Double-Carrousel Mechanism for Mn-Catalyzed Dehydrogenative Amide Synthesis from Alcohols and Amines

Abstract

We study with density functional theory calculations the mechanism of the original example of a base-metal-catalyzed synthesis of amides from alcohols and amines. A preliminary proposal of the mechanism of this reaction was experimentally reported by Milstein and co-workers. Instead of the proposed reaction mechanism with a hemilabile pincer amine arm, our DFT calculations describe a facile protocol, where the catalyst only produces aldehydes from alcohols. Once formaldehyde is formed from methanol, it reacts with the amine to form a second alcohol. This new alcohol undergoes the same procedure as methanol and creates the desired amide through a double-carrousel mechanism. The rate-determining step in the catalytic aldehyde synthesis corresponds to the H2 formation. However, in the nonmetal-catalyzed part of the mechanism, the interaction of formaldehyde with the amine is also quite kinetically demanding

J.A.L.-U. thanks Universitat de Girona for an IFUdG2017 Ph.D. fellowship. A.P. is a Serra Húnter Fellow. A.P. and M.S. thank the Ministerio de Economía y Competitividad (MINECO) of Spain for projects PGC2018-097722-B-I00 and CTQ2017-85341-P; Generalitat de Catalunya for project 2017SGR39 and ICREA Academia prize 2019 to A.P.