Organocatalytic Strategies for Higher‐Order Cycloadditions: A Review of Substrate Activation and Enantiocontrol

The construction of complex chiral cyclic architectures, ubiquitous in bioactive natural products, represents a perennial pursuit in organic synthesis. Among the myriad of strategies, cycloaddition reactions are unparalleled in their ability to efficiently assemble such structures with high atom economy. While higher-order cycloadditions (involving more than 6π electrons) provide a powerful and intriguing pathway to elaborate polycyclic systems, their development has been historically hampered by challenges in periselectivity, regiocontrol, and particularly, the achievement of high enantioselectivity. This review comprehensively summarizes the recent remarkable progress in this field, which has been revitalized by the burgeoning application of organocatalysis. We systematically categorize and discuss the advances based on the key substrate types involved, including aromatic aldehydes/esters, fulvenes, and tropones. For each substrate class, we elucidate the distinct activation modes enabled by two predominant organocatalytic strategies: nucleophilic amine catalysis and N-heterocyclic carbene catalysis, detailing their mechanisms and the resultant reaction paradigms. This review aims to provide a clear overview of the current state of catalytic higher-order cycloadditions, highlighting the scope, selectivity, and mechanistic insights of these transformations. Finally, we outline the challenges and future opportunities in this fast-evolving field.