Amine-Catalyzed Addition Reaction of Isatins with Allenoates for the Synthesis of Enyne-Containing 3-Hydroxyoxindoles

doi:10.6023/cjoc202510023

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (5): 2051-2058.DOI: 10.6023/cjoc202510023 Previous Articles Next Articles

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胺催化靛红与联烯酸酯的加成反应合成烯炔基-3-羟基氧化吲哚

郭盼盼^a^,^b, 张雅博^b, 史雯赫^b, 陈良军^b, 郭冉^b^,^*()

^a 山东省青岛第二卫生学校山东胶州 266308
^b 河北医科大学药学院河北石家庄 050017

收稿日期:2025-10-26 修回日期:2026-01-23 发布日期:2026-02-28
基金资助:
河北省教育厅青年拔尖人才(BJ2025192)

Amine-Catalyzed Addition Reaction of Isatins with Allenoates for the Synthesis of Enyne-Containing 3-Hydroxyoxindoles

Panpan Guo^a^,^b, Yabo Zhang^b, Wenhe Shi^b, Liangjun Chen^b, Ran Guo^b^,^*()

^a Qingdao Second Health School Shandong Province, Jiaozhou, Shandong 266308
^b School of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei 050017

Received:2025-10-26 Revised:2026-01-23 Published:2026-02-28
Contact: * E-mail: guoran@hebmu.edu.cn
Supported by:
Science and Technology Project of Hebei Education Department Foundation(BJ2025192)

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Abstract

An efficient synthetic methodology for constructing potentially bioactive enyne 3-hydroxyoxindole analogs was developed. The addition reaction between isatins and benzyl 2-(acetoxymethyl)buta-2,3-dienoate was successfully achieved under mild conditions using triphenylamine as an organocatalyst, potassium carbonate as base, and anhydrous N,N-dimethyl- formamide as solvent. This approach enabled the efficient synthesis of sixteen novel 3-hydroxyoxindole derivatives featuring conjugated enyne moieties. The developed protocol offers notable advantages, including mild reaction conditions, broad substrate scope, and excellent yields, thereby establishing a practical route for accessing this class of compounds. The applicability of the synthesis method was further verified by a gram-scale experiment.

Key words: amine catalyzed, isatins, benzyl 2-(acetoxymethyl)buta-2,3-dienoate, addition reaction, 3-hydroxyoxindole

Cite this article

Panpan Guo, Yabo Zhang, Wenhe Shi, Liangjun Chen, Ran Guo. Amine-Catalyzed Addition Reaction of Isatins with Allenoates for the Synthesis of Enyne-Containing 3-Hydroxyoxindoles[J]. Chinese Journal of Organic Chemistry, 2026, 46(5): 2051-2058.

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Fig. & Tab. 7

Figure 1. Typical pharmaceutical molecules containing 3-hydroxyoxindole and conjugated enyne skeletons

Scheme 1. Addition reaction of isatins with benzyl 2-(acetoxymethyl)buta-2,3-dienoate

Entry	Catalyst	Solvent	Base	Yield^b/%
1^a	Et₃N	DMF	K₂CO₃	61
2	Et₃N	CH₃CN	K₂CO₃	50
3	Et₃N	Toluene	K₂CO₃	n.r.
4	Et₃N	CH₂Cl₂	K₂CO₃	20
5	Et₃N	CHCl₃	K₂CO₃	30
6	Et₃N	THF	K₂CO₃	n.r.
7	Et₃N	DMSO	K₂CO₃	20
8	Et₃N	DMF	Cs₂CO₃	Trace
9	Et₃N	DMF	Na₂CO₃	42
10	Et₃N	DMF	KHCO₃	52
11	Et₃N	DMF	CH₃COOK	49
12	Et₃N	DMF	DBU	Trace
13	Et₃N	DMF	DABCO	29
14	DMAP	DMF	K₂CO₃	Trace
15	DBU	DMF	K₂CO₃	Trace
16	DABCO	DMF	K₂CO₃	Trace
17	DIPEA	DMF	K₂CO₃	72
18	Ph₃N	DMF	K₂CO₃	80
19^c	Ph₃N	DMF	K₂CO₃	79
20^d	Ph₃N	DMF	K₂CO₃	Trace
21^e	Ph₃N	DMF	K₂CO₃	75

Table 1. Screening of addition reaction conditions for isatin (1a) and benzyl 2-(acetoxymethyl)buta-2,3-dienoate (2)

Scheme 2. Investigation of substrate scope in the addition reaction of isatins 1 with benzyl 2-(acetoxymethyl)buta-2,3-dienoate 2 Reaction conditions: isatin (1, 0.5 mmol), benzyl 2-(acetoxymethyl)buta-2,3-dienoate (2, 0.75 mmol), K2CO3 (0.5 mmol), Ph3N (0.10 mmol), temperature (25 ℃).

Scheme 3. Gram-scale experiment of addition reaction of isatin and benzyl 2-(acetoxymethyl)buta-2,3-dienoate

Scheme 4. Proposed mechanism

Scheme 5. Verification of reaction intermediate B

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胺催化靛红与联烯酸酯的加成反应合成烯炔基-3-羟基氧化吲哚

Amine-Catalyzed Addition Reaction of Isatins with Allenoates for the Synthesis of Enyne-Containing 3-Hydroxyoxindoles

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