通过猪肝酯酶催化的去对称化反应和光驱动的加氢脱羧反应合成手性3-环己烯-1-羧酸

doi:10.6023/cjoc202511007

有机化学 ›› 2026, Vol. 46 ›› Issue (6): 2474-2481.DOI: 10.6023/cjoc202511007 上一篇下一篇

研究论文

通过猪肝酯酶催化的去对称化反应和光驱动的加氢脱羧反应合成手性3-环己烯-1-羧酸

曹唱, 沈超仁, 李宗晗, 董开武^*()

华东师范大学化学与分子工程学院庄长恭研究所上海市绿色化学与化工过程绿色化重点实验室上海 200062

收稿日期:2025-12-23 修回日期:2026-01-29 发布日期:2026-02-11
通讯作者: 董开武
基金资助:
国家自然科学基金(22271094); 国家自然科学基金(22571086); 上海教育科技创新计划(2023ZKZD37); 中央高校基础科研资助项目

Synthesis of Enantioenriched 3-Cyclohexene-1-carboxylic Acid via Porcine Liver Esterase-Catalyzed Desymmetrization and Photo-Driven Hydrodecarboxylation

Chang Cao, Chaoren Shen, Zonghan Li, Kaiwu Dong^*()

Shanghai Key Laboratory of Green Chemistry and Chemical Processes, Chang-Kung Chuang Institute, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062

Received:2025-12-23 Revised:2026-01-29 Published:2026-02-11
Contact: Kaiwu Dong
Supported by:
National Natural Science Foundation of China(22271094); National Natural Science Foundation of China(22571086); Innovation Program of Shanghai Municipal Education Commission(2023ZKZD37); Fundamental Research Funds for the Central Universities

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摘要/Abstract

具有光学活性的3-环己烯-1-羧酸是存在于多种药物中的重要结构单元. 以易获取的1,2,3,6-四氢邻苯二甲酸酐为原料, 通过猪肝酯酶催化的去对称化反应与光驱动加氢脱羧反应的组合, 发展了一种具有高对映体选择性制备3-环己烯-1-羧酸的催化合成. 实验与理论计算研究揭示了吖啶类光敏剂9-位的空间位阻与4-环己烯-1,6-二甲酸单甲酯加氢脱羧效果之间的关联.

关键词: 吖啶类光敏剂, 加氢脱羧反应, 猪肝酯酶

Optically active 3-cyclohexen-1-carboxylic acid is a prevalent structural unit in various pharmaceuticals. Herein, by utilizing porcine liver esterase-catalyzed desymmetrization and photo-driven hydrodecarboxylation, an unpresented cataly- tic asymmetric method for obtaining enantioenriched 3-cyclohexen-1-carboxylic acid from readily available 1,2,3,6-tetra- hydrophthalic anhydride was developed. Through experimental and computational investigations, the correlation between the steric hindrance at the 9-position of the acridine photosensitizer and the effect of hydrodecarboxylation of 4-cyclohexene- 1,6-dimethanoic acid monomethyl ester was revealed.

Key words: acridine photosensitizer, hydrodecarboxylation, porcine liver esterase

引用此文

曹唱, 沈超仁, 李宗晗, 董开武. 通过猪肝酯酶催化的去对称化反应和光驱动的加氢脱羧反应合成手性3-环己烯-1-羧酸[J]. 有机化学, 2026, 46(6): 2474-2481.

Chang Cao, Chaoren Shen, Zonghan Li, Kaiwu Dong. Synthesis of Enantioenriched 3-Cyclohexene-1-carboxylic Acid via Porcine Liver Esterase-Catalyzed Desymmetrization and Photo-Driven Hydrodecarboxylation[J]. Chinese Journal of Organic Chemistry, 2026, 46(6): 2474-2481.

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图/表 8

Scheme 1. Photo-driven hydrodecarboxylative synthesis of optically active methyl 3-cyclohexene-1-carboxylate (CHCM)

Figure 1. The response surface showing the effect of photosensitizer and thiophenol on the photo-driven hydrodecarboxylation. Green spheres with numbers on the left side represent the predicted yields. Blue cube with numbers on the right side represent the measured values

Entry	Deviation from standard conditions^a	Yield^b/%
1	None	79
2	w/o H₂O	75
3	CHD instead of H₂O	27
4	MeCN instead of CH₂Cl₂/H₂O	61
5	THF instead of CH₂Cl₂/H₂O	9
6	(CF₃)₂CHOH instead of CH₂Cl₂/H₂O	<5
7	365 nm instead of 395 nm	62
8	460 nm instead of 395 nm	39
9	n-PrSH instead of 4-FC₆H₄SH	8
10	(PhS)₂ instead of 4-FC₆H₄SH	65
11	TRIPSH instead of 4-FC₆H₄SH	67
12	L-cysteine instead of 4-FC₆H₄SH	11
13	Open atmosphere	0
14	w/o 9-(2-chlorophenyl)acridine	0
15	w/o 4-FC₆H₄SH	<5
16	w/o light	0

Table 1. The effects of conditions variation.

Scheme 1. Evaluation of different 9-position substituted acridine-type photocatalysts Reaction conditions: 1a (0.2 mmol, 1.0 equiv.), PC (10 mol%), 4-FC6H4SH (20 mol%), CH2Cl2/H2O (V/V=19/1, 1 mL), r.t., 24 h, 30-W 395-nm LEDs, N2 atmosphere. The yields were determined by calibrated GC with n-tridecane as the internal standard. In the parentheses are the values of percent buried volume (VBur/%) at the C9 position of 9-substituted acridine. In the cases of 2t~2v, the VBur/% is the average value of two independent conformers. The VBur/% of independent conformers are given in the square brackets.

Figure 2. Performances of 9-position substituted acridine-type photosensitizers with different VBur/%

Scheme 2. Decarboxylative hydrogenation of carboxylic acidsa a Reaction conditions: carboxylic acid 3 (0.2 mmol, 1.0 equiv.), 9-(2-(trifluoromethyl)phenyl)acridine (10 mol%), 4-FC6H4SH (20 mol%), CH2Cl2/H2O (V/ V = 19/1, 1 mL), r.t., 24 h, 395-nm LEDs (30 W), N2 atmosphere. b Determined by calibrated GC with n-tridecane as the internal standard. c Determined by 1H NMR using 1,3,5-trimethoxybenzene as the internal standard

Figure 3. (a) Stern-Volmer plot for fluorescence quenching of 9-(2-chlorophenyl)acridine with substrate 1a or 4-FC6H4SH (solutions were irradiated at 315 nm, and the fluorescence was recorded at 450 nm); (b) Variation of Stern-Volmer constant (KSV) depending on the temperature

Scheme 3. Proposed plausible reaction mechanism

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通过猪肝酯酶催化的去对称化反应和光驱动的加氢脱羧反应合成手性3-环己烯-1-羧酸

Synthesis of Enantioenriched 3-Cyclohexene-1-carboxylic Acid via Porcine Liver Esterase-Catalyzed Desymmetrization and Photo-Driven Hydrodecarboxylation

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