WO2008135386A1 - Chiral ligands of the n-heterocyclic carbene type for asymmetrical catalysis - Google Patents

Abstract

The invention relates to compounds of the formula (I) or the formula (II) in which : X is an anion ; n<SUP>1</SUP> = 0, 1, 2; n<SUP>2</SUP> = 1 to 4; R<SUP>1</SUP> is C<SUB>1</SUB>-C<SUB>6</SUB> alkyl or an optionally substituted C<SUB>5</SUB> or C<SUB>6</SUB> cycloalkyl or a C<SUB>1</SUB>-C<SUB>6</SUB> perhalogenoalkyl; R<SUP>2</SUP> is C<SUB>1</SUB>-C<SUB>8</SUB> alkyl or an optionally substituted C<SUB>5</SUB> or C<SUB>6</SUB> cycloalkyl or an optionally substituted aryl or an optionally substituted naphthyl or a -CH<SUB>3-</SUB>

Description

 N-heterocyclic carbene type chiral ligands for asymmetric catalysis.

The present invention relates to novel monodentate, bidentate or chiral tridentate ligands of N-heterocyclic carbene (NHC) type derived from [] -amino acids and [] - alkylbenzylamines.

Such chiral ligands are intended to be used in asymmetric catalysis processes using various transition metals such as enantioselective catalysis of conjugated addition, hydrogenation, CH activation, isomerization, coupling CC and CN. More particularly, the present invention relates in particular to the synthesis of alkyloxyimidazolinium, phenoxyimidazolinium, diphenylphosphinoimidazolinium, alkyloxytetrahydrodiazepinium, phenoxytetrahydrodiazepinium, diphenylphosphino-tetrahydrodiazepinium and alkyloxyquinolinium salts, of phenoxy - quinolinium and diphenylphosphino - quinolinium, direct precursors of carbon ligands complexed to various transition metals.

A family of azolium salts, namely the alkoxyimidazolinium salts of formula A, and the use of these compounds as chiral bidentate ligands of the carbene-N-heterocyclic type are known in the prior art ( CNH) in the context of a conjugate addition process of organometallic derivatives on cyclic enones catalyzed by copper complexes.

AT

This family of compounds and their syntheses are described in three articles by Mauduit et al. published in 2005 (H. Clavier, L. Coutable, JC Guillemin, M. Mauduit *, Tetrahedron.-Asymmetry, 2005, 16, 921-924 and H. Clavier, L. Coutable, L. Toupet, JC Guillemin, M. Mauduit *, J. Organome, Chem., 2005, 690, 5237-5254) and 2006 (D. Martin, S. Kehli, M. d'Augustin, H. Clavier, M. Mauduit *, A. Alexakis * J. Am Chem., Soc., 2006, 128, 8416-8417). These compounds of formula A have a stereogenic center on the chelating side chain at the alpha position with respect to the imidazolinium nucleus enabled to induce excellent stereo selectivities (up to 96% enantiomeric excess) in the conjugated addition reaction of derivatives. Organometallic compounds (dialkylzinc and organomagnesium) on cyclic enones catalyzed by copper complexes.

This previous work carried out on the alkoxy-imidazolinium type A provided crucial information on the design of this type of ligand with in particular the position of the stereogenic center in the alpha position of the nitrogen heterocycle.

The objective of the present invention is to provide novel chiral bidentate or tridentate monodentate ligands capable of exhibiting an improved reactivity and selectivity in asymmetric catalysis compared to those of these azolium salts of the prior art.

The invention relates to any compound of formula (I) or of formula (II):

<"(M)

in which :

X is an anion;

^ = O, 1, 2;

N = 1 to 4;

R is a C ₁ to C ₆ alkyl, or an optionally substituted C ₅ or C ₆ cycloalkyl, or a C ₁ to C ₆ perhaloalkyl; 2

R is a C ₁ to C ₈ alkyl, or an optionally substituted C ₅ or C ₆ cycloalkyl, or an optionally substituted aryl, or an optionally substituted naphthyl, or a -CH ₃ _ _n (Aryl) _n radical with n = 1 to 3, or a radical -CH (R) Z where R is hydrogen, or a C ₁ to C ₆ alkyl, or an optionally substituted C ₅ or C ₆ cycloalkyl, or a C ₁ to C ₆ perhaloalkyl ;

Z is a C ₁ to C ₈ alkyl, or a C ₅ or C ₆ cycloalkyl, or a radical of the formula:

Y is hydrogen, or OR, or SR, or P (R) ₂ , or halogen or OSO ₂ R ¹² ; n ³ = 1 to 4;

R, R, R, R, R, R, R, R, R, R are independently H or a C ₁ -C _6, or a perhaloalkyl C ₁ -C ₆ or cycloalkyl optionally substituted C ₅ or C ₆ or aryl; R and R on the one hand and R and R on the other hand

Which can form a 3, 4, 5, 6 and 7-membered ring; R and R may independently form a 6-membered aromatic ring.

The compounds according to the present invention may therefore have one or two structural originalities with respect to the compounds of formula A of the prior art, namely a first originality constituted by a change in the chelating function and a second originality consisting of a increase of steric repulsions between the stereogenic center (s) alpha of the azolium ring and the substituents (alkyl or aromatic) present on the nitrogen heterocycle.

In particular, the introduction of new chelating functions of the aryloxy, arylthioether and aryldiphenylphosphino- type makes it possible to extend the field of application of the chiral carbene ligands known from the prior art by coordinating with more noble metals such as palladium , rhodium, ruthenium and iridium. The compounds according to the invention are thus capable of being used for asymmetric reactions such as hydrogenations and CC coupling reactions (allylic substitution, bi-aryl coupling, 1,4 addition) and CN (hydroamination) and CH activations. .

Preferably, X ^" is selected from the group consisting of halogens, tetrafluoroborate ([BF ₄ ] ^" ), tetrakis (3,5-bis (trifluoromethyl) phenyl) borate ([BARF] ^" ), hexafluorophosphate ([PF ₆ ] ^" ), hexafluoroantimony ([SbF ₆ ] ^" ), hexafluoroarsenate ([AsF ₆ ] ^" ), trifluoromethylsulfonate ([(CF ₃ ) ₂ N] ^" ).

According to one variant, the compound according to the invention is a phenoxy-imidazolinium salt chosen from the group of compounds of the following formula:

la Ib Ic

the Ib Ic

ig Ih Selon une autre variante, le composé selon l'invention est un sel d'aryldiphényphosphino - imidazolinium choisi dans le groupe des composés selon la formule suivante :Id the

ig Ih According to another variant, the compound according to the invention is an aryldiphenylphosphinoimidazolinium salt chosen from the group of compounds according to the following formula:

Selon une autre variante, le composé selon l'invention est un un sel d'alkoxy- imidazolinium choisi dans le groupe des composés de formules suivantes :

According to another variant, the compound according to the invention is an alkoxyimidazolinium salt chosen from the group of compounds of the following formulas:

lu IvIn Io ip

read Iv

According to another variant, the compound according to the invention is a hydroxy-dihydroquinazolinium salt chosen from the group of compounds according to the following formula:

lia

lia

According to another variant, the compound according to the invention is an aryloxydihydroquinazolinium salt chosen from the group of compounds of the following formulas:

lld-2 Me Mf Selon une autre variante, le composé selon l'invention est un sel d' aryldiphényphosphino-dihydroquinazolinium choisi dans le groupe des composés de formules suivantes :Mb Mc lld-1

lld-2 Me Mf According to another variant, the compound according to the invention is a salt of aryldiphenyphosphino-dihydroquinazolinium chosen from the group of compounds of the following formulas:

iig Mh

iig Mh

According to another variant, the compound according to the invention is a dihydroquinazolinium salt chosen from the group of compounds of the following formulas:

Mm Mn

According to another variant, the compound according to the invention is a tetrahydropyrimidinium salt chosen from the group of compounds of the following formulas:

iw

According to another variant, the compound according to the invention is a diaryloxy-tetrahydropyrimidinium salt chosen from the group of compounds of the following formulas:

ix

According to another variant, the compound according to the invention is a dialkoxy-tetrahydropyrimidinium salt chosen from the group of compounds of the following formulas:

ly-1 ly-2 ly-3 L'invention ainsi que les différents avantages qu'elle présente seront plus facilement compris grâce à la description qui va suivre concernant d'une part la synthèse de deux exemples de composés de formule (I), à savoir les sels de phénoxy-imidazolinium (Ia-Cl et Ia-PF6) et les sels d'alkoxy-imidaolinium (Ik-PF6 et I1-PF6) et d'autre part la synthèse d'un composé de formule (II) à savoir un sel d'alkoxy-quinazolinium (IIa-PF6)

ly-1 ly-2 ly-3 The invention as well as the various advantages that it presents will be more easily understood thanks to the description which follows on the one hand the synthesis of two examples of compounds of formula (I), namely the phenoxy-imidazolinium salts ( Ia-Cl and Ia-PF6) and the alkoxy-imidaolinium salts (Ik-PF6 and I1-PF6) and on the other hand the synthesis of a compound of formula (II), namely an alkoxy-quinazolinium salt (IIa-PF6)

Synthesis of Phenoxy Imidazolinium Salts of Formula (Ia-Cl) and (Ia-PFe)

Phenyloxy-imidazolinium chlorine (Ia-Cl) and hexafluorophosphate (Ia-PF6) were synthesized according to the following synthesis scheme (scheme 1):

20°CCH ₂ Cl ₂ pyπdine K ₂ CO ₃

20 ° C

3) BBr ₃ 4) LiAIH ₄

(Ia-Cl) (Ia-PF ₆ )

Diagram 1

In these compounds, the LX nature of the ligand is conserved. In order to guarantee good selectivity, the stereogenic center is integrated on a new chelating chain and the size of the metallacycle is increased from 6 to 7 links.

Synthesis of the compound 2-bromo-N-mesitylethanamide 3

Bromoacetyl chloride (1 eq., 1 mmol, 82 μL) is added dropwise to a mixture of mesithylamine (1.2 eq., 1.2 mmol, 169 μL) and potassium carbonate (2 eq., 2 mmol, 276 g). mg) in solution in acetonitrile (3 mL). The reaction medium is stirred at room temperature for 14 hours. The heterogeneous mixture is then filtered and concentrated in vacuo. Recrystallization from a pentane / dichloromethane mixture makes it possible to obtain compound 3 in the form of a white solid with a yield of 82% (210 mg).

¹ H NMR (400 MHz, CDCl _3): D (ppm) 7.68 (s, IH, H-7), 6.91 (s, 2H, H-3), 4.06 (s, 2H, H-9), 2.27 ( s, 3H, HI), 2.20 (s, 6H, H-5)

¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 164.1 (C, C-8), 137.6 (C, C-6), 135.1 (2C, C-4), 130.2 (C, C-2) , 129.1 (2CH, C-3), 29.1 (CH ₂ , C-9), 20.9 (CH ₃ , Cl), 18.1 (2CH ₃ , C-5)

Synthesis of the compound (R) -7V-mesityl-2- (1- (2-methoxyphenyl) ethylamino) ethanamide 4

A mixture of bromoamide (1 eq., Lmmol, 256 mg), amine (2 eq., 2 mmol, 302 mg) and potassium carbonate (2eq., 2 mmol, 276 mg) is refluxed with acetonitrile. during 14h. The heterogeneous mixture is filtered and then concentrated in vacuo. Purification by chromatography on silica gel (dichloromethane / acetone: 8/2) allows the isolation of compound 4 as a white solid in quantitative yield.

20 _.

[Ω = +53.2 (c = 1, acetone) ¹ H NMR (400 MHz, CDCl ₃ ): D (ppm) 8.89 (s, 1H, H-8), 7.28-7.25 (m, 2H, H-14 + H-16), 6.97 (td, J = 7.4, 0.9 Hz, 1H, H-17), 6.92-6.90 (m, 3H, H-2 + H-15), 4.20 (q, J = 6.6 Hz, 1H); , HI l), 3.85 (s, 3H, H-19), 3.40 (d, J = 17.5 Hz, 1H, H-9), 3.29 (d, J = 17.5 Hz, 1H, H-9), 2.29 (s, , 3H, HI), 2.21 (s, 6H, H-5), 1.47 (d, J = 6.6 Hz, 3H, H-12)

¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 170.7 (C, C-8), 157.1 (C, C-18), 136.6 (C, C-6), 134.9 (2C, C-4) , 131.9 (C, C-13), 131.3 (C, C-2), 128.9 (2CH, C-3), 128.2 (CH, C-14), 127.1 (CH, C-16), 120.7 (CH, C-15), 110.7 (CH, C-17), 55.2 (CH ₃ , C-19), 53.4 (CH ₃ , Cl 1), 50.2 (CH ₂ , C-9), 21.6 (CH ₃ , C-1) 12), 20.9 (CH ₃ , Cl), 18.4 (2CH ₃ , C-5)

Synthesis of the compound (R) -2- (1- (2-hydroxyphenyl) ethylamino) -7V-mesitylethanamide

In a bicol, the amide (1 eq., 2.69 mmol, 878 mg) is dissolved in dichloromethane (65 mL). The temperature is lowered to ⁰ ° C and boron tribromide (6 eq., 16.14 mmol, 1.53 mL) is added slowly. The progress of the reaction is monitored by TLC. When the conversion is complete, sodium hydrogencarbonate is added dropwise. The aqueous phase is then extracted three times with dichloromethane. The organic phases are combined, dried over magnesium sulfate and finally concentrated under reduced pressure. The resulting oil is purified by chromatography on silica gel (dichloromethane / acetone: 95/5) and makes it possible to obtain compound 5 in the form of a beige solid with a yield of 82% (535 mg).

20 _.

[CJD = +12.8 (C = 1, acetone)

¹ H NMR (400 MHz, CDCl _3): D (ppm) 7.10 (m, IH, H-7), 6.90 (dd, J = 1.7, 7.5 Hz, IH, H- 14), 6.82 (s, 2H, H-3), 6.78-6.63 (m, 3H, H-15 + H-16 + H-17), 3.88 (q, J = 6.7 Hz, 1H, H-11), 3.43 (d, J = 15.7 Hz). , 1H, H-9), 3.29 (d, J = 15.7 Hz, 1H, H-9), 2.20 (s, 3H, HI), 2.09 (s, 6H, H-5), 1.42 (d, J = 6.7 Hz, H-12)

¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 169.2 (C, C-8), 157.3 (C, C-18), 137.8 (C, C-6), 135.4 (C, C-4) , 130.8 (C, C-2), 129.4 (CH, C-3), 129.1 (CH, C-14), 128.8 (CH, C-16), 126.4 (C, C-13), 119.8 (CH, C-15), 117.3 (CH, C-17), 59.5 (CH, Cl), 50.1 (CH ₂ , C-9), 22.9 (CH ₃ , C -12), 21.3 (CH ₃ , Cl), 18.7 (2 CH ₃ , C-5)

Synthesis of the compound (R) -2- (1- (2- (mesitylamino) ethylamino) ethyl) phenol 6

To a suspension of lithium aluminum hydride (5 eq., 16.87 mmol, 640 mg) in tetrahydrofuran (10 mL) is slowly added at 0 ^° C. the amide (1 eq., 3.37 mmol, Ig). ) in solution in tetrahydrofuran (10 mL). The reaction mixture is refluxed for 14 hours. After cooling to room temperature, 590 μl of water, 590 μl of a 15% aqueous solution of sodium hydroxide and 850 μl of water are added dropwise at 0 ^° C. The heterogeneous mixture is stirred and then filtered on celite, rinsed with boiling tetrahydrofuran and concentrated under reduced pressure. Compound 6 is isolated in 96% yield as a beige solid (960 mg).

¹ H NMR (400 MHz, CDCl _3): D (ppm) 7.07 (ddd, J = 8.2, 7.5, 1.8 Hz, IH, H-16), 6.89 (dd, J = 7.5, 1.8 Hz, IH, H- 14), 6.76-6.68 (m, 4H, H-3 + H-15 + H-17), 3.88 (q, J = 6.7 Hz, 1H, H-11), 3.04-2.94 (m, 2H, H- 8), 2.79-2.70 (m, 2H, H-9), 2.19 (s, 6H, H-5), 2.15 (s, 3H, HI), 1.40 (d, J = 6.7 Hz, 3H, H-12). )

¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 157.7 (C, C-18), 143.2 (C, C-6), 132.5 (C, C-2), 130.6 (C, C-4) , 130.0 (CH, C-3), 128.8 (CH, C-14), 128.5 (CH, C-16), 127.0 (C, C-13), 119.5 (CH, C-15), 117.2 (CH, C-17), 59.7 (CH, Cl 1), 48.7 (CH ₂ , C-8), 48.2 (CH ₂ , C-9), 23.0 (CH ₃ , C-12), 21.0 (CH ₃ , Cl) , 18.7 (CH ₃ , C-5)

Synthesis of the compound (R) -3- (1- (2-hydroxyphenyl) ethyl) -1-mesityl-4,5-dihydro-1H-imidazol-3-ium chloride (Ia-Cl)

The diamine (1 eq, 3.22 mmol, 960 mg) is dissolved in diethyl ether (16 mL). 2N Hydrochloric acid in methanol (2 eq., 6.44 mmol, 3.22 mL) is added dropwise. The reaction mixture is stirred for 10 minutes. The solvent is evaporated under reduced pressure. The hydrochloride formed is then dissolved in methyl orthoformate

(10 mL) and refluxed for 1 h. After returning to ambient temperature, the solvent is evaporated under reduced pressure and then distilled water is added. The aqueous phase is washed with ethyl acetate before being freeze-dried. The desired imidazolinium salt (Ia-Cl) was isolated as a white solid with a yield of 69% (770 mg).

¹ H NMR (400 MHz, D ₂ O): D (ppm) 8.56 (s, IH, H-7), 7.52 (d, J = 7.7 Hz, IH, H-13), 7.47 (td, J = 7.7 , 1.5 Hz, 1H, H-15), 7.18-7.08 (m, 4H, H-3 + H-14 + H-16), 5.30 (q, J = 6.9 Hz, 1H, H-10), 4.27- 4.13 (m, 2H, H-8), 4.11-4.02 (m, 2H, H-9), 2.40 (s, 3H, HI), 2.34 (s, 6H, H-5), 1.87 (d, J = 6.9 Hz, 3H, HI l)

¹³ C NMR (100 MHz, D ₂ O): D (ppm) 157.9 (CH, C-7), 154.9 (C, C-17), 140.8 (C, C-6), 136.2 (C, C-4) ), 131.2 (C, C-2), 130.8 (CH, C-13), 129.6 (CH, C-3), 128.5 (CH, C-15), 123.8 (C, C-12), 120.7 (CH); , C-14), 116.1 (CH, C-16), 53.7 (CH, C-10), 50.6 (CH ₂ , C-8), 46.8 (CH ₂ , C-9), 20.4 (CH ₃ , Cl) ), 16.8 (CH ₃ , C-5)

Synthesis of (R) -3- (1- (2-hydroxyphenyl) ethyl) -1-mesityl-4,5-dihydro-1H-imidazol-3-ium hexafluorophosphate compound (Ia-PFe)

The diamine (1 eq, 1.74 mmol, 520 mg) is dissolved in diethyl ether (9 mL). 2N Hydrochloric acid in methanol (2 eq, 3.48 mmol, 1.74 mL) is added dropwise. The reaction mixture is stirred for 10 minutes. The solvent is evaporated under reduced pressure. The hydrochloride formed is then dissolved in methyl orthoformate

(6 mL) and refluxed for 1h. After returning to ambient temperature, the solvent is evaporated under reduced pressure and then distilled water is added. The aqueous phase is washed with ethyl acetate before the addition of potassium hexafluorophosphate (1.3 eq., 2.27 mmol, 417 mg). The desired imidazolinium salt (Ia-PFe) was isolated as a white solid in 60% yield (472 mg).

[D] D ²⁰ = -32.2 (c = 1, acetone)

¹ H NMR (400 MHz, (CD _{3) 2} CO): D (ppm) 8.78 (s, IH, H-7), 7.52 (dd, J = 7.8, 1.8 Hz, IH, H-13), 7.47 ( m, 2H, H-14 + H-15), 7.04 (s, 2H, H-3), 7.18-7.08 (td, J = 7.2.1.8 Hz, 1H, H-16), 5.37 (q, J = 7.1 Hz, 1H, H-10), 4.39-4.20 (m, 3H, H-8 + H-9), 4.13-4.05 (dd, J = 21.9, 10.4Hz, 1H, H-9), 2.33 (s). , 6H, H-5), 2.30 (s, 3H, HI), 1.87 (d, J = 7.1 Hz, 3H, HI 1) ¹³ C NMR (100 MHz, (CD ₃ ) ₂ CO): D (ppm) 159.4 (CH, C-7), 157.2 (C, C-17), 141.2 (C, C-6), 137.2 (C, C-4), 132.7 (C, C-2), 131.3 (CH, C) -13), 130.8 (CH, C-3), 129.0 (CH, C-15), 124.2 (C, C-12), 120.8 (CH, C-14), 117.7 (CH, C-16), 55.3 (CH, C-10), 51.8 (CH ₂ , C-8), 47.9 (CH ₂ , C-9), 21.4 (CH ₃ , C-10), 18.0 (CH ₃ , C-5), 15.1 ( CH ₃ , Cl) ³¹ P NMR (162 MHz, (CD ₃ ) ₂ CO): D (ppm) -143.0 (sep, IP, J = -706.4 Hz) ¹⁹ F NMR (376 MHz, (CD ₃ ) ₂ CO) ): D (ppm) -75.8 (seven, IP, J = -707.2 Hz)

Synthesis of alkoxy-quinazolinium salts (Ila-PFβ):

The alkoxy-quinazolinium hexafluorophosphate (IIa-PF6) was synthesized according to the following synthetic scheme (scheme 2):

3) LiAIH ₄

THF, reflux

Figure 2

Compared to the prior art, this type of compound has an enlargement of the size of the heterocycle combined with the introduction of an aromatic group on the nitrogenous heterocyclic backbone, which makes it possible to amplify the phenomena of flexibility and to induce new steric repulsions with the stereogenic center (s) present on the lateral chain (s) linked to the nitrogen heterocycle.

These structural originalities make it possible to improve the activity as well as the induction of metal complexes coordinated with this type of ligand.

Synthesis of the compound (2-Bromo-benzyl) - (2,4,6-trimethylphenyl) -amine 7

Mesitylamine (1.06 mL, 7.5 mmol, 1.5 Eq.) Is added to a solution of 1-bromo-2-bromometylbenzene (1.25 g, 5 mmol, 1 eq.) And potassium carbonate (1.725 g). g, 12.5 mmol, 1 Eq.) in acetone (15 mL) under a nitrogen atmosphere. The mixture is then stirred under reflux (80 ^° C.) for 28 hours.

At the end of the reaction, the solvent is evaporated under reduced pressure and the residue is taken up with ethyl acetate. The organic phase is washed three times with a solution saturated with sodium chloride, dried over magnesium sulphate, filtered and concentrated. This compound 7 is obtained, after purification by chromatography on silica gel (eluent: petroleum ether / ethyl acetate: 9/1), with a yield of 92% (1.4 g, yellow oil).

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 7.49 (m, 1H, H _ar ); 7.29 (m, IH, H _ar); 7.18 (m, 1H, H _ar ); 7.06 (m, IH, H _ar); 6.75 (s, 2H, H ₂ ); 4.04 (s, 2H, H ₄ ); 3.15 (s, 1H, NH); 2.21 (s, 6H, H ₃ ); 2.14 (s, 3H, H ₁ ).

¹³ C NMR (100 MHz, CDCl ₃ ) δ (ppm): 145.7 (Cl, C ₅ ); 141.9 (Cl, C ₁₀ ); 131.6 (Cl, C ₉ ); 129.3 (Cl, C ₆ ); 127.7 (2C, C _ar ); 127.3 (2C, C ₂ ); 125.9 (C, C _n ); 121.3 (2C, C ₁₂ ); 129.4 (Cl, C ₄ ); 129.0 (2C, C ₃ ); 63.5 (Cl, C ₉ ); 49.9 (Cl, C ₄ ); 21.5 (1C, C ₁ ); 12.7 (2C, C ₃ ).

Synthesis of the compound (S) -methyl-2- (2 - ((mesitylamino) methyl) phenylamino) -3-methylbutanoate 8

Formation of the free amine:

A solution of L-valine metyl ester (0.7 g, 4.2 mmol, 1 eq.) In dichloromethane (30 mL) is stirred for one hour with a solution (65 mL) of buffer K2HPO4 / K3PO4 (pKa = 12). 4). After decantation and separation of the phases, the aqueous phase is extracted three times with dichloromethane. The combined organic phases are dried over magnesium sulfate, filtered and concentrated in a cold bath.

Arylamination reaction:

In a clean and dry Schlenk tube, the palladium acetate salt (48 mg, 0.21 mmol, 0.05 Eq.), (2,2'-Binaphthalene-2,2'-diyl) bis ( racemic diphenylphosphine) (rac-BINAP) (262 mg, 0.42 mmol, 0.1 Eq.), as well as cesium carbonate (4.57 g, 12.6 mmol, 3 Eq.) under an argon atmosphere. The medium is degassed three times. The toluene (13 mL) is then introduced into the reaction medium and the solution is degassed again three times and then placed under an argon atmosphere. Finally, the L-valine metyl ester obtained above and then the brominated compound (1.4 g, 4.6 mmol, 1.1 Eq.) Are added. The tube is sealed, brought to 110 ⁰ C and stirred for 88 hours.

At the end of the reaction, the reaction medium is left at room temperature and then diluted by addition of petroleum ether. The mixture is filtered on celite and the filtrate is concentrated. The residue is then filtered through silica (eluent: pentane / ethyl acetate: 9/1), to obtain a brown oil free of the residues of the catalytic system.

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 7.21 (m, 1H, H _ar ); 7.13 (m, 1H, H _ar ); 6.86 (s, 2H, H ₂ ); 6.71 (m, IH, H _ar); 6.65 (m, 1H, H _ar ); 6.21 (s, 1H, NH); 4.14 (m, 1H, H ₅ ); 3.93 (m, 2H, H ₄ ); 3.87 (s, 3H, H ₉ ); 3.05 (s, 1H, NH); 2.32 (s, 6H, H ₃ ); 2.31 (s, 3H, H ₁ ); 1.28 (sep, 1H, H ₆ ); 1.13 (d, 3H, H ₈ ); 1.06 (d, 3H, H ₇ ).

Synthesis of 3-Methyl-2- {2 - [(2,4,6-trimethyl-phenylamino) -methyl] -phenylamino} -butan-1-ol 9

To a suspension of lithium aluminum hydride (317 mg, 8.4 mmol, 2 eq.) In anhydrous tetrahydrofuran (10 mL) is slowly added a solution of 3 (1.48 g, 4.2 mmol). , 1 Eq.) In anhydrous tetrahydrofuran (10 mL) at 0 ° C. The mixture is stirred at this temperature for 6 hours under a nitrogen atmosphere.

At the end of the reaction, the lithium aluminum hydride in excess is neutralized by successively adding dropwise at 0 ° C, water (30 .mu.l per mmol of LiAlH ₄ introduced, or 0.25 mL ) of 15% sodium hydroxide (30 .mu.l per mmol of LiAlH ₄ introduced, 0.25 mL), then water (45 .mu.l per mmol of LiAlH ₄ introduced, 0, 375 mL). The mixture heterogeneous mixture is stirred for one hour and then filtered on celite. The residual salts are washed with boiling tetrahydrofuran. The filtrate is concentrated under reduced pressure. This compound 9 is obtained, after purification by chromatography on silica gel (eluent: petroleum ether / ethyl acetate: 8/2), with a yield of 71% (1.4 g, yellow oil).

¹ H NMR (400 MHz, CDCl ₃ ) δ (ppm): 7.21 (m, 1H, H _ar ); 7.13 (m, 1H, H _ar ); 6.79 (s, 2H, H ₂ ); 6.71 (m, IH, H _ar); 6.68 (m, 1H, H _ar ); 5.55 (s, 1H, NH); 4.04 (m, 1H, H ₄ ); 3.93 (m, 1H, H ₄ ); ; 3.83 (m, 1H, H ₉ ); 3.60 (m, 1H, H ₉ ); 3.44 (m, 1H, H ₅ ); 2.3 (s, 6H, H ₃ ); 2.28 (s, 3H, H ₁ ); 2.05 (sep, 1H, H ₆ ); 1.06 (d, 3H, H ₈ ); 1.02 (d, 3H, H ₇ ).

¹³ C NMR (100 MHz, CDCl ₃ ) δ (ppm): 142.1 (1C, C ₁₅ ); 141.1 (1C, C ₁₇ ); 127.7 (1C, C ₁₆ ) 127.1 (Cl, C ₁₀ ); 126.9 (IC, C _13); 126.3 (Cl, C ₁₁ ); 125.9 (IC, C _16); 121.3 (2C, C ₁₈ ); 116.7 (Cl, C ₁₂ ); 112.3 (IC, C _14); 67.5 (Cl, C ₅ ); 66.4 (Cl, C ₉ ); 49.2 (Cl, C ₄ ); 28.4 (Cl, C ₆ ); 28.7 (Cl, C ₁ ); 19.9 (1C, C ₇ ); 19.7 (1C, C ₈ ); 17.4 (2C, C ₃ ).

Synthesis of 1- (1-Hydroxymethyl-2-methyl-propyl) -3- (2,4,6-trimethyl-phenyl) -3,4-dihydro-quinazolin-1-ium hexafluorophosphate (IIa-PF6)

To a solution of diamine 4 (900 mg, 2.75 mmol, 1 eq.) In anhydrous ether (15 mL), a solution of 2N hydrochloric acid in anhydrous methanol (1.38 mL, 2.75 g. mmol, 1 Eq.) is added, dropwise, at 0 ^° C. After stirring for one hour at ambient temperature, the solution is concentrated in vacuo. The hydrochloride formed is taken up with anhydrous toluene (8 ml) and then the methyl orthoformate (1.5 ml, 13.75 mmol, 5 eq.) Is added. The reaction medium is heated at 90 ^° C. for 18 h. The medium is then concentrated under vacuum and then distilled water is added (30 ml). The aqueous phase is washed with ethyl acetate before adding potassium hexafluorophosphate (1.02 g, 5.5 mmol, 2 eq.). After stirring for two hours at room temperature, the product is extracted with dichloromethane. The The organic phase is dried over magnesium sulfate and concentrated in vacuo to give the desired imidazolinium salt.

¹ H NMR (400 MHz, acetone) D (ppm): 8.66 (s, 1H, H ₁₀ ); 7.74 (m, 1H, H _ar ); 7.55 (m, 1H, H _ar ); 7.46 (m, 1H, H _ar ); 7.37 (m, 1H, H _ar ); 7.12 (s, 2H, H ₂ ); 5.23 (m, 2H, H ₄ ); 4.56 (m, 1H, H ₅ ); 4.19 (m, 1H, H ₉ ); 4.01 (m, 1H, H ₉ ); 2.56 (sep, 1H, H ₆ ) 2.38 (s, 6H, H ₃ ); 2.33 (s, 3H, H ₁ ); 1.19 (d, 3H, H ₈ ); 1.14 (d, 3H, H ₇ ).

¹³ C NMR (100 MHz, CDCl ₃ ) δ (ppm): 154.5 (Cl, C ₁₉ ); 141.7 (1C, C ₁₅ ); 137.5 (Cl, C ₁₇ ); 136.1 (Cl, C ₁₀ ); 136.0 (1C, C ₁₈ ); 131.3 (1C, C ₁₃ ); 131.2 (Cl, C ₁₁ ); 129.75 (Cl, C ₁₂ ); 129.1 (IC, C _14); 120.6 (C, C ₁₆ ); 117.9 (2C, C ₂ ); 110.8 (1C, C ₁₈ ); 60.3 (Cl, C ₉ ); 50.34 (Cl, C ₄ ); 29.68 (Cl, C ₅ ); 29.1 (Cl, C ₆ ); 23.3 (Cl, C ₁ ); 19.9 (1C, C ₇ ); 19.7 (1C, C ₈ ); 17.9 (2C, C ₃ ). ³¹ P NMR (162 MHz, (CD _{3) 2} CO) D (ppm): -143.0 (sept, IP, J _{P F} = 708.1 ^{Hz!.). 19} F NMR (376 MHz, (CD _{3) 2} CO) D (ppm): -73.0 (d, 6F, j _{P F} = 708.1 Hz.). HRMS calc for C ₂₂ H ₂₉ N ₂ O [M] ⁺ : 337.2279 found: 337.2274. [D] _D ²⁰ = -23.4 (c = 1, acetone).

Synthesis of Alkoxy-Imidazolinium Salts of Formula (Ik-PFe) and (II-PFβ):

The alkoxyimidazolionium salts of hexafluorophosphate (Ik-PF6) and (I1-PF6) were synthesized according to the following synthesis scheme (scheme 3):

10

10

3) LiAIH ₄

THF, reflux

12

Figure 3 Compared to the prior art, this type of compound has an additional chiral center with the introduction of a 1-alpha-alkyl-naphthyl group on the nitrogenous heterocyclic backbone (instead of the mesylate group) which allows to increase the degree of desymmetrization at the level of the ligand architecture and to induce an amplification of the asymmetric induction during the catalysis reaction.

These structural originalities make it possible to improve the activity as well as the induction of metal complexes coordinated with this type of ligand.

Synthesis of compound 7V - ((1S) -1-naphthylethyl) -oxalamate ethyl IQa

To a solution of 1- (5) -naphthylethylamine (1.13 mmol, 182 μL) and triethylamine (1.2 eq.) In dichloromethane (1 mL per mmol of amine) is added dropwise at 0 ^° C. the chloride ethyloxalyl (1.2 eq.). The reaction medium is stirred at asbestos temperature for 15 hours, before being diluted in ethyl acetate. The organic phase thus obtained is washed twice with 1N hydrochloric acid solution, once with a saturated aqueous solution of sodium hydrogencarbonate and once with a saturated aqueous solution of sodium chloride. sodium. The organic phase is dried over magnesium sulphate and then concentrated under reduced pressure. Compound 10a is isolated, after purification by chromatography on silica gel (petroleum ether / ethyl acetate: 8/2) in the form of a white solid with a yield of 90% (293 mg).

¹ H NMR (400 MHz, CDCl ₃ ): D (ppm) 8.06 (d, J = 8.4 Hz, 1H, NH), 7.89-7.87 (m, 1H, H ₁₁₁ ), 7.83 (d, J = 8.2 Hz, 1H, H ₄₁₁ ), 7.58-7.45 (m, 4H, H ₁₁₁ ), 7.36-7.34 (m, 1 H, H ₄₁₁ ), 5.95 (quint, J = 6.8 Hz, 1H, HI), 4.31 (qd, J = 7.1 Hz, 0.9 Hz, 2H, H-15), 1.73 (d, J = 6.8 Hz, 3H, H-12), 1.37 (t, J = 7.1 Hz, 3H, H-16) ¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 161.1 (C 1, C-14), 155.8 (1 C, 13), 137.2 (1 C, C ₈₁ ), 134.3 (1C, Car), 131.4 ( IC, C ₈₁ ), 129.3 (ICH, C ₈₁ ), 129.2 (ICH, C ₈₁ ), 127.2 (ICH, C ₈₁ ), 126.4 (ICH, Car), 125.6 (ICH, C ₈₁ ), 123.5 (ICH, C); ₈₁ ), 123.2 (ICH, C ₈₁ ), 63.7 (ICH ₂ , C-15), 45.6 (ICH, Cl), 20.7 (ICH ₃ , C-12), 14.4 (ICH ₃ , C-16)

Synthesis of compound 7V - ((1R) -1-naphthylethyl) -oxalamate ethyl IQb

Using the same procedure for forming the ethyl α-oxalamates with 1- (R) -naphthylethylamine (1 mmol, 162 μL), compound 10b is isolated as a yellow oil in 90% yield (257). mg).

¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) 8.06 (d, J = 8.4 Hz, 1H, NH), 7.89-7.87 (m, 1 H, H _ar ), 7.83 (d, J = 8.2 Hz, 1H, H _ar ), 7.58-7.46 (m, 4H, U ₈₁ ), 7.34-7.32 (m, 1H, H _ar ), 5.95 (quint, J =

6.8 Hz, 1H, H-1), 4.32 (qd, J = 7.1, 0.7 Hz, 2H, H-15), 1.74 (d, J = 6.6 Hz, 3H, H-12), 1.37 (t,

J = 7.1 Hz, 3H, H-16)

¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 161.1 (1 C, 14), 155.8 (1 C, 13), 137.2 (C 1),

134.3 (IC, Car), 131.4 (IC, C _81), 129.3 (ICH, C _81), 129.2 (ICH, C _81), 127.2 (ICH, C _81), 126.4 (ICH, Car), 125.6 (ICH, Car), 123.5 (ICH, C ₈₁ ), 123.2 (ICH, C ₈₁ ), 63.7 (ICH ₂ , C-15), 45.6

(ICH, CI), 20.8 (1CH3, C-12), 14.4 (ICH ₃ , C-16)

Synthesis of compound 7V1 - ((S) -1-hydroxy-4-methylpentan-2-yl) -7V2 - ((S) -1- (naphthalen-1-yl) ethyl) ethanediamide IIa

A solution of ethyl oxalamate 10a (0.97 mmol, 250 mg) and (5) -leucinol (1.1 mmol, 138 μl, 1.1 eq.) In toluene (5 ml per mmol of ethyl oxalamate) is brought at reflux for 15 hours. After cooling to room temperature, the reaction medium is diluted with dichloromethane and then washed successively three times with 1N hydrochloric acid solution, once with saturated sodium hydrogencarbonate solution and once with saturated sodium chloride solution. sodium. The organic phase is dried using magnesium sulfate and then concentrated under reduced pressure. Compound IIa is quantitatively isolated as a beige solid (332 mg).

[D] _D ²⁰ = -11.9 (c = 1, acetone)

¹ H NMR (400 MHz, CDCl ₃ ): D (ppm) 8.04-7.98 (m, 2H, 2NH), 7.86-7.84 (m, 1H, H ₁₁₁ ), 7.80-7.74 (m, 2H, H ₄₁₁ ), 7.50-7.45 (m, 3H, H ₄₁₁ ), 7.39-7.35 (m, 1H, H ₄₁₁ ), 5.84 (quint, J = 6.8 Hz, HI), 4.02-3.94 (m, 1H, H-15), 3.50 (dd, J = 11.3, 3.8 Hz, 1H, H-16), 3.38 (dd, J = 11.3, 5.8 Hz, 1H, H-16), 1.65 (d, J = 6.9 Hz, 3H, H-12) , 1.61-1.53 (m, 1H, H-18), 1.41-1.34 (m, 1H, H-17), 1.24-1.18 (m, 1H, H-17), 0.87 (dd, J = 6.6, 4.0 Hz , 6H, H-19) ¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 160.0 (C 1, C-14), 158.8 (C 1, C-13), 137.6, 133.8

(IC, Car), 130.6 (1C, Car), 129.0 (IC, Car), 128.4 (ICH, Car), 128.2 (IC, Car), 126.5 (ICH, Car), 125.8 (ICH, C ₈₁ ), 125.3. (ICH, C ₈₁ ), 122.8 (ICH, C ₈₁ ), 122.4 (ICH, C ₈₁ ), 65.1 (CH ₂ , C-16), 50.4 (CH ₃ , C-15), 45.5 (CH, Cl), 39.7 (CH ₂ , C-17), 24.6 (CH ₃ , C-12), 23.0 (CH ₃ , C-18), 22.0 (CH ₃ , C-19), 21.1 (CH ₃ , C-19)

Synthesis of compound 7V1 - ((S) -1-hydroxy-4-methylpentan-2-yl) -7 V 2 - ((f) -1- (naphthalen-1-yl) ethyl) ethanediamide 11b

Using the same procedure as above with compound 10b (0.97 mmol, 250 mg) and (iS) -leucinol (1.1 mmol, 138 μL), compound 11b is isolated as a white solid with a yield of 90% ( 288 mg).

20_

[D] D = -37.8 (c = 1, acetone)

¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) 8.07 (d, J = 8.4 Hz, 1H, NH-Cl), 7.89-7.87 (m, 1H,

NH-C-15), 7.82-7.80 (m, 2H, H ₁₁₁ ), 7.57-7.44 (m, 5H, H ₄₁₁ ), 5.88 (quint, J = 6.8 Hz, 1H, HI), 4.05-3.96 (m.p. , IH, H-15), 3.70 (dd, J = 11.4, 3.4 Hz, 1H, H-16), 3.58 (dd, J = 11.4, 6.0 Hz,

1H, H-16), 1.71 (d, J = 6.8 Hz, 3H, H-12), 1.61-1.54 (m, 1H, H-18), 1.48-1.32 (m, 2H, H-17),

0.89 (t, J = 6.4 Hz, 6H, H-19)

¹³ C NMR (100 MHz, CDCl ₃ ): δ (ppm) 160.5 (Cl, C-14), 159.0 (Cl, C-13), 137.7 (Cl, C _ar ),

134.3 (1C, Car), 131.2 (Cl, C _ar ), 129.4 (ICH, C _ar ), 129.0 (ICH, C _ar ), 127.0 (ICH, C _ar ), 126.3 (ICH, Car), 125.7 (ICH, Car), 123.3 (ICH, Car), 123.1 (ICH, C ₈₁ ), 65.9 (CH ₂ , C-16), 51.1

(CH ₃ , C-15), 45.8 (CH 2 Cl 2), 40.2 (CH ₂ , C-17), 25.1 (CH ₃ , C-12), 23.4 (CH ₃ , C-18), 22.4

(CH ₃ , C-19), 21.5 (CH ₃ , C-19)

Synthesis of (S) -4-methyl-2- (2 - ((S) -1- (naphthalen-1-yl) ethylamino) ethylamino) pentan-1-ol 12a

A une suspension d'hydrure de lithium et d'aluminium (4 eq.) dans du tétrahydrofurane (5mL par mmol d'oxalamide) est additionné lentement à O⁰C une solution d'oxalamide lia (0.97 mmol, 319 mg), 1 eq.) solubilisé dans du tétrahydrofurane (5 mL par mmol d'oxalamide). Le mélange réactionnel est agité 15 heures à reflux. Après refroidissement, l'excès d'hydrure est neutralisé par ajout à O⁰C au goutte à goutte d'eau (60 μL par mmol de LiAlH₄) et d'une solution de soude à 15% (60 μL par mmol de LiAlH₄). Le mélange hétérogène est agité puis filtré sur célite et rincé au tétrahydrofurane bouillant. Le filtrat est concentré sous vide pour donner la diamine souhaitée 12a isolée quantitativement sous forme d'huile jaune (325 mg).

To a suspension of lithium hydride and aluminum (4 eq.) In tetrahydrofuran (5 mL per mmol oxalamide) is added slowly at ⁰ ° C a solution of oxalamide IIa (0.97 mmol, 319 mg), 1 eq.) solubilized in tetrahydrofuran (5 mL per mmol of oxalamide). The reaction mixture is stirred for 15 hours under reflux. After cooling, the excess hydride is neutralized by addition to 0 ^° C. dropwise with water (60 μl per mmol of LiAlH ₄ ) and with a 15% sodium hydroxide solution (60 μl per mmol of LiAlH). ₄ ). The heterogeneous mixture is stirred and then filtered on celite and rinsed with boiling tetrahydrofuran. The filtrate is concentrated in vacuo to give the desired diamine 12a quantitatively isolated as a yellow oil (325 mg).

¹ H NMR (400 MHz, CDCl ₃ ): δ (ppm) 8.18 (d, J = 8.0 Hz, 1H, H ₁₁₁ ), 7.87 (d, J = 7.6 Hz, 1H, H ₄₁₁ ), 7.75 (d, J). = 8.0 Hz, 1H, H _ar ), 7.61 (d, J = 6.4 Hz, 1H, H _ar ), 7.54-7.46 (m, 3H, H _ar ), 4.63 (q, J = 6.6 Hz, 1H, HI) , 3.58 (dd, J = 10.4, 4.0 Hz, 1H, H-16), 3.23 (dd, J = 10.4, 6.8 Hz, 1H, H-16), 2.77-2.60 (m, 5H, H-13 + H -14 + H-15), 1.61 (Sep, J = 6.8 Hz, 1H, H-18), 1.51 (d, J = 6.6 Hz, 3H, H-12), 1.30-1.22 (m, 1H, H-1); 17), 1.19-1.12 (m, 1H, H-17), 0.88 (d, J = 6.8 Hz, 6H, H-19)

¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 141.2 (Cl, C ar), 134.4 (Cl, Car), 131.6 (Cl, C ₈₁ ), 127.7 (ICH, Car), 126.3 (ICH, C _81); ), 126.1 (ICH, C ₈₁ ), 125.8 (ICH, C ₈₁ ), 123.2 (ICH, C ₈₁ ), 123.1 (ICH, C ₈₁ ), 63.8 (ICH ₂ , C-16), 57.3 (ICH, CI) , 47.9 (ICH ₂ , C-14), 46.8 (ICH ₂ , C-13), 41.3 (ICH ₂ , C-17), 30.7 (ICH, C-15), 25.3 (ICH, C-12), 23.9 (ICH ₃ , C-18), 23.4 (ICH ₃ , C-19), 23.0 (ICH ₃ , C-19)

Synthesis of (S) -4-methyl-2- (2 - ((R) -1- (naphthalen-1-yl) ethylamino) ethylamino) pentan-1-ol 12b

Using the same procedure as above with compound 11b (0.85 mmol, 280 mg), compound 12b is quantitatively isolated as a yellow oil (270 mg). ¹ H NMR (400 MHz, CDCl _3): D (ppm) 8.18 (d, J = 8.4 Hz, H _111), 7.87 (dd, J = 7.8, 1.8 Hz, IH, H _411), 7.74 (d, J = 8.2 Hz, 1H, H _ar ), 7.62 (d, J = 6.4 Hz, H _ar ), 7.53-7.45 (m, 3H, H _ar ), 4.65 (q, J = 6.6 Hz, 1H, HI), 3.59 (dd, J = 10.6, 4.0 Hz, 1H, H-16), 3.24 (dd, J = 10.6, 6.4Hz, 1H, H-16), 3.27-2.62 (m, 5H, H-13 + H-14). + H-15), 1.62 (m, 1H, H-18), 1.51 (d, J = 6.6 Hz, 3H, H-12), 1.35-1.28 (m, 1H, H-17), 1.21-1.14 ( m, 1H, H-17), 0.89 (dd, J = 6.4, 2.6 Hz, 6H, H-19)

¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 140.9 (1H, Car), 133.9 (1C, Car), 131.3 (1C, C ₈₁ ), 129.0 (ICH, Car), 127.2 (ICH, C ₈₁ ), 125.8 (ICH, C ₈₁ ), 125.7 (ICH, C ₈₁ ), 125.3 (ICH, C ₈₁ ), 122.9 (ICH, C ₈₁ ), 122.7 (ICH, C ₈₁ ), 63.7 (1CH2, C-16) , 56.7 (1CH2, C-14), 46.6 (1CH2, C-13) 12), 23.6 (1CH3, C-18), 22.9 (1CH3, C-19), 22.8 (1CH3, C-19)

Synthesis of compound 3 - ((S) -1-hydroxy-4-methylpentan-2-yl) -1 - ((S) -1- (naphthalen-1-yl) ethyl) -4,5-dihydro-1H -imidazol-3-ium hexafluorophosphate (V) I1-PF6

PF ₆ Θ

To a solution of diamine 12a (0.94 mmol, 295 mg) in diethyl ether (5 mL per mmol of diamine) is added dropwise a solution of 2N hydrochloric acid in anhydrous methanol (1 eq.). After stirring for 10 minutes at room temperature, the reaction mixture is evaporated to dryness. The hydrochloride thus formed is taken up in toluene

(3 mL per mmol of diamine) then the methyl orthoformate (10 eq.) Is added. The reaction medium is refluxed for 15 hours. After cooling, the medium is concentrated under vacuum and then distilled water is added. The aqueous phase is washed with ethyl acetate before the addition of potassium hexafluorophosphate (1.3 eq.). After stirring for 30 minutes at room temperature, the product is extracted with dichloromethane. The The organic phase is dried over magnesium sulfate and concentrated under vacuum. The salt I1-PF6 was isolated after chromatography on silica gel (dichloromethane / acetone: 9/1) in the form of a white solid with a yield of 56%.

[D] D ² ° = + 34.5 (c = 1, acetone)

¹ H NMR (400 MHz, CDCl _3): D (ppm) 7.89-7.85 (m, 4H, H-20 + H _111), 7.57 (td, J = 7.7, 1.3 Hz, IH, H _111), 7.52- 7.43 (m, 3H, H _ar ), 5.49 (q, J = 6.8 Hz, 1H, HI), 3.86-3.69 (m, 4H, H-13 + H-14), 3.66 (dd, J = 11.9, 3.6). Hz, IH, H-16), 3.46 (dd, J = 11.9, 8.9 Hz, 1H, H-16), 1.82 (d, J = 6.8 Hz, 3H, H-12), 1.49-1.41 (m, 2H). , H-15 + H-18), 1.39-1.34 (m, 1H, H-17), 1.28-1.21 (m, 1H, H-17), 0.85 (d, J = 2.6 Hz, 3H, H-19). ), 0.83 (d, J = 2.6 Hz, 3H, H-19)

¹³ C NMR (100 MHz, CDCl ₃ ): D (ppm) 157.2 (ICH, C-20), 134.9 (1C, C ₈₁ ), 133.1 (IC, C ₈₁ ), 131.1 (IC, Car), 130.7 (ICH , C ₈₁ ), 130.1 (ICH, C _ar ), 128.3 (ICH, C _ar ), 127.2 (ICH, C _ar ), 126.3 (ICH, Car), 124.9 (ICH, Car), 122.5 (ICH, Car), 61.7 (ICH ₂ , C-16), 60.0 (ICH, C-15), 55.3 (ICH, CI), 48.0 (ICH ₂ , C-14), 45.7 (ICH ₂ , C-13), 37.4 (ICH ₂ , C-17), 25.5 (ICH, C-12), 23.1 (ICH ₃ , C-18), 22.4 (2CH ₃ , C-19), 20.0 (2CH ₃ , C-19)

³¹ P NMR (162 MHz, CD ₂ Cl ₂ ): δ (ppm) -143.1 (sep, IP, J = 710.1 Hz). ¹⁹ F NMR (376 MHz, CD ₂ Cl ₂ ): D (ppm) -73.07 (d , 6F, J = 710.1 Hz)

Synthesis of 3 - ((S) -1-hydroxy-4-methylpentan-2-yl) -1 - ((1H) -1- (naphthalen-1-yl) ethyl) -4,5-dihydro- 1H-imidazol-3-ium hexafluorophosphate (V) Ik-PF6

PF ₆ θ

Using the same procedure as above with diamine 12b (0.5 mmol, 295 mg), the Ik-PF6 salt was isolated after chromatography on silica gel (dichloromethane / acetone: 9/1 to 7/3) as a solid white with a yield of 65%. ¹ H NMR (400 MHz, CD ₂ Cl ₂ ): D (ppm) 8.01-7.97 (m, 4H, H-20 + H ₁₁₁ ), 7.68 (td, J = 7.6, 1.6 Hz, 1H, H ₁₁₁ ), 7.64-7.58 (m, 2H, H ₈₁ ), 7.54-7.52 (m, 1H, H _ar ), 5.63 (q, J = 6.8 Hz, 1H, HI), 3.93-3.85 (m, 4H, H-13 +). H-14), 3.75 (dd, J = 12.0, 3.6 Hz, 1H, H-16), 3.56 (dd, J = 12.0, 8.8 Hz, 1H, H-16), 1.93 (d, J = 6.8 Hz, 3H, H-12), 1.59-1.47 (m, 3H, H-15 + H-17 + H-18), 1.39-1.33 (m, 1H, H-17), 0.98 (d, J = 6.8 Hz, 3H, H-19), 0.92 (d, J = 6.4 Hz, 3H, H-19)

¹³ C NMR (100 MHz, CD ₂ Cl ₂ ): δ (ppm) 157.2 (ICH, C-20), 134.9 (IC, Car), 133.1 (IC, Car), 131.1 (IC, Car), 130.3 (ICH , C ₈₁ ), 129.6 (ICH, C ₈₁ ), 127.7 (ICH, C ₈₁ ), 126.7 (ICH, C ₈₁ ), 125.7 (ICH, Car), 124.4 (ICH, C ₈₁ ), 122.0 (ICH, C ₈₁ ), 61.2 (ICH ₂ , C-16), 60.0 (ICH, C-15), 54.7 (ICH, CI), 47.3 (ICH ₂ , C-14), 44.9 (ICH ₂ , C-13), 36.7 ( ICH ₂ , C-17), 25.0 (1CH, C-12), 22.6 (ICH ₃ , C-18), 21.8 (2CH ₃ , C-19), 19.3 (2CH ₃ , C-19)

³¹ P NMR (162 MHz, CD ₂ Cl ₂ ): D (ppm) -143.1 (sep, IP, J = 711.5 Hz) ¹⁹ F NMR (376 MHz, CD ₂ Cl ₂ ): D (ppm) - 73.1 (d , 6F, J = 711.5Hz)

-Evaluation in catalysis:

The compounds according to the present invention are capable of being used in many types of asymmetric catalysis reaction such as, for example, the 1,4-addition of diethylzinc to cyclohexenone, according to the procedure described below:

1 ,5 Eq. de Et₂Zn, 0,08 Eq. de Base

Cu (OTf) ₂ (2 mol%) L ^* (3 mol%)

1, 5 Eq. Et ₂ Zn, 0.08 Eq. basic

And ₉ O

In a clean and dry Schlenk tube are introduced the copper triflate salt (7.2 mg, 0.02 mmol, 0.02 Eq.), The chiral ligand (L *) of formula (I) or (II) according to the present invention (0.03 mmol, 0.03 Eq) under an argon atmosphere. The medium is degassed three times. The diethyl ether (3 mL) is then introduced into the reaction medium and the solution is degassed again three times and then placed under an argon atmosphere. To this solution is added a base (0.08 mmol, 0.08 eq.) At 0 ⁰ C. Stirring is continued for ten minutes then diethylzinc in hexane solution (IM, 1.5 mL, 1 , 5 mmol, 1.5 Eq.) And finally the Substrate (cyclohexenone (100 μl, lmmol, IEq.)) is added at room temperature. The progress of the reaction is monitored by gas chromatography.

At the end of the reaction, a solution of 1N hydrochloric acid (5mL) is added. After decantation and phase separation, the aqueous phase is extracted with ether. The combined organic phases are washed with a saturated solution of sodium chloride, dried over magnesium sulphate and concentrated under vacuum. The enantiomeric excess is determined by gas chromatography (chiral capillary column-Lipodex E, 0.2 mm, 50 m, 0.25 mm).

Ligand Ia-Cl: 3h30, 100% conv, 78% ee Ligand I1-PF6: 2h30, 91% conv, 82% ee Ligand Ik-PF6: 3h, 100% conv, 92% ee

Claims

1. Compound of formula (I) or formula (II)

(I) (H) in which X is an anion ^ = O, 1, 2; n = 1 to 4; R is a C ₁ to C ₆ alkyl, or an optionally substituted C ₅ or C ₆ cycloalkyl, or a C ₁ to C ₆ perhaloalkyl; R is a C ₁ to C ₈ alkyl, or an optionally substituted C ₅ or C ₆ cycloalkyl, or an optionally substituted aryl, or an optionally substituted naphthyl, or a -CH ₃ _ _n (Aryl) _n radical with n = 1 to 3, or a radical -CH (R) Z where R is hydrogen, or a C ₁ to C ₆ alkyl, or an optionally substituted C ₅ or C ₆ cycloalkyl, or a C ₁ to C ₆ perhaloalkyl ; Z is a C ₁ to C ₈ alkyl, or a C ₅ or C ₆ cycloalkyl, or a radical of the formula:

9 10 11 12 Y is hydrogen, or OR, or SR, or P (R) ₂ , or halogen or OSO ₂ R n = 1 to 4 R, R, R, R, R, R, R, R, R, R are independently H or a C ₁ -C _6, or a perhaloalkyl C ₁ -C ₆ or cycloalkyl optionally substituted C ₅ or C ₆ or aryl; R and R on the one hand and R and R on the other hand being able to form a cycle to 5 8 3, 4, 5, 6 and 7 members; R and R may independently form a 6-membered aromatic ring. 2. Compound according to claim 1 characterized in that X is selected from the group consisting of halogens, tetrafluoroborate ([BF ₄ ]), tetrakis (3,5-bis (trifluoromethyl) phenyl) borate ([ BARF]), hexafluorophosphate ([PF ₆ ]), hexafluoroantimony ([SbF ₆ ]), hexafluoroarsenate ([AsF ₆ ]), trifluoromethylsulfonate ([(CF ₃ ) ₂ N] ^~ ). 3. Compound of formula (I) according to claim 1 or 2 consisting of a phenoximidazolinium salt chosen from the group of compounds of the following formula:

the Ib Ic

Id the If

ig Ih 4. Compound of formula (I) according to claim 1 or 2 consisting of an aryldiphenylphosphinoimidazolinium salt chosen from the group of compounds according to the following formula:

5. Compound of formula (I) according to claim 1 or 2 consisting of an alkoxy-imidazolinium salt chosen from the group of compounds of the following formulas:

In Io ip

read Iv 6. Compound of formula (II) according to claim 1 or 2 consisting of a hydroxy-dihydroquinazolinium salt selected from the group of compounds according to the following formula:

lia 7. Compound of formula (II) according to claim 1 or 2 consisting of an aryloxydrohydroquinazolinium salt chosen from the group of compounds of the following formulas:

Mb Mc lld-1

lld-2 Me Mf 8. Compound of formula (II) according to claim 1 or 2 consisting of a salt of aryldiphenyphosphino-dihydroquinazolinium chosen from the group of compounds of the following formulas:

iig Mh 9. Compound of formula (II) according to claim 1 or 2 consisting of a dihydroquinazolinium salt selected from the group of compounds of the following formulas:

Mm Mn 10. Compound of formula (I) according to claim 1 or 2 consisting of a tetrahydropyrimidinium salt selected from the group of compounds of the following formulas:

iw

lw-1 lw-2 11. Compound of formula (I) according to claim 1 or 2 consisting of a diaryloxy-tetrahydropyrimidinium salt selected from the group of compounds of the following formulas:

ix

12. Compound of formula (I) according to claim 1 or 2 consisting of a dialkoxy-tetrahydropyrimidinium salt selected from the group of compounds of the following formulas:

iy

ly-1 ly-2 ly-3