Unified Strategy to Amphenicol Antibiotics: Asymmetric Synthesis of (−)-Chloramphenicol, (−)-Azidamphenicol, and (+)-Thiamphenicol and Its (+)-3-Floride

Abstract

The asymmetric synthesis of (-)-chloramphenicol, (-)-azidamphenicol, and (+)-thiamphenicol and its (+)-3-floride, (+)-florfenicol, is reported. This approach toward the amphenicol antibiotic family features two key steps: (1) a cinchona alkaloid derived urea-catalyzed aldol reaction allows highly enantioselective access to oxazolidinone gem-diesters and (2) a continuous flow diastereoselective decarboxylation of thermally stable oxazolidinone gem-diesters to form the desired <i>trans</i>-oxazolidinone monoesters with two adjacent stereocenters that provide the desired privileged scaffolds of <i>syn</i>-vicinal amino alcohols in the amphenicol family.