Phase-transfer catalyzed enantioselective alpha-alkylation of alpha-acyloxymalonates: construction of chiral alpha-hydroxy quaternary stereogenic centers

Abstract

The enantioselective synthesis of alpha-acyloxy-alpha-alkylmalonates was developed as an efficient method for producing chiral alpha-tertiary alcohols, which are potentially valuable intermediates in the synthesis of natural products and pharmaceuticals. The efficient enantioselective alpha-alkylation of diphenylmethyl tert-butyl alpha-acyloxymalonates was accomplished via phase-transfer catalysis in the presence of (S, S)-3,4,5-trifluorophenyl-NAS bromide to afford the corresponding alpha-acyloxy-alpha-alkylmalonates at high chemical (up to 99%) and optical (up to 93% ee) yields, which could be readily converted to versatile chiral intermediates with a chiral alpha-tertiary alcohol group.