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

Abstract

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.

Keywords: aza-1,6-dienes; density functional calculations; organic dyes; silylative cyclization; visible light.