Catalyst-Free Photochemical Construction of Oxindoles via Electron Donor-Acceptor Complex-Enabled N-Arylacrylamide Cyclization

doi:10.6023/A25050196

Acta Chimica Sinica ›› 2025, Vol. 83 ›› Issue (11): 1379-1385.DOI: 10.6023/A25050196 Previous Articles Next Articles

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无催化剂光化学合成吲哚酮: 电子供体-受体复合物介导的N-芳基丙烯酰胺环化反应

雷平^a, 苏秦^a, 王栋^a, Shahid Ali Khan^b, 阿布拉江•克依木^a^,^*()

^a 新疆大学化学学院碳基能源化学与利用国家重点实验室乌鲁木齐 830017
^b 国立科技大学自然科学学院化学系巴基斯坦伊斯兰堡 44000

投稿日期:2025-05-29 发布日期:2025-07-11
通讯作者: 阿布拉江•克依木
基金资助:
上海合作组织科技伙伴计划(2022E01049); 国家自然科学基金(21961038)

Catalyst-Free Photochemical Construction of Oxindoles via Electron Donor-Acceptor Complex-Enabled N-Arylacrylamide Cyclization

Lei Ping^a, Su Qin^a, Wang Dong^a, Shahid Ali Khan^b, Ablajan Keyume^a^,^*()

^a State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources, College of Chemistry, Xinjiang University, Urumqi 830017, China
^b Department of Chemistry, School of Natural Sciences, National University of Sciences and Technology, Islamabad 44000, Pakistan

Received:2025-05-29 Published:2025-07-11
Contact: Ablajan Keyume
Supported by:
Shanghai Cooperation Organization Science and Technology Partnership Program(2022E01049); National Natural Science Foundation of China(21961038)

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Abstract

This work presents a catalyst-free, visible-light-driven protocol for constructing biologically relevant oxindoles via intramolecular hydroarylation of N-arylacrylamides, mediated by in situ-generated electron donor-acceptor (EDA) complexes. Diverging from conventional transition-metal catalysis or oxidative cyclization, which require metal pre-catalysts, pre-functionalized substrates, or strong oxidants, this strategy operates without external photocatalysts, acids, or chemical oxidants. Central to the mechanism is the weak base (Cs₂CO₃)-promoted hydrolysis of diphenyl disulfide (PhSSPh), which generates phenylthiolate anions (PhS^－) as potent electron donors. Mechanistic studies, including comprehensive UV-Vis spectroscopy, establish that these PhS^－ anions form a photoactive EDA complex with electron-deficient N-arylacrylamides (acceptors). Critically, this complex exhibits a distinct broad absorption band (450~500 nm), enabling direct visible-light irradiation (455~460 nm) to trigger single-electron transfer (SET) and initiate radical cyclization. Deuterium-labeling experiments (D₂O) confirm that trace water serves as the proton source in the reaction, while radical trapping studies corroborate the radical nature of the pathway. Substrate scope evaluation (33 diverse examples) demonstrates broad functional group tolerance on the aryl ring, accommodating both electron-donating (para-methyl, para-methoxy) and electron-withdrawing (para-halogen, trifluoromethyl, cyano, ester) substituents, as well as heterocyclic motifs (pyridyl). Ortho-substituted arenes cyclize with reduced efficiency due to steric hindrance, while meta-methyl substitution yields α/β-regioisomers. Diverse N-alkyl groups (isopropyl, cyclohexyl), functionalized N-substituents (benzyl, ester), and conformationally constrained diamides are compatible, highlighting versatility. A key limitation is the inactivity of free N-H acrylamides under the current conditions, suggesting the N-substituent is crucial for EDA complex formation or reactivity. Significant advantages of this strategy include operational simplicity (ambient temperature, 16 h reaction time), avoidance of precious metals and stoichiometric oxidants, demonstrated gram-scale feasibility, and the utilization of benign visible light. By leveraging the unique electron-donating capability of in situ-generated sulfur anions (PhS^－) to form catalytically active EDA complexes, this work provides a green, practical, and mechanistically distinct route to privileged oxindole scaffolds.

Key words: visible-light induction, oxindole, electron donor-acceptor (EDA) complex, N-arylacrylamide, catalyst-free synthesis

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Lei Ping, Su Qin, Wang Dong, Shahid Ali Khan, Ablajan Keyume. Catalyst-Free Photochemical Construction of Oxindoles via Electron Donor-Acceptor Complex-Enabled N-Arylacrylamide Cyclization[J]. Acta Chimica Sinica, 2025, 83(11): 1379-1385.

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Fig. & Tab. 8

Figure 1. Bioactive pharmaceuticals containing oxindole scaffolds

Scheme 1. Cyclization reactions of N-arylacrylamides

Entry	Variations from standard conditions	Yield^b/%
1	none	56
2	A2 instead of A1	trace
3	A3 instead of A1	35
4	A4 instead of A1	n.r.
5	A5 instead of A1	25
6	Cs₂CO₃ instead of K₂CO₃	70
7	DABCO instead of K₂CO₃	trace
8	DBU instead of K₂CO₃	45
9	DIPEA instead of K₂CO₃	35
10	H₂O instead of MeCN	n.r.
11	DMF instead of MeCN	90
12	DMSO instead of MeCN	trace
13	390~395 nm or white light	n.r.
14	air instead of N₂	55
15	O₂ instead of N₂	n.d
16	without A1 or Cs₂CO₃ or light irradiation	n.r.

Table 1. Conditions optimization

Table 2. Substrate scope of photocyclization of N-arylacrylamides

Scheme 2. Substrate scope expansion: hydrogenated derivatives Reaction conditions: N-arylacrylamides (0.2 mmol), PhSSPh (0.3 mmol), and Cs2CO3 (0.2 mmol) in DMF (2 mL) at room temperature for 16 h under N2, 18 W blue LED (λ=455~460 nm). Isolated yields.

Figure 2. UV-Vis spectroscopy experiments and color changes

Figure 3. Light on-off experiments

Scheme 3. Mechanism investigation

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无催化剂光化学合成吲哚酮: 电子供体-受体复合物介导的N-芳基丙烯酰胺环化反应

Catalyst-Free Photochemical Construction of Oxindoles via Electron Donor-Acceptor Complex-Enabled N-Arylacrylamide Cyclization

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