基于过渡金属π配位活化的芳香亲核取代反应研究进展

doi:10.6023/cjoc202408036

摘要/Abstract

以苯环为代表的芳香环作为一类重要的有机结构单元, 广泛存在于天然产物、药物与化工材料分子之中. 芳香亲核取代(S_NAr)反应是实现芳香化合物官能团转化的重要策略之一. 传统S_NAr反应主要适用于具有吸电子取代基的卤代苯和硝基苯类化合物, 存在显著的底物范围局限性. 化学家们发现亲电性过渡金属通过π配位活化模式, 可以有效地提高芳香化合物的亲电性, 因此通过制备η⁶-苯环类配合物极大地拓展了S_NAr反应的应用范围. 近年来, 化学家们也致力于探索过渡金属催化的S_NAr反应并取得了一定进展. 对铬(Cr)、铁(Fe)、钌(Ru)、锰(Mn)、铑(Rh)等过渡金属通过π配位活化芳香化合物而实现的S_NAr反应进行了梳理与总结.

关键词: 金属有机, 芳香亲核取代反应, π配位, 芳香化合物配合物

Aromatic rings are fundamental building blocks prevalent in natural products, pharmaceuticals, and chemical materials. Nucleophilic aromatic substitution (S_NAr) is one of the key strategies for functionalizing aromatic compounds. However, S_NAr reaction has primarily been applied to aromatic compounds bearing electron-withdrawing substituents, which facilitate nucleophilic attack on the ring. The π-coordination with electrophilic transition metals can overcome this limitation by enhancing the electrophilicity of aromatic rings, leading to the successful development of numerous S_NAr reactions involving arene π-complexes over the past several decades. Beyond stoichiometric reactions of preformed complexes, recent efforts have focused on exploring transition-metal-catalyzed S_NAr reaction and obtained notable progress. This review highlights S_NAr reactions mediated by transition metals, such as chromium (Cr), iron (Fe), ruthenium (Ru), manganese (Mn), and rhodium (Rh), emphasizing the role of π-coordination in activating the aromatic ring.

Key words: organometallics, nucleophilic aromatic substitution, π coordination, arene complexes

引用此文

马伊璇, 陈凯, 石航. 基于过渡金属π配位活化的芳香亲核取代反应研究进展[J]. 有机化学, 2025, 45(6): 2074-2085.

Yixuan Ma, Kai Chen, Hang Shi. Nucleophilic Aromatic Substitution Reactions via π-Coordination-Activation Transition Metals[J]. Chinese Journal of Organic Chemistry, 2025, 45(6): 2074-2085.

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图/表 24

图式1. 过渡金属π配位活化苯环

Scheme 1. π-Coordination activation of benzene rings with transition metals

图式2. (η6-arene)Cr(CO)3的烷氧基化反应

Scheme 2. Alkoxylation of (η6-arene)Cr(CO)3

图式3. (η6-arene)Cr(CO)3的分子内烷氧基化

Scheme 3. Intramolecular alkoxylation of (η6-arene)Cr(CO)3

图式4. (η6-arene)Cr(CO)3的胺化反应

Scheme 4. Amination of (η6-arene)Cr(CO)3

图式5. 硫和磷亲核试剂参与的SNAr反应

Scheme 5. SNAr reactions of (η6-arene)Cr(CO)3 with sulfur and phosphorus nucleophiles

图式6. 碳亲核试剂参与的SNAr反应

Scheme 6. SNAr reactions with carbon nucleophiles

图式7. 自由基参与的异位取代反应

Scheme 7. Radical aromatic substitutions reactions

图式8. [CpFe(η6-arene)]＋的羟基化与烷氧基化反应

Scheme 8. Hydroxylation and alkoxylation of [(η6-arene)-FeCp]＋

图式9. [CpFe(η6-arene)]＋的胺化反应

Scheme 9. Amination of [CpFe(η6-arene)]＋

图式10. [CpFe(η6-fluorobenzene)]＋的胺化反应

Scheme 10. Amination of [CpFe(η6-fluorobenzene)]＋

图式11. [CpFe(η6-chlorobenzene)]＋的叠氮化反应

Scheme 11. Azidation of [CpFe(η6-chlorobenzene)]＋

图式12. [CpFe(η6-arene)]＋的开环胺化

Scheme 12. Ring-opening amination of [CpFe(η6-arene)]＋

图式13. [CpFe(η6-arene)]＋的硫醚化反应

Scheme 13. Thioetherification of [CpFe(η6-arene)]＋

图式14. [CpFe(η6-arene)]＋的烷基化反应

Scheme 14. Alkylation of [CpFe(η6-arene)]＋

图式15. [CpRu(η6-hetorobenzene)]＋的SNAr反应

Scheme 15. SNAr reactions of [CpRu(η6-heterobenzene)]＋

图式16. [CpRu(Ⅱ)]＋活化的苯酚SNAr脱氧氟化反应

Scheme 16. SNAr deoxyfluorination of phenols via [CpRu(Ⅱ)]＋activation

图式17. [CpRu(η6-nitrobenzene)]PF6的三氟甲基化反应

Scheme 17. Trifluoromethylation of [CpRu(η6-nitrobenzene)]-PF6

图式18. [(η6-arene)Mn(CO)3]＋的SNAr反应

Scheme 18. SNAr reactions of [(η6-arene)Mn(CO)3]＋

图式19. 催化循环示意图

Scheme 19. Catalytic cycle

图式20. 过渡金属催化的氟苯类化合物的SNAr反应

Scheme 20. Transition-metal-catalyzed SNAr reactions of aryl fluorides

图式21. 过渡金属催化的其它卤代芳烃的SNAr反应

Scheme 21. Transition-metal-catalyzed SNAr reactions of other aryl halides

图式22. Rh(III)催化的苯酚的胺化反应

Scheme 22. Rh(III)-catalyzed amination reactions of phenols

图式23. Ru(Ⅱ)催化的苯酚的胺化反应

Scheme 23. Ru(Ⅱ)-catalyzed amination reactions of phenols

图式24. 过渡金属催化的氨基吡啶的胺化反应

Scheme 24. Transition-metal-catalyzed amination of aminopyridines

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