Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

Reducing agents with phosphorus-hydrogen bond, such as sodium hypophosphite, phosphite, and hypophosphorous acid are commercially available in bulk amounts, however, their usage is understudied in organic processes. While NaH₂PO₂ has proved to be an efficient four-electron reductant in the catalyst-free reductive amination, the influence of cation in hypophosphite salt has not been studied yet. This issue is a fundamentally important factor. In the present work, the reactivity of the hypophosphites of alkali metals (Li, K, Rb, and Cs) in reductive amination was explored for the first time. A set of secondary and tertiary amines was synthesized from various types of carbonyl compounds and amines. The remedy for Parkinson's disease, piribedil, was obtained in high yield. The plausible mechanism of the elaborated process was proposed and supported by DFT calculations.