TiF4-mediated, one-pot, reductive amination of carboxylic acids with borane–ammonia

Abstract

A facile one-pot, two-step, reductive alkylation of amines with carboxylic acids has been achieved with BH₃–NH₃ as an air- and moisture-stable reductant in the presence of TiF₄. The catalyst is effective for both amidation and reduction steps, and the product amines are isolated in high yields as either the free amines, for those products containing an arylamine, or the borane-complexes. The free amine can be separated from these complexes using BF₃–Et₂O, followed by hydrolysis. The amide reduction has been demonstrated for primary, secondary, and tertiary amides, as well as lactams, and the reductive amination is applicable to a wide variety of aromatic and aliphatic acids as well as amines.