Catalytic asymmetric alkylation of α-cyanocarboxylates and acetoacetates using a phase-transfer catalyst

The catalytic asymmetric alkylation of α-cyanocarboxylates and acetoacetates with an alkyl halide was performed under phase-transfer conditions to afford compounds which have a chiral quaternary carbon with up to 97% and 94% ee, respectively. As applications of this method, chiral 2-oxindole derivatives and a β-lactam derivative were synthesized.

Figure optionsDownload as PowerPoint slide

(R)-tert-Butyl 2-cyano-2-methyl-3-phenylpropanoateC15H19NO2Ee = 97%[α]D25=-14.7 (c 2.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-tert-Butyl 2-cyano-2-methylpent-4-enoateC11H17NO2Ee = 92%[α]D25=+2.2 (c 1.67, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-tert-Butyl 2-(2-bromophenyl)-2-cyanopent-4-enoateC16H18BrNO2Ee = 92%[α]D25=-9.2 (c 2.00, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-N-Benzyl-2-(2-bromophenyl)-2-cyanopent-4-enamideC19H17BrN2OEe = 93%[α]D25=-21.9 (c 3.07, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)

(R)-1-Benzyl-3-cyano-3-(prop-2-en-1-yl)-1,3-dihydroindol-2-oneC19H16N2OEe = 93%[α]D25=+27.3 (c 5.81, CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: (R)