Stereoselective Synthesis of gem-Difluoromethylenated Linear Azatriquinanes

The stereoselective synthesis of gem-difluoromethylenated linear azatriquinanes is described herein. The fluoride-catalyzed nucleophilic addition of PhSCF₂SiMe₃ (1), exploited as a gem-difluoromethylene (-CF₂-) building block, to chiral phthalimide 2 provided the corresponding gem-difluoromethylenated adduct 3 in high yield as a diastereomeric mixture. The stereoselective intramolecular radical cyclization of 3 furnished chiral linear azatriquinanes 4, the hydroxy group of which subsequently underwent nucleophilic substitution by organosilanes to provide 5 with high stereoselectivity. Treatment of 5 with Grignard reagents or a reducing agent provided a collection of chiral gem-difluoromethylenated linear azatriquinanes 6–8.