Nucleophilic Aromatic Substitution Reactions via π-Coordination-Activation Transition Metals

doi:10.6023/cjoc202408036

Abstract

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

Cite this article

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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Fig. & Tab. 24

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

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

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

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

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

Scheme 6. SNAr reactions with carbon nucleophiles

Scheme 7. Radical aromatic substitutions reactions

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

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

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

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

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

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

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

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

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

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

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

Scheme 19. Catalytic cycle

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

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

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

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

Scheme 24. Transition-metal-catalyzed amination of aminopyridines

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