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Published on: December 12, 2013
Selective α-Monomethylation by an Amine-Borane/N,N-Dimethylformamide System as the Methyl Source
Hui-Min Xia1, Feng-Lian Zhang1, Tian Ye1
1Hefei National Laboratory for Physical Sciences at the Microscale, Center for Excellence in Molecular Synthesis of CAS, and, Department of Chemistry, University of Science and Technology of China, 96 Jinzhai Road, Hefei, Anhui, 230026, China.
Abstract:
A new and practical α-monomethylation strategy using an amine-borane/N,N-dimethylformamide (R3 N-BH3 /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 R3 N-BH3 donated the remaining two hydrogen atoms. Such a unique reaction pathway enabled controllable assemblies of CDH2 -, CD2 H-, and CD3 - units using Me2 NH-BH3 /d7 -DMF, Me3 N-BD3 /DMF and Me3 N-BD3 /d7 -DMF systems, respectively. Further application of this method to the facile synthesis of anti-inflammatory flurbiprofen and its varied deuterium-labeled derivatives was demonstrated.
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