Reductive Aminomethylation Using Ammonium Formate and Methanol as N1 and C1 Source: Direct Synthesis of Mono- and Di-Methylated Amines

An Ir(III) complex catalyzed single and dual reductive amination followed by N-methylation of aldehydes and ketones to synthesize N,N-dimethyl as well as N-methyl tertiary amines, respectively, utilizing ammonium formate and methanol as N1 and C1 sources is reported. The protocol was efficiently extended to a tandem reductive amination/N-methylation/cyclization of keto acids/esters leading to N-methyl lactams. A broad substrate scope, synthesis of bioactive molecules, was also demonstrated. Control experiments, kinetic studies, and DFT calculations were performed based on which a plausible mechanism is proposed.