Accessing Polysubstituted Quinazolines via Nickel Catalyzed Acceptorless Dehydrogenative Coupling

J Org Chem. 2018 Sep 21;83(18):11154-11166. doi: 10.1021/acs.joc.8b01479. Epub 2018 Aug 22.

Abstract

Two environmentally benign methods for the synthesis of quinazolines via acceptorless dehydrogenative coupling of 2-aminobenzylamine with benzyl alcohol (Path A) and 2-aminobenzylalcohol with benzonitrile (Path B), catalyzed by cheap, earth abundant and easy to prepare nickel catalysts, containing tetraaza macrocyclic ligands (tetramethyltetraaza[14]annulene (MeTAA) or 6,15-dimethyl-8,17-diphenyltetraaza[14]annulene (MePhTAA)) are reported. A wide variety of substituted quinazolines were synthesized in moderate to high yields starting from cheap and easily available starting precursors. A few control reactions were performed to understand the mechanism and to establish the acceptorless dehydrogenative nature of the catalytic reactions.