Transition metal-free transfer hydrogenation of aryl azides with alcohols: direct synthesis of secondary amines and N-heterocycles

Abstract

Organic azides and alcohols were harnessed in a transition metal-free, base-mediated transfer hydrogenation system, which offers an efficient synthetic route to secondary amines. In the presence of KO^tBu, aryl azides underwent hydrogen transfer with alcohols to produce secondary amines in high yields. The method features a broad substrate scope, gram-scale applicability, and straightforward experimental setup. Furthermore, N-heterocycles such as quinoxalines and quinolines were synthesized under similar reaction conditions. Mechanistic studies demonstrated that both alcohols and KO^tBu were essential for facilitating hydrogen transfer to azides. The exclusion of a radical pathway, confirmation of alcohol as the reductant, and deuterium labeling experiments provided key insights into the reaction mechanism. DFT calculations revealed that the reduction of azides proceeded through a six-membered cyclic transition state, resembling the mechanism proposed for the Meerwein–Ponndorf–Verley (MPV) reduction. Notably, the potassium cation stabilized the transition state by interacting with both the aryl group and the nitrogen atom of the aryl azide.