Green Oxidation of Amines Using Salicylic Acid Derivatives as Organocatalysts and Its Application to One-pot Synthesis of Pharmaceutical Molecules

Abstract

Imines are one of the key intermediates for syntheses of N-containing pharmaceutical molecules, and catalytic green oxidation reactions of amines to imines have been energetically investigated over the past decades. Transition-metal-catalyzed reactions have been effective for the conversion of amines to imines under atmospheric oxygen. However, in order to directly utilize the products for further reactions, metal residues from the catalysts, stoichiometric or excess amounts of reagents, and byproducts must be strictly removed from the final products. Therefore, the development of one-pot and green methods for the synthesis of N-containing pharmaceutical scaffolds has been highly demanded. Recently, the authors have developed a novel method for the oxidation of benzylamines to imines with atmospheric oxygen using 4,6-dihydroxysalicylic acid as an organocatalyst. In this article, we describe our recent work on the development of one-pot synthesis methods for the green oxidation of amines to pharmaceutical molecules using salicylic acid as an organocatalyst. Furthermore, based on the results concerning the tolerance of this method to multi-component and multi-step reactions and the refinement of the catalytic system for industrial manufacturing, we also discuss the efficacy of this method in the synthesis of advanced pharmaceutical platform molecules and its future prospects.