Stereoselective Synthesis of gem‐Difluoromethylenated Linear Azatriquinanes

Abstract

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.