Catalytic Asymmetric Synthesis of Vicinal Chiral Carbonyl Bioisosteres

The strategic incorporation of α‐chiral centers into carbonyl bioisosteres is a powerful approach for improving the physicochemical and pharmacological profiles of drug candidates. This review summarizes recent advances in the catalytic asymmetric synthesis of vicinal chiral carbonyl bioisosteres, focusing on difluoromethylene, gem‐difluoroalkene, and oxetane motifs. We highlight transition‐metal and organocatalyzed methodologies that achieve high stereocontrol and broad functional group tolerance. Representative examples are analyzed to illustrate key mechanistic pathways, stereochemical models, and applications in late‐stage functionalization. While significant progress has been made, we also discuss persistent challenges regarding generality, efficiency, and mechanistic understanding. Finally, we outline future research directions to guide the rational design of catalytic systems and novel molecular scaffolds, thereby accelerating the discovery of high‐performance pharmaceuticals based on chiral bioisosteres.