Ready Synthesis of 3-Difluoromethylated Coumarins Enabled by Photosensitizer-Free Photoinduced Radical Difluoromethylation of Alkynoates

doi:10.6023/cjoc202407031

Chinese Journal of Organic Chemistry ›› 2025, Vol. 45 ›› Issue (5): 1739-1746.DOI: 10.6023/cjoc202407031 Previous Articles Next Articles

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无需光敏剂光诱导炔丙酸酯自由基二氟甲基化合成3-二氟甲基香豆素

陈旭欣, 张丹丹, 龙鸿新, 刘国凯^*()

深圳大学医学部药学院广东深圳 518055

收稿日期:2024-09-06 修回日期:2024-10-07 发布日期:2024-11-08
基金资助:
国家自然科学基金(92056201); 广东省自然科学基金面上项目(2023A1515011008); 深圳市高校稳定支持(20220808130958001)

Ready Synthesis of 3-Difluoromethylated Coumarins Enabled by Photosensitizer-Free Photoinduced Radical Difluoromethylation of Alkynoates

Xuxin Chen, Dandan Zhang, Hongxin Long, Guokai Liu^*()

School of Pharmacy, Shenzhen University Medical School, Shenzhen, Guangdong 518055

Received:2024-09-06 Revised:2024-10-07 Published:2024-11-08
Contact: * E-mail: gkliu@szu.edu.cn
Supported by:
National Natural Science Foundation of China(92056201); Guangdong Basic and Applied Basic Research Foundation(2023A1515011008); Shenzhen Science and Technology Program (the Stable Support Plan Program(20220808130958001)

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Abstract

A photocatalyst-free photoinduced radical difluoromethylation approach for the convenient synthesis of 3-CF₂H- coumarins from alkynoates by difluoromethyl phenoxathiinium salt (PT-CF₂H^＋BF₄^－) was developed. This transformation involves radical difluoromethylation/5-exo spirocyclization/ester migration rearrangement cascade process and features mild reaction conditions, broad substrate scope and good functional groups tolerance. Using this method, a wide range of alkynoates was successfully converted to desired 3-CF₂H-coumarins in moderate to good yields.

Key words: photoinduced, radical, difluoromethylation, coumarin

Cite this article

Xuxin Chen, Dandan Zhang, Hongxin Long, Guokai Liu. Ready Synthesis of 3-Difluoromethylated Coumarins Enabled by Photosensitizer-Free Photoinduced Radical Difluoromethylation of Alkynoates[J]. Chinese Journal of Organic Chemistry, 2025, 45(5): 1739-1746.

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Fig. & Tab. 4

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Entry	Base	Solvent	Time/h	Yield/%
1	KH₂PO₄	CH₃CN	8	47
2	LiOH	CH₃CN	8	45
3	t-BuOLi	CH₃CN	8	NR
4	Li₂CO₃	CH₃CN	8	78
5	Li₂CO₃	DCM	8	67
6	Li₂CO₃	DCE	8	70
7	Li₂CO₃	EtOAc	8	43
8^b	Li₂CO₃	CH₃CN	8	84
9^c	Li₂CO₃	CH₃CN	8	60
10^b	Li₂CO₃	CH₃CN	12	45
11^b	Li₂CO₃	CH₃CN	5	42

Entry	Base	Solvent	Time/h	Yield/%
1	KH₂PO₄	CH₃CN	8	47
2	LiOH	CH₃CN	8	45
3	t-BuOLi	CH₃CN	8	NR
4	Li₂CO₃	CH₃CN	8	78
5	Li₂CO₃	DCM	8	67
6	Li₂CO₃	DCE	8	70
7	Li₂CO₃	EtOAc	8	43
8^b	Li₂CO₃	CH₃CN	8	84
9^c	Li₂CO₃	CH₃CN	8	60
10^b	Li₂CO₃	CH₃CN	12	45
11^b	Li₂CO₃	CH₃CN	5	42

无需光敏剂光诱导炔丙酸酯自由基二氟甲基化合成3-二氟甲基香豆素

Ready Synthesis of 3-Difluoromethylated Coumarins Enabled by Photosensitizer-Free Photoinduced Radical Difluoromethylation of Alkynoates

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