Mechanistic Logic and Selectivity Challenges in Gold-Catalyzed Spirocyclization

Spirocyclic frameworks are privileged motifs in medicinal chemistry due to their threedimensional architecture and favorable physicochemical properties. Among available synthetic strategies, gold catalysis has emerged as a powerful platform for spirocycle construction through carbophilic π-activation under mild conditions and with broad functional group tolerance. Despite significant advances, a gap persists between reaction development and predictive mechanistic understanding. This review adopts a mechanism-centered perspective on gold-catalyzed spirocyclization, emphasizing the fundamental principles governing reactivity and selectivity. Key activation modes, including π-activation of alkynes and allenes, as well as the involvement of carbocationic and vinylgold intermediates, are critically examined. The analysis further explores cyclization logic, highlighting pathway selection between exo- and endo-dig processes, ipso-cyclization, and cascade transformations involving dearomatization and rearrangement steps. Selectivity remains a central challenge: regio- and diastereocontrol are largely dictated by substrate architecture, while enantioselective variants are comparatively underdeveloped despite advances in chiral ligand and counterion strategies. Importantly, common failure pathways, including rearomatization, catalyst deactivation, and competing side reactions such as hydration and oligomerization, are discussed to provide practical insight into reaction design. By integrating mechanistic understanding with representative synthetic applications, this review moves beyond descriptive reaction cataloging and aims to establish a predictive framework for designing efficient gold-catalyzed spirocyclizations.