CN1238361C - Spiro-diphosphine ligand - Google Patents
Spiro-diphosphine ligand Download PDFInfo
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- CN1238361C CN1238361C CN 03104700 CN03104700A CN1238361C CN 1238361 C CN1238361 C CN 1238361C CN 03104700 CN03104700 CN 03104700 CN 03104700 A CN03104700 A CN 03104700A CN 1238361 C CN1238361 C CN 1238361C
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- 239000003446 ligand Substances 0.000 title claims abstract description 26
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- 150000001875 compounds Chemical class 0.000 claims abstract description 14
- 150000002576 ketones Chemical class 0.000 claims abstract description 11
- 238000009903 catalytic hydrogenation reaction Methods 0.000 claims abstract description 10
- XKZQKPRCPNGNFR-UHFFFAOYSA-N 2-(3-hydroxyphenyl)phenol Chemical compound OC1=CC=CC(C=2C(=CC=CC=2)O)=C1 XKZQKPRCPNGNFR-UHFFFAOYSA-N 0.000 claims abstract description 5
- 239000000203 mixture Substances 0.000 claims abstract description 5
- 239000000126 substance Substances 0.000 claims abstract description 4
- ZDHXKXAHOVTTAH-UHFFFAOYSA-N trichlorosilane Chemical compound Cl[SiH](Cl)Cl ZDHXKXAHOVTTAH-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000005052 trichlorosilane Substances 0.000 claims abstract description 4
- 230000008878 coupling Effects 0.000 claims abstract description 3
- 238000010168 coupling process Methods 0.000 claims abstract description 3
- 238000005859 coupling reaction Methods 0.000 claims abstract description 3
- 239000002994 raw material Substances 0.000 claims abstract description 3
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 claims description 54
- 238000002360 preparation method Methods 0.000 claims description 33
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 19
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 8
- 125000002723 alicyclic group Chemical group 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 238000006555 catalytic reaction Methods 0.000 claims description 5
- 239000000758 substrate Substances 0.000 claims description 5
- 239000001257 hydrogen Substances 0.000 claims description 4
- 239000003960 organic solvent Substances 0.000 claims description 4
- 229910052763 palladium Inorganic materials 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 239000012298 atmosphere Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- 125000002769 thiazolinyl group Chemical group 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- 230000001476 alcoholic effect Effects 0.000 claims description 2
- 150000008064 anhydrides Chemical group 0.000 claims description 2
- 239000003054 catalyst Substances 0.000 claims description 2
- 239000012046 mixed solvent Substances 0.000 claims description 2
- YCWSUKQGVSGXJO-NTUHNPAUSA-N nifuroxazide Chemical group C1=CC(O)=CC=C1C(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 YCWSUKQGVSGXJO-NTUHNPAUSA-N 0.000 claims 1
- MDDUHVRJJAFRAU-YZNNVMRBSA-N tert-butyl-[(1r,3s,5z)-3-[tert-butyl(dimethyl)silyl]oxy-5-(2-diphenylphosphorylethylidene)-4-methylidenecyclohexyl]oxy-dimethylsilane Chemical compound C1[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)C(=C)\C1=C/CP(=O)(C=1C=CC=CC=1)C1=CC=CC=C1 MDDUHVRJJAFRAU-YZNNVMRBSA-N 0.000 claims 1
- -1 diaryl phosphine oxide, Chemical compound 0.000 abstract description 15
- 239000012327 Ruthenium complex Substances 0.000 abstract description 6
- 150000004985 diamines Chemical class 0.000 abstract description 5
- 230000003287 optical effect Effects 0.000 abstract description 3
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 abstract description 3
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 230000032050 esterification Effects 0.000 abstract 1
- 238000005886 esterification reaction Methods 0.000 abstract 1
- 230000009257 reactivity Effects 0.000 abstract 1
- 238000006722 reduction reaction Methods 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 20
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 238000004679 31P NMR spectroscopy Methods 0.000 description 16
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 11
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 9
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
- 238000004896 high resolution mass spectrometry Methods 0.000 description 7
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- 125000001072 heteroaryl group Chemical group 0.000 description 6
- 238000003756 stirring Methods 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 239000007810 chemical reaction solvent Substances 0.000 description 5
- 229910000073 phosphorus hydride Inorganic materials 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- 125000000590 4-methylphenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 3
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 3
- 150000001555 benzenes Chemical group 0.000 description 3
- VURFVHCLMJOLKN-UHFFFAOYSA-N diphosphane Chemical compound PP VURFVHCLMJOLKN-UHFFFAOYSA-N 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 235000019439 ethyl acetate Nutrition 0.000 description 3
- 238000005984 hydrogenation reaction Methods 0.000 description 3
- 229910052707 ruthenium Inorganic materials 0.000 description 3
- 230000009466 transformation Effects 0.000 description 3
- PONXTPCRRASWKW-ZIAGYGMSSA-N (1r,2r)-1,2-diphenylethane-1,2-diamine Chemical compound C1([C@@H](N)[C@H](N)C=2C=CC=CC=2)=CC=CC=C1 PONXTPCRRASWKW-ZIAGYGMSSA-N 0.000 description 2
- BCJVBDBJSMFBRW-UHFFFAOYSA-N 4-diphenylphosphanylbutyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(C=1C=CC=CC=1)CCCCP(C=1C=CC=CC=1)C1=CC=CC=C1 BCJVBDBJSMFBRW-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 2
- 239000012230 colorless oil Substances 0.000 description 2
- 239000012141 concentrate Substances 0.000 description 2
- 238000010790 dilution Methods 0.000 description 2
- 239000012895 dilution Substances 0.000 description 2
- 239000000706 filtrate Substances 0.000 description 2
- 238000000034 method Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 239000003921 oil Substances 0.000 description 2
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 238000010898 silica gel chromatography Methods 0.000 description 2
- 229960001866 silicon dioxide Drugs 0.000 description 2
- 230000007306 turnover Effects 0.000 description 2
- GLZPCOQZEFWAFX-YFHOEESVSA-N (Z)-Geraniol Chemical compound CC(C)=CCC\C(C)=C/CO GLZPCOQZEFWAFX-YFHOEESVSA-N 0.000 description 1
- HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 1
- YFPJFKYCVYXDJK-UHFFFAOYSA-N Diphenylphosphine oxide Chemical compound C=1C=CC=CC=1[P+](=O)C1=CC=CC=C1 YFPJFKYCVYXDJK-UHFFFAOYSA-N 0.000 description 1
- 238000010268 HPLC based assay Methods 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 description 1
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- 150000001336 alkenes Chemical class 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- MUALRAIOVNYAIW-UHFFFAOYSA-N binap Chemical compound C1=CC=CC=C1P(C=1C(=C2C=CC=CC2=CC=1)C=1C2=CC=CC=C2C=CC=1P(C=1C=CC=CC=1)C=1C=CC=CC=1)C1=CC=CC=C1 MUALRAIOVNYAIW-UHFFFAOYSA-N 0.000 description 1
- WXMZPPIDLJRXNK-UHFFFAOYSA-N butyl(diphenyl)phosphane Chemical compound C=1C=CC=CC=1P(CCCC)C1=CC=CC=C1 WXMZPPIDLJRXNK-UHFFFAOYSA-N 0.000 description 1
- 239000012018 catalyst precursor Substances 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 230000006837 decompression Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 230000009189 diving Effects 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 1
- 150000002431 hydrogen Chemical class 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 150000002466 imines Chemical class 0.000 description 1
- 229960004502 levodopa Drugs 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 229930014626 natural product Natural products 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 229910052756 noble gas Inorganic materials 0.000 description 1
- 125000002524 organometallic group Chemical group 0.000 description 1
- LRYYUQJFQWSHNC-UHFFFAOYSA-N phenyl(4-phenylphosphanylbutyl)phosphane Chemical compound C=1C=CC=CC=1PCCCCPC1=CC=CC=C1 LRYYUQJFQWSHNC-UHFFFAOYSA-N 0.000 description 1
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000011946 reduction process Methods 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
本发明属于手性化合物的合成，具体地讲是一种螺环双膦配体，即化学式(I)的化合物。该化合物以螺环二酚为原料经三氟甲磺酸酐酯化、钯催化与二芳基氧膦偶联、三氯硅烷还原反应合成。该螺环双膦配体中的螺二氢茚结构具有轴向手性，因此有右旋螺环双膦配体和左旋螺环双膦配体，该两个旋光异构体的等量混合物则成为外消旋螺环双膦配体。本发明可作为手性配体用于潜手性酮的不对称催化氢化反应，特别是与之相匹配的手性二胺形成的双膦-双胺-钌络合物对潜手性酮的不对称催化氢化反应具有很高的立体选择性，对映选择性(e.e.值)高达99.5%，同时兼具高反应活性、高转化数(S/C＝100,000)优点。
The present invention belongs to the synthesis of chiral compounds, specifically a spirocyclic bisphosphine ligand, namely the compound of chemical formula (I). The compound is synthesized by using spirocyclic diphenol as a raw material through esterification of trifluoromethanesulfonic anhydride, palladium-catalyzed coupling with diaryl phosphine oxide, and reduction reaction of trichlorosilane. The spiroindane structure in the spirocyclic bisphosphine ligand has axial chirality, so there are right-handed spirocyclic bisphosphine ligand and left-handed spirocyclic bisphosphine ligand, an equal mixture of the two optical isomers Then it becomes a racemic spirocyclic bisphosphine ligand. The present invention can be used as a chiral ligand for the asymmetric catalytic hydrogenation reaction of latent chiral ketones, especially the bisphosphine-bisamine-ruthenium complex formed by matching chiral diamines to latent chiral ketones The asymmetric catalytic hydrogenation reaction has high stereoselectivity, the enantioselectivity (ee value) is as high as 99.5%, and it has the advantages of high reactivity and high conversion number (S/C=100,000).
Description
Affiliated technical field
The invention belongs to the synthetic of chipal compounds, is a kind of C of having specifically
2Synthesizing of the spirophosphine ligand of symmetry axis, and the application of ruthenium complex aspect the asymmetric catalytic hydrogenation of prochiral ketone.
Background technology
Asymmetric hydrogenation to the unsaturated substrate of chirality (alkene, ketone, imines etc.) of diving is the important channel of synthetic various chiral materials.In transition metal-catalyzed asymmetric hydrogenation, chiral ligand plays critical effect to the optical purity of product.In three more than ten years in the past, the research of the right title catalyzed reaction of people has obtained very big achievement (as: enantiomeric excess of product can reach 100%e.e.), and it is synthetic to be applied to the industry of many important drugs (as: levodopa, Naproxen Base, Ibuprofen BP/EP) and natural product (as: vernol etc.).But still have many reactive activity and enantioselectivity not ideal.Therefore, design and develop the vital task that new chiral ligand and catalyzer thereof are asymmetric synthesis research always.
At present, as BINAP (Yasuda, A.; Takaya, H.; Miyashita, A.; Toriumi, K.; Lto, T.; Souchi, T.; Noyori, R.J.Am.Chem.Soc.1980,102,7932), DIOP (Kagan, H.B.; Dang, T.P.J.Chem.Soc., Chem.Commun.1971,481), DuPHOS (Burk, M.J.; Feaster, J.E.; Harlow, R.L.Organometallics 1990,9,2653) etc. has C
2The chiral diphosphine ligand of symmetry axis in industrialized catalytic hydrogenation, be applied (Brown, J.M.In ComprehensiveAsymmetric Catalysis; Jacobsen, E.N., Pfaltz, A., Yamamoto, H., Eds.; Springer:Berlin, 1999; Vol.1, Chapter 5.1.).Though these parts have higher enantioselectivity, they all have certain shortcoming, and that is exactly a poor stability, in most cases must use in degassing solvent and noble gas atmosphere, and operation is extremely inconvenient.
Summary of the invention
The object of the present invention is to provide a kind of spirophosphine ligand, it is the novel bidentate phosphine ligands with spirane structure.When the ruthenium complex of spirophosphine ligand of the present invention is applied to the asymmetric catalytic hydrogenation of prochiral ketone, not only have very high enantioselectivity, and have very high turn over number (S/C reaches 100,000) and transformation frequency, stability is also fine.
The present invention is the compound with following chemical structure of general formula:
In the formula: n=0～3, R
1, R
2Be H, C
1～C
6Alkyl, alkoxyl group, aryl (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), R
1, R
2Can be identical, also can be different; R
3, R
4, R
5, R
6Be H, C
1～C
6Alkyl, alkoxyl group or aryl (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), or R
3～R
5, R
4～R
6For and alicyclic ring and aromatic ring (as and phenyl ring and substituted benzene ring and hetero-aromatic ring and replace hetero-aromatic ring etc.), R
3, R
4, R
5, R
6Can be identical, also can be different; R
7, R
8Be C
1～C
6Alkyl or cycloalkyl, or aryl substituting groups such as (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), R
7, R
8Can be identical, also can be different.
Spirophosphine ligand of the present invention can synthesize by following method:
With the volution diphenol is starting raw material, at first in the presence of the pyridine of 3～10 times of amounts, with the trifluoromethanesulfonic acid anhydride reactant of 2～3 times of amounts 8～20 hours, obtains two triflate, and temperature of reaction is 0～50 ℃, and reaction solvent is a methylene dichloride.In 1%～5% palladium and 1, under 4-diphenylphosphino butane (dppb) catalysis,, obtain single phosphine substitution product with the diisopropyl ethyl amine of two triflate and 2～4 times of amounts and the reaction of diaryl phosphine oxide 1～20 hour, 50～150 ℃ of temperature of reaction, reaction solvent are dimethyl sulfoxide (DMSO).In the presence of the diisopropyl ethyl amine of 20～50 times of amounts, reduced 3～8 days then, obtain single phosphine reduzate, 100～110 ℃ of temperature of reaction, reaction solvent toluene with trichlorosilane.Repeat palladium catalysis and the coupling of diaryl phosphine oxide and trichlorosilane reduction process then, obtain spirophosphine ligand (1).
Spiro indan structure in the spirophosphine ligand has axial chirality, so two optically active isomers are arranged, one is the dextrorotation spirophosphine ligand, and it two is left-handed spirophosphine ligand, and the equal amount of mixture of these two optically active isomers then becomes racemize volution biphosphine ligand.Therefore, in fact the said spirophosphine ligand of the present invention comprises racemic modification, dextrorotatory form and levo form.Racemic modification, dextrorotatory form and levo form have identical chemical structure of general formula, but have different three-dimensional arrangements and rotary light performance.
The said spirophosphine ligand of the present invention is a kind of purposes compound very widely, its ruthenium complex is used for the catalytic hydrogenation of prochiral ketone, enantioselectivity (e.e. value) can reach 99.5%, catalyst levels is 0.001～0.02%, and temperature of reaction is 0～60 ℃, and hydrogen pressure is 10～100 normal atmosphere, reaction times is 1 hour～10 days, reaction solvent is alcoholic solvents such as Virahol, also can be the mixed solvent of pure and mild other organic solvent composition, and its reaction expression is:
In [Ru]: n=0～3, R
1, R
2Be H, C
1～C
6Alkyl, alkoxyl group, aryl (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), R
1, R
2Can be identical, also can be different; R
3, R
4, R
5, R
6Be H, C
1～C
6Alkyl, alkoxyl group, aryl (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), or R
3～R
5, R
4～R
6For and alicyclic ring and aromatic ring (as and phenyl ring and substituted benzene ring and hetero-aromatic ring and replace hetero-aromatic ring etc.), R
3, R
4, R
5, R
6Can be identical, also can be different; R
7, R
8Be C
1～C
6Alkyl or cycloalkyl, aryl substituting groups such as (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), R
7, R
8Can be identical, also can be different; R
9, R
10, R
11Be H, C
1～C
6Alkyl, aryl etc., R
9, R
10, R
11Can be identical, also can be different.In the substrate: R
12, R
13Be C
1～C
6Alkyl, thiazolinyl, aryl (phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl) etc., R
12, R
13Must be different.
The synthetic of the ruthenium complex of spirophosphine ligand of the present invention is to obtain in 1～10 hour by diamine and metal ruthenium catalyst precursors reaction with equivalent, 50～160 ℃ of temperature of reaction, and reaction solvent is a dimethyl formamide.
Spirophosphine ligand of the present invention forms the two phosphine-diamines-ruthenium complex that mates with corresponding chiral diamine, asymmetric catalytic hydrogenation reaction to prochiral ketone has higher stereoselectivity, enantioselectivity (e.e. value) has advantages such as high reaction activity, high turn over number concurrently simultaneously up to 99.5%.
Embodiment
Embodiment 1
(S)-7, the preparation of 7 '-two (trifluoro-methanesulfonyl oxies)-1.1 '-spiro indan
In the 250mL reaction flask, add (S)-volution diphenol (5.0g, 19.8mmol), pyridine (7.0mL, 86.7mmol) and 100mL CH
2Cl
2, dropping trifluoromethanesulfanhydride anhydride under 0 ℃ (8.2mL, 43.7mmol), stirred overnight at room temperature.Reaction solution concentrate the back with silicagel column filter (S)-7,7 '-two (trifluoro-methanesulfonyl oxy)-1,1 '-spiro indan, 9.9 grams, yield: 97%; White solid, fusing point: 62-64 ℃; [α]
D-64 (c 0.5 CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.35 (m, 4H, CH
2), 3.10 (m, 4H, CH
2), 7.15 (dd, 2H, J=1.8 and 6.6Hz, Ar-H), 7.26-7.30 (m, 4H, Ar-H);
13C NMR (75MHz, CDCl
3) δ 31.1,38.6,59.4,115.9,118.5,120.1,124.4,129.4,138.2,145.8,147.7; IR (KBr) 2958,1622,1579,1466,1405,1214,1144,994,934,860,830cm
-1MS (EI) m/z 516 (M
+); Ultimate analysis (theoretical value) C
19H
14F
6O
6S
2: C 43.97 (44.19); H 2.83 (2.73).
Embodiment 2
(S)-and 7-diphenylphosphine acyl group-7 '-trifluoro-methanesulfonyl oxy-1, the preparation of 1 '-spiro indan
In the 100mL reaction flask, add (S)-7,7 '-two (trifluoro-methanesulfonyl oxy)-1,1 '-spiro indan (4.0g, 7.75mmol), diphenyl phosphine oxide (3.13g, 15.5mmol), palladium (87mg, 0.39mmol), 1,4-diphenylphosphino butane (dppb, 166mg, 0.39mmol) and 25mL DMSO.(4.1g 32mmol), is heated to 100 ℃ of reactions 6 hours to add diisopropyl ethyl amine under stirring.Be chilled to room temperature, EtOAc dilution is filtered, filtrate sloughs solvent after the silicagel column column chromatography (leacheate: sherwood oil/EtOAc=3/1) (S)-7-diphenylphosphine acyl group-7 '-trifluoro-methanesulfonyl oxy-1,1 '-spiro indan, 4.0 grams, yield 90%; White solid, fusing point: 173-175 ℃; [α]
D-74 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.20-2.39 (m, 4H CH
2), 3.08 (m, 2H, CH
2), 3.23-3.41 (m, 2H, CH
2), 6.21 (d, 2H, J=8.1Hz, Ar-H), 7.14-7.20 (m, 11H, Ar-H);
31PNMR (121MHz, CDCl
3) δ 31.79 (s);
13C NMR (75MHz, CDCl
3) δ 21.1,30.8,31.8,39.8,40.1,61.8,117.5,123.9,126.1,128.0,128.2,131.3,131.4,131.7,131.8,133.6,140.7,144.8,146.1,149.8; IR (KBr) 3061,2943,1462,1439,1415,1398,1209,1142,853cm
-1MS (EI) m/z 569 (M+1
+); Ultimate analysis (theoretical value) C
30H
24F
3O
4PS:C63.47 (63.38); H4.15 (4.25); S5.45 (5.64).
Embodiment 3
(R)-and 7-two p-methylphenyl phosphono-7 '-trifluoro-methanesulfonyl oxies-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 2.Yield: 81%; White solid, fusing point: 222-224 ℃; [α]
D+ 116 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.18-2.42 (s, 3H, CH
3), 2.32 (s, 3H, CH
3), 2.39 (s, 3H, CH
3), 3.05 (m, 3H, CH
2), 3.21-3.19 (m, 2H, CH
2), 6.24 (d, 2H, J=8.1Hz, Ar-H), 7.00-7.10 (m, 2H, Ar-H), 7.10-7.23 (m, 10H, Ar-H), 7.20-7.23 (m, 2H, Ar-H), 7.29 (d, 2H, Ar-H);
31P NMR (121MHz, CDCl
3) δ 31.73 (s);
13C NMR (121MHz, CDCl
3): δ 21.5,30.7, and 31.8,39.8,40.0,61.9,115.6,117.5,123.7,125.9,126.2,127.5,127.6,127.9,128.2,128.6,128.8,128.9,131.3,131.5,131.7,131.8,132.2,133.2,133.4,133.6,140.9,141.3,144.9,145.9,146.1,149.7,152.9,152.9; IR (KBr) 3061,2943,1462,1439,1415,1398,1209,1142,853cm
-1MS (EI) m/z 596 (M
+); Ultimate analysis (theoretical value) C
32H
28F
3O
4PS:64.16 (64.42);
H4.92 (4.73).
Embodiment 4
(R)-and 7-di-p-methoxy Phenylphosphine acyl group-7 '-trifluoro-methanesulfonyl oxy-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 2.Yield: 90%; White solid, fusing point: 150-152 ℃; [α]
D+ 108 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.20-2.32 (m, 3H, CH
2), 3.04-3.18 (m, 3H, CH
2), 3.20-3.40 (m, 2H, CH
2), 3.78 (s, 3H, OCH
3), 3.85 (s, 3H, OCH
3), 6.24 (d, 2H, J=8.1Hz, Ar-H), 6.80-6.85 (m, 4H, Ar-H), 6.86-7.00 (m, 2H, Ar-H), 7.16-7.21 (m, 4H, Ar-H), 7.21-7.30 (m, 2H, Ar-H), 7.32 (d, 1H, J=7.2Hz, Ar-H);
31P NMR (121MHz, CDCl
3) δ 31.45 (s);
13C NMR (75MHz, CDCl
3) δ 29.7,30.1,30.8,38.7,38.9,54.2,60.8,112.4,112.6,116.3,118.8,121.1,122.6,124.9,125.1,125.9,126.4,126.9,127.2,127.4,127.8,131.9,132.1,132.4,132.5,139.7,143.8,1.44.8,145.0,148.6,151.7,160.7,160.9; IR (CH
2Cl
2) 3048,2948,1598,1570,1500,1460,1412,1292,1257,1214,1178,1142,1029,931; MS (EI) m/z 628 (M
+); HR-MS (FAB) (theoretical value) C
32H
28F
3O
6PS+H
+: 629.1362 (629.1369).
Embodiment 5
(S)-and 7-two-(3, the 5-dimethyl) Phenylphosphine acyl group-7 '-trifluoro-methanesulfonyl oxy-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 2.Yield: 92%; White solid, fusing point: 183-185 ℃; [α]
D-128 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.18-2.37 (m, 3H, CH
2), 2.23 (s, 6H, CH
3), 2.25 (s, 6H, CH
3), 2.90-3.18 (m, 3H, CH
2), 3.21-3.42 (m, 2H, CH
2), 6.26 (d, 1H, J=8.1Hz, Ar-H), 6.85 (d, 2H, J=12Hz, Ar-H), 6.90-7.10 (m, 6H, Ar-H), 7.10-7.20 (m, 2H, Ar-H), 7.39 (d, 1H, J=7.8Hz, Ar-H);
31P NMR (121MHz, CDCl
3) δ 31.16 (s);
13C NMR (75MHz, CDCl
3) δ 21.4,21.5,21.7,30.9,32.1,39.8,40.5,62.1,115.8,117.4,120.0,123.8,126.2,126.5,127.7,127.9,129.1,129.2,129.5,129.6,130.3,131.6,133.1,133.30,133.4,133.6,135.3,136.7,137.5,137.7,137.8,137.9,140.7,145.1,145.9,146.1,150.3,153.1; IR (CH
2Cl
2) 3053,2943,1605,1577,1460,1397,1267,1219,1188,1138,983,932,854; HR-MS (FAB) (theoretical value) C
34H
32F
3O
4PS+H
+: 625.1782 (625.1784).
Embodiment 6
(S)-and 7-diphenylphosphino-7 '-trifluoro-methanesulfonyl oxy-1, the preparation of 1 '-spiro indan
In the 100mL reaction flask, add (S)-7-diphenylphosphine acyl group-7 '-trifluoro-methanesulfonyl oxy-1, and 1 '-spiro indan (1.4g, 2.5mmol), (13.2g 102mmol) and toluene 50mL, stirs and adds Cl down diisopropyl ethyl amine
3SiH (4.0mL, 39mmol), 110 ℃ of stirring reactions of mixture 5 days.Be chilled to room temperature, the ether dilution is filtered, filtrate concentrates behind anhydrous sodium sulfate drying, silica gel column chromatography (leacheate: sherwood oil/EtOAc=3/1) get (S)-7-diphenylphosphino-7 '-trifluoro-methanesulfonyl oxy-1,1 '-spiro indan 1.26 restrains yield: 91%; White solid, fusing point: 72-74 ℃; [α]
D-73 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.26-2.33 (m, 3H, CH
2), 2.54 (m, 1H, CH
2), 3.09 (m, 4H, CH
2), 6.65 (d, 1H, J=8.1Hz, Ar-H), 6.90-7.04 (m, 5H, Ar-H), 7.04-7.28 (m, 10H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-20.54 (s);
13C NMR (75MHz, CDCl
3) δ 29.7,30.3,37.9,39.0,39.1,60.6,114.7,117.3,118.9,123.0,124.5,126.4,126.9,127.1,127.2,127.3,127.7,131.1,131.3,132.1,132.3,132.4,132.7,133.4,134.9,135.1,137.5,137.7,140.9,142.7,142.8,144.5,146.9,151.8; IR (KBr) 3072,3057,2948,2848,1614,1578,1462,1435,1415,1398,1214,1141,995,978,929,852,829cm
-1MS (EI) m/z 552 (M
+); Ultimate analysis (theoretical value) C
30H
24F
3O
4PS:65.20 (65.22);
H4.25 (4.38).
Embodiment 7
(R)-and 7-two p-methylphenyl phosphino--7 '-trifluoro-methanesulfonyl oxies-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 6.Yield: 81%; White solid, fusing point: 112-114 ℃; [α]
D+ 66 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.28 (s, 3H, CH
3), 2.31 (s, 3H, CH
3), 2.25-2.34 (m, 3H, CH
2), 2.42 (m, 1H, CH
2), 3.05 (m, 4H, CH
2), 6.70 (d, 1H, J=7.8Hz, Ar-H), 6.88-7.00 (m, 9H, Ar-H), 7.19-7.25 (m, 4H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-22.26 (s);
13C NMR (75MHz, CDCl
3) δ 21.5,30.9,31.6,39.2,40.0,61.8,116.0,118.6,120.2,124.3,125.6,126.5,127.6,128.6,128.9,129.2,133.2,133.4,133.7,133.9,134.7,135.1,135.3,135.4,138.3,138.4,142.3,144.0,145.8,148.1,152.4,152.7; IR (CH
2Cl
2) 2947,2848,1603,1577,1464,1415,1398,1273,1219,1141,932cm
-1HR-MS (FAB) (theoretical value) C
32H
28F
3O
3PS+H
+: 581.1530 (581.1521).
Embodiment 8
(R)-and 7-di-p-methoxy phenyl phosphino--7 '-trifluoro-methanesulfonyl oxy-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 6.Yield: 75%; Colorless oil, room temperature are placed and are solidified; [α]
D+ 72 (c0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.24-2.33 (m, 3H, CH
2), 2.50 (m, 1H, CH
2), 3.04 (m, 4H, CH
2), 3.75 (s, 3H, OCH
3), 3.78 (s, 3H, OCH
3), 6.70-6.78 (m, 5H, Ar-H), 6.89-7.00 (m, 5H, Ar-H), 7.17-7.25 (m, 4H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-23.65 (s);
13C NMR (75MHz, CDCl
3) δ 29.6,30.1,30.3,38.0,38.6,54.1,60.5,112.3,112.6,112.8,112.9,114.7,118.9,122.9,124.2,126.1,126.3,127.7,128.4,128.5,132.3,132.6,132.7,133.6,133.9,134.1,140.8,142.6,142.7,144.6,146.8,150.8,151.2,158.6,158.9; IR (CH
2Cl
2) 3053,2968,2935,2846,1595,1569,1496,1462,1413,1283,1243,1219,1178,1140,1030,930,831cm
-1HR-MS (FAB) (theoretical value) C
32H
28F
3O
6PS+H
+: 629.1362 (629.1369).
Embodiment 9
(S)-and 7-two-(3, the 5-dimethyl) phenyl phosphino--7 '-trifluoro-methanesulfonyl oxy-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 6.Yield: 75%; White solid, fusing point: 94-96 ℃; [α]
D-78 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 2.17 (s, 6H, CH
3), 2.19 (s, 6H, CH
3), 2.08-2.18 (m, 3H, CH
2), 2.56 (m, 1H, CH
2), 3.08 (m, 4H, CH
2), 6.61-6.70 (m, 5H, Ar-H), 6.84 (s, 1H, Ar-H), 6.98 (s, 1H, Ar-H), 7.00 (m, 1H, Ar-H), 7.11-7.26 (m, 4H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-20.66 (s);
13C NMR (75MHz, CDCl
3) δ 20.1,20.2,29.6,30.4,37.9,38.9,60.4,114.6,117.1,118.9,122.9,124.1,126.2,127.3,128.7,129.2,129.8,130.0,130.3,130.7,131.8,132.1,133.3,134.4,134.5,136.1,136.2,136.3,137.2,137.3,140.9,142.7,142.4,144.4,146.9,151.2,151.5; IR (CH
2Cl
2) 3053,2951,2854,1601,1579,1462,1415,1398,1267,1215,1142,988,930,853cm
-1MS (EI) m/z608 (M
+); Ultimate analysis (theoretical value) C
34H
32F
3O
3PS:C 66.87 (67.09); H 5.46 (5.30)
Embodiment 10
(S)-and 7-diphenylphosphino-7 '-diphenylphosphine acyl group-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 2.Yield: 92%; White solid, fusing point: 80-83 ℃; [α]
D-74 (c0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 1.80-2.15 (m, 3H, CH
2), 2.59-3.04 (m, 5H, CH
2), 6.84 (m, 2H, Ar-H), 6.92 (m, 1H, Ar-H), 7.10-7.23 (m, 14H, Ar-H), 7.23-7.42 (m, 9H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-17.29 (s), 30.99 (s);
13C NMR (75MHz, CDCl
3) δ 30.9,31.0,40.5,64.3,125.1,125.6,125.8,126.3,127.2,127.7,127.8,127.9,128.2,128.3,131.0,131.6,131.7,132.3,132.5,132.9,133.0,133.1,133.2,133.4,134.1,134.4,138.7,143.3,143.4,155.1,157.7,158.1; IR (KBr) 3142,3053,2935,1631,1586,1435,1412,1209,1114,744,696cm
-1MS (EI) m/z 604 (M
+); MS (FAB) (theoretical value) C
41H
34OP
2+ H
+: 605.2154 (605.2157).
Embodiment 11
(R)-and 7-di-p-tolyl phosphino--7 '-di-p-tolyl phosphono-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 2.Yield: 90%; White solid, fusing point: 203-205 ℃; [α]
D+ 90 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 1.80-2.10 (m, 3H, CH
2), 2.27 (s, 3H, CH
3), 2.30 (s, 3H, CH
3), 2.32 (s, 3H, CH
3), 2.35 (s, 3H, CH
3), 2.62-2.80 (m, 2H, CH
2), 2.80-3.05 (m, 3H, CH
2), 6.69 (t, 2H, J=6.9Hz, Ar-H), 6.88 (d, 2H, J=6.3Hz, Ar-H), 6.90-7.40 (m, 18H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-19.35 (s), 30.35 (s);
13C NMR (75MHz, CDCl
3) δ 20.3,20.5,30.0,39.5,39.7,63.3,123.9,124.5,124.6,125.1,126.7,127.5,127.7,127.8,129.4,130.6,130.7,131.3,131.5,131.7,131.9,132.2,132.5,133.0,133.3,134.1,134.3,134.5,134.6,135.7,137.0,140.0,142.4,146.3,154.1,156.6,156.9; IR (CH
2Cl
2) 3053,2935,2874,1604,1498,1413,1269,1196,1190,1018,811cm
-1MS (EI) m/z 660 (M
+); Ultimate analysis (theoretical value) C
45H
42OP
2: C 81.86 (81.80);
H6.41 (6.50)
Embodiment 12
(R)-and 7-di-p-methoxy phenyl phosphino--7 '-di-p-methoxy Phenylphosphine acyl group-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 2.Yield: 88%; White solid, fusing point: 205-207 ℃; [α]
D+ 94 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 1.80-1.98 (m, 1H, CH
2), 2.00-2.10 (m, 2H, CH
2), 2.65-2.80 (m, 2H, CH
2), 3.73 (s.3H, CH
3), 3.75 (s, 3H, CH
3), 3.77 (s, 3H, CH
3), 3.79 (s, 3H, CH
3), 6.60-6.66 (m, 5H, Ar-H), 6.77 (d, 2H, J=8.4Hz, Ar-H), 6.86 (dd, 2H, J=1.8and 8.7Hz, Ar-H), 6.90 (t, 1H, J=5.1Hz, Ar-H), 7.00-7.38 (m, 12H, Ar-H);
31PNMR (121MHz, CDCl
3) δ-21.01 (s), 29.80 (s);
13C NMR (75MHz, CDCl
3) δ 30.0,39.3,39.7,54.0,54.1,63.3,108.7,112.3,112.4,112.6,123.8,124.4,124.6,125.1,125.4,126.2,126.6,127.0,127.6,128.4,128.6,129.0,129.2,130.8,131.0,131.3,131.9,132.2,132.3,132.5,133.1,133.2,133.6,133.9,134.4,134.6,142.6,146.0,154.1,156.3,156.7,158.0,158.7,160.6; IR (CH
2Cl
2) 3049,2939,2838,1595,1567,1500,1460,1283,1245,1196,1182,1111,1028,831cm
-1MS (EI) m/z 724 (M
+); Ultimate analysis (theoretical value) C
45H
42O
5P
2: C 74.52 (74.58); H 5.93 (5.84)
Embodiment 13
(S)-and 7-two-(3, the 5-dimethyl) phenyl phosphino--7 '-two-(3, the 5-dimethyl) Phenylphosphine acyl group-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 2.Yield: 91%; White solid, fusing point: 116-118 ℃; [α]
D-42 (c 0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 1.70 (m, 2H, CH
2), 1.94 (m, 1H, CH
2), 2.20 (s, 12H, CH
3), 2.23 (s, 6H, CH
3), 2.27 (s, 6H, CH
3), 2.49 (m, 2H, CH
2), 2.80 (m, 1H, CH
2), 2.92 (m, 2H, CH
2), 6.56 (d, 2H, J=6.6Hz, Ar-H), 6.73 (s, 1H, Ar-H), 6.85 (d, 2H, J=8.1Hz, Ar-H), 6.91 (s, 1H, Ar-H), 6.95 (s, 1H, Ar-H), 7.10-7.25 (m, 10H, Ar-H), 7.38 (d, 1H, J=6.6Hz, Ar-H);
31P NMR (121MHz, CDCl
3) δ-16.24 (s), 31.05 (s);
13C NMR (75MHz, CDCl
3) δ 21.01,21.3,30.7,30.9,39.8,40.1,64.4,132.6,124.9,125.4,125.6,126.1,127.7,128.7,129.4,129.5,130.2,130.4,130.5,130.7,132.1,132.5,132.7,133.0,134.0,135.4,136.2,136.6,137.1,137.6,137.8,138.0,139.1,139.3,142.2,142.3,147.0,154.4,158.0; IR (CH
2Cl
2) 3065,3028,2980,2923,1597,1413,1275,1255,1196,1130,896,851cm
-1HR-MS (FAB) (theoretical value) C
49H
50OP
2+ H
+: 717.3414 (717.3409).
Embodiment 14
(S)-7,7 '-two (diphenylphosphino)-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 6.Yield: 86%; White solid, fusing point: 206-208 ℃; [α]
D-81 (c 0.5CH
2Cl
2).
1H NMR (300MHz CDCl
3) δ 1.80-2.00 (m, 4H, CH
2), 2.62-2.80 (m, 2H, CH
2), 2.80-2.96 (m, 2H, CH
2), 6.96 (m, 2H, Ar-H), 7.08-7.30 (m, 14H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-17.26 (s);
13C NMR (75MHz, CDCl
3) δ 30.7,40.1,64.1,125.3,126.9,127.5,127.9,128.2,128.5,133.3,133.4,133.5,134.4,134.5,134.6,138.4,144.5,144.6,154.5,154.7,154.8; IR (KBr) 3138,3052,2999,2938,1636,1586,1567,1479,1434,1412,1262,1091,1027cm
-1MS (EI) m/z 588 (M
+); Ultimate analysis (theoretical value) C
41H
34P
2: C 83.50 (83.65); H 6.05 (5.83)
Embodiment 15
(R)-7,7 '-two (two p-methylphenyl phosphino-s)-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 6.Yield: 85%; White solid, fusing point: 142-144 ℃; [α]
D+ 88 (c 0.5CH
2Cl
2).
1H NMR (300MHz CDCl
3) δ 1.94 (m, 4H, CH
2), 2.72 (m, 2H, CH
2), 2.79 (s, 6H, CH
3), 2.73 (s, 6H, CH
3), 2.87 (m, 2H, CH
2), 6.80-6.90 (m, 8H, Ar-H), 6.90-7.10 (m, 10H, Ar-H), 7.21-7.24 (m, 4H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-19.75 (s);
13CNMR (75MHz, CDCl
3) δ 21.5,21.6,31.0,40.4,64.3,125.3,127.0,128.9,129.2,133.4,133.6,133.8,133.9,134.5,134.6,134.8,135.3,137.4,138.4,144.7,154.7,154.9,155.1; IR (CH
2Cl
2) 2952,2928,2861,1598,1495,1452,1308,1377,1270,1255,1188,1088,1018,809,767cm
-1HR-MS (FAB) (theoretical value) C
45H
42P
2+ H
+: 645.2839 (645.2834).
Embodiment 16
(R)-7,7 '-two (di-p-methoxy phenyl phosphino-s)-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 6.Yield: 80%; White solid, fusing point: 183-185 ℃; [α]
D+ 106 (c 0.5CH
2Cl
2).
1H NMR (300MHz CDCl
3) δ 1.93 (m, 4H, CH
2), 2.72 (m, 2H, CH
2), 2.85 (m, 2H, CH
2), 3.74 (s, 3H, CH
3), 3.76 (s, 3H, CH
3), 3.78 (s, 3H, CH
3), 3.80 (s, 3H, CH
3), 6.68 (d, 4H, J=8.1Hz, Ar-H), 6.79 (d, 4H, J=9.0Hz, Ar-H), 6.85-6.90 (m, 4H, Ar-H), 7.01-7.09 (m, 6H, Ar-H), 7.15-7.25 (m, 4H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-20.61 (s);
13C NMR (75MHz, CDCl
3) δ 31.0,40.1,55.3,64.2,113.8,114.0,125.2,127.0,129.8,133.0,134.9,135.1,135.1,135.2,135.9,136.0,136.2,144.6,154.4,154.6,154.7,159.5,160.1; IR (CH
2Cl
2) 2946,2831,1598,1561,1489,1452,1285,1235,1177,1097,1024,821cm
-1MS (EI) m/z 708 (M
+); Ultimate analysis (theoretical value) C
45H
42O
4P:C 76.07 (76.26); H 5.95 (5.97)
Embodiment 17
(S)-7,7 '-two (two (3, the 5-dimethyl) phenyl phosphino-s)-1, the preparation of 1 '-spiro indan
The preparation method is identical with embodiment 6.Yield: 83%; Colorless oil, room temperature are placed and are solidified; [α]
D-36 (c0.5CH
2Cl
2).
1H NMR (300MHz, CDCl
3) δ 1.71 (m, 2H, CH
2), 1.88 (m, 2H, CH
2), 2.05 (s, 6H, CH
3), 2.17 (s, 3H, CH
3), 2.25 (s, 6H, CH
3), 2.28 (s, 3H, CH
3), 2.32 (s, 3H, CH
3), 2.65 (m, 2H, CH
2), 2.87 (m, 2H, CH
2), 6.68 (m, 3H, Ar-H), 6.85 (m, 5H, Ar-H), 6.98-7.50 (m, 10H, Ar-H);
31P NMR (121MHz, CDCl
3) δ-14.80 (s);
13C NMR (75MHz, CDCl
3) δ 20.1,20.3,28.6,29.6,38.4,63.1,124.0,125.7,126.6,127.9,128.5,129.4,129.6,129.7,129.8,131.8,132.1,133.7,135.9,136.2,137.6,143.1,152.7,152.9,153.1; IR (CH
2Cl
2) 3054,2963,2851,1591,1571,1458,1415,1273,1182,852cm
-1HR-MS (FAB) (theoretical value) C
49H
50P
2+ H
+: 701.3466 (701.3460).
Embodiment 18
The preparation of two phosphine diamine ruthenium complexs (with (S)-7,7 '-two (two (3, the 5-dimethyl) phenyl phosphino-s)-1,1 '-spiro indan with (R, R)-1,2-diphenyl ethylene diamine and [(C
6H
6) RuCl
2]
2Complex compound be example)
R＝3，5-(CH
3)
2C
6H
3
In nitrogen atmosphere with (S)-7,7 '-two [two (3, the 5-dimethyl) phenyl phosphino-s]-1,1 '-spiro indan (115.5mg, 0.165mmol) and [(C
6H
6) RuCl
2]
2(40mg 0.08mmol) is dissolved among the 3mL DMF, is heated to 100 ℃, stirring reaction 1.5～2.0 hours, add then (R, R)-1,2-diphenyl ethylene diamine (DPEN) (22.6mg, 0.165mmol), stirring at room 18～20 hours, slough behind the solvent the reddish-brown solid.This solid is directly used in hydrogenation.
All the other two phosphine diamine ruthenium complexs according to said method prepare.
Embodiment 19
The asymmetric catalytic hydrogenation reaction of prochiral ketone
In [Ru]: n=0～3, R
1, R
2Be H, C
1～C
6Alkyl, alkoxyl group, aryl (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), R
1, R
2Can be identical, also can be different; R
3, R
4, R
5, R
6Be H, C
1～C
6Alkyl, alkoxyl group, aryl (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), or R
3～R
5, R
4～R
6For and alicyclic ring and aromatic ring (as and phenyl ring and substituted benzene ring and hetero-aromatic ring and replace hetero-aromatic ring etc.), R
3, R
4, R
5, R
6Can be identical, also can be different; R
7, R
8Be C
1～C
6Alkyl or cycloalkyl, aryl substituting groups such as (as phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl etc.), R
7, R
8Can be identical, also can be different; R
9, R
10, R
11Be H, C
1～C
6Alkyl, aryl etc., R
9, R
10, R
11Can be identical, also can be different.In the substrate: R
12, R
13Be C
1～C
6Alkyl, thiazolinyl, aryl (phenyl, substituted-phenyl, heterocyclic aryl, substituted heterocycle aryl) etc., R
13, R
13Must be different.
In the hydrogenation still, add the 0.002mmol catalyzer, the 10mmol substrate, 0.14mmol potassium tert.-butoxide and 3.0mL Virahol, under the 50atm hydrogen-pressure, the stirring at room hydrogenation.Reaction finishes, and solvent is sloughed in decompression, separates obtaining target product through silica gel column chromatography.Transformation efficiency and optical purity by GC or HPLC assay products the results are shown in Table 1 (with R
1, R
2, R
3, R
4, R
5, R
6Be hydrogen, R
7, R
8Be 3,5-(CH
3)
2C
6H
3, R
9, R
10Be phenyl, R
11For hydrogen is example).
The asymmetric catalytic hydrogenation result of table 1 prochiral ketone
| Prochiral ketone | Reaction times h | Transformation efficiency % | Enantioselectivity %ee (configuration) | ||
| R 12 | R 13 | ||||
| 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 | C 6H 5 o-ClC 6H 4 o-BrC 6H 4 m-BrC 6H 4 m-CF 3C 6H 4 p-CH 3C 6H 4 p-CH 3OC 6H 4 p-ClC 6H 4 p-BrC 6H 4 C 6H 5 C 6H 5 2′-naphthyl ferrocenyl 2-furyl 2-thienyl | CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 CH 3 C 2H 5 PhCH 2 CH 3 CH 3 CH 3 CH 3 | 1.5 3.5 6.5 3 2 1.5 4.5 1.5 3 3.5 46 4 5 5 5 | 100 99 100 99 99 100 100 100 100 99 100 98 100 99 98 | 99(S) 98(S) 99.2(S) 99.2(S) 99(S) 99.2(S) 98(S) 99(S) 99(S) 99.5(S) 98(S) 99.2(S) 98(S) 98(S) 98(S) |
Claims (5)
1, a kind of spirophosphine ligand is characterized in that it is the compound of following chemical formula (I):
In the formula: n=0～3, R
1, R
2Be H, C
1～C
6Alkyl, alkoxyl group or aryl, R
1, R
2Can be identical, also can be different; R
3, R
4, R
5, R
6Be H, C
1～C
6Alkyl, alkoxyl group or aryl, or R
3～R
5, R
4～R
6Be also alicyclic ring or also aromatic ring, R
3, R
4, R
5, R
6Can be identical, also can be different; R
7, R
8Be C
1～C
6Alkyl, cycloalkyl or aryl, R
7, R
8Can be identical, also can be different.
2, according to the described compound of claim 1, it is characterized in that it is: the two parts of seeing of racemize volution: (±)-7,7 '-diaryl or (±)-7,7 '-dialkyl group phosphino--1,1 '-spiro indan; The two parts of seeing of dextrorotation volution: (R)-7,7 '-diaryl or (R)-7,7 '-dialkyl group phosphino--1,1 '-spiro indan; Or the two parts of seeing of left-handed volution: (S)-7,7 '-diaryl or (S)-7,7 '-dialkyl group phosphino--1,1 '-spiro indan.
3, the preparation method of compound according to claim 1, it is characterized in that it is through following step: with the volution diphenol is starting raw material, reaction through volution diphenol and trifluoromethanesulfanhydride anhydride forms two triflate, then under palladium catalysis with the coupling of diaryl phosphine oxide, trichlorosilane reduction is synthetic:
In the formula: n=0～3, R
1, R
2Be H, C
1～C
6Alkyl, alkoxyl group or aryl, R
1, R
2Can be identical, also can be different; R
3, R
4, R
5, R
6Be H, C
1～C
6Alkyl, alkoxyl group or aryl, or R
3～R
5, R
4～R
6Be also alicyclic ring or also aromatic ring, R
3, R
4, R
5, R
6Can be identical, also can be different; R
7, R
8Be C
1～C
6Alkyl, cycloalkyl or aryl, R
7, R
8Can be identical, also can be different.
4, the described application of compound of claim 1, it is characterized in that this compound makes ruthenium-diamine complex compound is used for prochiral ketone in the presence of organic solvent as catalyzer catalytic hydrogenation, catalyst levels is 0.001～0.02%, hydrogen pressure is 10～100 normal atmosphere, temperature of reaction is 0～60 ℃, and the reaction times is 1 hour～10 days:
In [Ru]: n=0～3, R
1, R
2Be H, C
1～C
6Alkyl, alkoxyl group or aryl, R
1, R
2Can be identical, also can be different; R
3, R
4, R
5, R
6Be H, C
1～C
6Alkyl, alkoxyl group or aryl, or R
3～R
5, R
4～R
6For and alicyclic ring and aromatic ring, R
3, R
4, R
5, R
6Can be identical, also can be different; R
7, R
8Be C
1～C
6Alkyl or cycloalkyl or aryl, R
7, R
8Can be identical, also can be different; R
9, R
10, R
11Be H, C
1～C
6Alkyl or aryl, R
9, R
10, R
11Can be identical, also can be different; In the substrate: R
12, R
13Be C
1～C
6Alkyl, thiazolinyl or aryl, R
12, R
13Must be different.
5, according to the described application of compound of claim 4, it is characterized in that described organic solvent is an alcoholic solvent, also can be the mixed solvent of pure and mild other organic solvent composition.
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