Amides made efficiently from aldehydes

Copper-catalyzed reaction of aldehydes with amine hydrochloride salts provides an efficient new route to amide bond formation, according to Woo-Jin Yoo and Chao-Jun Li of McGill University, Montreal (J. Am. Chem. Soc., DOI: 10.1021/ja064315b). The carbonyl-nitrogen amide moiety is ubiquitous in pharmaceuticals and polymers, the researchers note, and amide bond formation is necessary to couple peptides in protein synthesis. Amides are usually formed by reacting carboxylic acids with an amine, they add, but this and other approaches are limited by costly transition-metal catalysts and the number of available substrates. Building on their previous work on copper-catalyzed oxidative esterification of aldehydes, Yoo and Li reacted various benzaldehydes with alkyl, aryl, or glycine ester amine hydrochlorides in acetonitrile solvent (shown) in the presence of CuI with AgIO₃ as the catalyst, tert-butyl hydroperoxide as the oxidant, and CaCO₃ as a base. They believe their method is the first example of producing amides and peptides from aldehydes and simple amines.