Regio-reversed [3＋2] Cycloaddition of Triketone Enones with Nitrones

doi:10.6023/cjoc202507022

Chinese Journal of Organic Chemistry ›› 2026, Vol. 46 ›› Issue (1): 146-155.DOI: 10.6023/cjoc202507022 Previous Articles Next Articles

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三酮烯烃与硝酮的反常区域选择性[3＋2]环加成反应研究

韩天娇^b, 师迁迁^a^,^*(), 符运栋^a^,^*(), 梅光建^b^,^*()

^a 河南师范大学抗病毒性传染病创新药物全国重点实验室平原实验室河南新乡 453007
^b 郑州大学化学学院平原实验室郑州 450001

收稿日期:2025-07-15 修回日期:2025-08-26 发布日期:2025-09-17
通讯作者: 师迁迁, 符运栋, 梅光建
基金资助:
国家自然科学基金(22371265); 国家自然科学基金(22403027); 河南省自然科学基金(232301420047); 河南省自然科学基金(222300420084)

Regio-reversed [3＋2] Cycloaddition of Triketone Enones with Nitrones

Han Tianjiao^b, Shi Qianqian^a^,^*(), Fu Yundong^a^,^*(), Mei Guangjian^b^,^*()

^a State Key Laboratory of Antiviral Drugs, Pingyuan Laboratory, Henan Normal University, Xinxiang, Henan 453007
^b College of Chemistry and Pingyuan Laboratory, Zhengzhou University, Zhengzhou 450001

Received:2025-07-15 Revised:2025-08-26 Published:2025-09-17
Contact: Shi Qianqian, Fu Yundong, Mei Guangjian
Supported by:
National Natural Science Foundation of China(22371265); National Natural Science Foundation of China(22403027); Natural Science Foundation of Henan Province(232301420047); Natural Science Foundation of Henan Province(222300420084)

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Abstract

Triketone alkenes represent a class of highly electron-deficient unsaturated carbonyl compounds and serve as important and versatile synthetic building blocks. In previous work, triketone enones usually undergo β-selective conjugate addition or cycloaddition. It is challenging to achieve regio-reversed conjugate addition or cycloaddition of triketone enones. Based on previous work, regio-reversed [3＋2] cycloaddition of triketone enones with nitrones was achieved, and a series of isoxazolidines were synthesized effectively and stereoselectively under catalyst-free conditions, with up to 95% yield and 20∶1 dr. It exhibits green properties, easy operation and a wide substrate range, offering a reference for isoxazolidine synthesis. Density functional theory (DFT) study reveals that this regio-reversed [3＋2] cycloaddition is energetically favorable.

Key words: triketone enone, nitrone, reversed regioselectivity, cycloaddition

Cite this article

Han Tianjiao, Shi Qianqian, Fu Yundong, Mei Guangjian. Regio-reversed [3＋2] Cycloaddition of Triketone Enones with Nitrones[J]. Chinese Journal of Organic Chemistry, 2026, 46(1): 146-155.

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Fig. & Tab. 6

Scheme 1. Regio-reversed [3＋2] cycloaddition of triketone enones with nitrones

Entry	Solvent	Time/h	Temp./℃	Yield^b/% of 3a/4a	dr^c of 3a
1	Toluene	12	r.t.	25/0	>20∶1
2	CH₃CN	12	r.t.	N.D.	—
3	DCM	12	r.t.	N.D.	—
4	THF	12	r.t.	N.D.	—
5	Toluene	12	60	72/0	>20∶1
6	Toluene	12	70	88/0	>20∶1
7	Toluene	12	80	88/0	>20∶1
8	Toluene	18	80	90/0	>20∶1
9	Toluene	24	80	91/0	>20∶1

Table 1. Optimization of reaction condition

Scheme 2. Substrate scopes of triketone enones

Scheme 3. Substrate scopes of nitrones

Figure 1. X-ray single crystal diffraction of (±)-3i

Figure 2. Relative Gibbs free energy profiles for the different pathways

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三酮烯烃与硝酮的反常区域选择性[3＋2]环加成反应研究

Regio-reversed [3＋2] Cycloaddition of Triketone Enones with Nitrones

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Fig. & Tab. 6

References 34

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