REDUCTIVE AMINATION OF ALDEHYDES AND KETONES WITH SODIUM TRIACETOXYBOROHYDRIDE - STUDIES ON DIRECT AND INDIRECT REDUCTIVE AMINATION PROCEDURES

Sodium triacetoxyborohydride is presented as a general reducing agent for the reductive amination of aldehydes and ketones. Procedures for u sing this mild and selective reagent have been developed for a wide va riety of substrates. The scope of the reaction includes aliphatic acyc lic and cyclic ketones, aliphatic and aromatic aldehydes, and primary and secondary amines including a variety of weakly basic and nonbasic amines. Limitations include reactions with aromatic and unsaturated ke tones and some sterically hindered ketones and amines. 1,2-Dichloroeth ane (DCE) is the preferred reaction solvent, but reactions can also be carried out in tetrahydrofuran (THF) and occasionally in acetonitrile . Acetic acid may be used as catalyst with ketone reactions, but it is generally not needed with aldehydes. The procedure is carried out eff ectively in the presence of acid sensitive functional groups such as a cetals and ketals; it can also be carried out in the presence of reduc ible functional groups such as C-C multiple bonds and cyano and nitro groups. Reactions are generally faster in DCE than in THF, and in both solvents, reactions are faster in the presence of AcOH. In comparison with other reductive amination procedures such as NaBH3CN/MeOH, boran e-pyridine, and catalytic hydrogenation, NaBH(OAc)(3) gave consistentl y higher yields and fewer side products. In the reductive amination of some aldehydes with primary amines where dialkylation is a problem we adopted a stepwise procedure involving imine formation in MeOH follow ed by reduction with NaBH4.