The boron-hydrogen bond is stabilized by the steric and electron-withdrawing effects of the acetoxy groups, making sodium triacetoxyborohydride a mild reducing agent.
Sodium triacetoxyborohydride is especially suitable for reductive aminations. Since the reaction rate for the reduction of iminium ions is much faster than for ketones or even aldehydes, the reductive amination can be carried out as a one-pot procedure by introducing the reducing agent into a mixture of the amine and carbonyl compound. The presence of a stoichiometric amount of acetic acid, which catalyzes the imine formation and provides the iminium ion, doesn't present any problem under these conditions.
Reductive amination (simplified)
Secondary amines also undergo this reaction. This leads to the possibility that primary amines can be converted to the dialkylated products (tertiary amines), although the reaction rate is quite slow. Alternatively, the imine may be formed in a prior step and then reduced by NaBH4:
Sodium triacetoxyborohydride is a general, mild, and selective reducing agent for the reductive amination of various aldehydes and ketones. 1,2-Dichloroethane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran and occasionally in acetonitrile. Acetic acid may be used as catalyst with ketone reactions. Acid sensitive functional groups such as acetals and ketals, and reducible functional groups such as C-C multiple bonds and cyano and nitro groups are tolerated.
A. F. Abdel-Magid, K. G. Carson, B. D. Harris, C. A. Maryanoff, R. D. Shah, J. Org. Chem., 1996, 61, 3849-3862.
A one-pot two-step sequence involving an oxidation/imine-iminium formation/reduction allowed the N-alkylation of amines by alcohols. Optically active alcohols and amines can be converted without any epimerization.
C. Guérin, V. Bellosta, G. Guillamot, J. Cossy, Org. Lett., 2011, 13, 3478-3481.
A preparation of highly substituted β-amino acids involves a Vilsmeier-Haack reaction with nonaromatic carbon nucleophiles. The reaction enabled the synthesis of several β2,2,3-amino esters, such as derivatives of homoproline, homoalanine, and homopipecolinic esters.
A. Roamens, G. Bélanger, Org. Lett., 2015, 17, 322-325.