One-Pot Reductive N-Alkylation with Carbonyl Compounds To Give Tertiary Amines via Borane Reduction of Imines

摘要

One-pot synthesis of tertiary amines via borane-mediat-ed reduction of imines and reductive N-alkylation with carbonyl compounds is described. This protocol's reducing agent is only borane in the reduction of imines, and additional reductant is not necessary in reductive N-alkylation step. When using more than two equivalents of aldehydes, reductive N-alkylation proceeded in good yield. Reductive N-alkylation of primary and secondary amines with carbonyl compounds is a very useful reaction for the synthesis of a variety of amines. Various methods, such as metal hydride reactions and catalytic hydrogenations, have been developed thus far. The use of boron reagents has been especially widely investigated; NaBH_3CN, NaBH(OAc)_3, NaBH_4, and borane complexes have all been used as general reducing agents in this reaction. In many cases, however, these reagents have to be used either under acidic conditions or with molecular sieves and Lewis acids to generate iminium ions. Recently, Suginome et al. reported that aminoborane derivatives react as efficient iminium ion generators. These reagents can be used even in the absence of acid catalysts. In this method, however, reducing agents must be added into the reaction media. Since borane is often used as a reducing agent, reductive N-alkylation of aminoboranes with reducing ability with carbonyl compounds can be performed directly, without the need for externally added reducing agents. Such aminoboranes would seem to be generated in situ by borane reduction of the carbon-nitrogen double bond of imines (Scheme 1).