NHC-catalyzed atropoenantioselective synthesis of axially chiral biaryl amino alcohols via a cooperative strategy.

Abstract

Axially chiral biaryl amino-alcohols play a pivotal role in organic synthesis and drug discovery. However, only a very few enantioselective methods have been reported to synthesize chiral biaryl amino-alcohols. Therefore, the rapid enantioselective construction of optically active biaryl amino-alcohols still remains a formidable challenge. Here we report an N-heterocyclic carbene (NHC)-catalyzed atropoenantioselective acylation of biphenols triggered by a cooperative strategy consisting of desymmetrization followed by kinetic resolution. This protocol features broad substrate scope and good functional group tolerance, and allows for a rapid construction of axially chiral biaryl amino-alcohols in good to high yields and with excellent enantioselectivities. Furthermore, the structurally diverse axially chiral biaryl amino-alcohol derivatives provide multiple possibilities for chemists to develop catalysts or ligands for different chemical transformations.