Selective α‐Monomethylation by an Amine‐Borane/N, N‐Dimethylformamide System as the Methyl Source. (1st August 2018)

• Record Type: Journal Article
• Authors: Xia, Hui‐Min; Zhang, Feng‐Lian; Ye, Tian; Wang, Yi‐Feng
• Is Part Of: Angewandte Chemie. Volume 130:Number 36(2018)
• Page Start: 11944
• Page End: 11949
• Publication Date: 2018-08-01
• Subjects: Alkylierung -- Deuterierung -- Deuterierte Methylgruppen -- Methylierung -- Synthesemethoden; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201804794
• Languages: English
• ISSNs: 0044-8249

Abstract

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 / d 7 ‐DMF, Me3 N‐BD3 /DMF and Me3 N‐BD3 / d 7 ‐DMF systems, respectively. Further application of this method to the facile synthesis of anti‐inflammatory flurbiprofen and its varied deuterium‐labeled derivatives was demonstrated.