Asymmetric induction afforded by chiral azolylidene N-heterocyclic carbenes (NHC) catalysts

Screening studies of new chiral imidazolium and triazolium based NHC salts I–VIII as ligands in asymmetric organometallic catalysis and as organocatalysts showed that these catalysts efficiently promoted the reactions. Moderate enantioselectivities (55–57% ee) were obtained in the asymmetric Cu-NHC catalysed conjugate additions of diethylzinc to cyclohexenone, in accordance with most previous studies. The chiral induction afforded in the gold(I)-NHC catalysed cyclopropanation reactions was low (<28% ee). However, these results represent the first reported chiral gold(I)-NHC catalysed olefin cyclopropanation. The NHC-organocatalysed asymmetric cross-annulation of cinnamaldehyde and trifluoroacetophenone gave lower enantioselectivity (<50% ee) but higher yields of the γ-lactone product relative to previous reports. The enantioselectivities obtained varied considerably, even within a group of structurally closely related NHCs. This study demonstrates the challenge of designing NHCs with a general ability to induce asymmetry in a broader range of reactions.

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(S)-3-(2,6-Diisopropylphenyl)-1-((2-isopropyl-4,5-dihydrooxazol-4-yl)methyl)-4,5-dihydro-1H-imidazol-3-ium hexafluorophosphateC22H34N3O PF6[α]D20=-21.7 (c 1.01, DCM)Source of chirality: d-SerineAbsolute configuration: (4′S)

(R)-3-(2,6-Diisopropylphenyl)-1-((4-isopropyl-4,5-dihydrooxazol-2-yl)methyl)-4,5-dihydro-1H-imidazol-3-ium hexafluorophosphateC22H34N3O PF6[α]D20=+0.2 (c 1.0, DCM)Source of chirality: d-ValinolAbsolute configuration: (4′R)

(S)-3-(2,6-Diisopropylphenyl)-1-(2-hydroxy-1-phenylethyl)-4,5-dihydro-1H-imidazol-3-ium chlorideC23H31N2O Cl[α]D20=+39.5 (c 0.75, DCM)Source of chirality: l-PhenylglycineAbsolute configuration: (1′S)

(S)-(1-(2,6-Diisopropylphenyl)-3-(1-hydroxy-3-phenylpropan-2-yl)imidazolidin-2-ylidene)gold(I) chlorideC24H32AuN2O Cl[α]D20=-17.8 (c 0.55, MeOH)Source of chirality: l-PhenylalanineAbsolute configuration: (2′S)

(S)-(1-(2,6-Diisopropylphenyl)-3-(2-hydroxy-1-phenylethyl)imidazolidin-2-ylidene)gold(I) chlorideC23H30AuN2O Cl[α]D20=+47.7 (c 0.72, DCM)Source of chirality: l-PhenylglycineAbsolute configuration: (1′S)

(S)-(4-(1-(Benzyloxy)-3-phenylpropan-2-yl)-3-methyl-1-phenyl-1H-1,2,4-triazol-5(4H)-ylidene)gold(I) chlorideC25H25AuN3O Cl[α]D20=-65.0 (c 1.00, DCM)Source of chirality: l-PhenylalanineAbsolute configuration: (2′S)