非过渡金属条件下β,γ-不饱和α-胺基腈锂试剂的直接偕二氟烯丙基化反应

doi:10.6023/cjoc202605002

有机化学

研究论文

非过渡金属条件下β,γ-不饱和α-胺基腈锂试剂的直接偕二氟烯丙基化反应

黄明琛^a, 赵海洋^a, 张新刚^*,a

^a中国科学院中国科学院大学上海有机化学研究所先进氟氮材料全国重点实验室上海 200032

收稿日期:2026-05-02 修回日期:2026-06-16
基金资助:
国家重点研发计划(No. 2025YFA1511100)、国家自然科学基金委(Nos. 22301307)、中国科学院先导专项(No. XDB0590000)资助.

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

Huang Ming-Chen^a, Zhao Hai-Yang^a, Zhang Xingang^*,a

^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:2026-05-02 Revised:2026-06-16
Contact: *E-mail: xgzhang@mail.sioc.ac.cn
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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摘要/Abstract

本文报道了一种非过渡金属条件下β,γ-不饱和α-胺基腈锂试剂的直接偕二氟烯丙基化反应。基于软硬酸碱理论,通过亲核与亲电位点的反应性匹配,以原位生成的β,γ-不饱和α-胺基腈锂试剂为亲核试剂、偕二氟烯丙基铵盐为亲电试剂,本文实现了高区域选择性的偕二氟烯丙基化反应。该方法所得产物可进一步转化为系列β-偕二氟烯丙基取代羧酸衍生物。该反应无需过渡金属参与,区域选择性优异,锂试剂前体制备简便,反应可克级规模放大,官能团兼容性良好,为偕二氟烯丙基化合物的合成提供了新方法。

关键词: β,γ-不饱和α-胺基腈, 有机锂试剂, 偕二氟烯丙基铵盐, 偕二氟烯丙基化反应

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

引用此文

黄明琛, 赵海洋, 张新刚. 非过渡金属条件下β,γ-不饱和α-胺基腈锂试剂的直接偕二氟烯丙基化反应[J]. 有机化学, doi: 10.6023/cjoc202605002.

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, doi: 10.6023/cjoc202605002.

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参考文献

[1] Luisi R.; Capriati V.Lithium compounds in organic synthesis: from fundamentals to applications.John Wiley & Sons, 2014.
[2] Rappoport Z.; Marek I.(eds) The Chemistry of Organolithium Compounds.John Wiley & Sons, 2004.
[3] Nájera C.; Yus, M. Curr. Org. Chem. 2003, 7, 867-926.
[4] De Meijere, A.; Bräse, S.; Oestreich, M. Metal-catalyzed cross-coupling reactions and more.John Wiley & Sons, 2013.
[5] Clayden J.Organolithiums: Selectivity for Synthesis; Tetrahedron Organic Chemistry Series, Vol. 23; Pergamon Press: Oxford, 2002.
[6] Krause N.; Thorand, S. Inorg. Chim. Acta1999, 296, 1-11.
[7] Goh S. S.; Guduguntla S.; Kikuchi T.; Lutz M.; Otten E.; Fujita M.; Feringa, B. L. J. Am. Chem. Soc. 2018, 140(23), 7052-7055.
[8] Egami H.; Usui Y.; Kawamura S.; Shimizu R.; Nagashima S.; Sodeoka, M. J. Fluorine Chem.,2015, 179, 121-128.
[9] (a) Giannerini M.; Fañanás-Mastral M.; Feringa B. Nat. Chem. 2013, 5, 667-672. (b) Tong F.-F.; Luo Y.-C.; Zhao H.-Y.; Fu X.-P.; Zhang, X. Angew. Chem. Int. Ed. 2025, 64, e202417858.
[10] (a) Hiyama, T. Organofluorine Compounds, Chemistry and Applications, Springer-Verlag, Berlin Heidelberg, 2000. (b) Muller, K.; Faeh, C.; Diederich, F.Science 2007, 317, 1881-1886.(c) O’ Hagan, D. Chem. Soc. Rev. 2008, 37, 308-319. (d) Purser, S.; Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320-330. (d) Huang Weiyuan. Chin. J. Org. Chem., 1985, 5, 16-20 (in Chinese). (黄维垣. 有机化学, 1985, 5, 16-20.)(e) Yang, Y.; You, Z.; Qing, F.-L. Acta Chim. Sinica 2012, 70, 2323-2336 (in Chinese). (杨义, 游正伟, 卿凤翎, 化学学报, 2012, 70, 2323-2336). (f) Feng, Z.; Xiao, Y.-L.; Zhang, X. Acc. Chem. Res. 2018, 51, 2264-2278. (g) An, L.; Tong, F.; Zhang, X. Acta Chim. Sinica, 2018, 76, 977-982 (in Chinese). (安伦, 童非非, 张新刚, 化学学报, 2018, 76, 977-982). (h) Wang, W.; Yu, Q.; Zhang, Q.; Li, J.; Hui, F.; Yang, J.; Lü, J. Chin. J. Org. Chem. 2018, 38, 1569-1585 (in Chinese). (王为强, 余秦伟, 张前, 李江伟, 惠丰, 杨建明, 吕剑, 有机化学, 2018, 38, 1569-1585). (i) Luo, Y.-C.; Zhang, X. Chin. J. Chem. 2024, 42,3499—3517. (j) Luo, Y.-C.; Xu, Y.-H.; Zhang, X. Chin. J. Chem. 2026, 44, 1073-1082. (k) Luo, Y.-C.; Xu, C.; Zhang, X. Chin. J. Chem. 2020, 38, 1371-1394. (l) Zhang, F.-G.; Peng, X.; Ma, J.-A. Chin. J. Org. Chem. 2019, 39, 109-116 (in Chinese).(张发光, 彭星, 马军安, 有机化学, 2019, 39, 109-116). (m) Huang, H.; Wang, X.; Wang, J.-B. Chin. J. Org. Chem. 2019, 39, 1-14 (in Chinese). (黄航, 王兮, 王剑波, 有机化学, 2019, 39, 1-14). (n) Zhang, P.-P.; Lu, L.; Shen, Q.-L. Acta Chim. Sinica 2017, 75, 744-769 (in Chinese). (张盼盼, 吕龙, 沈其龙, 化学学报, 2017, 75, 744-769).
[11] (a) Zhang X.; Xia H.; Dong X.; Jin J.; Meng W.-D.; Qing, F.-L. J. Org. Chem. 2003, 68, 9026-9033. (b) Yue X.; Zhang X.; Qing F.-L. Org. Lett. 2009, 11, 73-76.(c) Min, Q.-Q.; Yin, Z.; Feng, Z.; Guo, W.-H.; Zhang, X. J. Am. Chem. Soc. 2014, 136, 1230-1233. (d) Tang, L.; Liu, Z.-Y.; She, W.; Feng, C. Chem. Sci. 2019, 10, 8701-8705. (e) Ye, F.; Ge, Y.; Spannenberg, A.; Neumann, H.; Xu, L.-W.; Beller, M. Nat. Commun. 2021, 12, 3257. (f) Feng, X.-T.; Ren, J.-X.; Gao, X.; Min, Q.-Q.; Zhang, X. Angew. Chem. Int. Ed. 2022, 61, e202210103.
[12] VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976, 17, 1973-1976.
[13] Chattopadhyay S. K.; Ghosh S.; Sil, S. Beilstein J. Org. Chem. 2018, 14, 3070-3075.
[14] Chen D.; Xu L.; Yu Y.; Mo Q.; Qi X.; Liu, C. Angew. Chem. Int. Ed. 2023, 62, e202215168

非过渡金属条件下β,γ-不饱和α-胺基腈锂试剂的直接偕二氟烯丙基化反应

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

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