Research Progress on Photocatalyzed Protic C(sp3)—HFunctionalization

doi:10.6023/cjoc202407049

Abstract

Compounds containing protic C(sp³)—H bonds are widely used as nucleophiles in organic synthesis due to their cheaply available sources, and reaction products are readily converted into diverse functional molecules. In the past decade, visible light-catalyzed C(sp³)—H bond functionalization in mild conditions, atom- and step-economical manner has made rapid progress. Under visible-light catalytic conditions, protic C(sp³)—H feedstocks are readily converted into electrophilic alkyl radical intermediates, enabling a series of previously inaccessible transformations, which provides a new perspective on the efficient utilization of such compounds. This review focuses on the recent research progress of visible light-catalyzed protic C(sp³)—H functionalization in the absence of stoichiometric oxidants. Based on the different activation modes of protic C(sp³)—H bonds, the reactions are divided into photoredox catalysis, synergistic photoredox/amine organocatalysis, and synergistic photoredox/hydrogen atom transfer catalysis. Aside from the substrate scopes, the mechanisms and potential applications of some representative methodologies are also included.

Key words: visible-light catalysis, protic C(sp³)—H bond, photoredox catalysis, amine organocatalysis, hydrogen atom transfer catalysis

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Yang Hong, Hongping Deng. Research Progress on Photocatalyzed Protic C(sp³)—HFunctionalization[J]. Chinese Journal of Organic Chemistry, 2025, 45(5): 1569-1590.

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Fig. & Tab. 38

Scheme 1. Representative protic C(sp3)—H feedstocks

Scheme 2. Reaction models of protic C(sp3)—H functionalization

Scheme 3. Representative hydridic C(sp3)—H feedstocks

Scheme 4. Strategies of photoredox catalysis

Scheme 5. Photoredox-catalyzed protic C(sp3)—H addition with styrenes

Scheme 6. Photoredox-catalyzed protic C(sp3)—H double-addition with styrenes

Scheme 7. Photoredox-catalyzed intramolecular protic C(sp3)—H addition with C=C bonds

Scheme 8. Photoredox-catalyzed addition of styrenes with protic α-C(sp3)—H bonds of ketones

Scheme 9. Photoredox-catalyzed protic C(sp3)—H addition with conjugated enynes

Scheme 10. Photoredox-catalyzed protic C(sp3)—H addition with unactivated alkenes

Scheme 11. Photoredox-catalyzed addition of coumarin with unactivated alkenes

Scheme 12. Photoredox-catalyzed cascade addition/annulation of aromatic α-ketoesters with alkynes

Scheme 13. Photoredox-catalyzed cascade addition/annulation benzylmalonates with terminal alkynes

Scheme 14. Photoredox-catalyzed cascade addition/annulation of 1,6-enynes with protic C(sp3)—H feedstocks

Scheme 15. Asymmetric [3＋2] cycloaddition of β-ketoesters with vinyl azides enabled by photoredox/Lewis acid dual catalysis

Scheme 16. Asymmetric addition of β-ketoesters with vinylcyclopropanes enabled by photoredox/Lewis acid dual catalysis

Scheme 17. Photoredox-catalyzed defluorinative [4＋2] annulation of gem-difluoroalkenes with unactivated alkenes

Scheme 18. Photoelectrocatalyzed cascade addition/arylation of aromatic-derived alkenes with protic C(sp3)—H feedstocks

Scheme 19. Photoredox-catalyzed three-component carboarylation of unactivated alkenes

Scheme 20. Proposed mechanism of photoredox-catalyzed three-component carboarylation of unactivated alkenes

Scheme 21. Photoredox-catalyzed three-component coupling of 1,1-diarylalkenes with aromatic aldehydes

Scheme 22. Photoredox-catalyzed alkylarylation of alkenes with α-arylsulfonyl esters

Scheme 23. Photoredox-catalyzed alkylarylation of alkynes with α-arylsulfonyl esters

Scheme 24. Photoredox/cobalt-catalyzed intramolecular hydrogen-evolution cross-coupling of 1,3-dicarbonyl derivatives

Scheme 25. Hydrogen-evolution alkylation of allylic C(sp3)—H bonds enabled by triplet photoredox/Brønsted base/cobalt catalysis

Scheme 26. Proposed mechanism of hydrogen-evolution alkylation of allylic C(sp3)—H bonds enabled by triplet photoredox/Brønsted base/cobalt catalysis

Scheme 27. Photoredox/cobalt-catalyzed acceptorless dehydrogenation of cyclohexanones

Scheme 28. Synergistic merger of photoredox and amine catalysis

Scheme 29. Asymmetric addition of alkenes with α-C(sp3)—H of aldehydes enabled by photoredox/amine dual catalysis

Scheme 30. Photoredox/cobalt-catalyzed hydrogen-evolution cross-coupling of cyclohexanones with amines

Scheme 31. Photoredox/cobalt-catalyzed hydrogen-evolution cross-coupling of 4-piperidones with amines

Scheme 32. Photoredox/amine/cobalt-catalyzed hydrogen-evolution intramolecular allylation of α-C(sp3)—H of aldehydes

Scheme 33. Asymmetric hydrogen-evolution alkylation of allylic C(sp3)—H bonds enabled by ternary photoredox/cobalt/chiral primary amine catalysis

Scheme 34. Asymmetric hydrogen-evolution alkylation of vinyl C(sp2)—H bonds enabled by ternary photoredox/cobalt/chiral primary amine catalysis

Scheme 35. Photoredox/iron/chiral amine-catalyzed asymmetric protic C(sp3)—H alkylation of 1,3-dicarbonyl derivatives

Scheme 36. Proposed mechanism of photoredox/iron/chiral amine-catalyzed asymmetric protic C(sp3)—H alkylation of 1,3-dicarbonyl derivatives

Scheme 37. Photoredox/hydrogen atom transfer-catalyzed protic C(sp3)—H addition of unactivated alkenes

Scheme 18. Photoredox/hydrogen atom transfer-catalyzed difunctionalization of styrenes

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可见光催化的酸性C(sp³)—H键官能团化反应研究进展

Research Progress on Photocatalyzed Protic C(sp³)—HFunctionalization

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可见光催化的酸性C(sp3)—H键官能团化反应研究进展