Selective N-Monomethylation of Primary Amines via N-Trialkylsilyl-Lithioamines

Transformation of a primary amine to a secondary amine can be achieved by reaction with an alkyl halide in the presence of an excess of the primary amine to suppress multiple alkylation, but, in general, direct alkylation is not the preferred method when the product alkylated amine is more nucleophilic than the startirg amine. More efficient procedures involve a relative vitiation of the nucleophilicity of the monoalkylated product with respect to that of the unalkylated substrate. Such an effect may be realised by the incorporation of monovalent activating groups (Z), which increase the acidity of the amido-proton and allow alkylation of a stabilised amidoanion, often generated in situ, this species being more reactive than a simple amine. Since in the conversion of a primary to a secondary amine only one amido-proton remains after incorporation of the activating group, further N-alkylation is obviated (Scheme 1.)