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Gold-catalyzed carbocyclization and imidization of alkyne-tethered diazo compounds with nitrosoarenes for the synthesis of nitrones and naphthalene derivatives

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Abstract

A gold-catalyzed carbocyclization/imidization cascade reaction has been developed,leading a facile access to the synthesis of functionalized nitrones in moderate to good yields under mild conditions. The reaction initiated by a catalytic 6-endo-dig diazo-yne carbocyclization to form the key endocyclic vinyl carbene from alkyne-tethered diazo compounds, followed by addition with nitrosoarenes that features an imidization process. Notably, these resulting nitrone products could be smoothly converted into different substituted naphthalenol analogues, such as 4-aminonaphthalen-1-ol, naphthalene-1,4-dione, and naphthalene-1,4-diol derivatives, in high yields. Moreover, the generated products exhibited potential tumor suppression activity in tested cancer celllines; compound 3c (HCT116 cells, IC50 = 7.41 μM; MCF-7 cells, IC50 = 14.28 μM) exhibits higher anticancer potency than other tested compounds.

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Acknowledgements

Support for this research from the National Natural Science Foundation of China (21971262, 81973176), Guangdong Provincial Keylaboratory of Chiral Molecule and Drug Discovery (2019B030301005), The Program for Guangdong Introducing Innovative and Entrepreneurial Teams (No. 2016ZT06Y337) is greatly acknowledged.

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Authors and Affiliations

  1. Guangdong Provincial Keylaboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China

    Mengting Liu, Xiongda Xie, Ming Bao, Zhijing Zhang, Wenhao Hu, Yu Qian & Xinfang Xu

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  1. Mengting Liu
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Correspondence to Xinfang Xu.

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Liu, M., Xie, X., Bao, M. et al. Gold-catalyzed carbocyclization and imidization of alkyne-tethered diazo compounds with nitrosoarenes for the synthesis of nitrones and naphthalene derivatives. Mol Divers 27, 1971–1978 (2023). https://doi.org/10.1007/s11030-022-10530-5

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