Indolinylmethanol catalyzed enantioselective Reformatsky reaction with ketones

A series of chiral indolinylmethanol ligands have been applied for the first time in the asymmetric Reformatsky reaction of an α-bromoester with ketones. In the presence of NiBr2 and zinc powder, up to 75% yield and 87% ee were obtained for a variety of aromatic and aliphatic ketones. The use of Ni(acac)2 resulted in 96% ee although the corresponding yield was low. This process provided a convenient method to access synthetically useful chiral β-hydroxyesters.

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(S)-2-(Indolin-2-yl)-1,3-diphenylpropan-2-olC23H23NO[α]D20=-18.4 (c 1.0, CHCl3)Source of chirality: (S)-indoline-2-carboxylic acidAbsolute configuration: (S)

Bis(3,5-bis(trifluoromethyl)phenyl)((2S,3aS,7aS)-octahydro-1H-indol-2-yl)methanolC25H21NOF12[α]D20=-50.6 (c 1.0, CHCl3)Source of chirality: (2S,3aS,7aS)-octahydro-1H-indole-2-carboxylic acidAbsolute configuration: (S)

(S)-(+)-Ethyl 3-(4-bromophenyl)-3-hydroxybutanoateC12H15BrO3Ee = 86%[α]D20=+13.9 (c 0.4, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-(−)-Ethyl 3-hydroxy-3-phenylbutanoateC12H16O3Ee = 81%[α]D20=-12.1 (c 1.7, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)

(S)-(−)-Ethyl 2-(1-hydroxy-2,3-dihydro-1H-inden-1-yl)acetateC13H16O3Ee = 71%[α]D20=-6.1 (c 0.6, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (S)