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Chinese Journal of Organic Chemistry >

0 202605002 - 202605002

DOI: https://doi.org/10.6023/cjoc202605002

ARTICLE

Transition-Metal-Free Direct gem - Difluoroallylation of β,γ‑Unsaturated α‑Amino Nitrile Derived Lithium Reagents

  • Huang Ming-Chen ,
  • Zhao Hai-Yang ,
  • Zhang Xingang
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  • aState Key Laboratory of Fluorine and Nitrogen Chemistry and Advanced Materials, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China

Received date: 2026-05-02

  Revised date: 2026-06-16

  Online published: 2026-07-14

Supported by

National Key R&D Program of China (2025YFA1511100), the National Natural Science Foundation of China (22301307), and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB0590000).

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Abstract

Herein, we report a transition-metal-free protocol for the direct gem-difluoroallylation of β,γ-unsaturated α-amino nitrile-derived lithium reagents. The reaction proceeds via the in situ generation of β,γ-unsaturated α-amino nitrile lithium species, which react with gem-difluoroallylic ammonium salts with high regioselectivity. This selectivity is governed by the hard-soft acid-base (HSAB) principle, wherein the softness of the nucleophile is matched with that of the electrophile. The resulting products can be readily transformed into a diverse array of β-gem-difluoroallyl-substituted carboxylic acid derivatives. Notable features of this reaction include the absence of transition metals, the synthetic simplicity inherent in organolithium reagents, scalability to gram quantities, and good functional-group compatibility. This strategy offers an efficient approach to the synthesis of gem-difluoroallyl compounds.

Key words： β,γ-unsaturated α-aminonitriles; organolithium reagents; gem-difluoroallylic ammonium salts; gem-difluoroallylation

Cite this article

Huang Ming-Chen , Zhao Hai-Yang , Zhang Xingang . Transition-Metal-Free Direct gem - Difluoroallylation of β,γ‑Unsaturated α‑Amino Nitrile Derived Lithium Reagents[J]. Chinese Journal of Organic Chemistry, 0 : 202605002 -202605002 . DOI: 10.6023/cjoc202605002

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