Catalytic asymmetric acylation reactions using isothiourea catalysts: a Decade's update

Abstract

Acyl transfer reactions have gained significant research attention as crucial asymmetric transformations in organic synthesis over the past few decades. Among various chiral nucleophilic catalysts, the chiral isothiourea catalysts, first introduced by Birman in 2006, have emerged as remarkably effective tools for achieving high enantioselectivity in acylation processes. Recent advances in density functional theory (DFT) calculations have elucidated the underlying mechanisms, revealing that S⋯O isothiouronium interactions between the catalyst and the acyl group, along with other non-covalent interactions, play a vital role in stabilizing the transition state. This review presents a comprehensive documentation of isothiourea-catalyzed enantioselective acylation reactions across a diverse array of alcohols and amines, outlining their methodologies, such as kinetic resolution, dynamic kinetic resolution, and atroposelective approaches. Additionally, we discuss the pertinent stereochemical models and highlight the synthetic utility of the resulting enantioenriched products, illustrating the broad applications of this catalytic strategy.