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

A 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 Br & oslash;nsted 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 degrees and 3 degrees alcohol substrates.

Automated summary

This study presents a synthetic method for efficiently preparing enantioenriched secondary and tertiary 3-amido allylic alcohols. By utilizing stereoablative enantioselective kinetic resolution (KR) catalyzed by a chiral Brønsted acid, the researchers achieved product yields up to 50%, with ee and s values exceeding 99% and >200, respectively. The developed divergent catalytic protocol demonstrated excellent functional group tolerance and was further exemplified by the preparation of one tertiary example on a 1 mmol scale, followed by reduction or bromination to yield corresponding 1,3-amino alcohol and 2-bromo-1,3-amino alcohol derivatives.