Direct Dearomatization of Pyridines via an Energy-Transfer-Catalyzed Intramolecular [4+2] Cycloaddition

Abstract

Summary The catalytic dearomatization of pyridines, accessing medicinally relevant N-heterocycles, is of high interest. Currently direct, dearomative strategies rely generally on reduction or nucleophilic addition, thus limiting the architecture of the dearomatized products to a six-membered ring. We herein introduce a catalytic, dearomative cycloaddition reaction with pyridines using photoinduced energy transfer catalysis, thereby advancing dearomatization methodology and increasing the topology of pyridine dearomatization products. This unprecedented method features high yields, broad substrate scope (44 examples), excellent functional group tolerance, and facile scalability. Furthermore, a recyclable and sustainable polymer immobilized photocatalyst was employed. Computational and experimental investigations support a mechanism in which a cinnamyl moiety is promoted to its corresponding excited triplet state through visible-light-mediated energy transfer catalysis, followed by a regioselective and dearomative [4+2] cycloaddition to pyridines. This work demonstrates the contribution of visible light catalysis toward enabling thermally challenging organic transformations.