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0 202603015

DOI: https://doi.org/10.6023/cjoc202603015

研究论文

碱促进脱氟[3+3]环化反应: 6-氟-1,4-二氢嘧啶类化合物的模块化合成

  • 李琰琦 ,
  • 皮超 ,
  • 高宁 ,
  • 吴养洁 ,
  • 崔秀灵
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  • a河南省化学生物学与有机化学重点实验室 河南省高校应用化学重点实验室 炼焦煤资源绿色开发全国重点实验室 平原实验室 郑州大学化学学院 郑州大学 郑州 450052

收稿日期: 2026-03-11

  修回日期: 2026-05-22

  网络出版日期: 2026-07-24

基金资助

河南省自然科学基金(No. 252300423136),国家重点研发国际合作项目(No. 2016YFE0132600)资助项目.

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Base-Promoted Defluorinative [3+3] Annulation: Modular Access to 6-Fluoro-1,4-dihydropyrimidines

  • Li Yanqi ,
  • Pi Chao ,
  • Gao Ning ,
  • Wu Yangjie ,
  • Cui Xiuling
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  • aHenan Key Laboratory of Chemical Biology and Organic Chemistry, Key Laboratory of Applied Chemistry of Henan Universities, State Key Laboratory of Coking Coal Resources Green Exploitation, Pingyuan Laboratory and College of Chemistry, Zhengzhou University, Zhengzhou 450052

Received date: 2026-03-11

  Revised date: 2026-05-22

  Online published: 2026-07-24

Supported by

Natural Science Foundation of Henan (No. 252300423136), the Ministry of Science and Technology of China (No. 2016YFE0132600).

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摘要

本研究报道了一种无过渡金属参与的脱氟[3+3]环加成反应。该反应以N-苯基芳基甲脒和β-三氟甲基-1,3-烯炔为原料,高效合成了一系列结构多样化的6-氟-1,4-二氢嘧啶类化合物（DHPs）。本方法具有广泛的底物适用性（涵盖36种底物实例）、优异的区域选择性及高原子经济性,目标产物收率最高可达94%。机理研究以及相关文献表明,该反应历程先后涉及碱促进的去质子化、亲核加成/原位亲核取代、选择性C-F键断裂以及分子内SNV环化等分步过程。放大实验表明该反应体系具有良好的可扩展性,所得产物亦具备优异的后期官能化潜力,充分证实了本策略的重要合成价值。

关键词： β-三氟甲基-1; 3-烯炔; [3+3]环化; α; γ-双选择性脱氟; 6-氟-1; 4-二氢嘧啶

本文引用格式

李琰琦 , 皮超 , 高宁 , 吴养洁 , 崔秀灵 . 碱促进脱氟[3+3]环化反应: 6-氟-1,4-二氢嘧啶类化合物的模块化合成[J]. 有机化学, 0 : 202603015 . DOI: 10.6023/cjoc202603015

Abstract

Herein, we reported a defluorinative [3+3] annulation between N-Phenyl arylformamidines and β-trifluoromethyl-1,3-enynes, enabling direct access to structurally diversified 6-fluoro-1,4-dihydropyrimidines (DHPs) up to 94% yields for 36 examples under transition-metal-free conditions. This protocol features broad substrate generality, excellent regioselectivity, and high atom economy. Mechanistic studies and related literature support sequence base-promoted deprotonation, nucleophilic addition/in situ nucleophilic substitution, selective C-F bond cleavage, and an intramolecular SNV cyclization. The scalability and broad potential for late-stage functionalization of the products further attest to the synthetic value of this protocol.

Key words： β-CF3-1; 3-enynes; [3+3] annulation; α; γ-dual selective defluorination; 6-fluoro-1; 4-dihydropyrimidines

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