Enantioselective Synthesis of Antifungal Agent Voriconazole via Asymmetric Epoxidation of Tetrasubstituted (Z)‐Alkene

Abstract

AbstractA concise asymmetric synthesis of triazole antifungal agent voriconazole is described. Salient features of this synthesis include a LiOH‐controlled highly stereospecific formation of (Z)‐enol triflate from 2‐difluorobenzene acetoacetate to access the crucial tetrasubstituted (Z)‐allylic alcohol, and a highly enantioselective VO(OiPr)3/BHA ligand‐catalyzed epoxidation to construct the critical contiguous carbon stereocenters in a single step.