Ni‐Catalyzed Enantioselective Difunctionalization of Alkynes to Azepine Derivatives Bearing a Quaternary Center and an Unprotected Imine

• Published in: Chinese journal of chemistry Vol. 42; no. 8; pp. 873 - 878
• Main Authors: Long, Jian, Lu, Zhiwu, Li, Xiao‐Lin, Xue, Peng, Liu, Wen‐Bo
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY‐VCH Verlag GmbH & Co. KGaA 15.04.2024; Wiley; Wiley Subscription Services, Inc
• Subjects: Alkyne functionalization; Alkynes; Asymmetric catalysis; Chemistry; Chemistry, Multidisciplinary; Enantiomers; Functional groups; Nickel; N‐Heterocycles; Physical Sciences; Quaternary centers; Science & Technology; Synthesis; CYCLOADDITION; Alkyne functionalization; N-Heterocycles; VINYL AZIRIDINES; MECHANISM; Quaternary centers; STEREOCHEMISTRY; Nickel; ASYMMETRIC HYDROGENATION; Asymmetric catalysis
• ISSN: 1001-604X; 1614-7065
• DOI: 10.1002/cjoc.202300647

Comprehensive Summary The azepine ring is a prominent structural scaffold in biologically significant molecules. In this study, we present a Ni(II)‐catalyzed asymmetric difunctionalization of alkynes, involving intermolecular regioselective arylation and intramolecular nitrile addition, enabling the synthesis of enantioenriched azepine derivatives. This reaction simultaneously installs an all‐carbon quaternary stereocenter and introduces an unprotected imine functionality, showing great promise for subsequent transformations. The reaction exhibits good tolerance toward various functional groups, resulting in high yields and enantioselectivities. The synthetic utility of this methodology is further demonstrated through gram‐scale synthesis and product derivatization. This research offers an efficient approach to the synthesis of seven‐membered nitrogen heterocycles. A Ni(II)‐catalyzed asymmetric difunctionalization of alkynes is reported. This method involves intermolecular regioselective arylation of the alkynes and intramolecular desymmetrization of dinitriles, enabling the synthesis of enantioenriched azepine derivatives. The reaction exhibits good tolerance toward various functional groups, resulting in high yields and enantioselectivities.