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

被引：48

作者：

Xia, Hui-Min ^{[1
,2
]}

Zhang, Feng-Lian ^{[1
,2
]}

Ye, Tian ^{[1
,2
]}

Wang, Yi-Feng ^{[1
,2
,3
]}

机构：

[1] Univ Sci & Technol China, Ctr Excellence Mol Synth CAS, Hefei Natl Lab Phys Sci Microscale, 96 Jinzhai Rd, Hefei 230026, Anhui, Peoples R China

[2] Univ Sci & Technol China, Dept Chem, 96 Jinzhai Rd, Hefei 230026, Anhui, Peoples R China

[3] Nankai Univ, State Key Lab Elementoorgan Chem, Tianjin 300071, Peoples R China

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2018年 / 57卷 / 36期

基金：

中国博士后科学基金;

关键词：

alkylation; deuterated methyl groups; deuterium labeling; methylation; synthetic methods; HYDROGEN ISOTOPE-EXCHANGE; DIMETHYL CARBONATE; METHYLENATING REAGENT; DEUTERATED DRUGS; H/D EXCHANGE; NITRILES; ALKYLATION; DEUTERIUM; METHANOL; N; N-DIMETHYLFORMAMIDE;

D O I：

10.1002/anie.201804794

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A new and practical alpha-monomethylation strategy using an amine-borane/N,N-dimethylformamide (R3N-BH3/DMF) system as the methyl source was developed. This protocol has been found to be effective in the alpha-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 R3N-BH3 donated the remaining two hydrogen atoms. Such a unique reaction pathway enabled controllable assemblies of CDH2-, CD2H-, and CD3- units using Me2NH-BH3/d(7)-DMF, Me3N-BD3/DMF and Me3N-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.

引用

页码：11770 / 11775

页数：6

共 66 条

[11] Pd- and Pt-catalyzed H/D exchange methods and their application for internal MS standard preparation from a Sanofi-Aventis perspective [J].