选择性C—H键氯化反应进展

doi:10.6023/cjoc202406030

摘要/Abstract

由于有机氯化物在药物化学、材料化学以及合成化学领域的重要作用, 碳氯键的构建一直是有机化学方向热点研究领域. 由于通过碳氢键断裂并直接转化为目标官能团具有高度的原子经济性, 其被认为是新一代极具潜力的物质构建和转化途径. 近年来, 随着碳氢键活化转化研究的发展, 一些C—H键氯化反应已被开发为传统卤化方法的实用替代方案, 此综述对近十年C—H键氯化反应的发展进行了归纳总结.

关键词: 氯化, C—H键, 选择性, 极性反转

The importance of organic chlorides in pharmaceutical, material, and synthetic chemistry has made the constru- ction of C—Cl bonds a significant focus in organic chemistry. The cleavage and functionalization of C—H bonds with high atomic efficiency, leading to direct conversion into desired functional groups, is seen as a promising approach for creating new substances. Recent advancements in C—H bond activation/tranformation have led to the development of C—H chlorination reactions as viable alternatives to traditional halogenation methods. This review provides an overview of the progress made in C—H bond chlorination reactions over the last decade.

Key words: chlorination, C—H bonds, selective, umpolung

引用此文

王娟娟, 史妍, 田英贤, 刘丙贤. 选择性C—H键氯化反应进展[J]. 有机化学, 2025, 45(2): 574-591.

Juanjuan Wang, Yan Shi, Yingxian Tian, Bingxian Liu. Recent Progress in Selective C—H Chlorination[J]. Chinese Journal of Organic Chemistry, 2025, 45(2): 574-591.

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图/表 44

图式1. 氯化物的转化

Scheme 1. Conversions of chlorides

图式2. C—H氯代反应

Scheme 2. C—H chlorination reaction

图式3. 苯胺催化选择性C(sp2)—H氯化

Scheme 3. Selective C(sp2)—H chlorination catalyzed by aniline

图式4. Lewis碱催化芳烃和杂环C(sp2)—H氯化

Scheme 4. Lewis base catalyzed chlorination of aromatic hydrocarbons and heterocyclic C(sp2)—H

图式5. BHT催化芳烃和杂环C(sp2)—H氯化

Scheme 5. BHT catalyzed chlorination of aromatic hydrocarbons and heterocyclic C(sp2)—H

图式6. Lewis催化剂控制的苯酚区域选择性C(sp2)—H氯化

Scheme 6. Lewis catalyst controlled regioselective C(sp2)—H chlorination of phenol

图式7. 铵盐催化苯酚的高实用性邻位选择性C(sp2)—H氯化

Scheme 7. High practicality of ammonium salt catalyzed ortho-selective C(sp2)—H chlorination of phenol

图式8. 二甲基亚砜催化的(杂)芳烃的氯化反应

Scheme 8. Chlorination reaction of (hetero) aromatic hydrocarbons catalyzed by dimethyl sulfoxide

图式9. 钌催化芳烃邻位选择性双C(sp2)—H键功能化

Scheme 9. Ruthenium catalyzed ortho-selective functionalization of aromatic hydrocarbons with dual C(sp2)—H bonds

图式10. Ru催化C(sp2)—H氯化反应

Scheme 10. Ru catalyzed C(sp2)—H chlorination reaction

图式11. 铜催化选择性远程C(sp2)—H氯化

Scheme 11. Copper catalyzed selective remote C(sp2)—H chlorination

图式12. 通过瞬态非对称碘对(杂)芳烃的位点选择性C(sp2)—H氯化

Scheme 12. Site selective C(sp2)—H chlorination of (hetero) aromatic hydrocarbons through transient asymmetric iodine

图式13. 碘(III)/AlCl3介导的芳烃亲电C(sp2)—H氯化

Scheme 13. Iodine(III)/AlCl3 mediated electrophilic C(sp2)—H chlorination of aromatic hydrocarbons

图式14. 利用高价碘试剂原位生成氯化芳烃

Scheme 14. In situ generation of chlorinated aromatic hydrocarbons using high valent iodine reagents

图式15. 光催化芳烃C(sp2)—H氯化

Scheme 15. Photocatalytic chlorination of aromatic hydrocarbons C(sp2)—H

图式16. 富电子芳烃的原位溴化氧化光C(sp2)—H氯化

Scheme 16. In situ bromination oxidation of electron rich aromatic hydrocarbons and C(sp2)—H chlorination

图式17. 可见光催化活化芳烃和杂芳烃氯化

Scheme 17. Visible light catalytic activation of aromatic and heteroaromatic chlorination

图式18. 光氧化还原催化氧化C(sp2)—H氯化

Scheme 18. Photoredox catalytic oxidation of C(sp2)—H chlorination

图式19. 光/有机共催化(杂)苯胺C(sp2)—H氯化

Scheme 19. C(sp2)—H chlorination of (hetero)anilines via photo/organo co-catalysis

图式20. 丙烯酰胺的选择性氧化Z型C(sp2)—H氯化机理及应用

Scheme 20. Mechanism and application of selective oxidation of Z-type C(sp2)—H chlorination of acrylamide

图式21. 噻吩的电化学选择性C(sp2)—H一氯化和多氯化

Scheme 21. Electrochemical selectivity of thiophene for C(sp2)—H monochlorination and polychlorination

图式22. Pd促进的偶氮苯邻位C(sp2)—H氯化

Scheme 22. Pd promoted ortho-C(sp2)—H chlorination of azobenzene

图式23. Pd催化苯甲腈的邻位C(sp2)—H氯化反应

Scheme 23. Pd catalyzed ortho-C(sp2)—H chlorination reaction of benzonitrile

图式24. 吡啶为导向基团的区域选择性C(sp2)—H氯化

Scheme 24. Regional selectivity of C(sp2)—H chlorination with pyridine as the directing group

图式25. 1,2-二氯乙烷作为氯源在铑催化的C(sp2)—H位选择性氯化

Scheme 25. Selective chlorination of 1,2-dichloroethane at the C(sp2)—H position catalyzed by rhodium as a chlorine source

图式26. 由PIP作为可移除导向基团的定向C(sp2)—H氯化

Scheme 26. Targeted C(sp2)—H chlorination using PIP as a removable directing group

图式27. 铱(III)/l?MPAA催化(杂)苯胺的C(sp2)—H键氯化反应

Scheme 27. Iridium (III)/l-MPAA catalyzed C(sp2)—H bond chlorination reaction of (hetero) aniline

图式28. 配体促进苯胺和苯酚的定向C(sp2)—H氯化

Scheme 28. Ligands promote directed C(sp2)—H chlorination of aniline and phenol

图式29. 可见光促进的叔脂肪族C(sp3)—H键氯化反应

Scheme 29. Visible light promoted chlorination reaction of tertiary aliphatic C(sp3)—H bonds

图式30. 光照条件下亚甲基氯化反应

Scheme 30. Methylene chlorination reaction under illumination conditions

图式31. Mn介导的原子转移引导的C(sp3)—H键的氯化

Scheme 31. Chlorination of C(sp3)—H bonds by Mn mediated atomic transfer

图式32. 脂族酰胺的光诱导选择性C(sp3)—H氯化反应

Scheme 32. Photoinduced selective C(sp3)—H chlorination rea- ction of fatty amides

图式33. 新型烷氧基前体引发1,5-HAT引导C(sp3)—H键的氯化

Scheme 33. Chlorination of C(sp3)—H bonds guided by 1,5-HAT initiated by novel alkoxy precursors

图式34. 光诱导铜电荷转移催化的酰胺衍生物氯化反应

Scheme 34. Photoinduced copper charge transfer catalyzed chlorination reaction of amide derivatives

图式35. 氨基磺酸酯1,6-HAT引导γ-C(sp3)—H键的氯化

Scheme 35. Aminosulfonic acid ester 1,6-HAT guided chlorination of γ-C(sp3)—H bonds

图式36. 苄基C(sp3)—H键的电化学氯化

Scheme 36. Electrochemical chlorination of benzyl C(sp3)—H bond

图式37. 银催化的C(sp3)—H氯化反应

Scheme 37. Silver catalyzed C(sp3)—H chlorination reaction

图式38. 高氟化锰卟啉催化的选择性氯化反应

Scheme 38. Selective chlorination reaction catalyzed by high fluoride manganese porphyrin

图式39. CuOTf催化的位点选择性C(sp3)—H键氯化反应

Scheme 39. Site selective C(sp3)—H bond chlorination reaction catalyzed by CuOTf

图式40. Cu催化的位点选择性苄基氯化反应

Scheme 40. Site selective benzyl chloride reaction catalyzed by Cu

图式41. 硝酸作氧化还原助的钯催化氯化反应

Scheme 41. Palladium catalyzed chlorination reaction with nitric acid as redox aid

图式42. Pd(II)催化连续α-C(sp3)—H键氯化

Scheme 42. Pd(II) catalyzed continuous chlorination of α-C(sp3)—H bonds

图式43. Pd(II)催化β-C(sp3)—H键氯化

Scheme 43. Sulfonimide assisted Pd(II) catalytic chlorination of β-C(sp3)—H bonds

图式44. Pd催化室温下未活化C(sp3)—H键的定向氯化反应

Scheme 44. Pd catalyzed directed chlorination reaction of unactivated C(sp3)—H bonds at room temperature

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