyl. In the case of ruthenium catalyzed dihydroxylation conditions the“ruthenium species” can also refer to Grubbs-type Ru-alkylidenes 1^st or 2^nd generation catalysts. In the case of ruthenium catalyzed dihydroxylation conditions, the“ruthenium species” may also refer to an in situ generated Ru-based oxidation catalyst, wherein the in situ generated Ru-based oxidation catalyst is derived from a C-H activated catalyst complex as described and used herein. Without being bound by theory, an in situ Ru-based oxidation catalyst is thought to be generated upon subjecting a C-H activated catalyst complex (or a cross- metathesis mixture comprising a C-H activated catalyst complex) to oxidation conditions and/or oxidizing agents and/or dihydroxylation conditions.

[0069] Those of ordinary skill in the art would understand the meaning of terms“syn” and“anti” as used within the context of the invention. Examples used herein include,“syn-diol” and“anti-diol” or “syn-stereochemistry” and“anti-stereochemistry.”

[0070] The term“multitasking Ru-catalyst” refers to a cyclometalated ruthenium complex which catalyses first a Z-selective cross-metathesis of two terminal olefins followed by a stereospecific dihydroxylation. Both steps are catalyzed by the ruthenium Ru, as the Ru-complex is converted to a dihydroxylation catalyst upon addition of NaIO_4. [0071] The term“enantioenriched,” refers to mirror images, when one chiral center is present or when 2 or more chiral centers are present and the enantiomeric or diastereomeric ratio is greater than 50:50 but less than 100:1.

[0072] The term“enantiopure,” refers to mirror images, when one chiral center is present or when 2 or more chiral centers are present and the enantiomeric or diastereomeric ratio is greater than 95%.

[0073] “Optional” or“optionally” means that the subsequently described circumstance may or may not occur, so that the description includes instances where the circumstance occurs and instances where it does not. For example, the phrase“optionally substituted” means that a non-hydrogen substituent may or may not be present on a given atom, and, thus, the description includes structures wherein a non- hydrogen substituent is present and structures wherein a non-hydrogen substituent is not present.

[0074] Functional groups may be protected in cases where the functional group interferes with the metathesis catalyst, and any of the protecting groups commonly used in the art may be employed.

Acceptable protecting groups may be found, for example, in Greene et al., Protective Groups in Organic Synthesis, 3rd Ed. (New York: Wiley, 1999).

[0075] The term“C-H activated” refers to the cleavage of a carbon-hydrogen (C-H) bond of a ligand by the metal in a transition metal complex to form a resultant transition metal complex having a metal-carbon (M-C) bond. This reaction type is also called cyclometallation. See C. Elschenbroich in “Organometallics” 1989 VCH page 439; ACS Symposium Series, Vol. 485“Organometallic C—H Bond Activation: An Introduction” A. Goldman and K. Goldberg, publication date July 12, 2004, Copyright © 2004 American Chemical Society; and Janowicz, A. H. & Bergman, R. G. J. Am. Chem. Soc.1982, 104, 352-354. The terms“C-H activated” and“cyclometalated” are used interchangeably herein.

Catalyst Complexes

[0076] In general, the C-H activated catalyst complexes of the invention comprise a Group 8 metal (M), an alkylidene moiety (=CR¹R²), an anionic ligand (X¹), a neutral ligand (L¹), and a heterocyclic carbene ligand that is linked to the metal via a 2-electron anionic donor bridging moiety (Q*). The olefin metathesis catalyst complex is preferably a Group 8 transition metal complex may be represented by the structure of Formula (I):

in which:

L¹ is a neutral electron donor ligand;

Q* is a 2-electron anionic donor bridging moiety linking R³ and Ru; and may be hydrocarbylene (including substituted hydrocarbylene, heteroatom-containing hydrocarbylene, and substituted heteroatom-containing hydrocarbylene, such as substituted and/or heteroatom-containing alkylene) or - (CO)-;

Q is a linker, typically a hydrocarbylene linker, including substituted hydrocarbylene, heteroatom- containing hydrocarbylene, and substituted heteroatom-containing hydrocarbylene linkers, wherein two or more substituents on adjacent atoms within Q may also be linked to form an additional cyclic structure, which may be similarly substituted to provide a fused polycyclic structure of two to about five cyclic groups. Q is often, although again not necessarily, a two-atom linkage or a three-atom linkage;

X is an atom selected from C, N, O, S, and P. Since O and S are divalent, n is necessarily zero when X is O or S. Similarly, when X is N or P, then n is 1, and when X is C, then n is 2;

R¹ and R² are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), heteroatom-containing hydrocarbyl (e.g., heteroatom-containing C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), and substituted heteroatom-containing hydrocarbyl (e.g., substituted heteroatom-containing C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), and functional groups. R¹ and R² may also be linked to form a cyclic group, which may be aliphatic or aromatic, and may contain substituents and/or heteroatoms. Generally, such a cyclic group will contain 4 to 12, preferably 5, 6, 7, or 8 ring atoms;

R³ and R⁴ are independently selected from hydrocarbyl, substituted hydrocarbyl, heteroatom- containing hydrocarbyl, and substituted heteroatom-containing, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), heteroatom-containing hydrocarbyl (e.g., heteroatom-containing C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), and substituted heteroatom-containing hydrocarbyl (e.g., substituted heteroatom-containing C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, C₂-C₂₀ alkynyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), and functional groups; and

X¹ is a bidentate anionic ligand. Typically, X¹ is nitrate, C₁-C₂₀ alkylcarboxylate, C₆-C₂₄ arylcarboxylate, C₂-C₂₄ acyloxy, C₁-C₂₀ alkylsulfonato, C₅-C₂₄ arylsulfonato, C₁-C₂₀ alkylsulfanyl, C₅- C₂₄ arylsulfanyl, C₁-C₂₀ alkylsulfinyl, or C₅-C₂₄ arylsulfinyl. In some embodiments, X¹ is benzoate, pivalate, nitrate, an N-acetyl amino carboxylate, O-methyl mandelate, or a carboxylate derived from 2- phenylbutyric acid. More specifically, X¹ may be is CF₃CO₂, CH₃CO₂, CH₃CH₂CO₂, CFH₂CO₂, (CH3)3CO2, (CH3)2CHCO2, (CF3)2(CH3)CO2, (CF3)(CH3)2CO2, benzoate, naphthylate, tosylate, mesylate, or trifluoromethane-sulfonate. In one embodiment, X¹ is nitrate (NO - 3 ).

[0077] In certain catalysts, R¹ is hydrogen and R² is selected from C₁-C₂₀ alkyl, C₂-C₂₀ alkenyl, and C₅-C₂₄ aryl, more preferably C₁-C₆ alkyl, C₂-C₆ alkenyl, and C₅-C₁₄ aryl. Still more preferably, R² is phenyl, vinyl, methyl, isopropyl, or t-butyl, optionally substituted with one or more moieties selected from C₁-C₆ alkyl, C₁-C₆ alkoxy, and phenyl. Most preferably, R² is phenyl or vinyl substituted with one or more moieties selected from methyl, ethyl, chloro, bromo, iodo, fluoro, nitro, dimethylamino, methyl, methoxy, ethoxy, isopropoxy, butoxy, and phenyl. More specifically, R² may be phenyl or - CH=C(CH₃)₂. In another embodiment, R² is phenyl. In another embodiment, R² is phenyl substituted with one or more moieties selected from methyl, ethyl, chloro, bromo, iodo, fluoro, nitro,

dimethylamino, methyl, methoxy, ethoxy, isopropoxy, butoxy, and phenyl. [0078] Any two or more (typically two, three, or four) of X¹, L¹, R¹, and R² can be taken together to form a cyclic group, including bidentate or multidentate ligands, as disclosed, for example, in U.S. Patent No. 5,312,940 to Grubbs et al. When any of X¹, L¹, R¹, and R² are linked to form cyclic groups, those cyclic groups may contain 4 to 12, preferably 4, 5, 6, 7, or 8 atoms, or may comprise two or three of such rings, which may be either fused or linked.

[0079] In particular embodiments, Q is a two-atom linkage having the structure -CR¹¹R¹²-CR¹³R¹⁴- or -CR¹¹=CR¹³-, preferably -CR¹¹R¹²-CR¹³R¹⁴-, wherein R¹¹, R¹², R¹³, and R¹⁴ are independently selected from hydrogen, hydrocarbyl, substituted hydrocarbyl, heteroatom-containing hydrocarbyl, substituted heteroatom-containing hydrocarbyl, and functional groups. Examples of suitable functional groups include carboxyl, C₁-C₂₀ alkoxy, C₅-C₂₄ aryloxy, C₂-C₂₀ alkoxycarbonyl, C₅-C₂₄ alkoxycarbonyl, C₂-C₂₄ acyloxy, C₁-C₂₀ alkylthio, C₅-C₂₄ arylthio, C₁-C₂₀ alkylsulfonyl, and C₁-C₂₀ alkylsulfinyl, optionally substituted with one or more moieties selected from C₁-C₁₂ alkyl, C₁-C₁₂ alkoxy, C₅-C₁₄ aryl, hydroxyl, sulfhydryl, formyl, and halide. R¹¹, R¹², R¹³, and R¹⁴ are preferably independently selected from hydrogen, C₁-C₁₂ alkyl, substituted C₁-C₁₂ alkyl, C₁-C₁₂ heteroalkyl, substituted C₁-C₁₂

heteroalkyl, phenyl, and substituted phenyl. Alternatively, any two of R¹¹, R¹², R¹³, and R¹⁴ may be linked together to form a substituted or unsubstituted, saturated or unsaturated ring structure, e.g., a C4- C₁2 alicyclic group or a C₅ or C₆ aryl group, which may itself be substituted, e.g., with linked or fused alicyclic or aromatic groups, or with other substituents. In one further aspect, any one or more of R¹¹, R¹², R¹³, and R¹⁴ comprises one or more of the linkers.

[0080] In more particular aspects, R³ and R⁴ may be alkyl or aryl, and may be independently selected from alkyl, aryl, cycloalkyl, heteroalkyl, alkenyl, alkynyl, and halo or halogen- containing groups. More specifically, R³ and R⁴ may be independently selected from C₁-C₂₀ alkyl, C₅-C₁₄ cycloalkyl, C₁-C₂₀ heteroalkyl, or halide. Suitable alkyl groups include, without limitation, methyl, ethyl, n-propyl, isopropyl, isopropyl, n-butyl, isobutyl, t-butyl, octyl, decyl, and the like; suitable cycloalkyl groups include cyclopentyl, cyclohexyl, adamantyl, pinenyl, terpenes and terpenoid derivatives and the like; suitable alkenyl groups include ethenyl, n-propenyl, isopropenyl, n-butenyl, isobutenyl, octenyl, decenyl, tetradecenyl, hexadecenyl, eicosenyl, tetracosenyl, and the like; suitable alkynyl groups include ethynyl, n-propynyl, and the like. [0081] When R³ or R⁴ are aromatic, each may be independently composed of one or two aromatic rings, which may or may not be substituted, e.g., R³ and R⁴ may be phenyl, substituted phenyl, biphenyl, substituted biphenyl, or the like. In a particular embodiment, R³ and R⁴ are independently an

unsubstituted phenyl or phenyl substituted with up to three substituents selected from C₁-C₂₀ alkyl, C₁- C₂₀ alkylcarboxylate, substituted C₁-C₂₀ alkyl, C₁-C₂₀ heteroalkyl, substituted C₁-C₂₀ heteroalkyl, C₅-C₂₄ aryl, substituted C₅-C₂₄ aryl, C₅-C₂₄ heteroaryl, C₆-C₂₄ aralkyl, C₆-C₂₄ alkaryl, or halide. Preferably, any substituents present are hydrogen C₁-C₁2 alkyl, C₁-C₁2 alkoxy, C₅-C₁4 aryl, substituted, C₅-C₁4 aryl, or halide. More particularly, R³ and R⁴ may be independently substituted with hydrogen, C₁-C₄ alkyl, C₁- C4 alkylcarboxylate, C₁-C4 alkoxy, C₅-C₁4 aryl, substituted C₅-C₁4 aryl, or halide. As an example, R³ and R⁴ are selected from cyclopentyl, cyclohexyl, adamantyl, norbonenyl, pinenyl, terpenes and terpenoid derivatives, mesityl, diisopropylphenyl or, more generally, cycloalkyl substituted with one, two or three C₁-C₄ alkyl or C₁-C₄ alkoxy groups, or a combination thereof.

[0082] Particular complexes wherein R² and L¹ are linked to form a chelating carbene ligand are examples of another group of catalysts, and are commonly called“Grubbs-Hoveyda” catalysts. In one embodiment, C-H activated catalysts are C-H activated Grubbs-Hoveyda metathesis-active metal carbene complexes, C-H activated Grubbs-Hoveyda metathesis-active metal carbene complexes of the invention may be represented by the structure of Formula (II):

wherein,

X¹, Q, Q*, R³, and R⁴ are as previously defined for Formula (I);

Y is a heteroatom selected from N, O, S, and P; preferably Y is O or N; more preferably O;

R⁵, R⁶, R⁷, and R⁸ are each, independently, selected from hydrogen, halogen, alkyl, alkenyl, alkynyl, aryl, heteroalkyl, heteroatom containing alkenyl, heteroalkenyl, heteroaryl, alkoxy, alkenyloxy, aryloxy, alkoxycarbonyl, carbonyl, alkylamino, alkylthio, aminosulfonyl, monoalkylaminosulfonyl, dialkylaminosulfonyl, alkylsulfonyl, nitrile, nitro, alkylsulfinyl, trihaloalkyl, perfluoroalkyl, carboxylic acid, ketone, aldehyde, nitrate, cyano, isocyanate, hydroxyl, ester, ether, amine, imine, amide, halogen- substituted amide, trifluoroamide, sulfide, disulfide, sulfonate, carbamate, silane, siloxane, phosphine, phosphate, or borate, wherein any combination of R⁵, R⁶, R⁷, and R⁸ can be linked to form one or more cyclic groups; preferably R⁵, R⁶, R⁷, and R⁸ are each hydrogen;

X is an atom selected from C, N, O, S, and P. Since O and S are divalent, n is necessarily zero when X is O or S. Similarly, when X is N or P, then n is 1 , and when X is C, then n is 2; preferably X is N and n is 1;

m is 1 or 2, such that m is 1 for the divalent heteroatoms O or S, and m is 2 for the trivalent heteroatoms N or P; and

Z is a group selected from hydrogen, alkyl, aryl, functionalized alkyl, functionalized aryl where the functional group(s) may independently be one or more or the following: alkoxy, aryloxy, halogen, carboxylic acid, ketone, aldehyde, nitrate, cyano, isocyanate, hydroxyl, ester, ether, amine, imine, amide, trifluoroamide, sulfide, disulfide, carbamate, silane, siloxane, phosphine, phosphate, or borate; methyl, isopropyl, sec-butyl, t-butyl, neopentyl, benzyl, phenyl and trimethylsilyl; and wherein any combination or combinations of X¹, Q*, Y, Z, R⁵, R⁶, R⁷, and R⁸ may be linked to a support. In one embodiment, Z is selected from C₁-C₆ alkyl, functionalized C₁-C₆ alkyl, aryl, and functionalized aryl. In another embodiment, Z is selected from C₁-C₆ alkyl and aryl. In another embodiment, Z is selected from C₁-C₆ alkyl and phenyl. In another embodiment, Z is selected from methyl, ethyl, n-butyl, n-propyl, iso-butyl, iso-propyl, and sec-butyl. In another embodiment, Z is isopropyl.

[0083] Unless otherwise specified, C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II), as well as any specific C-H activated catalyst complexes shown herein or incorporated herein by reference may be used in racemate (racemic) form or in enantioenriched (enantiomerically enriched) form or in enantiopure (enantiomerically pure) form or in diastereoenriched (diastereomerically enriched) form or in diastereopure (diastereomerically pure) form.

[0084] Examples of C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) include the following:

,

[0085] Examples of C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) include the following:

,

[0086] Examples of C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) include the following:

or

[0087] Examples of C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) include the following:

.

xes represented by the structure of Formula (I) or Formula (II) include the following:

.

[0089] An example of a C-H activated catalyst complex represented by the structure of Formula (I) or Formula (II) includes the following:

.

[ ] p es of C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) include the following: .

[0091] Examples of C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) include the following: )

, , ,

, , ,

, .

[0093] Examples of C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) include the following:

,

.

[0094] C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) for use in the present invention include those mentioned above and those further disclosed in International Pat. App. No. PCT/US2012/021609, the contents of which are incorporated herein by reference.

[0095] C-H activated catalyst complexes represented by the structure of Formula (I) or Formula (II) for use in the present invention include those mentioned above and those further disclosed in International Pat. App. No. PCT/US2013/074783, the contents of which are incorporated herein by reference.

Tandem Z-Selective Cross-Metathesis / Stereospecific Dihydroxylation

[0096] In general the tandem Z-selective cross-metathesis / stereospecific dihydroxylation reaction comprises a cross-metathesis reaction comprising:

contacting a first olefin reactant and a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, and wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and

an oxidation reaction comprising contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [0097] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[0098] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis reaction is performed under static vacuum; and

contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[0099] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00100] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis reaction is performed under static vacuum; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00101] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under oxidation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00102] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with an oxidizing agent under oxidation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00103] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under oxidation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00104] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis reaction is performed under static vacuum; and

contacting the cross-metathesis mixture with an oxidizing agent under oxidation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00105] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and reacting the cross-metathesis mixture under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00106] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00107] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and reacting the cross-metathesis mixture under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00108] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00109] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and reacting the cross-metathesis mixture under oxidation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00110] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under oxidation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00111] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and reacting the cross-metathesis mixture under oxidation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00112] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under oxidation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00113] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and reacting the cross-metathesis mixture under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00114] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00115] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and reacting the cross-metathesis mixture under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00116] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00117] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and reacting the cross-metathesis mixture under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00118] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00119] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00120] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00121] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00122] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross- metathesis reaction is performed under static vacuum; and contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00123] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00124] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00125] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00126] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis reaction is performed under static vacuum; and

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00127] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product; and

[00128] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the cross- metathesis reaction is performed under static vacuum; and

[00129] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00130] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00131] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00132] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the cross- metathesis reaction is performed under static vacuum; and contacting the cross-metathesis mixture with an oxidizing agent under oxidation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00133] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00134] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00135] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00136] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00137] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00138] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00139] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product; and

[00140] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00141] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00142] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00143] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00144] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00145] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product; and reacting the cross-metathesis mixture under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00146] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00147] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00148] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the cross- metathesis reaction is performed under static vacuum; and contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00149] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00150] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00151] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry. [00152] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00153] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00154] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00155] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product; and

contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00156] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00157] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00158] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00159] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin; and

[00160] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the cross-metathesis reaction is performed under static vacuum; and

[00161] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00162] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00163] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00164] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00165] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00166] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00167] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin; and

[00168] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00169] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00170] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00171] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00172] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00173] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin; and

[00174] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00175] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00176] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the cross-metathesis reaction is performed under static vacuum; and

[00177] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00178] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the cross-metathesis mixture under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00179] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00180] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00181] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00182] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00183] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00184] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the cross-metathesis reaction is performed under static vacuum; and contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00185] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00186] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00187] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin; and contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00188] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00189] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00190] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00191] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the product internal olefin with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00192] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00193] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the product internal olefin with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one vicinal diol, wherein the at least one vicinal diol has anti stereochemistry.

[00194] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00195] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and

[00196] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and

contacting the at least one cross-metathesis product with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00197] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration, wherein the cross-metathesis reaction is performed under static vacuum; and

[00198] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration, wherein the cross-metathesis reaction is performed under static vacuum; and

contacting the at least one cross-metathesis product with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00199] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00200] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and

contacting the at least one cross-metathesis product with an oxidizing agent under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00201] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration, wherein the cross-metathesis reaction is performed under static vacuum; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00202] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00203] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00204] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the at least one cross-metathesis product with an oxidizing agent under oxidation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00205] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00206] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00207] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and

[00208] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the at least one cross-metathesis product with an oxidizing agent under oxidation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00209] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with an oxidizing agent under oxidation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00210] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00211] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00212] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the at least one cross-metathesis product under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00213] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00214] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the at least one cross-metathesis product under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00215] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and reacting the cross-metathesis mixture under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00216] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the at least one cross-metathesis product under conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00217] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00218] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00219] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00220] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the at least one cross-metathesis product under oxidation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00221] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00222] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00223] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00224] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and

reacting the at least one cross-metathesis product under oxidation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00225] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00226] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the at least one cross-metathesis product under oxidation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00227] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00228] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the at least one cross-metathesis product under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00229] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration, wherein the cross-metathesis reaction is performed under static vacuum; and reacting the cross-metathesis mixture under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00230] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00231] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00232] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

reacting the at least one cross-metathesis product under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00233] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00234] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00235] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and

[00236] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00237] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry. [00238] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00239] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00240] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00241] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00242] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00243] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00244] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00245] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00246] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00247] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the cross-metathesis mixture with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00248] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00249] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration, wherein the cross-metathesis reaction is performed under static vacuum; and

[00250] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00251] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry. [00252] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00253] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00254] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration, wherein the cross-metathesis reaction is performed under static vacuum; and contacting the at least one cross-metathesis product with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00255] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00256] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00257] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00258] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00259] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the product internal olefin with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00260] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration; and

[00261] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00262] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the product internal olefin with a ruthenium species under dihydroxylation conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry. [00263] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting the product internal olefin with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00264] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00265] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture, wherein the cross-metathesis mixture comprises at least one cross-metathesis product, wherein the at least one cross-metathesis product comprises a product internal olefin, wherein the product internal olefin is in a Z-configuration, wherein the cross-metathesis reaction is performed under static vacuum; and contacting the product internal olefin with a ruthenium species under dihydroxylation conditions to promote a stereospecific dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00266] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

[00267] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry; and

further contacting the cross-metathesis mixture with an acid.

[00268] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

further contacting the cross-metathesis mixture with a Brønsted acid.

[00269] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

further contacting the cross-metathesis mixture with a Lewis acid.

[00270] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

further contacting the cross-metathesis mixture with a Brønsted acid selected from H2SO4, HOAc, H₃PO₄, TFA, benzoic acid, citric acid, MeSO₃H, p-toluene sulfonic acid, HCl, and HNO_3.

[00271] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent, wherein the oxidizing agent comprises a ruthenium species, under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00272] In one embodiment, the invention provides a method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant, wherein the first olefin or the second olefin lack an electron withdrawing group at the allylic position, in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and

contacting the cross-metathesis mixture with an oxidizing agent, wherein the oxidizing agent comprises a ruthenium species, under conditions to promote a dihydroxylation reaction to form at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00273] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

further contacting the cross-metathesis mixture with a Lewis acid is selected from CeCl3 and YbCl₃ or La(OTf)_3.

ther embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant comprising a reactant terminal olefin with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00275] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant comprising a reactant terminal olefin, in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and

contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one vicinal diol, wherein the vicinal diol has anti stereochemistry.

[00276] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant comprising a reactant terminal olefin with a second olefin reactant comprising a reactant terminal olefin in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and

[00277] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant comprising a reactant terminal olefin with a second olefin reactant comprising a reactant internal olefin in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and

[00278] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising: contacting a first olefin reactant comprising a reactant internal olefin with a second olefin reactant comprising a reactant terminal olefin in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and

[00279] In another embodiment, the invention provides a method for tandem Z-selective cross- metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant comprising a reactant internal olefin with a second olefin reactant comprising a reactant internal olefin in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and

[00280] A method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one compound comprising an anti-diol.

[00281] A method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

contacting a first olefin reactant with a second olefin reactant in the presence of a C-H activated catalyst under conditions to promote a cross-metathesis reaction to form a cross-metathesis mixture; and contacting the cross-metathesis mixture with an oxidizing agent under conditions to promote a dihydroxylation reaction to form at least one compound comprising an anti 1,2-diol.

[00282] Any of the embodiments described herein may be optionally performed under any conditions that remove any inhibitory bi-products (e.g., ethylene, or any bi-product that inhibits dihydroxylation) from a reaction (e.g., a cross-metathesis reaction, or a dihydroxylation reaction). In any of the embodiments described herein, the reaction (e.g., a cross-metathesis reaction, or a dihydroxylation reaction) may be optionally performed under inert gas purge (e.g., argon purge, nitrogen purge, helium purge), under vacuum (vacuum conditions), for example static vacuum (static vacuum conditions) or dynamic vacuum (dynamic vacuum conditions). Preferably, in any of the embodiments described herein, the cross-metathesis reaction is performed under static vacuum. In another example, any inhibitory bi-products (e.g., ethylene, or any bi-product that inhibits dihydroxylation) may be removed from a cross-metathesis mixture during a cross-metathesis reaction or subsequent to performing a cross- metathesis reaction using any known technique including without limitation inert gas purge (e.g., argon purge, nitrogen purge, helium purge), under vacuum (vacuum conditions), for example static vacuum (static vacuum conditions) or dynamic vacuum (dynamic vacuum conditions).

Metathesis Conditions

[00283] Any set of conditions suitable for performing the cross-metathesis reaction may be utilized in the present invention. The cross-metathesis reactions utilized herein, may be homo-metathesis reactions or hetero-metathesis reactions. The term“homo-metathesis” as used herein, refers to a cross-metathesis reaction between a first olefin reactant and a second olefin reactant, wherein the first olefin reactant and the second olefin reactant are the same. The product formed from a“homo-metathesis” reaction comprises an internal C=C double bond, wherein the C=C double bond comprises one carbon atom from the C=C double bond of the first olefin reactant and one carbon atom from the C=C double bond of the second olefin reactant. As known by one of skill in the art, the internal C=C double bond of the homo-metathesis product may have either a Z-configuration or and E-configuration or a cis- configuration or a trans-configuration. Those of ordinary skill in the art would understand the meaning of terms“cis-configuration” or“trans-configuration” or“Z-configuration” or“E-configuration” as used within the context of the invention. Preferably, as provided herein, the internal C=C double bond of the homo-metathesis product is in the Z-configuration.

[00284] The term“hetero-metathesis” as used herein, refers to a cross-metathesis reaction between a first olefin reactant and a second olefin reactant, wherein the first olefin reactant and the second olefin reactant are different. The product formed from a“hetero-metathesis” reaction comprises an internal C=C double bond, wherein the C=C double bond comprises one carbon atom from the C=C double bond of the first olefin reactant and one carbon atom from the C=C double bond of the second olefin reactant. As known by one of skill in the art, the internal C=C double bond of the hetero-metathesis product may have either a Z-configuration or and E-configuration or a cis-configuration or a trans- configuration. Those of ordinary skill in the art would understand the meaning of terms“cis- configuration” or“trans-configuration” or“Z-configuration” or“E-configuration” as used within the context of the invention. Preferably, as provided herein, the internal C=C double bond of the hetero- metathesis product is in the Z-configuration.

[00285] According to the invention, the first olefin reactant and the second olefin reactant selected for the cross-metathesis reaction can both be reactant terminal olefins, both can be reactant internal olefins, or one can be a reactant terminal olefin and the other can be a reactant internal olefin, where the term reactant terminal olefin and reactant internal olefin are described herein. Moreover, those of ordinary skill in the art would understand the meaning of the terms terminal olefin and internal olefin. In one example, if two reactant terminal olefins are subjected to metathesis conditions, the two reactant terminal olefins may be the same or different. In another example, if two reactant internal olefins are subjected to metathesis conditions, the two reactant internal olefins may be the same or different. In another example, if a reactant terminal olefin and a reactant internal olefin are subjected to metathesis conditions, the reactant terminal olefin may be a single reactant terminal olefin or mixture of different reactant terminal olefins, and the reactant internal olefin may be a single reactant internal olefin or a mixture of different reactant internal olefins.

[00286] The cross-metathesis reaction may be performed in the presence or absence of solvent. Any solvent that does not interfere with the metathesis catalyst or the cross-metathesis reaction and/or the dihydroxylation reaction may be used in the present invention. An example of solvents for use in the cross-metathesis reaction include, without limitation, THF, dioxane, diethyl ether (Et₂O), CH₂Cl₂, ethyl acetate (EtOAc), or mixtures thereof.

[00287] The cross-metathesis reaction may be optionally performed under inert gas purge (e.g., argon purge, nitrogen purge, helium purge), under vacuum (vacuum conditions), for example static vacuum (static vacuum conditions) or dynamic vacuum (dynamic vacuum conditions). In one embodiment, the cross-metathesis reaction is performed under vacuum. In one embodiment, the cross-metathesis reaction is performed under static vacuum. Preferably, the cross-metathesis reaction is performed under static vacuum. In another example, any inhibitory bi-products (e.g., ethylene, or any bi-product that inhibits dihydroxylation) may be removed from a cross-metathesis mixture during a cross-metathesis reaction or subsequent to performing a cross-metathesis reaction using any known technique including without limitation inert gas purge (e.g., argon purge, nitrogen purge, helium purge), under vacuum (vacuum conditions), for example static vacuum (static vacuum conditions) or dynamic vacuum (dynamic vacuum conditions).

Oxidation Conditions

[00288] Any set of oxidation conditions suitable for performing the dihydroxylation reaction of a cross-metathesis product (e.g., a compound comprising a product internal olefin) may be utilized in the present invention. More particularly, any set of oxidation conditions suitable for performing a dihydroxylation reaction of a compound comprising a product internal olefin, wherein the product internal olefin is in the Z-configuration, to provide at least one compound comprising a vicinal diol, wherein the vicinal diol has anti stereochemistry, may be utilized in the present invention.

[00289] One example of ruthenium catalyzed dihydroxylation conditions include contacting a compound comprising a product internal olefin (e.g., a compound comprising a product internal olefin in the Z-configuration) with a mixture of NaIO₄ and CeCl₃ in MeCN:EtOAc:H₂O in the presence of a ruthenium species (see B. Plietker, J. Org. Chem. 2005, 70, 2402-2405).

[00290] Another example of ruthenium catalyzed dihydroxylation conditions include contacting a compound comprising a product internal olefin (e.g., a compound comprising a product internal olefin in the Z-configuration) with a mixture of NaIO4 and YbCl3 in MeCN:EtOAc:H2O in the presence of a ruthenium species (see S. Blechert, Angew. Chem. Int. Ed. 2006, 45, 1900-1903). Moreover, other Lanthanide based Lewis acids may also be suitable for use, such as La(OTf)₃.

[00291] Another example of ruthenium catalyzed dihydroxylation conditions include contacting a compound comprising a product internal olefin (e.g., a compound comprising a product internal olefin in the Z-configuration) with a mixture of NaIO₄ and H₂SO₄ in MeCN:EtOAc:H₂O in the presence of a ruthenium species (see B. Plietker, Org. Lett. 2003, 5, 3353-3356).

[00292] Another example of ruthenium catalyzed dihydroxylation conditions include contacting a compound comprising a product internal olefin (e.g., a compound comprising a product internal olefin in the Z-configuration) with a mixture of NaI0₄ and acid in MeCN:EtOAc:H₂0 in the presence of a ruthenium species, wherein the acid was selected from HOAc, H3PQ4, TFA, Benzoic acid, citric acid, MeSOsH, p-toluene sulfonic acid, HC₁, or HNOs (see B. Plietker, Org. Biomol. Chem. 2004, 5, 1 116).

[0Θ293] From the above examples, a phase transfer catalyst such as tetrabutylammonium iodide or chloride may also be used in addition to the other reagents. From the above examples, solvents such as THF, Et₂0, dioxane, and CH2CI2 may be used in place of or in conjunction with EtOAc. From the above examples, the addition of nucleophilic or basic additives such as NEtiCl, NEt.40H, NBIMOAC, and methane sulfonamide may be used in place or in conjunction with the acid. From the above examples, oxidizing agents other than NaI0₄ include N-methylmorpholine N-oxide, K3(Fe(CN)₆), HIO4,

Olefin Reactant Comprising a Reactant Terminal Olefin

[00294] In one example an olefin reactant comprising a reactant terminal olefin may be represented by the structure of Formula (III):

Formula (III) wherein, D¹ and D² are independently selected from nil, C 2, O, or S; and E¹ and E² are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-G.0 alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., Ci-C₂o heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom-containing hydrocarbyl (e.g., substituted Ci-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups ("Fn") such as halo, hydroxyl, sulf ydryl, C₁-C₂4 alkoxy, C₅-C₂4 aryloxy, Ce-Ci aralkyloxy, C₆-C₂4 alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (- COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)2), mono-(C₁- C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)₂), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di- (C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH2), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH₂), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH2), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁- C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (- CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆- C₂₄ aralkyl, etc.), nitro (-NO2), nitroso (-NO), sulfo (-SO2-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO₂-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO2-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO2-N(alkyl)2), C₅-C₂₄ arylsulfonyl (-SO₂-aryl), boryl (-BH₂), borono (-B(OH)₂), boronato (-B(OR)₂ where R is alkyl or aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), and phosphino (-PH2); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁2 alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁4 aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); where if E¹ and E² are the same, then D¹ and D² must be different, and if D¹ and D² are the same then E¹ and E² must be different.

[00295] Moreover, in one embodiment, for an olefin reactant comprising a reactant terminal olefin represented by the structure of Formula (III), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO2R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO₂R), sulfonic acid (-SO3H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), or nitro (-NO2), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂- C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO2R), sulfonyl (-SO2R), fluoromethyl (-CFn), fluroaryl (e.g., -C₆F5, p-CF3C₆H4), epoxide (e.g., epoxybutadiene), or cyano (-CN), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-COOR), ketone (-COR), aldehyde (-COH), halides (-Cl, -F, -Br, -I), carboxylic acid (-COOH), sulfonic acid (-SO3H), 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO₂), or phthalamide.

[00296] Another example an olefin reactant comprising a reactant terminal olefin may be represented by the structure of Formula (IV):

Formula (IV)

wherein, D³ is selected from nil, CH2, O, or S; and E³ is selected from hydrogen, hydrocarbyl (e.g., C₁- C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom-containing hydrocarbyl (e.g., substituted C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups (“Fn”) such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)- O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (-COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH2), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)₂), mono-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)2), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH2), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)₂), di- N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH2), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (– N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH₂), mono-(C₁- C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁-C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂- C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (-CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), nitro (-NO₂), nitroso (-NO), sulfo (-SO2-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (- (SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO₂-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO₂-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO₂-N(alkyl)₂), C₅-C₂₄ arylsulfonyl (-SO₂-aryl), boryl (-BH₂), borono (-B(OH)₂), boronato (-B(OR)2 where R is alkyl or aryl), phosphono (-P(O)(OH)2), phosphonato (-P(O)(OǦ)2), phosphinato (-P(O)(OǦ)), phospho (-PO₂), and phosphino (-PH₂); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁₂ alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁₄ aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); and where if E³ is hydrogen then D³ cannot be nil.

[00297] Moreover, in one embodiment, for an olefin reactant comprising a reactant terminal olefin represented by the structure of Formula (IV), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CFn), fluroaryl (e.g., -C₆F5, p-CF3C₆H4), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO₂R), sulfonic acid (-SO₃H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), or nitro (-NO₂), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂- C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO₂R), sulfonyl (-SO₂R), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), epoxide (e.g., epoxybutadiene), or cyano (-CN), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂- C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-COOR), ketone (-COR), aldehyde (-COH), halides (-Cl, -F, -Br, -I), carboxylic acid (-COOH), sulfonic acid (-SO₃H), 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO2), or phthalamide.

[00298] In another embodiment of the invention, an olefin reactant comprising a reactant terminal olefin may be represented by the structure of Formula (IV): wherein, D³ is CH₂, or substituted heteroatom-containing hydrocarbyl and E³ is a functional group (“Fn”) such as: acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carbamido (-NH-(CO)- NH2),–NH-(CO)-NHR,–NH-(CO)-NR², C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH- (CO)-aryl), nitro (-NO₂), nitroso (-NO), sulfo (-SO₂-OH), sulfonato (-SO₂-OǦ), C₁-C₂₄ alkylsulfinyl (- (SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO₂-alkyl), C₁-C₂₄

monoalkylaminosulfonyl (-SO2-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO2-N(alkyl)2), C₅-C₂₄ arylsulfonyl (-SO₂-aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), -O-P(O)(OR)_2, (wherein R is C₁-C₂₄ alkyl, (C₅-C₂₄ aryl), C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl), or an electron withdrawing group such as: ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (- NCO2R), sulfoxide (-SOR), sulfonyl (-SO2R), sulfonic acid (-SO3H), phthalamide, or nitro (-NO2), wherein R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl.

[00299] In another embodiment of the invention, an olefin reactant comprising a reactant terminal olefin may be represented by the structure of Formula (IV): wherein, D³ is CH₂, and E³ is an electron withdrawing group such as: ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), sulfonyl (-SO2R), sulfonic acid (-SO3H), phthalamide, or nitro (-NO₂), wherein R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl.

[00300] One or more olefin reactants comprising a reactant terminal olefin may be used with the invention described herein, wherein the one or more olefin reactants comprising a reactant terminal olefin may be the same or different.

Olefin Reactant Comprising a Reactant Internal Olefin

[00301] One or more olefin reactants comprising a reactant internal olefin may be used with the invention described herein, wherein the one or more olefin reactants comprising a reactant internal olefin may be the same or different.

[00302] In the one or more olefin reactants comprising a reactant internal olefin, the reactant internal olefin may be in the Z- or E-configuration. In one embodiment, in the one or more olefin reactants comprising a reactant internal olefin, the reactant internal olefin is in the Z-configuration. In one embodiment, in the one or more olefin reactants comprising a reactant internal olefin, the reactant internal olefin is in the E-configuration.

[00303] In one example an olefin reactant comprising a reactant internal olefin may be represented by the structure of Formula (V): _E ⁶ _D ^{6 D4 E4} ⁵

wherein, D⁴, D⁵, D⁶, and D⁷ are independently selected from nil, CH2, O, or S; and E⁴, E⁵, E⁶, and E⁷ are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅- C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom- containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom- containing hydrocarbyl (e.g., substituted C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅- C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups (“Fn”) such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (- COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH2), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)₂), mono-(C₁- C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)2), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di- (C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH₂), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH₂), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁- C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (- CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆- C₂₄ aralkyl, etc.), nitro (-NO2), nitroso (-NO), sulfo (-SO2-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO2-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO2-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO2-N(alkyl)2), C₅-C₂₄ arylsulfonyl (-SO₂-aryl), boryl (-BH₂), borono (-B(OH)₂), boronato (-B(OR)₂ where R is alkyl or aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), and phosphino (-PH2); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁₂ alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁₄ aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); where if E⁴ and E⁵ are the same, then D⁴ and D⁵ must be different, and if D⁴ and D⁵ are the same then E⁴ and E⁵ must be different, and where if E⁶ and E⁷ are the same, then D⁶ and D⁷ must be different, and if D⁶ and D⁷ are the same then E⁶ and E⁷ must be different.

[00304] Moreover, in one embodiment, for an olefin reactant comprising a reactant internal olefin represented by the structure of Formula (V), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CFn), fluroaryl (e.g., -C₆F5, p-CF3C₆H4), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO₂R), sulfonic acid (-SO₃H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), or nitro (-NO₂), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂- C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), sulfonyl (-SO₂R), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), epoxide (e.g., epoxybutadiene), or cyano (-CN), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-COOR), ketone (-COR), aldehyde (-COH), halides (-Cl, -F, -Br, -I), carboxylic acid (-COOH), sulfonic acid (-SO₃H), 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO2), or phthalamide.

[00305] In one example an olefin reactant comprising a reactant internal olefin may be represented by the structure of Formula (VI):

wherein, D⁸, D⁹, and D¹⁰ are independently selected from nil, CH₂, O, or S; and E⁸, E⁹, and E¹⁰ are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅- C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom- containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom- containing hydrocarbyl (e.g., substituted C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅- C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups (“Fn”) such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (- COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)2), mono-(C₁- C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)₂), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di- (C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH2), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH₂), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH2), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁- C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (- CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆- C₂₄ aralkyl, etc.), nitro (-NO2), nitroso (-NO), sulfo (-SO2-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO₂-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO2-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO2-N(alkyl)2), C₅-C₂₄ arylsulfonyl (-SO2-aryl), boryl (-BH2), borono (-B(OH)2), boronato (-B(OR)2 where R is alkyl or aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), and phosphino (-PH2); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁2 alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁4 aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); where if E⁸ and E⁹ are the same, then D⁸ and D⁹ must be different, and if D⁸ and D⁹ are the same then E⁸ and E⁹ must be different; and where if E¹⁰ is hydrogen, then D¹⁰ cannot be nil.

[00306] Moreover, in one embodiment, for an olefin reactant comprising a reactant internal olefin represented by the structure of Formula (VI), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CFn), fluroaryl (e.g., -C₆F5, p-CF3C₆H4), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO2R), sulfonic acid (-SO3H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), or nitro (-NO₂), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂- C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO₂R), sulfonyl (-SO₂R), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), epoxide (e.g., epoxybutadiene), or cyano (-CN), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-COOR), ketone (-COR), aldehyde (-COH), halides (-Cl, -F, -Br, -I), carboxylic acid (-COOH), sulfonic acid (-SO₃H), 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO2), or phthalamide.

[00307] In one example, an olefin reactant comprising a reactant internal olefin may be represented by the structure of Formula (VII):

wherein, D¹¹ and D¹² are independently selected from nil, CH₂, O, or S; and E¹¹ and E¹² are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom-containing hydrocarbyl (e.g., substituted C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups (“Fn”) such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (- COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)2), mono-(C₁- C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)₂), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di- (C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH₂), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH2), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁- C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (- CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆- C₂₄ aralkyl, etc.), nitro (-NO2), nitroso (-NO), sulfo (-SO2-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO2-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO2-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO2-N(alkyl)2), C₅-C₂₄ arylsulfonyl (-SO₂-aryl), boryl (-BH₂), borono (-B(OH)₂), boronato (-B(OR)₂ where R is alkyl or aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), and phosphino (-PH2); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁2 alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁₄ aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); and where if E¹¹ is hydrogen, then D¹¹ cannot be nil; and where if E¹² is hydrogen, then D¹² cannot be nil.

[00308] Moreover, in one embodiment, for an olefin reactant comprising a reactant internal olefin represented by the structure of Formula (VII), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO2R), sulfonic acid (-SO3H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), or nitro (-NO₂), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂- C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO2R), sulfonyl (-SO2R), fluoromethyl (-CFn), fluroaryl (e.g., -C₆F5, p-CF3C₆H4), epoxide (e.g., epoxybutadiene), or cyano (-CN), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-COOR), ketone (-COR), aldehyde (-COH), halides (-Cl, -F, -Br, -I), carboxylic acid (-COOH), sulfonic acid (-SO₃H), 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO₂), or phthalamide.

[00309] In another embodiment of the invention, an olefin reactant comprising a reactant terminal olefin may be represented by the structure of Formula (VII): wherein D¹¹ and D¹² are CH_2, and E¹¹ and E¹² are independently functional groups (“Fn”) such as: acyloxy (-O-acyl, including C₂-C₂₄

alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkylcarbonato (-O- (CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carbamido (-NH-(CO)-NH2),–NH-(CO)-NHR, –NH-(CO)-NR², C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), nitro (-NO₂), nitroso (-NO), sulfo (-SO2-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO2-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO2- N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO₂-N(alkyl)₂), C₅-C₂₄ arylsulfonyl (-SO₂-aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), -O-P(O)(OR)_2, (wherein R is C₁-C₂₄ alkyl, (C₅-C₂₄ aryl), C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl), or an electron withdrawing group such as: ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), sulfoxide (-SOR), sulfonyl (-SO₂R), sulfonic acid (-SO₃H), phthalamide, or nitro (-NO₂), wherein: R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl.

[00310] In another embodiment of the invention, an olefin reactant comprising a reactant terminal olefin may be represented by the structure of Formula (VII): wherein D¹¹ and D¹² are CH_2, and E¹¹ and E¹² are independently electron withdrawing groups such as: ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO₂R), sulfonyl (-SO₂R), sulfonic acid (-SO₃H), phthalamide, or nitro (-NO₂), wherein: R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl.

[00311] In one example an olefin reactant comprising a reactant internal olefin may be represented by the structure of Formula (VIII):

wherein, D¹³ and D¹⁴ are indepen

, or S; and E¹³ and E¹⁴ are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom-containing hydrocarbyl (e.g., substituted C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups (“Fn”) such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (- COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH2), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)₂), mono-(C₁- C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)2), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di- (C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH₂), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH2), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁- C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (- CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆- C₂₄ aralkyl, etc.), nitro (-NO2), nitroso (-NO), sulfo (-SO2-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO₂-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO2-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO2-N(alkyl)2), C₅-C₂₄ arylsulfonyl (-SO2-aryl), boryl (-BH2), borono (-B(OH)2), boronato (-B(OR)2 where R is alkyl or aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), and phosphino (-PH2); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁2 alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁4 aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); and where if E¹³ is hydrogen, then D¹³ cannot be nil; and where if E¹⁴ is hydrogen, then D¹⁴ cannot be nil.

[00312] Moreover, in one embodiment, for an olefin reactant comprising a reactant internal olefin represented by the structure of Formula (VIII), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO2R), sulfonic acid (-SO3H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO₂), or phthalamide.

Cross-Metathesis Product Comprising a Product Internal Olefin

[00313] One or more cross-metathesis products comprising a product internal olefin, wherein the product internal olefin is in the Z-configuration may be used with the invention described herein, wherein the one or more cross-metathesis products comprising a product internal olefin may be the same or different.

[00314] In one example an at least one cross-metathesis product comprising a product internal olefin, wherein the product internal olefin is in the Z-configuration may be represented by the structure of

Formula (IX):

wherein, D¹⁵, D¹⁶, D¹⁷, and D¹⁸ are independently selected from nil, CH₂, O, or S; and E¹⁵, E¹⁶, E¹⁷, and E¹⁸ are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom-containing hydrocarbyl (e.g., substituted C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom- containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups (“Fn”) such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (- COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH2), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)2), mono-(C₁- C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)2), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di- (C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)2), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH₂), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH2), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁- C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)2), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (- CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆- C₂₄ aralkyl, etc.), nitro (-NO₂), nitroso (-NO), sulfo (-SO₂-OH), sulfonato (-SO₂-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO2-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO₂-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO₂-N(alkyl)₂), C₅-C₂₄ arylsulfonyl (-SO₂-aryl), boryl (-BH₂), borono (-B(OH)₂), boronato (-B(OR)₂ where R is alkyl or aryl), phosphono (-P(O)(OH)2), phosphonato (-P(O)(OǦ)2), phosphinato (-P(O)(OǦ)), phospho (-PO2), and phosphino (-PH2); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁2 alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁₄ aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); where if E¹⁵ and E¹⁶ are the same, then D¹⁵ and D¹⁶ must be different, and if D¹⁵ and D¹⁶ are the same then E¹⁵ and E¹⁶ must be different, and where if E¹⁷ and E¹⁸ are the same, then D¹⁷ and D¹⁸ must be different, and if D¹⁷ and D¹⁸ are the same then E¹⁷ and E¹⁸ must be different.

[00315] Moreover, in one embodiment, for at least one cross-metathesis product comprising a product internal olefin represented by the structure of Formula (IX), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO2R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CFn), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO₂R), sulfonic acid (- SO₃H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), or nitro (-NO₂), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-OCOR), sulfonamide (-NRSO₂Ar), carbamate (-NCO₂R), sulfonyl (-SO₂R), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F5, p-CF3C₆H4), epoxide (e.g., epoxybutadiene), or cyano (-CN), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-COOR), ketone (-COR), aldehyde (-COH), halides (-Cl, -F, -Br, -I), carboxylic acid (-COOH), sulfonic acid (-SO3H), 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO2), or phthalamide.

[00316] In one example an at least one cross-metathesis product comprising a product internal olefin, wherein the product internal olefin is in the Z-configuration may be represented by the structure of

Formula (X):

wherein, D¹⁹, D²⁰, and D²¹ are independently selected from nil, CH₂, O, or S; and E¹⁹, E²⁰, and E²¹ are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅- C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom- containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom- containing hydrocarbyl (e.g., substituted C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅- C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups (“Fn”) such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (- COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)₂), mono-(C₁- C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)2), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di- (C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH2), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH2), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH₂), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁- C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (- CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆- C₂₄ aralkyl, etc.), nitro (-NO₂), nitroso (-NO), sulfo (-SO₂-OH), sulfonato (-SO₂-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO₂-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO₂-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO₂-N(alkyl)₂), C₅-C₂₄ arylsulfonyl (-SO2-aryl), boryl (-BH2), borono (-B(OH)2), boronato (-B(OR)2 where R is alkyl or aryl), phosphono (-P(O)(OH)2), phosphonato (-P(O)(OǦ)2), phosphinato (-P(O)(OǦ)), phospho (-PO2), and phosphino (-PH₂); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁₂ alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁4 aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); where if E¹⁹ and E²⁰ are the same, then D¹⁹ and D²⁰ must be different, and if D¹⁹ and D²⁰ are the same then E¹⁹ and E²⁰ must be different; and where if E²¹ is hydrogen, then D²¹ cannot be nil.

[00317] Moreover, in one embodiment, for at least one cross-metathesis product comprising a product internal olefin represented by the structure of Formula (X), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO₂R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F5, p-CF3C₆H4), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO2R), sulfonic acid (- SO3H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), or nitro (-NO2), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO2R), sulfonyl (-SO2R), fluoromethyl (-CFn), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), epoxide (e.g., epoxybutadiene), or cyano (-CN), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-COOR), ketone (-COR), aldehyde (-COH), halides (-Cl, -F, -Br, -I), carboxylic acid (-COOH), sulfonic acid (-SO₃H), 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO₂), or phthalamide. [00318] In one example an at least one cross-metathesis product comprising a product internal olefin, wherein the product internal olefin is in the Z-configuration may be represented by the structure of

Formula (XI):

wherein, D²² and D²³ are independently selected from nil, CH₂, O, or S; and E²² and E²³ are independently selected from hydrogen, hydrocarbyl (e.g., C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), substituted hydrocarbyl (e.g., substituted C₁-C₂₀ alkyl, C₅-C₂₀ aryl, C₅-C₃₀ aralkyl, or C₅-C₃₀ alkaryl), heteroatom-containing hydrocarbyl (e.g., C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl), and substituted heteroatom-containing hydrocarbyl (e.g., substituted C₁-C₂₀ heteroalkyl, C₅-C₂₀ heteroaryl, heteroatom-containing C₅-C₃₀ aralkyl, or heteroatom-containing C₅-C₃₀ alkaryl) and, if substituted hydrocarbyl or substituted heteroatom-containing hydrocarbyl, wherein the substituents may be functional groups (“Fn”) such as halo, hydroxyl, sulfhydryl, C₁-C₂₄ alkoxy, C₅-C₂₄ aryloxy, C₆-C₂₄ aralkyloxy, C₆-C₂₄ alkaryloxy, acyl (including C₂-C₂₄ alkylcarbonyl (-CO-alkyl) and C₆-C₂₄ arylcarbonyl (-CO-aryl)), acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkoxycarbonyl (-(CO)-O-alkyl), C₆-C₂₄ aryloxycarbonyl (-(CO)-O-aryl), halocarbonyl (-CO)-X where X is halo), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carboxy (- COOH), carboxylato (-COOǦ), carbamoyl (-(CO)-NH2), mono-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)₂), mono-(C₁- C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-NH(C₁-C₂₄ haloalkyl)), di-(C₁-C₂₄ haloalkyl)-substituted carbamoyl (-(CO)-N(C₁-C₂₄ haloalkyl)2), mono-(C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-NH-aryl), di- (C₅-C₂₄ aryl)-substituted carbamoyl (-(CO)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)- substituted carbamoyl (-(CO)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), thiocarbamoyl (-(CS)-NH₂), mono-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-NH(C₁-C₂₄ alkyl)), di-(C₁-C₂₄ alkyl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)₂), mono-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-NH-aryl), di-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₅-C₂₄ aryl)₂), di-N-(C₁-C₂₄ alkyl), N-(C₅-C₂₄ aryl)-substituted thiocarbamoyl (-(CS)-N(C₁-C₂₄ alkyl)(C₅-C₂₄ aryl), carbamido (-NH-(CO)-NH2), cyano (-CŁN), cyanato (-O-CŁN), thiocyanato (-S-CŁN), isocyanate (–N=C=O), thioisocyanate (–N=C=S), formyl (-(CO)-H), thioformyl (-(CS)-H), amino (-NH₂), mono-(C₁-C₂₄ alkyl)-substituted amino (-NH(C₁-C₂₄ alkyl), di-(C₁- C₂₄ alkyl)-substituted amino (-N(C₁-C₂₄ alkyl)2), mono-(C₅-C₂₄ aryl)-substituted amino (-NH(C₅-C₂₄ aryl), di-(C₅-C₂₄ aryl)-substituted amino (-N(C₅-C₂₄ aryl)₂), C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), imino (-CR=NH where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), C₂-C₂₀ alkylimino (-CR=N(alkyl), where R includes without limitation hydrogen, C₁-C₂₄ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl, etc.), arylimino (- CR=N(aryl), where R includes without limitation hydrogen, C₁-C₂₀ alkyl, C₅-C₂₄ aryl, C₆-C₂₄ alkaryl, C₆- C₂₄ aralkyl, etc.), nitro (-NO2), nitroso (-NO), sulfo (-SO2-OH), sulfonato (-SO2-OǦ), C₁-C₂₄ alkylsulfanyl (-S-alkyl; also termed“alkylthio”), C₅-C₂₄ arylsulfanyl (-S-aryl; also termed“arylthio”), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (-(SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO₂-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO₂-N(H) alkyl), C₁-C₂₄ dialkylaminosulfonyl (-SO₂-N(alkyl)₂), C₅-C₂₄ arylsulfonyl (-SO2-aryl), boryl (-BH2), borono (-B(OH)2), boronato (-B(OR)2 where R is alkyl or aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), and phosphino (-PH₂); and the hydrocarbyl moieties C₁-C₂₄ alkyl (preferably C₁-C₁₂ alkyl, more preferably C₁-C₆ alkyl), C₅-C₂₄ aryl (preferably C₅-C₁4 aryl), C₆-C₂₄ alkaryl (preferably C₆-C₁₆ alkaryl), and C₆-C₂₄ aralkyl (preferably C₆-C₁₆ aralkyl); and where if E²² is hydrogen, then D²² cannot be nil; and where if E²³ is hydrogen, then D²³ cannot be nil.

[00319] Moreover, in one embodiment, for at least one cross-metathesis product comprising a product internal olefin represented by the structure of Formula (XI), the functional groups may be selected from electron withdrawing groups. Examples of electron withdrawing groups of various embodiments may include, but are not limited to, aldehyde (-COH), ketone (-COR), acyl (-COR), carbonyl (-CO), carboxylic acid (-COOH), ester (-COOR), ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO₂R), epoxide (e.g., epoxybutadiene), halides (-Cl, -F, -Br, -I), fluoromethyl (-CF_n), fluroaryl (e.g., -C₆F₅, p-CF₃C₆H₄), cyano (-CN), sulfoxide (-SOR), sulfonyl (-SO₂R), sulfonic acid (- SO3H), phthalamide, 1°, 2°, and 3° ammonium (-NR ⁺

3 ), or nitro (-NO2), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO2R), sulfonyl (-SO2R), fluoromethyl (-CFn), fluroaryl (e.g., -C₆F5, p-CF3C₆H4), epoxide (e.g., epoxybutadiene), or cyano (-CN), wherein n is 1, 2, or 3, and R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl. Examples of electron withdrawing groups of various embodiments include ester (-COOR), ketone (-COR), aldehyde (-COH), halides (-Cl, -F, -Br, -I), carboxylic acid (-COOH), sulfonic acid (-SO3H), 1°, 2°, and 3° ammonium (-NR ⁺

3 ), nitro (-NO₂), or phthalamide.

[00320] In another embodiment of the invention, an at least one cross-metathesis product comprising a product internal olefin, wherein the product internal olefin is in the Z-configuration, may be represented by the structure of Formula (XI): wherein, D²² and D²³ are CH2, and E²² and E²³ are independently functional groups (“Fn”) such as: acyloxy (-O-acyl, including C₂-C₂₄ alkylcarbonyloxy (-O-CO-alkyl) and C₆-C₂₄ arylcarbonyloxy (-O-CO-aryl)), C₂-C₂₄ alkylcarbonato (-O-(CO)-O-alkyl), C₆-C₂₄ arylcarbonato (-O-(CO)-O-aryl), carbamido (-NH-(CO)-NH2),–NH-(CO)-NHR,–NH-(CO)- NR², C₂-C₂₄ alkylamido (-NH-(CO)-alkyl), C₆-C₂₄ arylamido (-NH-(CO)-aryl), nitro (-NO₂), nitroso (-NO), sulfo (-SO₂-OH), sulfonato (-SO₂-OǦ), C₁-C₂₄ alkylsulfinyl (-(SO)-alkyl), C₅-C₂₄ arylsulfinyl (- (SO)-aryl), C₁-C₂₄ alkylsulfonyl (-SO2-alkyl), C₁-C₂₄ monoalkylaminosulfonyl (-SO2-N(H) alkyl), C₁- C₂₄ dialkylaminosulfonyl (-SO₂-N(alkyl)₂), C₅-C₂₄ arylsulfonyl (-SO₂-aryl), phosphono (-P(O)(OH)₂), phosphonato (-P(O)(OǦ)₂), phosphinato (-P(O)(OǦ)), phospho (-PO₂), -O-P(O)(OR)_2, (wherein R is C₁- C₂₄ alkyl, (C₅-C₂₄ aryl), C₆-C₂₄ alkaryl, C₆-C₂₄ aralkyl), or an electron withdrawing group such as: ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO2R), sulfoxide (-SOR), sulfonyl (-SO2R), sulfonic acid (-SO₃H), phthalamide, or nitro (-NO₂), wherein R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or unsubstituted aryl.

[00321] In another embodiment of the invention, an at least one cross-metathesis product comprising a product internal olefin, wherein the product internal olefin is in the Z-configuration, may be represented by the structure of Formula (XI): wherein, D²² and D²³ are CH_2, and E²² and E²³ are independently electron withdrawing groups such as: ester (-OCOR), sulfonamide (-NRSO2Ar), carbamate (-NCO₂R), sulfonyl (-SO₂R), sulfonic acid (-SO₃H), phthalamide, or nitro (-NO₂), wherein R is a hydrogen, methyl, substituted C₂-C₆ alkyl, unsubstituted C₂-C₆ alkyl, substituted aryl, or

unsubstituted aryl.

[00322] It is to be understood that while the invention has been described in conjunction with specific embodiments thereof, that the description above as well as the examples that follow are intended to illustrate and not limit the scope of the invention. Other aspects, advantages, and modifications within the scope of the invention will be apparent to those skilled in the art to which the invention pertains. EXPERIMENTAL

[00323] In the following examples, efforts have been made to ensure accuracy with respect to numbers used (e.g., amounts, temperature, etc.) but some experimental error and deviation should be accounted for. Unless indicated otherwise, temperature is in degrees C and pressure is at or near atmospheric. The examples are to be considered as not being limiting of the invention as described herein and are instead provided as representative examples of the C-H activated catalyst compounds described herein or incorporated herein by reference, the methods that may be used in their preparation, and the methods of using the C-H activated catalysts described herein or incorporated herein by reference.

[00324] All metathesis reactions were setup in a Vacuum Atmospheres glovebox under a nitrogen atmosphere. Solvents were purified by passage through solvent purification columns and further degassed with Argon, (see A. B. Pangborn, M. A. Giardello, R. H. Grubbs, R. K. Rosen, F. J. Timmers, Organometallics 1996, 15, 1518-1520). Commercially available liquid reagents were degassed by three freeze pump thaw cycles (for volatile substrates) or under vacuum (for nonvolatile substrates) prior to entering the glove box. Stock solutions of the cyclometalated ruthenium catalysts were prepared in the glovebox, stored at -35 °C in the glovebox freezer, and used within four weeks. NaIO₄ was purchased from Aldrich and used as is. CeCl3 was purchased as CeCl3•7H2O from Aldrich and used as is.

[00325] Standard NMR spectroscopy experiments were conducted on a Varian INOVA 500 (¹H: 500 MHz, ¹³C: 126 MHz) or a Bruker Avance HD 400 (¹H: 400 MHz, ¹³C: 101 MHz, equipped with a cryoprobe) spectrometer. Chemical shifts are referenced to the residual solvent peak (CDCl₃, C₆D₆ or DMSO-d6). Multiplicity is reported as follows: (s: singlet, d: doublet, t: triplet: q: quartet, br: broad, m: multiplet). Spectra were analyzed and processed using MestReNova. High-resolution mass spectra were provided by the California Institute of Technology Mass Spectrometry Facility using JEOL JMS- 600H High Resolution Mass Spectrometer.

[00326] The following abbreviations are used in the examples:

NaIO₄ Sodium periodate

EWG electron withdrawing group EtOAc ethyl acetate

MeCN acetonitrile

H2O water

RuCl3 ruthenium chloride H₂SO₄ sulfuric acid

YbCl₃ ytterbium (III) chloride

mL milliliter

μL microliter

°C degrees Celsius

THF tetrahydrofuran

CDCl3 deuterated chloroform

C₆D₆ deuterated benzene

DMSO-d⁶ deuterated dimethylsufoxide Na2S2O3 sodium thiosulfate

HCl hydrochloride acid

CH₂Cl₂ dichloromethane

NaHCO3 sodium bicarbonate

CDCl₃ deuterated chloroform

iPr isopropyl (-CH(CH₃)₂)

Me methyl (-CH3)

Ph phenyl (-C₆H5)

PCy₃ tricyclohexylphosphine (P(C₆H₁₁)₃)

[00327] The following experimental methods illustrate how compounds according to the invention can be made. Those skilled in the art will be routinely able to modify and/or adapt the following methods to synthesize any compound of the invention.

[00328] Compound 2

To a acetate (20.0 mg, 0.2 mmol) in a 20 mL Schlenk tube was added a solution of Ru-4 in THF (100

μL, 0.02 M, 0.002 mmol, 1 mol%). The tube was evacuated by two freeze-pump-thaw cycles, and the mixture was stirred at 35 °C under static vacuum for 4 hr. Meanwhile, a solution of CeCl3•7H2O (3.7 mg, 0.01 mmol) in H2O (170 μL) was added to NaIO4 (32.1 mg, 0.15 mmol). The suspension was heated gently with a heat gun until a color change from pale to bright yellow occurred. The mixture was then cooled to 0 °C, and MeCN (500 μL) was added. The metathesis mixture was then transferred to the NaIO₄ mixture with 500 μL EtOAc. This biphasic mixture was stirred vigorously at 0 °C for 20 minutes, and then quenched with saturated Na₂S₂O₃ (2 mL), and extracted with EtOAc (4 x 2 mL). The organic extracts were concentrated in vacuo, and then purified by column chromatography (50% - 80% EtOAc in hexanes) to yield 2 as a clear oil (12.3 mg, 60%). The ¹H NMR data matched literature values.

[00329] Compound 5

To a ution of N-tosyl allylamine (42.3 mg, 0.2 mmol) in dioxane (100 μL) in a 2 dr vial was added a

solution of Ru-4 in THF (600 μL, 0.005 M, 0.003 mmol, 1.5 mol%). The mixture was stirred uncapped at 35 °C in a nitrogen-filled glove box for 4 hr. Meanwhile, a solution of CeCl₃•7H₂O (7.4 mg, 0.02 mmol) in H2O (330 μL) was added to NaIO4 (64.2 mg, 0.3 mmol). The suspension was heated gently with a heat gun until a color change from pale to bright yellow occurred. The mixture was then cooled to 0 °C, and MeCN (1.0 mL) and EtOAc acetate (0.5 mL) were then added. The metathesis mixture was then transferred to NaIO₄ mixture with 500 μL EtOAc. This biphasic mixture was stirred vigorously at 0 °C for 20 minutes, and then quenched with saturated Na₂S₂O₃ (2 mL), and extracted with EtOAc (4 x 2 mL). The organic extracts were concentrated in vacuo, and then purified by column chromatography (80% EtOAc in hexanes). The title compound 5, was then further purified by trituration with Et₂O to yield a white solid (28.3 mg, 66%). ¹H NMR (500 MHz, CDCl₃) į 7.66 (d, J = 8.2 Hz, 4H), 7.38 (d, J = 8.1 Hz, 4H), 7.28 (dd, J = 6.8, 5.4 Hz, 2H), 4.88 (br s, 2H), 3.23 (d, J = 7.0 Hz, 2H), 2.98 (ddd, J = 12.7, 6.9, 2.2 Hz, 2H), 2.56-2.50 (m, 2H), 2.37 (s, 6H); ¹³C NMR (126 MHz, DMSO) į 142.55, 137.52, 129.60, 126.65, 71.26, 46.22, 21.01. HRMS (FAB+) m/z calculated for [C₁₈H₂₄O₆S₂N+H]⁺: 429.1154; found: 429.1175.

[00330] Compound 7

To N-tosyl lylamine (21.1 mg, 0.1 mmol) and allyl butyrate (64.1 mg, 0.5 mmol) in a 2 dr vial was

added a solution of Ru-4 in THF (300 μL, 0.005 M, 0.0015 mmol, 1.5 mol%). The mixture was stirred uncapped at 35 °C in a nitrogen-filled glove box for 4 hr. Meanwhile, a solution of CeCl3•7H2O (11.2 mg, 0.03 mmol) in H2O (500 μL) was added to NaIO4 (96.3 mg, 0.45 mmol). The suspension was heated gently with a heat gun until a color change from pale to bright yellow occurred. The mixture was then cooled to 0 °C, and MeCN (1.5 mL) and EtOAc acetate (750 μL) were then added. The metathesis mixture was then transferred to NaIO4 mixture with 750 μL EtOAc. This biphasic mixture was stirred vigorously at 0 °C for 20 minutes, and then quenched with saturated Na₂S₂O₃ (2 mL), and extracted with EtOAc (4 x 2 mL). The organic extracts were concentrated in vacuo, and then purified by column chromatography (50% to 70% EtOAc in hexanes) to yield the title compound 7, as a clear oil (21.8 mg, 63%). ¹H NMR (500 MHz, CDCl₃) į 7.74 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 5.51 (t, J = 6.5 Hz, 1H), 4.33-4.22 (m, 2H), 3.82 (br s, 1H), 3.62 (br s, 1H), 3.48 (d, J = 5.5 Hz, 1H), 3.22– 3.07 (m, 3H), 2.42 (s, 3H), 2.32 (t, J = 7.5 Hz, 2H), 1.63 (hex, J = 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H); ¹³C NMR (126 MHz, CDCl3) į 175.01, 143.86, 136.53, 129.98, 127.18, 71.06, 70.31, 65.64, 45.33, 36.11, 21.67, 18.48, 13.76. HRMS (FAB+) m/z calculated for [C₁₅H₂₃O₆SN+H]⁺: 346.1324; found: 346.1315.

[00331] Compound 9

To ethyl p noate (25.6 mg, 0.2 mmol) was added a solution of Ru-4 in THF (100 μL, 0.01 M, 0.001

mmol, 0.5 mol%) in a glove box. The solution was transferred to a 20 mL Schlenk tube and removed from the glove box. The headspace was removed by two freeze-pump-thaw cycles, and the solution was then stirred under static vacuum at 35 °C for 2 hr. Meanwhile, a solution of CeCl3•7H2O (3.7 mg, 0.01 mmol) in H₂O (170 μL) was added to NaIO₄ (32.1 mg, 0.15 mmol). The suspension was heated gently with a heat gun until a color change from pale to bright yellow occurred. The mixture was then cooled to 0 °C, and MeCN (1.5 mL) and EtOAc acetate (750 μL) were then added, followed by a solution of RuCl3 in H₂O (0.001 mmol, 100 μL, 0.01 M). The metathesis mixture was then transferred to NaIO₄ mixture with 250 μL EtOAc. This biphasic mixture was stirred vigorously at 0 °C for 20 minutes, and then quenched with saturated Na2S2O3 (2 mL), and extracted with EtOAc (4 x 2 mL). The organic extracts were concentrated in vacuo, and then purified by column chromatography (50% to 100% EtOAc in hexanes) to yield the title compound 9, as a clear oil (13.9 mg, 53%). ¹H NMR (500 MHz, CDCl₃) į 4.14 (q, J = 7.1 Hz, 4H), 3.58 (d, J = 9.8 Hz, 2H), 2.83 (br s, 2H), 2.56-2.45 (m, 4H), 1.88-1.80 (m, 2H), 1.80- 1.72 (m, 2H), 1.25 (t, J = 7.1 Hz, 6H); ¹³C NMR (126 MHz, CDCl3) į 174.73, 74.09, 60.85, 31.07, 26.68, 14.33. HRMS (FAB+) m/z calculated for [C₁₂H₂₂O₆+H]⁺: 263.1495; found: 263.1487.

[00332] Note: For all substrates, an independent metathesis reaction under identical conditions as the tandem process was performed and the Z-selectivity assessed by ¹H NMR, to ensure that isomerization did not occur in the time scale of the metathesis. Z-selectivity was >90% in all cases. The ¹H NMR signals were compared to those observed in an early conversion (30 minute) metathesis reaction, (1 mol% Ru-4, reaction in an open vial), to aid in peak assignment. In general, static vacuum conditions for the metathesis step were successful in minimizing Z to E isomerization (due to removal of ethylene from solution). An alternative strategy to remove ethylene from the reaction is to perform the metathesis step in an open vial inside an inert atmosphere glove box. This was an effective strategy for substrates which are not volatile and do not become highly viscous or solid upon loss of solvent during cross-metathesis. This open vial procedure was used for allyl phenyl carbonate and the hetero cross- metathesis / dihydroxylation reactions.

[00333] Next, the tandem methodology on gram scale was examined, in order to probe scalability of the process. Allyl benzoate was subjected to cross-metathesis with 0.5 mol% catalyst Ru-4 in an open vial in an inert atmosphere glove box, followed by dihydroxylation using the standard conditions outside the glove box (Scheme 5). Isolation of the target diol was conveniently achieved without the need for column chromatography: trituration of the crude reaction mixture with ether provided 6c in 66% yield. Scheme 5. Gram scale tandem Z-selective metathesis– dihydroxylation

General procedures and product characterization

[00334] General procedure A: Optimization for tandem Z-selective homodimerization– dihydroxylation: In a nitrogen filled glove box, allyl butyrate (25.6 mg, 0.2 mmol, 1 eq) was transferred to a 25 mL Schlenk tube using three 50 μL portions of a solution of the appropriate metathesis catalyst (0.003 mmol, 1.5 mol%, 150 μL, 0.02M in THF) to ensure quantitative transfer. The tube was capped, and then brought to a Schlenk line where it was evacuated using one freeze-pump- thaw cycle, capping the flask under static vacuum. The solution was then heated in an oil bath with stirring at 40 °C for 4 hr. A solution of the appropriate Lewis acid (10 mol %) in distilled H₂O (170 μL) was added to NaIO₄ (42.8 mg, 0.2 mmol, 2 eq relative to the homodimerization metathesis product at full conversion). MeCN (500 μL) was then added, and the mixture was cooled to 0 °C in an ice bath. The crude metathesis mixture was then added, using ethyl acetate (3 x 167 μL) to rinse the flask and ensure complete transfer. The mixture was vigorously stirred at 0 °C for 20 min and then quenched with 2 mL of a saturated Na2S2O3 aqueous solution. The mixture was extracted with ethyl acetate (4 x 2.5 mL), and then concentrated under reduced pressure. Mesitylene (27.8 μL, 0.2 mmol) was added as an internal standard, and the mixture was dissolved in CDCl₃ for NMR studies (¹H NMR, 8 scans, 25 s relaxation delay).

[00335] General procedure B: Z-selective homodimerization under static vacuum. In a nitrogen filled glove box, the terminal olefin was transferred to a 25 mL Schlenk tube using three 50 μL portions of a solution of Ru-4 (0.003 mmol, 1.5 mol%, 150 μL, 0.02M in THF) to ensure quantitative transfer. The tube was capped, and then brought to a Schlenk line where it was evacuated using one freeze- pump-thaw cycle, capping the flask under static vacuum. The solution was then heated in an oil bath with stirring at 40 °C for 4 hr.

[00336] General procedure C: Z-selective homodimerization in an open vial. In a nitrogen filled glove box, a solution of Ru-4 (0.001 mmol, 0.5 mol%, 200 μL, 0.005M in THF) was added to the terminal olefin (0.2 mmol, 1 eq) in a 2 dram vial. The mixture was stirred in an open vial in the glove box at 40 °C for 3 hr.

[00337] General procedure D: Dihydroxylation for 0.2 mmol scale homodimerizations. A solution of CeCl₃•7H₂O (3.7 mg, 0.01 mmol, 10 mol%) in distilled H₂O (170 μL) was added to NaIO₄ (42.8 mg, 0.2 mmol, 2 eq relative to the homodimerization metathesis product at full conversion). MeCN (500 μL) was then added, and the mixture was cooled to 0 °C in an ice bath. The crude metathesis mixture was then added, using ethyl acetate (3 x 167 μL) to rinse the flask and ensure complete transfer. The mixture was vigorously stirred at 0 °C for 20 min and then quenched with 2 mL of a saturated Na₂S₂O₃ aqueous solution. The mixture was extracted with ethyl acetate (4 x 2.5 mL), and then concentrated under reduced pressure. The anti-diol product was purified by column chromatography.

[00338] General procedure E: Z-selective cross-metathesis in an open vial followed by

dihydroxylation. In a nitrogen filled glove box, a solution the excess olefin reagent (0.5 mmol, 5 eq) in THF (150 μL) was added to the limiting olefin reagent (0.1 mmol, 1 eq) in a 2 dram vial. A solution of Ru-4 (0.003 mmol, 3 mol%, 150 μL, 0.02 M in THF) was added. The mixture was stirred in the open vial in the glove box at 40 °C for 4 hr. A solution of CeCl₃•7H₂O (11.2 mg, 0.03 mmol) in distilled H₂O (0.5 mL) was added to NaIO4 (128.3 mg, 0.6 mmol). MeCN (1.5 mL) was then added, and the mixture was cooled to 0 °C in an ice bath. The crude metathesis mixture was then added, using ethyl acetate (3 x 0.5 mL) to rinse the flask and ensure complete transfer. The mixture was vigorously stirred at 0 °C for 20 min and then quenched with 6 mL of a saturated Na2S2O3 aqueous solution. The mixture was extracted with ethyl acetate (4 x 4 mL), and then concentrated under reduced pressure. The anti-diol product was purified by column chromatography.

[00339] Note: For all substrates, an independent metathesis reaction under identical conditions as the tandem process was performed and the Z-selectivity assessed by ¹H NMR, to ensure that isomerization did not occur in the time scale of the metathesis. Z-selectivity was >90% in all cases. The ¹H NMR signals were compared to those observed in an early conversion (30 minute) metathesis reaction, (1 mol% Ru-4, reaction in an open vial), to aid in peak assignment. In general, static vacuum conditions for the metathesis step were successful in minimizing Z to E isomerization (due to removal of ethylene from solution). An alternative strategy to remove ethylene from the reaction is to perform the metathesis step in an open vial inside an inert atmosphere glove box. This was an effective strategy for substrates which are not volatile and do not become highly viscous or solid upon loss of solvent during cross-metathesis. This open vial procedure was used for allyl phenyl carbonate and the hetero cross- metathesis / dihydroxylation reactions.

Synthesis of substrates

[00340]

)

e): To a flame dried round bottom flask under argon was added

p-anisidine (1.85 g, 15 mmol, 1 equiv), CH2Cl2 (45 mL) and diisopropylethylamine (2.79 mL, 16 mmol, 1.07 equiv), and the flask was cooled to 0 °C and stirred. Allyl chloroformate (1.70 mL, 16 mmol, 1.07 equiv) was then added dropwise. After 30 min, the flask was allowed to warm to ambient temperature and stirred for an additional 30 min. The reaction mixture was quenched with 20 mL HCl (1M) and extracted with 150 mL EtOAc. The organic extract was then washed with saturated NaHCO₃ (20 mL), brine (20 mL), and then dried with Na₂SO₄ and concentrated in vacuo. The title compound was isolated by column chromatography (15– 30% EtOAc in Hexanes) to give a white solid (2.853 g, 92%). ¹H NMR (400 MHz, CDCl3) į 7.29 (d, J = 8.2 Hz, 2H), 6.85 (d, J = 9.1 Hz, 2H), 6.52 (br s, 1H), 5.97 (ddt, J = 16.9, 10.4, 5.7 Hz, 2H), 5.35 (dd, J = 17.2, 1.6 Hz, 2H), 5.25 (dd, J = 10.5, 1.3 Hz, 1H), 4.66 (dt, J = 5.7, 1.4 Hz, 4H), 3.78 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) į 156.2, 153.7, 132.7, 131.0, 120.8, 118.3, 114.4, 65.9, 55.7. HRMS (FAB+): m/z calculated for [C₁₁H₁₃O₃N]⁺: 207.0895; found: 207.0895.

[00341]

f)

To a flame dried round bottom flask under argon was added 4-

methylbenzylamine (1.91 mL, 15 mmol, 1 equiv), CH2Cl2 (45 mL) and diisopropylethylamine (2.79 mL, 16 mmol, 1.07 equiv), and the flask was cooled to 0 °C and stirred. Allyl chloroformate (1.70 mL, 16 mmol, 1.07 equiv) was then added dropwise. After 30 min, the flask was allowed to warm to ambient temperature and stirred for an additional 30 min. The reaction mixture was quenched with 20 mL HCl (1M) and extracted with 150 mL EtOAc. The organic extract was then washed with saturated NaHCO3 (20 mL), brine (20 mL), and then dried with Na₂SO₄ and concentrated in vacuo. The title compound was isolated by column chromatography (15– 30% EtOAc in Hexanes) to give a white solid (2.655 g, 86%). 1H NMR (400 MHz, CDCl3) į 7.18 (d, J = 8.1 Hz, 2H), 7.14 (d, J = 8.3 Hz, 2H), 5.93 (ddt, J = 17.2, 10.4, 5.6 Hz, 1H), 5.31 (dd, J = 17.1, 1.6 Hz, 1H), 5.21 (dq, J = 10.5, 1.4 Hz, 1H), 4.99 (br s, 1H), 4.60 (d, J = 6.0 Hz, 2H), 4.34 (d, J = 5.9 Hz, 2H), 2.34 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) į 156.4, 137.3, 135.5, 133.0, 129.5, 127.7, 117.8, 65.8, 45.0, 21.2. HRMS (FAB+): m/z calculated for [C₁2H15O2N+H]⁺: 206.1181; found: 206.1183.

[00342] (5h)

5h): Prepared according to a literature procedure, and the spectroscopic data

matched the literature data. (H. Teller, M. Corbet, L. Mantilli, G. Gopakumar, R. Goddard, W. Thiel, A. Fürstner, J. Am. Chem. Soc. 2012, 134, 15331–15342.) [00343]

)

utyrate (6a): Synthesized according to the general procedure B

for homodimerization under static vacuum followed by the general procedure D for dihydroxylation. The title compound was purified by column chromatography (50-75% ethyl acetate in hexanes). This material was then triturated with ether to afford a white solid (18.8 mg, 72%). ¹H NMR (500 MHz, DMSO-d₆) į 4.34-4.31 (m, 4H), 3.80-3.75 (m, 2H), 2.90-2.70 (br s, 2H), 2.35 (t, J = 7.4 Hz, 4H), 1.67 (hex, J = 7.4 Hz, 4H), 0.95 (t, J = 7.4 Hz, 6H); ¹³C NMR (126 MHz, CDCl3) į 174.7, 70.6, 65.6, 36.1, 18.5, 13.8. HRMS (FAB+): m/z calculated for [C₁₂H₂₂O₆+H]⁺: 263.1495; found: 263.1490.

[00344]

(6b) or 2

iacetate (6b) or 2: Synthesized according to the general procedure

B for homodimerization under static vacuum followed by the general procedure D for dihydroxylation. The title compound was isolated by column chromatography (60-80% ethyl acetate in hexanes) to give a clear oil (12.2 mg, 59%). Spectroscopic data matched literature data. ¹H NMR (400 MHz, DMSO-d6) į 4.36-4.26 (m, 4H), 3.79 (s, 2H), 2.80 (br s), 2.12 (s, 6H); ¹³C NMR (101 MHz, CDCl3) į 172.0, 70.5, 65.8, 21.0; HRMS (FAB+): m/z calculated for [C₈H₁₄O₆+H]⁺: 207.0869; found: 207.0861.

[00345]

iyl dibenzoate (6c): Synthesized according to the general procedure B for homodimerization under static vacuum followed by the general procedure D for dihydroxylation. The title compound was purified by column chromatography (60-80% ethyl acetate in hexanes). This material was then triturated with ether to afford a white solid (23.4 mg, 71%) which was sparingly soluble in CDCl₃ but soluble in DMSO. ¹H NMR (500 MHz, DMSO-d₆) į 8.03 (dd, J = 8.4, 1.3 Hz, 4H), 7.66 (tt, J = 7.5, 1.5 Hz, 2H), 7.53 (t, J = 7.5 Hz, 4H), 5.36 (d, J = 5.9 Hz, 2H), 4.50 (dd, J = 11.3, 2.1 Hz, 2H), 4.31 (dd, J = 11.2, 5.7 Hz, 2H), 3.87-3.83 (m, 2H); ¹³C NMR (126 MHz, DMSO-d₆) į 165.9, 133.3, 130.0, 129.3, 128.7, 69.2, 66.7. HRMS (FAB+): m/z calculated for [C₁₈H₁₈O₆+H]⁺: 331.1182; found: 331.1182.

[00346] Procedure for large scale synthesis: In a nitrogen filled glove box, a solution of Ru-4 (20.8 mg, 0.0309 mmol, 0.5 mol%) in THF (2.17 mL) was added to allyl benzoate (1.0 g, 6.17 mmol) in a 10 dram vial. The mixture was stirred in an open vial in the glove box at 40 °C for 7.5 hr. A solution of CeCl3•7H2O (115 mg, 0.309 mmol) in distilled H2O (5.1 mL) was added to NaIO4 (1.32 g, 6.17 mmol, 2 eq relative to the homodimerization metathesis product at full conversion) in a round bottom flask.

MeCN (15.4 mL) was then added, and the mixture was cooled to 0 °C in an ice bath. The crude metathesis mixture was then added, using ethyl acetate (3 x 5.1 mL) to rinse the flask and ensure complete transfer. The mixture was vigorously stirred at 0 °C for 20 min and then quenched with 25 mL of a saturated Na₂S₂O₃ aqueous solution. The mixture was extracted with ethyl acetate (3 x 60 mL), dried with Na₂SO₄ and then concentrated under reduced pressure. The resulting solid was then triterated with diethyl ether (5 x 5 mL) to give the title compound as a white solid (669 mg, 66%).

[00347]

)

phenyl bis(carbonate) (6d): Synthesized according to the

general procedure C for homodimerization in an open vial followed by the general procedure D for dihydroxylation. The title compound was purified by column chromatography (60–75% ether in pentane) to give a white solid (22.1 mg, 61%). ¹H NMR (400 MHz, CDCl₃) į 7.42 (dd, J = 8.6, 7.3 Hz, 4H), 7.35 – 7.24 (m, 2H), 7.24– 7.14 (m, 4H), 4.64– 4.54 (m, 2H), 4.54– 4.45 (m, 2H), 4.08– 3.97 (m, 2H), 2.67 (br s, 2H). ¹³C NMR (101 MHz, CDCl3) į 154.1, 151.0, 129.6, 126.3, 120.9, 70.0, 69.5. HRMS (FAB+): m/z calculated for [C₁8H18O8+H]⁺: 363.1080; found: 363.1081. [00348]

)

te) (6e): Synthesized according to

the general procedure B for homodimerization under static vacuum followed by the general procedure D for dihydroxylation. The title compound was purified by column chromatography (80-100% ethyl acetate in hexanes) followed by trituration of the impure fractions with diethyl ether to afford a white solid (26.6 mg, 63%). ¹H NMR (400 MHz, DMSO-d₆) į 9.45 (br s, 2H), 7.37 (d, J = 8.6 Hz, 4H), 6.85 (d, J = 8.9 Hz, 4H), 5.07 (d, J = 4.8 Hz, 2H), 4.29 (dd, J = 11.4, 2.3 Hz, 2H), 4.04 (dd, J = 11.1, 5.5 Hz, 2H), 3.70 (s, 6H), 3.7-3.65 (m, 2H); ¹³C NMR (101 MHz, CDCl3) į 154.7, 153.9, 132.3, 119.7, 113.9, 69.7, 66.1, 55.1; HRMS (FAB+): m/z calculated for [C₂₀H₂₄O₈N₂+H]⁺: 421.1611; found: 421.1606.

[00349]

f)

e) (6f): Synthesized according to

the general procedure B for homodimerization under static vacuum followed by the general procedure D for dihydroxylation. The title compound was purified by column chromatography (80% ethyl acetate in hexanes to 10% MeOH in ethyl acetate) followed by trituration with diethyl ether to afford a pale yellow solid (16.4 mg, 39%). ¹H NMR (400 MHz, DMSO-d₆) į 7.61 (t, J = 6.2 Hz, 1H), 7.16-7.08 (m, 8H), 4.93 (d, J = 4.9 Hz, 2H), 4.20-4.10 (m, 8H), 3.91 (dd, J = 11.4, 5.7 Hz, 2H), 3.57– 3.51 (m, 2H), 2.27 (s, 6H); 1³C NMR (101 MHz, DMSO) į 156.7, 136.9, 135.7, 128.8, 127.0, 69.9, 66.0, 43.5, 20.7; HRMS (FAB+): m/z calculated for [C₂₂H₂₈O₆N₂+H]⁺: 417.2026; found: 417.2036. [00350]

)

ne-1,4-diyl)bis(4-methylbenzenesulfonamide) (6g): Synthesized

according to the general procedure B for homodimerization under static vacuum followed by the general procedure D for dihydroxylation. The title compound was purified by column chromatography (80% ethyl acetate in hexanes) to give a white solid (30.1 mg, 70%). ¹H NMR (500 MHz, CDCl₃) į 7.66 (d, J = 8.2 Hz, 4H), 7.38 (d, J = 8.1 Hz, 4H), 7.28 (dd, J = 6.8, 5.4 Hz, 2H), 4.88 (br s, 2H), 3.23 (d, J = 7.0 Hz, 2H), 2.98 (ddd, J = 12.7, 6.9, 2.2 Hz, 2H), 2.56-2.50 (m, 2H), 2.37 (s, 6H); ¹³C NMR (126 MHz, DMSO) į 142.55, 137.52, 129.60, 126.65, 71.26, 46.22, 21.01. HRMS (FAB+) m/z calculated for [C₁8H24O6S2N2+H]⁺: 429.1154; found: 429.1175.

[00351]

)

e-1,4-diyl)dicarbamate (6h): Synthesized according to the

general procedure B for homodimerization under static vacuum followed by the general procedure D for dihydroxylation. The title compound was purified by column chromatography (60–85% ethyl acetate in hexanes) to give a white solid (20.7 mg, 53%). ¹H NMR (400 MHz, CDCl3) į 7.40– 7.34 (m, 10H), 5.25 (br s, 2H), 5.12 (s, 4H), 3.91 (br s, 2H), 3.66 (dd, J = 15.0, 7.8 Hz, 2H), 3.46 (s, 2H), 3.30 (d, J = 14.8 Hz, 2H). ¹³C NMR (101 MHz, DMSO) į 156.8, 137.7, 128.8, 128.2, 128.2, 71.9, 65.7, 44.5. HRMS (FAB+) m/z calculated for [C₂₀H24O6N2+H]⁺: 389.1713; found: 389.1721.

[00352]

(6i)

PCT Patent Application Docket No. CIT-6959-PCT (Anti)-2,3-dihydroxy-4-((4-methylphenyl)sulfonamido)butyl butyrate (6i): Synthesized according to general procedure E for cross-metathesis / dihydroxylation using allyl butyrate as the olefin in excess. The metathesis was performed at 35 °C using 1.5 mol% Ru (0.0015 mmol). The title compound was purified by column chromatography (50-70% ethyl acetate in hexanes) to give a white solid (21.8 mg, 63%). ¹H NMR (500 MHz, CDCl₃) į 7.74 (d, J = 8.3 Hz, 2H), 7.30 (d, J = 7.9 Hz, 2H), 5.51 (t, J = 6.5 Hz, 1H), 4.33-4.22 (m, 2H), 3.82 (br s, 1H), 3.62 (br s, 1H), 3.48 (d, J = 5.5 Hz, 1H), 3.22– 3.07 (m, 3H), 2.42 (s, 3H), 2.32 (t, J = 7.5 Hz, 2H), 1.63 (hex, J = 7.4 Hz, 2H), 0.93 (t, J = 7.4 Hz, 3H); ¹³C NMR (126 MHz, CDCl₃) į 175.0, 143.9, 136.5, 130.0, 127.2, 71.1, 70.3, 65.6, 45.3, 36.1, 21.7, 18.5, 13.8. HRMS (FAB+) m/z calculated for [C15H23O6SN+H]⁺: 346.1324; found: 346.1315.

[00353]

(6j)

(4-methylphenyl)sulfonamido)butyl benzoate (6j): Synthesized according to general procedure E for cross-metathesis / dihydroxylation using allyl benzoate as the olefin in excess. The title compound was purified by column chromatography (50-60% ethyl acetate in hexanes) followed by preparatory thin layer chromatography (60% ethyl acetate in hexanes) to give a white solid (14.6 mg, 39%). ¹H NMR (400 MHz, DMSO-d₆) į 7.99 (d, J = 8.5 Hz, 2H), 7.70 (d, J = 8.3 Hz, 2H), 7.66 (tt, J = 7.6, 1.6 Hz, 1H), 7.53 (t, J = 7.6 Hz, 2H), 7.42-7.36 (m, 1H), 7.38 (d, J = 7.7 Hz, 2H), 5.16 (d, J = 5.7 Hz, 1H), 5.06 (d, J = 5.7 Hz, 1H), 4.37 (dd, J = 11.3, 2.8 Hz, 1H), 4.18 (dd, J = 11.3, 5.8 Hz, 1H), 3.63– 3.47 (m, 2H), 3.11 (ddd, J = 12.7, 6.8, 3.1 Hz, 1H), 2.67 (ddd, J = 12.8, 7.7, 5.4 Hz, 1H), 2.37 (s, 3H); ¹³C NMR (101 MHz, DMSO-d6) į 165.8, 142.5, 137.6, 133.2, 129.9, 129.5, 129.3, 128.6, 126.6, 70.3, 70.1, 66.5, 46.4, 21.0. HRMS (FAB+): m/z calculated for [C18H21O6SN+H]⁺: 380.1168; found: 380.1152.

[00354]

)

145 Anti-4-(((benzyloxy)carbonyl)amino)-2,3-dihydroxybutyl butyrate (6k): Synthesized according to general procedure E for cross-metathesis / dihydroxylation using allyl butyrate as the olefin in excess. The title compound was purified by column chromatography (50-70% ethyl acetate in hexanes) followed by preparatory thin layer chromatography (60% ethyl acetate in hexanes) to give a white solid (15.4 mg, 47%). ¹H NMR (400 MHz, CDCl₃-d₆) į 7.39-7.29 (m, 5H), 5.37 (t, J = 7.2 Hz, 1H), 5.11 (s, 2H), 4.40 (dd, J = 12.0, 4.5 Hz, 1H), 4.34-4.23 (m, 1H), 3.68-3.52 (m, 4H), 3.44-3.34 (m, 2H), 2.35 (dd, J = 8.1, 6.8 Hz, 2H), 1.66 (hex, J = 7.4 Hz, 2H), 0.95 (t, J = 7.4 Hz, 3H); ¹³C NMR (101 MHz, CDCl3) į 175.2, 158.5, 136.2, 128.7, 128.5, 128.3, 71.2, 70.7, 67.5, 65.8, 43.5, 36.2, 18.5, 13.8. HRMS (FAB+): m/z calculated for [C₁₆H23O6N+H]⁺: 326.1604; found: 326.1613.

[00355]

(6l)

onyl)amino)-2,3-dihydroxybutyl benzoate (6l): Synthesized according to general procedure E for cross-metathesis / dihydroxylation using allyl benzoate as the olefin in excess. The title compound was purified by column chromatography (50-70% ethyl acetate in hexanes) to give a clear oil (19.9 mg, 55%). ¹H NMR (400 MHz, CDCl3-d6) į 8.06 (d, J = 6.8 Hz, 2H), 7.57 (ddt, J = 8.0, 7.0, 1.4 Hz, 1H), 7.43 (t, J = 7.8 Hz, 2H), 7.37-7.27 (m, 5H), 5.46 (d, J = 6.7 Hz, 1H), 5.1 (s, 2H), 4.64 (dd, J = 12.0, 4.8 Hz, 1H), 4.52 (dd, J = 12.0, 2.5 Hz, 1H), 3.82-3.73 (m, 2H), 3.67-3.53 (m, 3H), 3.41 (ddd, J = 15.3, 5.9, 2.6 Hz, 1H); ¹³C NMR (101 MHz, CDCl3) į 167.9, 158.6, 136.2, 133.6, 130.0, 129.6, 128.7, 128.6, 128.4, 128.3, 71.2, 70.9, 67.5, 66.5, 43.5. HRMS (FAB+): m/z calculated for [C₁9H21O6N+H]⁺: 360.1447; found: 360.1456.

Mechanistic experiments

[00356] Dihydroxylation studies Z)-but-2-ene-1,4-diyl diacetate (3): A

solution of CeCl₃•7H₂O (3.7 mg, 0.01 mmol) in distilled H₂O (170 μL) was added to NaIO₄ (42.8 mg, 0.2 mmol). MeCN (500 μL) was then added, and the mixture was cooled to 0 °C in an ice bath. A solution of Ru catalyst Ru-4 (0.001 mmol, 200 μL, 0.005 M in THF) was then added if required. Either (Z)-4-octene 11 (11.2 mg, 0.1 mmol) and/or (Z)-but-2-ene-1,4-diyl diacetate 3 (17.2 mg, 0.1 mmol) in ethyl acetate (0.5 ml) was then added. The mixture was vigorously stirred at 0 °C for 20 min and then quenched with 2 mL of a saturated Na₂S₂O₃ aqueous solution. The mixture was extracted with ethyl acetate (4 x 2.5 mL), and then concentrated under reduced pressure. Mesitylene was added as an internal standard (27.8 μL, 0.2 mmoL). The product distribution was analyzed by ¹H NMR.

Using (Z)-but-2-ene-1,4-diyl diacetate 3, without Ru: No dihydroxylation observed.

Using (Z)-but-2-ene-1,4-diyl diacetate 3, with Ru: Anti-diol 6b or 2 was isolated in 58% yield (11.9 mg), and no olefin starting material remains.

Using (Z)-4-octene 11, with Ru: No dihydroxylation products observed

Using (Z)-4-octene 11 and (Z)-but-2-ene-1,4-diyl diacetate 3, with Ru: No dihydroxylation products observed.

[00357]

(13)

yl benzoate (13): In a nitrogen filled glove box, 1-pentene 12 (35.1 mg, 0.5 mmol, 5 eq) was added to allyl benzoate 5c (16.2 mg, 0.1 mmol, 1 eq) using Ru-4 (0.003 mmol, 3 mol%, 150 μL, 0.02 M in THF) to quantitatively transfer to a Schlenk tube. The tube was capped, and then brought to a Schlenk line where it was evacuated using one freeze-pump-thaw cycle, capping the flask under static vacuum. The solution was then heated in an oil bath with stirring at 40 °C for 4 hr. Subsequently, the volatiles were removed with a high vacuum for 5 minutes. A solution of CeCl3•7H2O (3.7 mg, 0.01 mmol, 10 mol%) in distilled H2O (170 μL) was added to NaIO4 (42.8 mg, 0.2 mmol, 2 eq relative to the homodimerization metathesis product at full conversion). MeCN (500 μL) was then added, and the mixture was cooled to 0 °C in an ice bath. The crude metathesis mixture was then added, using ethyl acetate (3 x 167 μL) to rinse the flask and ensure complete transfer. The mixture was vigorously stirred at 0 °C for 20 min and then quenched with 2 mL of a saturated Na₂S₂O₃ aqueous solution. The mixture was extracted with ethyl acetate (4 x 2.5 mL), and then concentrated under reduced pressure. The anti-diol product was purified using preparatory thin layer chromatography (one purification at 50% ethyl acetate in hexanes, then a second purification at 30% ethyl acetate in hexanes) to yield a clear oil (7.9 mg, 33%). If this procedure is followed without removing volatiles after the metathesis step, no dihydroxylation is observed– only cross-metathesis products. ¹H NMR (500 MHz, CDCl₃-d₆) į 8.05 (dd, J = 8.4, 1.3 Hz, 1H), 7.59 (ddt, J = 7.7, 7.3, 1.4 Hz, 1H), 7.46 (tt, J = 8.0, 1.5 Hz, 1H), 4.52 (s, 1H), 4.51 (d, J = 1.2 Hz, 1H), 3.91 (q, J = 4.9 Hz, 1 H), 3.80-3.74 (m, 1H), 2.64 (br s, 1H), 2.22 (br s, 1H), 1.65-1.50 (m, 3H), 1.45-1.37 (m, 1H), 0.97 (t, J = 7.1 Hz, 1H); ¹³C NMR (101 MHz, CDCl₃) į 167.4, 133.5, 129.9, 129.8, 128.6, 73.3, 72.4, 66.3, 34.7, 19.2, 14.2; HRMS (FAB+): m/z calculated for [C₁₃H₁₈O₄+H]⁺: 239.1283; found: 239.1285.

Claims

CLAIMS The claimed invention is:

1. A method for tandem Z-selective cross-metathesis / stereospecific dihydroxylation, the method comprising:

2. The method of claim 1, wherein the cross-metathesis mixture comprises at least one cross-metathesis product.

3. The method of claim 2, wherein the at least one cross-metathesis product comprises a product internal olefin.

4. The method of claim 3, wherein the product internal olefin is in a Z-configuration.

5. The method of claim 1, further comprising contacting the cross-metathesis mixture with a ruthenium species.

6. The method of claim 5, wherein the ruthenium species is an in situ generated Ru-based oxidation catalyst.

7. The method of claim 5, wherein the ruthenium species is selected from RuCl₃, RuO₄, Ru(III)(acetylacetonate), RuI₃, Dichloro(p-cymene)ruthenium(II) dimer, and triruthenium

dodecacarbonyl.

8. The method of claim 5, wherein the ruthenium species is RuCl₃.

9. The method of claim 1, wherein the first olefin reactant and the second olefin reactant may be the same or different.

10. The method of claim 1, wherein the oxidizing agent is selected from NaIO4, N-methylmorpholine N-oxide, K₃(Fe(CN)₆), HIO₄, O₂, and H₂O₂.

11. The method of claim 1, wherein the oxidizing agent is NaIO4.

12. The method of claim 1, further comprising contacting the cross-metathesis mixture with an acid.

13. The method of claim 12, wherein the acid is selected from a Brønsted acid and a Lewis acid.

14. The method of claim 13, wherein the Lewis acid is selected from CeCl3, YbCl3, and La(OTf)3.

15. The method of claim 13, wherein the Lewis acid is CeCl₃.

16. The method of claim 13, wherein the Brønsted acid is selected from H2SO4, HOAc, H3PO4, TFA, benzoic acid, citric acid, MeSO₃H, p-toluene sulfonic acid, HCl, and HNO₃.

17. The method of claim 1, wherein the first olefin reactant comprises a reactant terminal olefin; and the second olefin reactant comprises a reactant terminal olefin.

18. The method of claim 1, wherein the first olefin reactant comprises a reactant terminal olefin; and the second olefin reactant comprises a reactant internal olefin.

19. The method of claim 1, wherein the first olefin reactant comprises a reactant internal olefin; and the second olefin reactant comprises a reactant internal olefin.

20. The method of claim 1, wherein the cross-metathesis reaction is performed under static vacuum.