Chiral Brønsted Acid Catalysed Kinetic Resolution of Secondary and Tertiary 3‐Amido Allylic Alcohols

Abstract

AbstractA synthetic method to prepare enantioenriched secondary and tertiary 3‐amido allylic alcohols efficiently that relies on their stereoablative enantioselective kinetic resolution (KR) catalysed by a chiral Brønsted acid is described. Achieved at room temperature, the stereoablative asymmetric KR protocol was shown to exhibit excellent functional group tolerance and provided product yields up to 50%, and ee and s values up to 99% and >200. The synthetic utility of the divergent catalytic protocol was exemplified by the 1 mmol scale preparation of one tertiary example and its reduction or bromination to give the corresponding 1,3‐amino alcohol and 2‐bromo‐1,3‐amino alcohol derivatives. The suggested asymmetric KR pathways provide rare instances of accomplishing enantioselective discrimination through the dehydration or imine‐enamine tautomerisation/retro‐aza‐aldol reaction of the respective 2° and 3° alcohol substrates.