Microwave-Enabled Oxidative Alkoxycyclization of 2'-Aminochalcones by Gold Catalysis

Described herein is a microwave protocol for the synthesis of 4-alkoxyquinolines via oxidative cyclization of 2'-aminochalcones in the presence of alcohols. The reaction employs AuCl3 as a catalyst, with alcohol serving the dual role of both solvent as well as nucleophile. The developed chemistry accommodates linear, branched, cyclic, and terpene-based alcohols affording products in moderate to good yields. The methodology also allowed the one-step preparation of natural alkaloids suh as 4-methoxy-2-phenylquinoline (2a) and graveolinine (2e). Beyond quinolines, our methodology is amenable to the synthetic access of benzofuropyridines. Preliminary mechanistic studies revealed that AuCl3 not only catalyzes the initial aza-cyclization but also triggers the subsequent alcohol addition step. The use of isotopomeric alcohol as nucleophilic partners provides insights on the catalytic C-H bond activation of the products after being formed. Replacing alcohol by toluene halts the reaction at the Michael cyclization step affording dihydroquinolinones with complete product control. Unlike the existing methods, our catalytic approach holds merits such as low solvent quantities, no external oxidants, and no toxic by-products.