Enantiodivergent Reactions in Central and Axial Chirality: Concepts, Classifications, and Catalytic Strategies

Enantiodivergent reactions enable the selective synthesis of either an enantiomer from a common precursor or catalytic system, offering a versatile and conceptually elegant strategy in asymmetric synthesis. This Perspective provides a comprehensive classification of enantiodivergent transformations involving both central and axial chirality, with a particular emphasis on stereochemical complexity and condition-dependent control. Reactions are categorized based on the origin of chirality and the number of stereogenic elements involved, ranging from well-established cases featuring a single stereocenter to rare and challenging examples involving multiple (two to four) stereocenters. Notably, we highlight our recent development of the first enantiodivergent reaction involving the complete inversion of five stereocenters, achieved using a single chiral organocatalyst by simply varying the reaction conditions. This unprecedented transformation underscores the powerful potential of condition-dependent stereocontrol in constructing highly complex stereochemical architectures. In addition, we discuss a one-pot enantiodivergent central-to-axial chirality transfer in which both atropisomers of a biaryl product are obtained with excellent enantioselectivity using only a catalytic amount of a chiral organocatalyst. This represents a rare and practical example of enantiodivergence in axial chirality proceeding from a common intermediate.