Transformation of racemic ethyl 3-hydroxybutanoate into the (R)-enantiomer exploiting lipase catalysis and inversion of configuration

Racemic ethyl 3-hydroxybutanoate rac-1 was transformed into ethyl (R)-acetoxybutanoate (ee = 92%) with 85–90% chemical yields using enantioselective acylation with isopropenyl acetate in the presence of Candida antarctica lipase B (CAL-B, Novozym 435) under solvent-free conditions, followed by mesylation of the unreacted (S)-alcohol in the reaction mixture and inversion of configuration with cesium acetate in DMF in one pot. When the (R)-acetoxybutanoate was subjected to alcoholysis with ethanol and CAL-B, enantiopure (R)-1 (ee >99%) was produced.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide

Ethyl (R)-3-acetoxybutanoateC8H14O4Ee = 92%[α]D25=+2.9 (c 1, CHCl3)Source of chirality: enzymatic catalysisAbsolute configuration: (3R)

Ethyl (R)-3-hydroxybutanoateC6H12O3Ee >99%[α]D25=-43.1 (c 1, CHCl3)Source of chirality: enzymatic catalysisAbsolute configuration: (3R)