Diastereoselective Synthesis of Polysubstituted Piperidines through Visible‐Light‐Driven Silylative Cyclization of Aza‐1,6‐Dienes: Experimental and DFT Studies

• Published in: Chemistry : a European journal 2019-12, Vol.25 (72), p.16506-16510
• Main Authors: Cui, Wei‐Chen, Zhao, Wenxuan, Gao, Ming, Liu, Wei, Wang, Shaozhong, Liang, Yong, Yao, Zhu‐Jun
• Format: Article
• Language: English
• Subjects: Acrylonitrile; aza-1,6-dienes; Chemistry; Cyano groups; density functional calculations; Dienes; Electrons; Hydrogen bonding; organic dyes; Piperidine; silylative cyclization; Stereoselectivity; Synthesis; visible light
• ISSN: 0947-6539; 1521-3765
• DOI: 10.1002/chem.201903440

A visible‐light‐driven radical silylative cyclization of aza‐1,6‐dienes featuring an acrylonitrile or acrylate moiety and an electron‐neutral olefin was developed, which allows for stereoselective synthesis of densely functionalized piperidines in a highly atom‐economical manner. Depending on the substitution pattern of the electron‐neutral olefin, poor‐to‐excellent diastereoselectivity was observed. It was suggested that the 6‐exo‐trig cyclization was initiated by a chemoselective addition of silyl radical toward electron‐deficient olefin and the geometry of the remaining olefin is closely associated with the cis‐stereoselectivity. DFT calculations supported that a transition state with a cyano group locating at the axial position of the forming piperidine ring might be involved, in which either the increase of 1,3‐diaxial repulsion or the lack of hydrogen bonding interaction will diminish diastereoselectivity. cis‐Stereoselectivity of polysubstituted piperidines was observed in a visible‐light‐driven 6‐exo‐trig radical silylative cyclization of aza‐1,6‐dienes. DFT calculations supported that a transition state with an axial cyano group is involved.