Palladium-catalyzed highly chemoselective dearomative spirocyclization of Ugi adducts: facile access to functionalized benzoazepinespiroindolenines with diastereoselectivity

An efficient palladium-catalyzed post-Ugi dearomative cyclization has been achieved, enabling the rapid assembly of diverse benzoazepinespiroindolenine derivatives with excellent chemoselectivity and good diastereoselectivity. This methodology can controllably introduce functionality and complexity into the dearomatized alicyclic products in a cost-effective and step-economical manner with a wide range of substrate scope. The highly precise dearomatization of complex Ugi adducts opens the door to address formidable chemoselectivity issues among nucleophilic sites, and complements the functional group compatibility of the classical dearomatization protocols. Density functional theory (DFT) calculations shed light on the reaction mechanism as well as the origin of chemoselectivity. The development of chemoselective strategies for complex molecules is intrinsically challenging. In this paper, a facile and diversity-oriented access to benzoazepinespiroindolenines is elaborated via Pd-catalyzed highly chemoselective dearomative spirocyclization of Ugi adducts.

Automated summary

A efficient palladium-catalyzed post-Ugi dearomative cyclization was developed for the rapid synthesis of diverse benzoazepinespiroindolenine derivatives. This methodology offers excellent chemoselectivity and good diastereoselectivity, and provides a cost-effective and step-economical approach for introducing functionality and complexity into dearomatized alicyclic products. The precise dearomatization of complex Ugi adducts resolves challenging chemoselectivity issues and complements classical dearomatization protocols in terms of functional group compatibility.