Selective Synthesis of 2-Substituted Quinolines via Amine-Assisted Heck Reaction of 2-Iodoanilines with...

2-Substituted quinoline has been identified as a significant structural scaffold, with prevalence in a variety of biologically active molecules. In this study, we propose an amine-assisted Heck reaction as a novel approach for the selective synthesis of 2-substituted quinolines while inhibiting the formation of 3-benzyl-1H-indole derivatives and 4-substituted quinoline isomers. A variety of α,β-unsaturated aldehydes and 2-iodoanilines were compatible with this protocol, affording the desired quinoline products in good-to-excellent yields. Moreover, the reaction can be effectively scaled up to gram quantities, and the usefulness of this protocol in the synthesis of the cystic fibrosis drug candidate Cavosonstat derivative was demonstrated.