Synthesis of axially chiral thiourea by NHC-catalyzed desymmetrizative amidation

Abstract

Chiral thiourea, with a double hydrogen-bonding motif, has emerged as an attractive structural template for asymmetric catalysis. Catalytic synthesis of enantioenriched NH-free thiourea via functionalization of easily accessible racemic thiourea is highly desirable, albeit a formidable challenge. We herein describe NHC-catalyzed desymmetrizative amidation of axially biaryl dialdehydes, providing structurally diverse axially chiral thiourea. Sequential kinetic resolution improves the enantioenrichment of the desymmetrization product, dramatically expanding the range of applicable substrates. This strategy features a broad substrate scope and extremely excellent enantioselectivity. NHC-catalyzed desymmetrizative amidation of axially prochiral biaryl dialdehydes provides modular platforms for synthesizing challenging axially chiral thiourea and derivatives.