铜催化远程炔-烯丙基取代反应研究进展

doi:10.6023/cjoc202507019

摘要/Abstract

铜催化远程炔-烯丙基取代反应是构建含不饱和键功能分子的高效途径, 目前已成功开发出多种新型催化体系和反应模式. 具有远端离去基团的炔-烯丙基酯类底物在铜/配体催化作用下转化为铜-乙烯基亚丙二烯中间体, 亲核试剂对其γ位或ε位进行亲核加成, 可高效构建结构多样的1,3-烯炔、1,4-烯炔、联烯、螺环化合物以及C—C/C—N/N—N轴手性化合物等重要骨架. 从亲核试剂类型的角度系统总结了铜催化远程炔-烯丙基取代反应在碳、氮和硫等各类亲核试剂参与下的最新研究进展, 重点探讨了反应机理, 并对该领域未来的发展方向进行了展望.

关键词: 铜催化, 炔-烯丙基取代, 远程, 铜-乙烯基亚丙二烯中间体

Copper-catalyzed remote yne-allylic substitution system is an efficient approach for constructing functional molecules containing unsaturated bonds, and a variety of new catalytic systems and reaction modes have been successfully developed. Yne-allylic ester substrates with remote leaving groups are converted into copper vinyl-allenylidene intermediates under the cooperative catalysis of copper/ligands. The nucleophilic addition of nucleophiles to the γ-position or ε-position of the intermediates can efficiently construct important skeletons such as structurally diverse 1,3-enynes, 1,4-enynes, allenes, spirocyclic compounds, and C—C/C—N/N—N axially chiral compounds. From the perspective of classification by nucleophile types, the latest research progress of copper-catalyzed remote yne-allylic substitution reactions involving various nucleophiles such as carbon, nitrogen, and sulfur is systematically summarized. It focuses on the discussion of reaction mechanisms and prospects for the future development direction of this field.

Key words: copper-catalysis, yne-allylic substitution, remote, copper vinyl-allenylidene intermediate

引用此文

李梦蝶, 王紫涵, 林桃燕. 铜催化远程炔-烯丙基取代反应研究进展[J]. 有机化学, 2026, 46(2): 356-378.

Mengdie Li, Zihan Wang, Taoyan Lin. Recent Progress in Copper-Catalyzed Remote Yne-Allylic Substitution Reaction[J]. Chinese Journal of Organic Chemistry, 2026, 46(2): 356-378.

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图/表 31

图式1. 铜催化炔-烯丙基取代反应机理

Scheme 1. Mechanism of copper-catalyzed yne-allylic substitution reaction

图式2. 铜催化软亲核试剂的炔-烯丙基取代反应

Scheme 2. Copper-catalyzed propargylic substitution of soft nucleophiles

图式3. 1,3-二羰基化合物的不对称[4＋1]环化反应

Scheme 3. Asymmetric [4＋1] annulation of 1,3-dicarbonyl compounds

图式4. 炔基铜驱动的远程不对称去芳构化和再芳构化反应

Scheme 4. Remote asymmetric dearomatization and rearomatization via alkynyl copper driven

图式5. 乙烯基乙炔碳酸酯的对映选择性[4＋1]及[3＋3]环加成反应

Scheme 5. Enantioselective [4＋1] and [3＋3] cycloaddition of ethynylethylene carbonates

图式6. 富电子芳烃的不对称炔-烯丙基取代反应

Scheme 6. Asymmetric yne-allylic substitution of electron-rich arenes

图式7. 炔基-噻吩碳酸酯的远程对映选择性取代反应

Scheme 7. Remote enantioselective substitution of yne-thiophene carbonates

图式8. 氟代丙二酸酯的不对称炔丙基单氟烷基化反应

Scheme 8. Asymmetric alkynylallylic monofluoroalkylations of fluorinated malonates

图式9. 非功能化1-萘酚的对映选择性[4＋1]螺环化反应

Scheme 9. Enantioselective [4＋1] spiroannulation of nonfunctionalized 1‑naphthols

图式10. β-萘酚/吲哚的不对称去芳香螺环化反应

Scheme 10. Dearomative spiroannulation of β‑naphthols or indoles

图式11. 蒽酮的不对称炔-烯丙基取代反应

Scheme 11. Asymmetric yne-allylic substitution of anthrones

图式12. 香豆素的双远程不对称炔-烯丙基取代反应

Scheme 12. Dual remote asymmetric yne-allylic substitution of coumarins

图式13. 4-甲基香豆素的不对称炔-烯丙基取代反应

Scheme 13. Asymmetric yne-allylic substitution of 4-methylcoumarin

图式14. 噻唑酮衍生物的不对称炔-烯丙基取代反应

Scheme 14. Asymmetric yne-allylic substitution of thiazolone derivatives

图式15. 吡唑啉酮的不对称炔-烯丙基取代反应

Scheme 15. Asymmetric yne-allylic substitution of pyrazolones

图式16. 铜催化不对称炔-烯丙基胺化反应

Scheme 16. Copper catalyzed asymmetric yne-allylic amination

图式17. 不对称炔-烯丙基二甲基胺化反应

Scheme 17. Asymmetric yne-allylic dimethylamination

图式18. 二氧化碳穿梭与固定的不对称炔-烯丙基取代反应

Scheme 18. Asymmetric yne-allylic substitution via carbon dioxide shuttling and fixation

图式19. 胺的不对称环化反应构建轴手性芳基吡咯

Scheme 19. Asymmetric annulation of amines to access axially chiral arylpyrroles

图式20. 乙烯基乙炔碳酸酯催化合成吡咯

Scheme 20. Catalytic synthesis of pyrroles from vinyl ethynylethylene carbonates

图式21. 铜催化胺/肼参与的[4＋1]/[4＋2]环化反应

Scheme 21. Copper-catalyzed [4＋1] and [4＋2] reactions involving amines or hydrazines

图式22. 脂肪胺的Larock型环化/脱苄基化反应

Scheme 22. Larock-type cyclization/debenzylation of aliphatic amines

图式23. 铜-芳酰胺协同催化的不对称环化反应

Scheme 23. Asymmetric annulation catalyzed via cooperative copper-squaramide catalysis

图式24. 含极小位阻差异烷基的N—N轴向手性化合物的不对称合成

Scheme 24. Atroposelective synthesis of N—N axially chiral compounds bearing minimally different alkyl groups

图式25. 亚磺酸钠的远程对映选择性磺酰化反应

Scheme 25. Remote enantioselective sulfonylation of sodium sulfonates

图式26. 配体控制的铜催化区域发散性磺酰化反应

Scheme 26. Ligand-controlled copper-catalyzed regiodivergent sulfonylation

图式27. 通过铜催化二炔环化及动力学拆分实现的未活化C(sp³)—H键对映选择性官能团化

Scheme 27. Enantioselective functionalization of unactivated C(sp3)—H bonds through copper-catalyzed diyne cyclization via kinetic resolution

图式28. 铜催化的分子内形式上一碳插入反应

Scheme 28. Copper-catalyzed intramolecular formal one-carbon insertion reaction

图式29. 铜催化二炔环化实现多种氮杂环的不对称一碳扩环反应

Scheme 29. Copper-catalyzed diyne cyclization for asymmetric one-carbon ring expansion of diverse N-heterocycles

图式30. 铜催化通过烯基正离子实现的配体控制发散性不对称插入反应

Scheme 30. Copper-catalyzed ligand-controlled divergent asymmetric insertion reaction via vinyl cations

图式31. 铜催化(杂)芳烃与烯基正离子的对映选择性C(sp²)—H官能团化反应

Scheme 31. Copper-catalyzed enantioselective C(sp²)—H functionalization of (hetero)arenes with vinyl cations

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