Synthesis of Isochromanes and Isothiochromanes Bearing Fluorinated One-Carbon Units via Intramolecular Cyclizations of ortho-Substituted α-(Trifluoromethyl)styrenes

Abstract

α-(Trifluoromethyl)styrenes bearing a nucleophilic oxygen or sulfur atom tethered by a methylene or methyne unit at the ortho carbon were prepared by the coupling reaction of 2-bromo-3,3,3-trifluoropropene with aryl iodides via (3,3,3-trifluoroprop-1-en-2-yl)boronic acid. The styrenes thus obtained readily undergo an intramolecular nucleophilic addition or substitution (SN2'-type) of the oxygen and sulfur under basic conditions, leading to 4-trifluoromethyl- or 4-difluoromethylene-substituted isochromanes and isothiochromanes, respectively.