Work Up of Borane Reductions of Amides and Imides

26 March 2007

Care The initial product of the borane reduction of an amide or imide is not usually the desired amine, but the amine:borane complex. Cleaving these complexes can be problematic and if carried out with acids or inorganic bases hydrogen is liberated which creates potential fire and explosion hazards. If the next step in the synthetic sequence is another reduction then the borane complex can be used as a source of hydrogen for catalytic
hydrogenation / hydrogenolysis (see M. Couturier et al (Pfizer), Org. Lett., 2001, 3, 465; Org. Proc. Res. Dev., 2002, 6, 42; Tet. Letts., 2001, 42, 2285). Alternatively addition of an excess of a simple amine can break the complex forming a different amine:borane complex that can be separated by partitioning between the organic layer and an aqueous layer.

For example, addition of excess piperazine hydrate generates a piperazine:borane complex, which can be extracted into the aqueous layer, leaving the product in the organic layer. Alternatively use of excess dimethylamine or diethylamine produces and dimethylamine:borane complex (or diethylamine:borane), which is soluble in the organic layer allowing the product amine to be extracted in to aqueous acid.