Recent Advances in Photocatalytic Radical-Mediated Lactone Synthesis

doi:10.6023/cjoc202512036

Abstract

Lactones represent a significant class of compounds that are widely present in various natural products and pharmaceutical molecules. Due to their distinctive properties and broad applications, organic chemists have conducted extensive research on their synthesis. In recent years, the rapid development of photocatalysis and radical chemistry has provided many new strategies for the synthesis of lactones. This review is organized into two main approaches: intramolecular cyclization and intermolecular cycloaddition reactions. This review aims to discuss the mechanisms and advantages of these methodologies, offering new perspectives for further research in this field.

Key words: lactones, photocatalysis, radicals, single electron transfer

Cite this article

Ning Yu, Yuqiang Zhou, Ye Wei. Recent Advances in Photocatalytic Radical-Mediated Lactone Synthesis[J]. Chinese Journal of Organic Chemistry, 2026, 46(4): 1222-1254.

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Fig. & Tab. 47

Scheme 1. Typicaexamples of lactones in pharmaceuticals and bioactive molecules

Scheme 2. Synthesis of disubstituted butyrolactones through a visible light photocatalytic arylation lactonization

Scheme 3. Synthesis of alkyl substituted lactone through photoredox catalyzed alkylation lactonization

Scheme 4. Generation of sulfonated lactones through photocatalystic insertion of sulfur dioxide

Scheme 5. Synthesis of lactones through difluoroalkylesterification

Scheme 6. Synthesis of lactones through organophotocatalytic carboheterofunctionalization

Scheme 7. Synthesis of lactones through atom transfer radical coupling

Scheme 8. Synthesis of lactones through cooperative photoredox and copper catalysis

Scheme 9. Synthesis of lactones through the aerobic dehydrogenative lactonization of alkenoic acids

Scheme 10. Synthesis of lactones through ketyl-olefin cyclizations

Scheme 11. Synthesis of lactones through photocatalytic radical cascade reaction of aroylhydrozones

Scheme 12. Synthesis of lactones through an alkoxycarbonyl radical cyclization protocol

Scheme 13. Synthesis of lactones through a cyclizative alkynylation

Scheme 14. Synthesis of lactones through allene alkoxycarbonylations

Scheme 15. Synthesis of lactones through Iron/photoredox dual catalysis

Scheme 16. Synthesis of lactones through radical spirocyclization cascades

Scheme 17. Synthesis of lactones through C—H lactonization of carboxylic acid

Scheme 18. Synthesis of lactones through Enantioselective photoenolization/Diels-Alder reaction

Scheme 19. Synthesis of lactones through cycloisomerization/addition cascades of 2-acyl benzaldehydes

Scheme 20. Synthesis of lactones through cascade cyclization reactions of alkylidenecyclopropanes

Scheme21. Synthesis of macrocyclic oxalactones through photocyclization

Scheme 22. Synthesis of macrocyclic lactones through radical photocyclization

Scheme 23. Synthesis of macrocyclic lactones through oxidative ring expansion of cyclic ketones

Scheme 24. Synthesis of macrocyclic lactones through ring expansion/aminocarbonylation cascade

Scheme 25. Synthesis of lactones through visible light mediated macrocyclization

Scheme 26. Synthesis of macrocyclic lactones through hydroxyaldehydes of C—H bromination

Scheme 27. Synthesis of lactones through alkene difunctionalization with photoredox catalysis

Scheme 28. Synthesis of difluorolactones through photoredox catalyzed hydroxydifluoroacetylation

Scheme 29. Synthesis of δ-lactones through alkene-alkene coupling

Scheme 30. Synthesis lactones through polar radical crossover cycloaddition reactions

Scheme 31. Synthesis of α-benzyloxyamino-γ-butyrolactones through polar radical crossover cycloaddition reactions

Scheme 32. Synthesis of lactones through the [3＋2] cycloaddition of α,β-unsaturated carboxylic acids with olefins

Scheme 33. Synthesis lactones through the addition of iodoacetic acid in olefins

Scheme 34. Synthesis of lactones through difluoroalkylation lactonization of alkenes

Scheme 35. Synthesisof lactones through the atom transfer radical additions of iodo reagents and alkenes

Scheme 36. Synthesis of lactones through photoredox activation of CDFA and α-halo carboxylic acids

Scheme 37. Synthesis of lactones through C-alkylation of alcohols

Scheme 38. Synthesis of lactones through photoorganocatalytic of alcohols

Scheme 39. Synthesis of lactones through alkenes with α-carbonyl alkyl halides

Scheme 40. Synthesis of lactones through photoredox activation of anhydrides

Scheme 41. Synthesis of lactones through trifunctionalization of cinnamyl alcohols

Scheme 42. Synthesis of lactones through cyclization of bicyclo[1.1.0] butanes

Scheme 43. Synthesis of lactones through phenothiazine sulfoxides as active photocatalysts

Scheme 44. Synthesis of lactones through photochemical dual radical coupling

Scheme 45. Synthesis of lactones through C-H functionalization of amides

Scheme 46. Synthesis of lactones through carboxy cyclization of alkene

反应类型	光敏剂类型	底物类型	产率
分子内环化合成五元环或六元环内酯	钌, 铱, 铜, 铁, 钪, 小分子光敏剂	烯酸及其衍生物, 草酸衍生物, 醛, 酮, 羟胺衍生物, 羧酸及其衍生物	良好至优异
分子内环化合成中环内酯	铱	亚甲基环丙烷的溴代物	良好
分子内环化合成大环内酯	铈, 铜, 小分子光敏剂	不饱和酯, 环酮, 半缩醛过氧化物	部分产率低
分子间环加成反应合成五元环或六元环内酯	钌, 铱, 小分子光敏剂, 酮酸	烯烃, 不饱和羧酸及其衍生物, 卤代羧酸及其衍生物, 二羰基化合物	良好至优异
分子间环加成反应合成中环内酯	铱, 小分子光敏剂	羟胺衍生物, 烯烃	良好

Table 1. Representative methods comparison table

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