Electrochemical Synthesis of 4-Sulfenylisocoumarins via Radical Cascade Annulation of o-Alkynylbenzoates with Thiophenols

doi:10.6023/cjoc202508022

Abstract

The first electrochemical method that employs commercially available, stable, and inexpensive thiophenols as sulfenylating agents for the efficient synthesis of valuable 4-sulfenylisocoumarins is presented. Various thiophenols containing both electron-donating and electron-withdrawing groups reacted smoothly with o-alkynylbenzoates to afford the corresponding 4-sulfenylisocoumarins in moderate to good yields. Preliminary mechanistic investigation, including controlled experiments and cyclic voltammetry (CV) experiments, indicated that this electrochemical cyclization might proceed via a radical pathway. In comparison to existing methods, this strategy circumvents the need for moisture-sensitive and pre-functionalized sulfenylating reagents, such as aryl sulfenyl chloride (ArSCl), diaryl disulfide (ArSSAr) and N-thiosuccinimide, significantly broadens the substrate scope, and offers a practical and sustainable alternative for the synthesis of 4-sulfenylisocoumarins.

Key words: 4-sulfenylisocoumarin, thiophenol, o-alkynylbenzoate, electrochemical synthesis, radical cascade annulation

Cite this article

Chao Ma, Xiaoling Xu, Xiang Luo, Ruijuan Lu, Guoqi Yu, Tao Cai. Electrochemical Synthesis of 4-Sulfenylisocoumarins via Radical Cascade Annulation of o-Alkynylbenzoates with Thiophenols[J]. Chinese Journal of Organic Chemistry, 2026, 46(3): 1039-1049.

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Entry	Electrode (＋/－)	Electrolyte	Solvent	Yield^b/%
1	Pt/Pt	Bu₄NBF₄	CH₃CN	Trace
2	GF/Pt	Bu₄NBF₄	CH₃CN	24
3	RVC/Pt	Bu₄NBF₄	CH₃CN	12
4	Carbon rod/Pt	Bu₄NBF₄	CH₃CN	25
5	C100/Pt	Bu₄NBF₄	CH₃CN	45
6	C200/Pt	Bu₄NBF₄	CH₃CN	70
7	C200/C100	Bu₄NBF₄	CH₃CN	46
8	C100/C100	Bu₄NBF₄	CH₃CN	14
9	C200/Pt	Bu₄NBF₄	THF	Trace
10	C200/Pt	Bu₄NBF₄	HFIP	20
11	C200/Pt	Bu₄NBF₄	EtOH	0
12	C200/Pt	Bu₄NBF₄	Acetone	25
13	C200/Pt	Bu₄NBF₄	DMSO	0
14	C200/Pt	Bu₄NBF₄	CH₃CN/acetone (V∶V=10∶1)	45
15	C200/Pt	Bu₄NBF₄	CH₃CN/H₂O (V∶V=10∶1)	38
16	C200/Pt	Bu₄NBF₄	CH₃CN/HFIP (V∶V=10∶1)	82
17	C200/Pt	Bu₄NClO₄	CH₃CN/HFIP (V∶V=10∶1)	24
18	C200/Pt	Bu₄NPF₆	CH₃CN/HFIP (V∶V=10∶1)	15
19	C200/Pt	Bu₄NBr	CH₃CN/HFIP (V∶V=10∶1)	Trace
20	C200/Pt	CF₃SO₃Li	CH₃CN/HFIP (V∶V=10∶1)	30
21	C200/Pt	LiClO₄	CH₃CN/HFIP (V∶V=10∶1)	66
22^c	C200/Pt	Bu₄NBF₄	CH₃CN/HFIP (V∶V=10∶1)	70
23^d	C200/Pt	Bu₄NBF₄	CH₃CN/HFIP (V∶V=10∶1)	80
24^e	C200/Pt	Bu₄NBF₄	CH₃CN/HFIP (V∶V=10∶1)	48

Entry	Electrode (＋/－)	Electrolyte	Solvent	Yield^b/%
1	Pt/Pt	Bu₄NBF₄	CH₃CN	Trace
2	GF/Pt	Bu₄NBF₄	CH₃CN	24
3	RVC/Pt	Bu₄NBF₄	CH₃CN	12
4	Carbon rod/Pt	Bu₄NBF₄	CH₃CN	25
5	C100/Pt	Bu₄NBF₄	CH₃CN	45
6	C200/Pt	Bu₄NBF₄	CH₃CN	70
7	C200/C100	Bu₄NBF₄	CH₃CN	46
8	C100/C100	Bu₄NBF₄	CH₃CN	14
9	C200/Pt	Bu₄NBF₄	THF	Trace
10	C200/Pt	Bu₄NBF₄	HFIP	20
11	C200/Pt	Bu₄NBF₄	EtOH	0
12	C200/Pt	Bu₄NBF₄	Acetone	25
13	C200/Pt	Bu₄NBF₄	DMSO	0
14	C200/Pt	Bu₄NBF₄	CH₃CN/acetone (V∶V=10∶1)	45
15	C200/Pt	Bu₄NBF₄	CH₃CN/H₂O (V∶V=10∶1)	38
16	C200/Pt	Bu₄NBF₄	CH₃CN/HFIP (V∶V=10∶1)	82
17	C200/Pt	Bu₄NClO₄	CH₃CN/HFIP (V∶V=10∶1)	24
18	C200/Pt	Bu₄NPF₆	CH₃CN/HFIP (V∶V=10∶1)	15
19	C200/Pt	Bu₄NBr	CH₃CN/HFIP (V∶V=10∶1)	Trace
20	C200/Pt	CF₃SO₃Li	CH₃CN/HFIP (V∶V=10∶1)	30
21	C200/Pt	LiClO₄	CH₃CN/HFIP (V∶V=10∶1)	66
22^c	C200/Pt	Bu₄NBF₄	CH₃CN/HFIP (V∶V=10∶1)	70
23^d	C200/Pt	Bu₄NBF₄	CH₃CN/HFIP (V∶V=10∶1)	80
24^e	C200/Pt	Bu₄NBF₄	CH₃CN/HFIP (V∶V=10∶1)	48

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电化学促进邻炔基苯甲酸酯与硫酚的自由基串联环化反应合成4-硫代异香豆素