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Divergent asymmetric synthesis of azaarene-functionalized cyclic alcohols through stereocontrolled Beckwith-Enholm cyclizations

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Abstract

The first enantioselective Beckwith-Enholm cyclization reaction is reported herein. Under cooperative photoredox and chiral hydrogen-bonding catalysis mediated by visible light, cyclization of carbonyls with azaarene-based olefins as a new reaction system offers a general and divergent synthetic pathway to furnish a variety of highly valuable enantioenriched azaarene-functionalized carbocyclic and heterocyclic alcohols, which bear adjacent 1,2- or nonadjacent 1,3-stereocentres on distinct cyclic frameworks, in high yields and enantio- and diastereoselectivities. The good compatibility of various azaarenes and carbonyls as well as the diversity of cyclic structures of the products underscores the generality of the catalysis platform. In addition to the ability to precisely introduce deuterium into molecules in an enantioselective manner, the considerable synthetic value of this method includes the excellent antioxidant stress potential of the products. In particular, molecule 29 was determined to be a promising lead compound for antioxidant stress drug design.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (21925103, 21901062), Key Technologies R&D Program of Henan (202102310005), Henan Normal University and Henan University.

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. International Scientific and Technological Cooperation Base of Chiral Chemistry, Henan University, Kaifeng, 475004, China

    Zhanghong Guo, Xiaowei Chen, Hao Fang, Xiaowei Zhao & Zhiyong Jiang

  2. School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang, 453007, China

    Zhiyong Jiang

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  1. Zhanghong Guo
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  2. Xiaowei Chen
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  3. Hao Fang
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  4. Xiaowei Zhao
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Correspondence to Xiaowei Zhao or Zhiyong Jiang.

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Divergent asymmetric synthesis of azaarene-functionalized cyclic alcohols through stereocontrolled Beckwith-Enholm cyclizations

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Guo, Z., Chen, X., Fang, H. et al. Divergent asymmetric synthesis of azaarene-functionalized cyclic alcohols through stereocontrolled Beckwith-Enholm cyclizations. Sci. China Chem. 64, 1522–1529 (2021). https://doi.org/10.1007/s11426-021-1019-2

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