可见光诱导的α-三氟甲基烯烃与芳香酸酐的脱氟酰化反应

doi:10.6023/A25060238

摘要/Abstract

报道了一种在可见光诱导下, 利用芳香酸酐的酰基自由基与α-三氟甲基烯烃进行二氟烯基化的新策略. 该方法以廉价易得的芳香酸酐为酰基源, 在温和条件下通过蓝光照射实现酰基自由基的原位生成, 展现出优异的官能团兼容性和宽泛的底物普适性(32个实例, 最高产率82%). 另外, 酸酐上取代基的电子性质(吸电子基团促进C—O键断裂)和空间位阻(影响区域选择性)是调控反应选择性的关键因素. 机理研究表明, 可见光引发的单电子转移在自由基链的激活中起关键作用, 并通过自由基/极性交叉过程成功构建了γ,γ-二氟烯丙基酮. 放大试验和后修饰验证了该方法的实用性, 预示其在有机合成中具有广阔的应用前景.

关键词: 可见光诱导, α-三氟甲基烯烃, 酸酐, β-氟消除, 脱氟酰化, γ,γ-二氟烯丙基酮

Fluorine-containing organic molecules offer beneficial biological activity, lipophilicity, and metabolic stability. Among these, gem-difluoroalkenes are known for their distinctive structures and wide-ranging uses in biology, medicine, and agriculture. As important synthetic building blocks, converting them into various functionalized compounds attracts significant scientific interest. Recent progress has focused on innovative methods for synthesizing gem-difluoroalkenes, especially through C—F bond activation of α-trifluoromethyl alkenes. This study introduces a new defluorinative difluoroalkenylation reaction that uses acyl radicals from readily available, cost-effective aromatic carboxylic anhydrides. Under visible-light irradiation, these anhydrides react with α-trifluoromethyl alkenes to produce γ,γ-difluoroallylic ketones. The optimized procedure employs 4CzIPN as the photocatalyst, Cs₂CO₃ as the base, PPh₃ as the reductant, and N,N-dimethylformamide (DMF) as the solvent, with blue light emitting diode (LED) light. This gentle, in situ formation of acyl radicals shows excellent tolerance for various functional groups and works with a broad range of substrates (32 examples, up to 82% yield). Additionally, mechanistic studies show that the electronic and steric properties of substituents on asymmetric anhydrides influence selectivity; electron-withdrawing groups promote C—O bond cleavage, while steric hindrance determines regioselectivity. Importantly, this method avoids the use of transition metals and ligands, reducing steps and costs. Scale-up experiments confirmed its potential for practical applications, including late-stage functionalization. Mechanistic insights suggest visible-light-induced single-electron transfer in radical chain activation and a radical/polar crossover process. This straightforward and eco-friendly approach efficiently synthesizes γ,γ-difluoroallylic ketones by breaking C—O and C—F bonds.

Key words: visible-light-induced, α-trifluoromethyl alkenes, anhydrides, β-fluorine eliminating, defluorinative acylation, γ,γ-difluoroallylic ketones

引用此文

苏秦, 雷平, 王栋, Shahid Ali Khan, 阿布拉江•克依木. 可见光诱导的α-三氟甲基烯烃与芳香酸酐的脱氟酰化反应[J]. 化学学报, 2025, 83(11): 1372-1378.

Su Qin, Lei Ping, Wang Dong, Shahid Ali Khan, Ablajan Keyume. Visible-Light-Induced Defluorinative Acylation of α-Trifluoromethyl Alkenes with Aromatic Carboxylic Anhydrides[J]. Acta Chimica Sinica, 2025, 83(11): 1372-1378.

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图/表 8

图1. 具有偕二氟烯烃骨架的生物活性分子

Figure 1. Bioactive pharmaceuticals with gem-difluoroalkene molecules

图2. 偕二氟烯烃的合成方法

Figure 2. Methods for the synthesis of gem-difluoroalkenes

Entry	Variations from standard conditions	Yield^b/%
1	None	82
2	Ir[dF(CF₃)ppy]₂(dtbbpy)PF₆ or Eosin Y was used	43, 16
3	Ru(bpy)₃Cl₂ was used	N.R.
4	DBU or DIPEA was used	46, 50
5	NaHCO₃ or K₂CO₃ was used	36, 38
6	EA, MeOH, DCE or DMSO was used	34, Trace, 33, 30
7	Addition 4 Å molecular sieves	64
8	No PC, or no Cs₂CO₃	trace
9	No light, or no Ph₃P	N.R.
10	Under air	N.R.
11	λ=390~395 nm	69

表1. 反应条件优化a

Table 1. Conditions optimization

图3. 底物范围

Figure 3. Substrate scope a Reaction conditions: 1a~1v (0.3 mmol), 2a~2j (0.6 mmol), 4CzIPN (0.009 mmol), PPh3 (0.45 mmol), and Cs2CO3 (0.15 mmol) in DMF (3 mL) under 10 W blue LED light, under nitrogen atmosphere at room temperature for 12 h; the ratio of product 3 or 4 to byproduct 5 is given in parentheses, determined by 19F NMR. b Isolated yield.

图4. 光催化芳基酸酐脱羰酰基化反应的选择性研究

Figure 4. Study on the selectivity of photocatalytic decarbonylation of aryl anhydrides

图5. γ,γ-二氟烯丙基酮的按比例放大合成及其应用

Figure 5. Proportional enlargement of the synthesis of γ,γ-difluoroallyl ketones and their applications

图6. 机理研究

Figure 6. Mechanistic studies

图7. 可能的反应机理

Figure 7. Plausible reaction mechanism

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