Contra-thermodynamic Hydrogen Atom Abstraction in the Selective C–H Functionalization of Trialkylamine N-CH3 Groups

详细信息    查看全文

• 作者：Joshua P. Barham ; Matthew P. John ; John A. Murphy
• 刊名：Journal of the American Chemical Society
• 出版年：2016
• 出版时间：November 30, 2016
• 年：2016
• 卷：138
• 期：47
• 页码：15482-15487
• 全文大小：514K
• ISSN：1520-5126

文摘

We report a simple one-pot protocol that affords functionalization of N-CH₃ groups in N-methyl-N,N-dialkylamines with high selectivity over N-CH₂R or N-CHR₂ groups. The radical cation DABCO^+•, prepared in situ by oxidation of DABCO with a triarylaminium salt, effects highly selective and contra-thermodynamic C–H abstraction from N-CH₃ groups. The intermediates that result react in situ with organometallic nucleophiles in a single pot, affording novel and highly selective homologation of N-CH₃ groups. Chemoselectivity, scalability, and recyclability of reagents are demonstrated, and a mechanistic proposal is corroborated by computational and experimental results. The utility of the transformation is demonstrated in the late-stage site-selective functionalization of natural products and pharmaceuticals, allowing rapid derivatization for investigation of structure–activity relationships.