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Chinese Journal of Organic Chemistry >

2023 , Vol. 43 >Issue 5: 1832 - 1842

DOI: https://doi.org/10.6023/cjoc202212030

ARTICLES

Selective Mono- and Di-deuterodefluorination of Trifluoroacetamides Promoted by Boryl Radicals

  • Qiuyu Gu ,
  • Tianyu Peng ,
  • Mingcheng Bo ,
  • Yifeng Wang
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  • Department of Chemistry, University of Science and Technology of China, Hefei 230026
* Corresponding author. E-mail:

Received date: 2022-12-23

  Revised date: 2023-02-10

  Online published: 2023-03-07

Supported by

National Natural Science Foundation of China(21971226); Fundamental Research Funds for the Central Universities(WK2060000017)

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Abstract

Deuterated mono- and difluoroalkyl groups have attracted increasing attention in medicinal and biological studies. Controllable snipping one or two fluorine atoms from widely accessible trifluoromethyl groups followed by deuteration is an attractive method to access these molecules, whereas this has been hindered by the challenges associated with the chemoselectivity control during the defluoriantion process. Herein, a strategy for chemoselective deuterodefluorination reaction of trifluoro- and difluoroalkylacetamides via spin-center shifts is reported. The reaction starts with the attack of a deuterated 4-dimethylaminopyridine-boryl radical (DMAP-BD2) to the amide oxygen atom, followed by a spin-center shift process to trigger the C—F bond scission. The resulting α,α-difluorocarbonyl radicals undergo deuterium atom transfer to afford the CF2D-products in high yields and high levels of D-incorporation. Notably, increasing the amount of DMAP-BD3 enables the selective cleavage of the two C—F bonds, leading to CFD2-products in good yields meanwhile maintaining good levels of D-incorporation.

Key words： Lewis base-boryl radical; C—F bond cleavage; deuterodefluorination; spin-center shift

Cite this article

Qiuyu Gu , Tianyu Peng , Mingcheng Bo , Yifeng Wang . Selective Mono- and Di-deuterodefluorination of Trifluoroacetamides Promoted by Boryl Radicals[J]. Chinese Journal of Organic Chemistry, 2023 , 43(5) : 1832 -1842 . DOI: 10.6023/cjoc202212030

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