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Synlett 2021; 32(15): 1565-1569
DOI: 10.1055/s-0040-1706553
cluster
Modern Nickel-Catalyzed Reactions

Access to α,α-Difluoro-γ-amino Acids by Nickel-Catalyzed Reductive Aryldifluoroacetylation of N-Vinylacetamide

Qing-Wei Zhao
a   College of Chemistry, Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, P. R. of China
,
Zhi-Fang Yang
b   Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, P. R. of China   Email: xgzhang@mail.sioc.ac.cn
,
Xia-Ping Fu
b   Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, P. R. of China   Email: xgzhang@mail.sioc.ac.cn
,
Xingang Zhang  ∗
a   College of Chemistry, Henan Institute of Advanced Technology, Zhengzhou University, Zhengzhou 450001, P. R. of China
b   Key Laboratory of Organofluorine Chemistry, Center for Excellence in Molecular Synthesis, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai, 200032, P. R. of China   Email: xgzhang@mail.sioc.ac.cn
› Author AffiliationsThis work was financially supported by the National Natural Science Foundation of China (21931013, 21672238, 21991122, and 21421002) and the Strategic Priority Research Program of the Chinese Academy of Sciences (No. XDB20000000).
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Abstract

A nickel-catalyzed reductive aryldifluoroacetylation of N-vinylacetamide with ethyl chloro(difluoro)acetate and aryl iodides is described. This chelating amide carbonyl group-assisted strategy provides rapid access to a variety of protected α,α-difluoro-γ-amino acids that might have potential applications in peptide chemistry and protein engineering. An advantage of this method is its synthetic simplicity, with no preparation of organometallic reagents.

Key words

dicarbofunctionalization - enamides - fluoro amino acids - cross-coupling - nickel catalysis - vinylacetamide

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1706553.
  • Supporting Information


Publication History

Received: 09 September 2020

Accepted after revision: 28 September 2020

Article published online:
02 November 2020

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