Organocatalytic Enantioselective Synthesis From Carboxylic Acids via In Situ Activation

ABSTRACT

In situ activation of bench‐stable functional groups represents a significant advancement in organic synthesis, offering practical and sustainable strategies for constructing complex molecules. Among these functional groups, carboxylic acids are particularly valuable due to their prevalence in natural products, pharmaceuticals, and agrochemicals. While metal‐catalyzed methodologies have traditionally dominated carboxylate activation, enantioselective organocatalytic approaches have recently emerged as powerful alternatives, avoiding the need for transition metals and enabling greener synthetic routes. This review highlights key developments in the organocatalytic activation of carboxylic acid derivatives, focusing on versatile catalysts such as N‐heterocyclic carbenes (NHCs), isothioureas, boronic acids, chiral amines, and Brønsted acids. By examining their mechanisms and applications, we aim to provide a comprehensive overview of this rapidly evolving field and inspire further innovation in enantioselective synthesis.