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

• Published in: Angewandte Chemie International Edition Vol. 56; no. 45; pp. 14232 - 14236
• Main Authors: Chen, Xiu‐Wen, Zhao, He, Chen, Chun‐Lian, Jiang, Huan‐Feng, Zhang, Min
• Format: Journal Article
• Language: English
• Published: WEINHEIM Wiley 06.11.2017
• Subjects: 1,8-naphthyridines; Chemistry; Chemistry, Multidisciplinary; hydrogen donor; iridium catalysis; Physical Sciences; Science & Technology; tetrahydroquinolines; transfer hydrogenative coupling; CATALYSIS; 1,8-naphthyridines; ALKYLATION; ARYLATION; iridium catalysis; PLANAR CHIRAL FERROCENES; C-H ACTIVATION; tetrahydroquinolines; LIGANDS; REGIOSELECTIVE SYNTHESIS; TRIAZOLE ASSISTANCE; METAL; ALKENYLATION; hydrogen donor; transfer hydrogenative coupling
• ISSN: 1433-7851; 1521-3773
• DOI: 10.1002/anie.201707702

A general catalytic hydrogen transfer‐mediated α‐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 α‐site selectively couples with the C8‐site of various tetrahydroquinolines (THQs) to afford novel α‐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. Two become one: A general catalytic hydrogen‐transfer‐mediated α‐functionalization of 1,8‐naphthyridines is reported for the first time. The pyridyl α‐site selectively couples with the C8‐site of various tetrahydroquinolines to afford novel tetrahydro‐1,8‐naphthyridines (see scheme). The reaction features operational simplicity, a readily available catalyst and good functional group tolerance.