Hydrogen-Bonding Assisted Catalytic Kinetic Resolution of Acyclic β-Hydroxy Amides

Enantioenriched acyclic alpha-substituted beta-hydroxy amides are valuable compounds in chemical, material and medicinal sciences, but their enantioselective synthesis remains challenging. A catalytic kinetic resolution (KR) of such amides with selectivity factor(s) up to >200 is developed via enantioselective acylation of primary alcohol with N-heterocyclic carbene. An enhanced selectivity for the catalytic KR process is realized using cyclic tertiary amine as base additive. Diastereomeric transition state models for the process are proposed to rationalize the origin of enantioselectivity.

Automated summary

Enantioenriched acyclic alpha-substituted beta-hydroxy amides were successfully synthesized via enantioselective acylation of primary alcohol with N-heterocyclic carbene, with enhanced selectivity achieved by using cyclic tertiary amine as base additive. Diastereomeric transition state models were proposed to rationalize the origin of enantioselectivity in the catalytic kinetic resolution process.