Asymmetric Strategies for the Synthesis of Enantiopure α‐/β‐/γ‐Thio‐Carboxylic Acids Bearing a Stereocentre at CS Bond

Abstract

Enantiomerically pure α‐/β‐/γ‐thiocarboxylic acids bearing a stereocentre at the C–S bond represent a class of compounds of notable significance in organic and medicinal chemistry. The chirality at the C–S bond presents both challenges and opportunities in synthetic chemistry. Traditionally, the enantioselective synthesis of these α‐/β‐/γ‐thiocarboxylic acids has relied on chiral pool strategies using naturally derived precursors such as amino acids and hydroxycarboxylic acids. In recent years, the expansion of organo‐ and metal‐catalysed methodologies, employing catalysts such as cinchona alkaloids, copper, and rhodium complexes, has led to strategies with improved efficiency and stereocontrol. Additionally, advances in biocatalysis have enabled more sustainable routes toward s these valuable compounds, using enzymes such as hydrolases and nitrilases. Given the growing academic and industrial interest in these compounds, this review provides an overview of the methods developed and the progresses made over the past two decades in the asymmetric synthesis of thiocarboxylic acids bearing a stereocentre at C–S bond.