Enantiodivergent Chemoenzymatic Dynamic Kinetic Resolution: Conversion of Racemic Propargyl Alcohols into Both Enantiomers

Horino S, Nishio T, Kawanishi S, et al. Enantiodivergent Chemoenzymatic Dynamic Kinetic Resolution: Conversion of Racemic Propargyl Alcohols into Both Enantiomers. Chemistry - A European Journal . 2022.Natural lipases typically recognize enantiomers of alcohols based on size differences of substituents near the carbinol moiety and selectively react with ( R )-enantiomers of secondary alcohols. Therefore, lipase-catalyzed dynamic kinetic resolution (DKR) of racemic secondary alcohols produces only ( R )-enantiomers. We report herein a method for obtaining ( S )-enantiomers by DKR of secondary 3-(trialkylsilyl)propargyl alcohols using a well-known ( R )-selective Pseudomonas fluorescens lipase in combination with a racemization catalyst VMPS4, in which the silyl group reverses the size relationship of substituents near the carbinol moiety. Since we have already reported ( R )-selective DKR of the corresponding propargyl alcohols without substituents on the ethynyl terminal carbon, the presence of an easily removable silyl group has enabled us to produce both enantiomers of propargyl alcohols in high chemical yields and with high enantiomeric excess. In addition, the immobilization of the lipase on Celite was found to be important for achieving the high efficiency of the DKR. © 2022 Wiley-VCH GmbH