Hydrogen-Transfer-Mediated α-Functionalization of 1,8-Naphthyridines by a Strategy Overcoming the Over-Hydrogenation Barrier

A general catalytic hydrogen transfer-mediated alpha-functionalization of 1,8-naphthyridines is reported for the first time that benefits from a hydrogen transfer-mediated activation mode for non-activated pyridyl cores. The pyridyl a-site selectively couples with the C8-site of various tetrahydroquinolines (THQs) to afford novel alpha-functionalized tetrahydro 1,8-naphthyridines, a class of synthetically useful building blocks and potential candidates for the discovery of therapeutic and bio-active products. The utilization of THQs as inactive hydrogen donors (HDs) appears to be a key strategy to overcome the over-hydrogenation barrier and address the chemoselectivity issue. The developed chemistry features operational simplicity, readily available catalyst and good functional group tolerance, and offers a significant basis for further development of new protocols to directly transform or functionalize inert N-heterocycles.