Selective α-Monomethylation by an Amine-Borane/N,N-Dimethylformamide System as the Methyl Source.

A new and practical α-monomethylation strategy using an amine-borane/N,N-dimethylformamide (R N-BH /DMF) system as the methyl source was developed. This protocol has been found to be effective in the α-monomethylation of arylacetonitriles and arylacetamides. Mechanistic studies revealed that the formyl group of DMF delivered the carbon and one hydrogen atoms of the methyl group, and R N-BH donated the remaining two hydrogen atoms. Such a unique reaction pathway enabled controllable assemblies of CDH -, CD H-, and CD - units using Me NH-BH /d -DMF, Me N-BD /DMF and Me N-BD /d -DMF systems, respectively. Further application of this method to the facile synthesis of anti-inflammatory flurbiprofen and its varied deuterium-labeled derivatives was demonstrated.