Pd(ii)-catalyzed cyclization of 2-methyl aromatic ketones with maleimides through weak chelation assisted dual C–H activation

Abstract

A palladium-catalyzed dual C–H functionalization of substituted aromatic ketones and ester with maleimides leading to tricyclic heterocyclic molecules with good to excellent yield is reported. In this protocol, weak chelation of the carbonyl groups has been successfully utilized for the selective activation of the ortho-methyl C(sp³)–H bond instead of the ortho-C(sp²)–H bond in the presence of an external bidentate ligand Ac-Ile-OH. The reaction proceeds through two-fold C–H activation to generate a five-membered cyclic ring. The first C–H activation takes place selectively at the benzylic position followed by a second C–H bond activation at the meta position. The protocol demonstrates compatibility among diverse substituted aromatic ketones and ester as well as various substituted maleimides. Further derivatization of the tricyclic ketone to an alcohol exhibits the synthetic applicability of the protocol. Also, a plausible reaction mechanism has been proposed.