经历Pd(I)途径的钯催化自由基反应: 反应模式简述和近期进展

doi:10.6023/cjoc202512048

摘要/Abstract

在现代有机合成的工具箱中, 钯催化的有机合成反应作为一类重要的反应类别, 长期以来被认为遵循经典双电子途径. 然而, 近二十年的研究, 特别是近期的突破表明, 在钯化学中存在着一个平行且同样重要的领域: 涉及单电子转移、卤原子转移和自由基机理的钯催化反应. 这一新反应范式不仅扩展了钯的催化能力, 使其能够活化传统上“惰性”的化学键, 也为在反应中实现新的化学选择性、区域选择性和立体选择性提供了可能. 本文旨在梳理这一前沿领域, 主要关注历经Pd(I)的自由基途径. 在这类反应中, Pd主要扮演自由基引发者的角色, 通过基态或激发态的Pd(0)发生氧化还原过程, 或者Pd(II)—C键的均裂产生自由基, 典型的Pd价态变化是Pd(0)-Pd(I)-Pd(II). 本文将从自由基产生方式的角度, 梳理包含Pd(I)中间体的自由基反应模式, 总结该领域近期研究进展, 并对相关反应机理进行评述.

关键词: 钯催化, 自由基化学, 有机金属化学

In the toolbox of modern organic synthesis, palladium-catalyzed reactions represent a vital category that has long been considered to follow classical two-electron pathways. However, research over the past two decades, and particularly recent breakthroughs, has demonstrated the existence of a parallel and equally significant field: palladium-catalyzed reactions involving single-electron transfer (SET), halogen atom transfer (XAT), and radical mechanisms. This new reaction paradigm not only expands the catalytic capability of palladium, enabling the activation of traditionally inert chemical bonds, but also offers the potential to achieve novel chemoselectivity, regioselectivity, and stereoselectivity. This review aims to organize this frontier field, focusing primarily on radical pathways that proceed via Pd(I) intermediates. In these reactions, palladium primarily acts as a radical initiator, generating radicals through redox processes of ground-state or excited-state Pd(0), or via the homolysis of Pd(II)—C bonds. The typical palladium oxidation state cycle is Pd(0)-Pd(I)-Pd(II). From the perspective of radical generation methods, this review categorizes radical reaction patterns involving Pd(I) intermediates, summarizes recent progress in the field, and provides commentary on the underlying reaction mechanisms.

Key words: palladium catalysis, radical chemistry, organometallic chemistry

引用此文

谈逸凡, 焦雷. 经历Pd(I)途径的钯催化自由基反应: 反应模式简述和近期进展[J]. 有机化学, 2026, 46(4): 1303-1319.

Yi-Fan Tan, Lei Jiao. Palladium-Catalyzed Radical Reactions via Pd(I) Pathway: A Brief Summary of Reaction Patterns and Recent Progress[J]. Chinese Journal of Organic Chemistry, 2026, 46(4): 1303-1319.

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图/表 39

图式1. 钯催化中的典型双电子与单电子过程

Scheme 1. Typical two-electron and single-electron processes in palladium catalysis

图式2. 产生Pd(I)和自由基的两种模式

Scheme 2. Two modes of generating Pd(I) and free radicals

图式3. 自由基串联环化合成苯二氮卓

Scheme 3. Benzoazepine synthesis by radical cascade cyclization reaction

图式4. 光促进的分子内Heck反应

Scheme 4. Photopromoted intramolecular Heck reaction

图式5. 预活化醇的Heck反应

Scheme 5. Heck reaction of pre-activated alcohol

图式6. 自由基环化反应合成多环芳烃

Scheme 6. PAHs synthesis enabled by radical cyclization

图式7. 发散性合成氮杂[2.1.1]和[4.1.1]桥环化合物

Scheme 7. Divergent synthesis of aza-[2.1.1] and [4.1.1]bicycles

图式8. 硼-碘交换反应

Scheme 8. Boron-iodide swap reaction

图式9. 1,3-丁二烯的1,4-氨基芳基化反应

Scheme 9. 1,4-Aminoarylation of 1,3-butadienes

图式10. 吲哚的不对称串联去芳构化反应

Scheme 10. Asymmetric cascade dearomatization of indoles

图式11. 酚羟基导向的苯乙烯1,2-氨基烷基化

Scheme 11. Hydroxyl directed 1,2-aminoalkylation of aromatic alkenes

图式12. 使用光促进Heck反应合成烯基偕二氟代环丙烷

Scheme 12. Access to vinyl gem-difluorinated cyclopropanes via photopromoted Heck reaction

图式13. 使用自由基烯丙基化反应合成C2-烯丙基糖

Scheme 13. Access to C2-allyl carbohydrates via radical allylic alkylation

图式14. 汇聚式合成官能化烯丙基化合物的方法

Scheme 14. Convergent approach to functionalized allylic compounds

图式15. 通过二烯的不对称烷基-氨基化反应合成γ-内酰胺

Scheme 15. Enantioselective cascade carboamidation of dienes to access γ-lactams

图式16. 1,3-丁二烯的1,4-双碳官能化反应

Scheme 16. 1,4-Dicarbofunctionalization of 1,3-butadiene

图式17. α-氨基酸酯的立体选择性三组分烯丙基烷基化反应

Scheme 17. Enantioselective three-component allylic alkylation of α-amino esters

图式18. 氯代烃参与的二烯的1,4-双官能化反应

Scheme 18. 1,4-Bifunctionalization of dienes by alkyl chloride

图式19. 氯代烃的自由基Heck反应

Scheme 19. Radical Heck reaction of alkyl chloride

图式20. 选择性脱氯反应用于合成异奎宁环骨架

Scheme 20. Synthesis of isoquinuclidines via selective dechlorination

图式21. 三氟甲苯衍生物的脱氟Suzuki偶联

Scheme 21. Defluorinative Suzuki coupling of trifluorome- thylarenes

图式22. 氟代烃参与的二烯的1,4-双官能化反应

Scheme 22. 1,4-Difunctionalization of dienes by trifluoromethylarenes

图式23. 三氟甲苯衍生物的脱氟多组分串联反应

Scheme 23. Defluorinative multicomponent cascade reaction of trifluoromethylarenes

图式24. 异腈与芳基乙烯的自由基Heck偶联

Scheme 24. Radical Heck coupling of isonitriles and vinyl arenes

图式25. 与激发态Pd(0)作用的亲电底物

Scheme 25. Scope of electrophiles that can interact with photoexcited Pd(0)

图式26. C—H键活化介导的1,3-二烯的1,4-双碳官能化反应

Scheme 26. 1,4-Dicarbofunctionalization of 1,3-dienes mediated by C—H activation

图式27. 氢-碘交换反应

Scheme 27. Hydrogen-iodide swap reaction

图式28. 立体发散性烯丙基化合物合成

Scheme 28. Stereodivergent synthesis of functionalized allylic compounds

图式29. 烷基芳烃与亚胺的形式[2＋2]环加成

Scheme 29. Formal [2＋2] cycloaddition of alkylarenes and imines

图式30. 烯烃的烯丙位C—H烷基化反应

Scheme 30. Allylic C—H alkylation of alkenes

图式31. 经由自由基Heck反应的脂肪胺α-烯基化反应

Scheme 31. α-Alkenylation of amines through radical Heck reaction

图式32. 芳基羰基自由基的生成及后续反应

Scheme 32. Formation of aryl ketyl radicals and its reaction

图式33. 烷基羰基自由基的生成及后续反应

Scheme 33. Formation of alkyl ketyl radicals and its reaction

图式34. 光促进的钯催化卤代烃的酰基化反应

Scheme 34. Photopromoted palladium-catalyzed acylation of halides

图式35. Pd(0)和底物作用的三种模式

Scheme 35. Three modes of interaction between Pd(0) and substates

图式36. Pd(0)和底物发生XAT的证据

Scheme 36. Evidence for XAT between Pd(0) and the substrate

图式37. 光促进的Pd(II)—R键均裂反应

Scheme 37. Photopromoted homolysis of Pd(II)—R bond

图式38. tBu-Xantphos-Pd(I)配合物的合成及相关反应证据

Scheme 38. Synthesis of tBu-Xantphos-Pd(I) complex and evidence for related reactions

图式39. dtbpf-Pd(I)配合物的合成及相关反应证据

Scheme 39. Synthesis of dtbpf-Pd(I) complex and evidence for related reactions

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