Development and Application of Radical‐Mediated Stereochemical Epimerization in Natural Product Synthesis

Abstract Precise control over stereochemistry (enantio‐ and diastereo‐selectivity) is essential in the long‐step synthetic protocol of complex molecules bearing multiple stereocenters, such as natural products and pharmaceuticals. Stereospecificity is the ideal goal for the formation of the first and subsequent chiral centers in the specific chemical environment through either an exo ‐ or endo ‐genous molecule–molecule interaction. In this context, epimerization and isomerization offer valuable supplemental strategies for modifying preexisting stereocenters, thereby enhancing synthetic efficiency, enabling molecular diversification, and facilitating late‐stage modification. Recent advances in radical‐mediated epimerization have further enabled site‐specific inversion of stereocenters, allowing late‐stage access to diverse stereoisomers from a common intermediate. This minireview highlights emerging approaches in radical‐based stereochemical epimerization and discusses their potential applications in the synthesis of complex molecules, emphasizing their role as a complementary strategy to previously established epimerization tactics. Also covered are recent developments in the epimerization of quaternary carbon stereocenters, an underexplored yet promising area that offers new opportunities for innovation in synthetic design.