Palladium-Catalyzed Annulations via Sequential C–H Activations of C(sp²)–H/C(sp³)–H or C(sp³)–H/C(sp³)–H Bonds

Abstract

Palladium-catalyzed C−H annulation reactions represent a compelling strategy to construct complex ring systems with high step economy. While there are many approaches to annulate structures by activation of a single C−H bond, transformations that proceed by activation of multiple C−H bonds are less explored. This is especially true for examples where one of the reacting C−H bonds is located at an sp 3 center. However, exciting developments in palladium-catalyzed C−H activation continue to expand the scope of these transformations and provide innovative strategies to construct challenging carbon− carbon bonds. From these discoveries, sequential C−H activations have emerged as a powerful tool to access complex ring systems through the activation of C(sp 2 )−H/C(sp 3 )−H or C(sp 3 )−H/C(sp 3 )−H bonds. In this Perspective, we showcase recent examples that use this strategy in order to highlight the synthetic potential of C−H activation-enabled annulations and inspire future use of these disconnections for diverse scaffold synthesis.