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Selective α‐Monomethylation by an Amine‐Borane/ N , N ‐Dimethylformamide System as the Methyl Source
Author(s) -
Xia HuiMin,
Zhang FengLian,
Ye Tian,
Wang YiFeng
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201804794
Subject(s) - chemistry , borane , amine gas treating , dimethylformamide , methyl group , medicinal chemistry , hydrogen , deuterium , photochemistry , catalysis , organic chemistry , group (periodic table) , physics , quantum mechanics , solvent
A new and practical α‐monomethylation strategy using an amine‐borane/ N , N ‐dimethylformamide (R 3 N‐BH 3 /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 3 N‐BH 3 donated the remaining two hydrogen atoms. Such a unique reaction pathway enabled controllable assemblies of CDH 2 ‐, CD 2 H‐, and CD 3 ‐ units using Me 2 NH‐BH 3 / d 7 ‐DMF, Me 3 N‐BD 3 /DMF and Me 3 N‐BD 3 / 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.