Direct carbonyl reductive functionalizations by diphenylphosphine oxide.

Abstract

Reductive functionalization of aldehydes and ketones is one of the most challenging but ultimately rewarding areas in synthetic chemistry and related sciences. We report a simple and extremely versatile carbonyl reductive functionalization strategy achieving direct, highly selective, and efficient reductive amination, etherification, esterification, and phosphinylation reactions of (hetero)aryl aldehydes and ketones, which are extremely challenging or unattainable to achieve by traditional strategies, using only diphenylphosphine oxide and an inorganic base. It enables modular synthesis of functionally and structurally diverse tertiary amines, ethers, esters, phosphine oxides, etc., as well as related pesticides, drug intermediates, and pharmaceuticals. Compared to phosphorus-mediated name reactions, this strategy firstly transformed C═O bonds into C-element single bonds. Mechanistically, phosphinates are formed as intermediates, which undergo unconventional nucleophilic substitution at the C atom within their C─O─P unit. Thus, this work provides important strides in the field of reductive functionalization of aldehydes/ketones, phosphorus-mediated transformation, and various fundamental reactions.