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0 26060227 - 26060227

DOI: https://doi.org/10.6023/A26060227

Article

Photocatalytic Cyanomethyl Radical-Involved Tandem Cyclization Reaction

  • Bao Deyu ,
  • Chen Caiping ,
  • Pan Jutong ,
  • Zhou Bingjie ,
  • Yang Hui ,
  • Li Kangkui ,
  • Zhou Yongyun ,
  • Fan Baomin
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  • aSchool of Chemistry and Environment, Yunnan Key Laboratory of Chiral Functional Substance Research and Application,Yunnan Minzu University, Kunming 650504, China;
    bSchool of Ethnic Medicine, Key Laboratory of Chemistry in Ethnic Medicinal Resources, Ministry of Education, Yunnan Minzu University, Kunming 650504, China;
    cSchool of Science, Sichuan Engineering Research Center of Molecular Targeted Diagnostic & Therapeutic Drugs, Xihua University, Chengdu 610039, China

Received date: 2026-06-29

  Online published: 2026-08-25

Supported by

Project supported by Project supported by the National Natural Science Foundation of China (No. 22501244), the Yunnan Province Science and Technology Department (Nos. 202402AN360010, 202401BC070018, 202605AF350008), the Yunnan Provincial Department of Education Science Research Fund Project (No. 2025J0473) and the Opening Project of Sichuan Engineering Research Center for Molecular Targeted Diagnostic & Therapeutic Drug (No. XFZBXZLYW2025-003).

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Abstract

Benzocyclonone structures, represented by 4-chromanone and 1-indanone, are widely found in natural compounds and pharmaceuticals with important biological activities. Since cyano modification is an important strategy for structural modification and optimization in medicinal chemistry, the introduction of a cyano group into these structures is of great significance. Radical-driven cascade cyclization reactions have been developed as an effective means to build benzocyclones bearing various functional groups. However, existing methods for synthesizing cyanated 4-chromanone and 1-indanone are limited and often require harsh conditions. In this study, bromoacetonitrile was employed both as a radical precursor and a cyano source to develop an efficient photocatalytic radical cascade cyclization method for constructing cyano-substituted benzocyclonones. Under mild photocatalytic conditions, bromoacetonitrile generates a cyanomethyl radical that initiates a two-step addition and cyclization with 2-(allyloxy) aromatic aldehydes or its analogues, enabling the effective synthesis of cyano-modified 4-chromanone, 1-indanone, and dihydroquinolone derivatives. This reaction system demonstrates a wide substrate scope and enables the rapid construction of these structures under uniform standard conditions. Meanwhile, it shows good tolerance for various functional groups. Substrates containing iodine, bromine, ester, and sulfonyl groups all successfully undergo the desired transformations, producing target products in moderate to good yields. Notably, compared to previously used cyanide sources like trimethylsilyl cyanide and diazo compounds, bromoacetonitrile is safer and more readily accessible. Mechanistic investigations suggest the reaction proceeds through the addition of a cyanomethyl radical to a carbon-carbon double bond, forming an alkyl radical, which then undergoes intramolecular addition to the carbonyl group to create an oxygen radical intermediate. This intermediate undergoes an intramolecular 1,2-hydrogen atom transfer (1,2-HAT), which is then followed by single-electron oxidation and deprotonation, resulting in the final desired cyclization product. Overall, this research provides a mild and efficient method for simultaneously constructing benzocyclonone and performing cyano-modification, which is expected to advance the synthesis and discovery of related bioactive molecules.

Key words： photocatalysis; radical cyclization; bromoacetonitrile; cyanomethylation; 4-chromanone

Cite this article

Bao Deyu , Chen Caiping , Pan Jutong , Zhou Bingjie , Yang Hui , Li Kangkui , Zhou Yongyun , Fan Baomin . Photocatalytic Cyanomethyl Radical-Involved Tandem Cyclization Reaction[J]. Acta Chimica Sinica, 0 : 26060227 -26060227 . DOI: 10.6023/A26060227

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