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

• Published in: Science China. Chemistry 2021-09, Vol.64 (9), p.1522-1529
• Main Authors: Guo, Zhanghong, Chen, Xiaowei, Fang, Hao, Zhao, Xiaowei, Jiang, Zhiyong
• Format: Article
• Language: English
• Subjects: Alcohol; Alcohols; Alkenes; Antioxidants; Carbonyls; Catalysis; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Deuterium; Enantiomers; Hydrogen bonding; Lead compounds; Light emitting diodes; NMR; Nuclear magnetic resonance
• ISSN: 1674-7291; 1869-1870
• DOI: 10.1007/s11426-021-1019-2

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.