Catalytic Asymmetric Synthesis of Chiral Caged Hydrocarbons as Arenes Bioisosteres

The utilization of caged hydrocarbons as bioisosteres for arenes, especially the phenyl ring, in bioactive compounds has resulted in significant enhancements in potency, solubility, and metabolic stability. These improvements highlight the potential of C(sp3)‐rich polycyclic scaffolds as a promising motif for the development of drug candidates. However, this strategy has also increased the structural complexity of these molecules, posing synthetic challenges in controlling the chirality of caged and highly decorated bioactive scaffolds. Over the past two years, remarkable progress has been achieved in catalytic asymmetric methodologies for the synthesis of caged hydrocarbons, significantly advancing their utility in chiral drug discovery and development. This Minireview provides a comprehensive summary of recent breakthroughs in the catalytic asymmetric synthesis of chiral caged hydrocarbons, encompassing bicyclo[n.1.1]alkanes, cubanes, and related three‐dimensional scaffolds. Additionally, we highlight the intriguing applications of enantiomerically pure caged hydrocarbons in biological studies. It is anticipated that this Minireview will inspire further advancements in the enantioselective synthesis of these pharmaceutically valuable caged hydrocarbons.