Hydrogen Atom Transfer-Induced Functional Group Migration

doi:10.6023/cjoc202512041

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (4): 1284-1302.DOI: 10.6023/cjoc202512041 Previous Articles Next Articles

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氢原子迁移(HAT)介导的官能团迁移反应

赵丽玮, 张梁^*(), 胡鹏^*()

中山大学化学学院绿色化学与分子工程研究所广东省高等学校功能分子工程基础研究卓越中心Lehn功能材料研究所广州 510006

收稿日期:2025-12-27 修回日期:2026-03-15 发布日期:2026-03-27
通讯作者: 张梁, 胡鹏
基金资助:
中央高校青年教师科研创新能力支持(ZYGXQNJSKYCXNLZCXM−M28); 国家自然科学基金(22471298); 广州市科学技术局(2025A04J7100)

Hydrogen Atom Transfer-Induced Functional Group Migration

Liwei Zhao, Liang Zhang^*(), Peng Hu^*()

Lehn Institute of Functional Materials, Guangdong Basic Research Center of Excellence for Functional Molecular Engineering, Institute of Green Chemistry and Molecular Engineering, School of Chemistry, Sun Yat-sen University, Guangzhou 510006

Received:2025-12-27 Revised:2026-03-15 Published:2026-03-27
Contact: Liang Zhang, Peng Hu
Supported by:
Scientific Research Innovation Capability Support Project for Young Faculty(ZYGXQNJSKYCXNLZCXM−M28); National Natural Science Foundation of China(22471298); Guangzhou Municipal Science and Technology Bureau(2025A04J7100)

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

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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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Fig. & Tab. 17

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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氢原子迁移(HAT)介导的官能团迁移反应

Hydrogen Atom Transfer-Induced Functional Group Migration

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