Recent Advances in Enantioselective Radical Reactions of C(sp3)—H Bond

doi:10.6023/cjoc202406042

Abstract

The activation of carbon-hydrogen bonds is considered one of the most attractive techniques in synthetic organic chemistry due to its potential to shorten synthetic routes and complement traditional synthetic strategies. In recent years, owing to the significant growth in foundational knowledge and advancements in various technologies, new ideas about asymmetric radical reactions have continuously emerged, leading to numerous novel catalytic methods. The enantioselective radical reactions involving C(sp³)—H bonds published since 2020 are reviewed. The methods of directly or indirectly breaking C—H bonds through various pathways, such as energy transfer, single-electron transfer, and hydrogen atom transfer, to form carbon radicals and subsequently construct chiral C—C, C—N, and C—O bonds, are discussed.

Key words: C—H bond, radical reaction, enantioselectivity

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Tianpeng Ling, Haitao Qin, Feng Liu. Recent Advances in Enantioselective Radical Reactions of C(sp³)—H Bond[J]. Chinese Journal of Organic Chemistry, 2025, 45(2): 498-515.

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Fig. & Tab. 35

Scheme 1. Enantioselective synthesis of pyrrolidine derivatives

Scheme 2. Radical trifluoromethylation of C(sp3)—H bonds

Scheme 3. Electrochemical radical allylation

Scheme 4. Asymmetric synthesis of β-amino alcohols

Scheme 5. Asymmetric acylation of α-amino C(sp3)—H bonds

Scheme 6. Asymmetric acylation of C(sp3)—H bonds

Scheme 7. Asymmetric carbamoylation of benzylic C(sp3)—H bonds

Scheme 8. Asymmetric reaction mechanism of dual nickel/ photoredox catalysis

Scheme 9. C(sp3)—H arylation of amides

Scheme 10. Enantioselective α-C(sp3)—H arylation of oxacycles

Scheme 11. Asymmetric, remote C(sp3)—H arylation via sulfinyl-Smiles rearrangement

Scheme 12. Enantioselective benzylic C—H alkenylation

Scheme 13. Asymmetric C(sp3)—H alkynylation

Scheme 14. Remote C(sp3)—H alkynylation of primary sulfonamides

Scheme 15. Asymmetric α-C(sp3)—H alkynylation of cyclic amines

Scheme 16. Electrophotocatalytic enantioselective cyanation of benzylic C—H bonds

Scheme 17. Enantioselective cyanation of benzylic C—H bonds

Scheme 18. Reaction mechanism

Scheme 19. Enantioselective cyanation of propargylic C—H bonds

Scheme 20. Enantioselective remote C(sp3)—H cyanation

Scheme 21. Enzymatic C—H amination

Scheme 22. Enantioselective radical C—H amination for the synthesis of β-amino alcohols

Scheme 23. Intermolecular enantioselective benzylic C(sp3)—H amination

Scheme 24. Ctatlytic cycle for the benzylic C(sp3)—H amination reaction

Scheme 25. Enantioconvergent tertiary β-C(sp3)—H amination of racemic ketones

Scheme 26. Asymmetric synthesis of enantiopure pyrrolidines

Scheme 27. Stereocontrolled 1,3-nitrogen migration to access chiral α-amino acids

Scheme 28. Regio- and enantioselective δ-C—H amidation of dioxazolones

Scheme 29. Enzyme-catalyzed asymmetric amination reactions

Scheme 30. Mn-catalyzed benzylic C—H azidation of indolines

Scheme 31. Abiological radical-relay C(sp3)—H azidation

Scheme 32. Mechanism of cytochrome P450 HAT/Oxygen Rebound

Scheme 33. Biocatalytic β-hydroxylation of unactivated C—H bonds in aliphatic carboxylic acids

Scheme 34. Enantioselective radical esterification of propargylic C—H bonds

Scheme 35. Enantioselective C(sp3)—F bond formation via radical fluorine transfer

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C(sp³)—H键对映选择性自由基反应的最新进展

Recent Advances in Enantioselective Radical Reactions of C(sp³)—H Bond

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Fig. & Tab. 35

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