Organocatalysis for Enantioselective Decarboxylative Nucleophilic Addition Reactions

The catalytic decarboxylation of malonic acid half oxy- and thioesters, beta-ketocarboxylic acids, and their related compounds is a straightforward, powerful, and atom-economical strategy for the in-situ formation of enolates, which are important and well-studied synthons for various functional materials and natural products. This strategy, inspired by the biosynthesis of polyketides and fatty acids, is an attractive method for synthesizing enols from carboxyl compounds with less reactive alpha-hydrogen atoms under mild conditions. In addition, these reactions are environmentally friendly and are of great interest to chemists because the use of a stoichiometric amount of base can be avoided, and the only byproduct is CO2. Thus far, remarkable progress has been made, especially in the field of organocatalytic enantioselective decarboxylation reactions, allowing for the stereocontrolled formation of new C-H, C-C, C-heteroatom, and C-X bonds. This review provides a comprehensive overview of organocatalytic enantioselective decarboxylation reactions and highlights the significant progress made since 2020. In particular, it focuses on chiral catalyst systems and transition states as key parameters for decarboxylation reactions. Organocatalytic decarboxylation is a straightforward and environmentally friendly strategy for synthesizing various new carbon scaffolds. This methodology, inspired by natural biosynthetic processes, has been established for the formal preparation of enols from carboxyl compounds under mild conditions. Remarkable advances in the field of organocatalysis have enabled the control of stereoselectivity in this strategy. image