Second-Generation Palladium Catalyst System for Transannular C–H Functionalization of Azabicycloalkanes

This article describes the development of a second-generation catalyst system for the transannular C–H functionalization of alicyclic amines. Pyridine- and quinoline-carboxylate ligands are shown to be highly effective for increasing the reaction rate, yield, and scope of Pd-catalyzed transannular C–H arylation reactions of azabicyclo[3.1.0]­hexane, azabicyclo[3.1.1]­heptane, azabicyclo[3.2.1]­octane, and piperidine derivatives. Mechanistic studies reveal that the pyridine/quinoline-carboxylates play a role in impeding both reversible and irreversible catalyst decomposition pathways. These ligands enable the first reported examples of the transannular C–H arylation of the ubiquitous tropane, 7-azanorbornane, and homotropane cores. Finally, the pyridine/quinoline-carboxylates are shown to promote both transannular C–H arylation and transannular C–H dehydrogenation on a homotropane substrate.