Main-Group-Catalyzed Reductive Alkylation of Multiply Substituted Amines with Aldehydes Using H2.

Abstract

Given the growing demand for green and sustainable chemical processes, the catalytic reductive alkylation of amines with main-group catalysts of low toxicity and molecular hydrogen as the reductant would be an ideal method to functionalize amines. However, such a process remains challenging. Herein, a novel reductive alkylation system using H2 is presented, which proceeds via a tandem reaction that involves the B(2,6-Cl2C6H3)( p-HC6F4)2-catalyzed formation of an imine and the subsequent hydrogenation of this imine catalyzed by a frustrated Lewis pair (FLP). This reductive alkylation reaction generates H2O as the sole byproduct and directly functionalizes amines that bear a remarkably wide range of substituents including carboxyl, hydroxyl, additional amino, primary amide, and primary sulfonamide groups. The synthesis of isoindolinones and aminophthalic anhydrides has also been achieved by a one-pot process that consists of a combination of the present reductive alkylation with an intramolecular amidation and intramolecular dehydration reactions, respectively. The reaction showed a zeroth-order and a first-order dependence on the concentration of an imine intermediate and B(2,6-Cl2C6H3)( p-HC6F4)2, respectively. In addition, the reaction progress was significantly affected by the concentration of H2. These results suggest a possible mechanism in which the heterolysis of H2 is facilitated by the FLP comprising THF and B(2,6-Cl2C6H3)( p-HC6F4)2.