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

Abstract

<p class="first" id="P1">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. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/b82fa9f8-7d92-4d78-8bec-e8fa9f1e3d58/PubMedCentral/image/nihms964472u1.jpg"/> </div> </p>