A green and sustainable catalytic protocol for methoxymethylation of primary amides using methanol with dihydrogen release

Abstract

A highly efficient and selective catalytic method for the methoxymethylation of primary amides with the liberation of dihydrogen under Mn(I) catalysis is reported. This marks the first report on the synthesis of N-(methoxymethyl)benzamide derivatives, including the synthesis of pharmaceutically important amides through the interrupted borrowing hydrogen (IBH) strategy. The current method showcases a broad substrate scope and utilizes methanol as a methoxy methylating agent and solvent medium. The present unprecedented strategy obviates the need for toxic reagents and multi-step synthesis protocols. Mechanistic, kinetic studies and isotopic labeling experiments were also performed to gain mechanistic insights.