Reductive Amination Reactions Using Sodium Hypophosphite: a Guide to Substrates

The reactions of reductive amination are of paramount importance as tools of synthetic organic chemistry. Recently, the applicability of sodium hypophosphite as a promising reductant for such reactions has been demonstrated. However, the limited set of substrates used in those works does not allow for a reliable evaluation of the versatility of the approach for synthesizing amines from starting materials of different natures. Herein, we report a comprehensive study of using NaH2PO2 in the catalyst-free reductive amination. Reaction conditions suitable for various combinations of different classes of amines and carbonyl compounds have been discovered, and limitations of the process have been revealed. The study includes reaction kinetics elucidation, and the relationship between amine nucleophilicity and the outcome of this reaction has been established.