氢原子迁移(HAT)介导的官能团迁移反应

doi:10.6023/cjoc202512041

摘要/Abstract

氢原子转移(HAT)介导的官能团迁移反应因其优异的原子经济性和步骤经济性, 为非活化C(sp³)—H键的选择性官能团化提供了高效策略, 能够实现烷烃及复杂分子的简便结构修饰, 近年来引起广泛关注. 然而, C(sp³)—H键固有的化学惰性以及不同位点间细微的键能差异, 使区域选择性的精准调控仍面临重大挑战. 重点综述了近期HAT介导的C(sp³)—H键选择性官能团迁移反应的研究进展, 系统介绍了各类反应的催化体系与反应机理, 涵盖芳基化、氰基迁移、硼基迁移和酰基迁移等典型官能团迁移过程及其在复杂分子后期修饰中的应用. 最后, 对当前HAT介导官能团化迁移方法的主要局限与技术瓶颈进行总结, 并展望了其在医药化学和材料科学等领域的潜在应用与未来发展方向.

关键词: 官能团迁移, 氢原子转移, C(sp³)—H键官能团化, 区域选择性

Hydrogen atom transfer (HAT)-mediated functional group migration reactions have emerged as powerful strategies for the selective functionalization of unactivated C(sp³)—H bonds, owing to their excellent atom and step economy. These methods enable efficient structural modification of alkanes and complex molecules, and have therefore attracted significant attention in recent years. Nevertheless, the intrinsic inertness of C(sp³)—H bonds and the minimal bond dissociation energy differences among various sites render precise control of regioselectivity highly challenging. Recent advances in hydrogen atom transfer (HAT)-mediated selective functional group migration of C(sp³)—H bonds are summarized, with a focus on catalytic systems, mechanistic features, and representative transformations including aryl migration, cyano migration, boryl migration, and acyl migration, as well as their applications in late-stage functionalization of complex molecules. Finally, current limitations and technical challenges associated with HAT-mediated functional group migration are outlined, and future opportunities and potential applications in medicinal chemistry and materials science are discussed.

Key words: functional group migration, hydrogen atom transfer, C(sp³)—H bond functionalization, regioselectivity

引用此文

赵丽玮, 张梁, 胡鹏. 氢原子迁移(HAT)介导的官能团迁移反应[J]. 有机化学, 2026, 46(4): 1284-1302.

Liwei Zhao, Liang Zhang, Peng Hu. Hydrogen Atom Transfer-Induced Functional Group Migration[J]. Chinese Journal of Organic Chemistry, 2026, 46(4): 1284-1302.

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图/表 17

图式1. 三级醇导向的远程C(sp3)—H键基团迁移杂芳基化

Scheme 1. Tertiary alcohol-directed heteroarylation of remote C(sp3)—H bonds via functional group migration

图式2. 三级醇导向的远程C(sp3)—H键基团迁移氰化反应

Scheme 2. Tertiary alcohol-directed cyanation of remote C(sp3)—H bonds via functional group migration

图式3. 醇介导的远程C(sp3)—H键的基团迁移官能团化

Scheme 3. Alcohol-mediated functionalization of remote C(sp3)—H bonds via functional group migration

图式4. 二级醇的远程C(sp3)—H芳基迁移反应

Scheme 4. Remote C(sp3)—H aryl migration of secondary alcohols

图式5. 酰胺α-C(sp3)—H键的芳基迁移反应

Scheme 5. Aryl migration of amide α-C(sp3)—H Bonds

图式6. 1,5-HAT介导的乙烯基砜合成方法

Scheme 6. 1,5-HAT-Mediated synthesis of vinyl sulfones

图式7. 通过芳基迁移构建酰胺衍生物季碳中心

Scheme 7. Construction of quaternary carbon centers in amide derivatives via aryl migration

图式8. 经历分子内1,n-氢原子迁移的Smiles重排反应

Scheme 8. Smiles rearrangement via intramolecular 1,n-HAT

图式9. 二烷基酰胺的选择性α-C(sp3)—H键芳基迁移反应

Scheme 9. Selective α-C(sp3)—H aryl migration of dialkyl amides

图式10. 芳基酮β-C(sp3)—H键的选择性烷基化

Scheme 10. Selective alkylation of β-C(sp3)—H bonds in aryl ketones

图式11. 砜亚胺介导远程C(sp3)—H杂芳基化

Scheme 11. Sulfoximine-mediated remote C(sp3)—H heteroarylation

图式12. 硅基自由基介导的(杂)芳基/烯烃官能团化

Scheme 12. Silyl radical-mediated (hetero)aryl/alkene functionalization

图式13. 三级醇γ-C(sp3)—H杂芳酰基化反应

Scheme 13. Heteroaryl acylation of γ-C(sp3)—H bonds of tertiary alcohols

图式14. 三级醇γ-C(sp3)—H杂芳基化羰基化反应

Scheme 14. Carbonylative heteroarylation of γ-C(sp3)—H bonds of tertiary alcohols

图式15. 基于C(sp3)—H采样策略的氰基迁移反应

Scheme 15. Cyanide migration via a C(sp3)—H sampling strategy

图式16. 烷基硼酸酯的1,2-硼基/氢转换反应

Scheme 16. 1,2-Boryl/hydrogen exchange of alkyl boronates

图式17. 七元环远程C(sp3)—H酮基迁移反应

Scheme 17. Remote C(sp3)—H ketyl migration of seven-membered rings

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