Synthesis of 1,6-Dihydropyridine-3-carbonitrile Derivatives via Lewis Acid-Catalyzed Annulation of Propargylic Alcohols with (E)-3-Amino-3-phenylacrylonitriles

J Org Chem. 2020 Aug 7;85(15):9863-9875. doi: 10.1021/acs.joc.0c01171. Epub 2020 Jul 24.

Abstract

A novel Lewis acid-catalyzed, highly efficient, practical, and atom-economical protocol for the synthesis of functionalized 1,2-dihydropyridine-3-carbonitrile derivatives in the presence of Bi(OTf)3 (10 mol %) in tetrahydrofuran (2.0 mL) at 80 °C for 8 h in air is described, starting from readily accessed propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles. This cycloaddition protocol, which is scalable and proceeds under mild conditions, is amenable to the gram-scale construction of valuable 1,2-dihydropyridine-3-carbonitriles. Furthermore, the good functional group compatibility and broad scope of this strategy were demonstrated by a broad range of propargylic alcohols and (E)-3-amino-3-phenylacrylonitriles, with yields ranging from 34 to 96%.