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2026 26070252

DOI: https://doi.org/10.6023/A26070252

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光/氮杂环卡宾协同催化苄位碳氢不对称氧酰化反应★

  • 李曹波 ,
  • 李志成 ,
  • 高中华 ,
  • 叶松
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  • a北京分子科学国家研究中心, 中国科学院分子识别与功能重点实验室, 中国科学院化学研究所, 北京 100190;
    b中国科学院大学 化学科学学院 北京 100049
★不对称协同催化”专辑

收稿日期: 2026-07-17

  网络出版日期: 2026-08-19

基金资助

国家自然科学基金(Nos. 22571305, 22471277)资助.

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Cooperative Photoredox and N-Heterocyclic Carbene Catalysis for Enantioselective Benzylic C-H Oxyacylation

  • Li Cao-Bo ,
  • Li Zhi-Cheng ,
  • Gao Zhong-Hua ,
  • Ye Song
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  • aBeijing National Laboratory for Molecular Sciences, CAS Key Laboratory of Molecular Recognition and Function, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190;
    bSchool of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049

Received date: 2026-07-17

  Online published: 2026-08-19

Supported by

National Natural Science Foundation of China (Nos. 22571305 and 22471277).

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摘要

手性α-芳基羧酸是一类常见的结构单元, 也是许多药物分子发挥药效功能的关键基团. 其手性制备制备通常依赖不对称过渡金属催化. 本文报道通过光/氮杂环卡宾协同催化实现的苄位碳氢不对称氧酰化反应. 该反应能以中等到良好的产率和较为优异的对映选择性制备一系列手性α-芳基酯类化合物, 可作为手性α-芳基羧酸的前体, 为这类重要的活性骨架提供了原子经济性更高的合成新途径. 在这一反应中, 光催化诱导产生高活性的自由基物种, 卡宾催化调控反应的对映选择性, 两种催化模式起到了很好的协同作用.

关键词： 氮杂环卡宾催化; 光催化; 协同催化; 对映选择性; 氧酰化反应

本文引用格式

李曹波 , 李志成 , 高中华 , 叶松 . 光/氮杂环卡宾协同催化苄位碳氢不对称氧酰化反应★[J]. 化学学报, 2026 : 26070252 . DOI: 10.6023/A26070252

Abstract

Chiral α-aryl carboxylic acids are a common structural motif and serve as the key pharmacophore in many drug molecules. Traditional methods for constructing such chiral structures typically rely on asymmetric transition-metal catalysis. In this communication, we report an asymmetric benzylic C-H oxyacylation reaction enabled by cooperative photoredox and N-heterocyclic carbene (NHC) catalysis. This reaction affords a series of chiral α-aryl esters in moderate to good yields with high enantioselectivities. These chiral esters could serve as precursors for α-aryl carboxylic acids, providing a more atom-economical synthetic route to this important class of bioactive frameworks. A plausible mechanism was proposed for this reaction: First, the free NHC adds to diethyl pyrocarbonate to form the corresponding acyl azolium intermediate, while the excited-state photosensitizer oxidizes the alkyl arene substrate to generate the aryl radical cation intermediate, which subsequently forms benzyl radical under basic conditions; Then, the acyl azolium intermediate was reduced by the reduced-state photosensitizer to give the corresponding ester radical, which then couples with the benzyl radical to form the zwitterionic intermediate; Finally, the zwitterionic intermediate releases the target product and regenerates the NHC catalyst to complete the catalytic cycle. In this reaction, photocatalysis generates highly active radical species, while NHC catalysis controls the enantioselectivity, with the two catalytic modes working in excellent synergy. A representative procedure is described as follows. To an oven-dried 4-mL vial equipped with a magnetic stirring bar was charged with alkylarene 1 (0.2 mmol, 1 equiv.), diethyl pyrocarbonate 2a (0.8 mmol, 4.0 equiv.) and the NHC F (0.04 mmol, 20 mol%), K2CO3 (0.3 mmol, 1.5 equiv.), photocatalyst PC3 (Ir[dFCF3ppy]2[bpy]PF6) (0.004 mmol, 2 mol%). The tube was evacuated and backfilled with N2 for three times. To this mixture was added dry CH3CN (3 mL) and stirred at room temperature under blue LED irradiation for 24 h. The reaction mixture was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel to give the desired product 3.

Key words： N-heterocyclic carbene catalysis; photocatalysis; cooperative catalysis; enantioselectivity; oxyacylation reaction

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