Palladium-catalyzed regioselective carbonylation of 2-amino-2,3-diphenylpropanoate to 5/6-membered benzolactams

Abstract

Five/six-membered benzolactams are significant blocks in both organic and medicinal chemistry. Achieving 5/6-membered benzolactams from the same starting compound under varying reaction conditions presents a significant challenge. Herein, palladium-catalyzed free amine-oriented regioselective C–H activations/carbonylations mediated by hexacarbonylmolybdenum, leading to diverse sizes of benzolactams, respectively, have been developed. Six-membered dihydroisoquinolinones can be obtained selectively in acetic acid using benzoquinone as an oxidant. While unfavorable five-membered isoindolinones were formed in the presence of Cu(II) as an oxidant and dihydrooxazole ligands in 1,2-dichlorobenzene. The substituents on the phenyl ring also had a great influence on the regioselectivity of the reaction. In addition, an asymmetric version of the reaction has also been attempted preliminarily.