New Method for the Preparation of Some 2′- and 3′-Trifluoromethyl-2′,3′-dideoxyuridine Derivatives

Reaction of 5′-O-dimethoxytrityl-2′-oxo-3′-O-trimethylsilylethoxymethyluridine (2) and 5′-O-dimethoxytrityl-3′-oxo-2′-O-trimethylsilylethoxymethyluridine (10), with bromodifluoromethyl[tris(dimethylamino)]phosphonium bromide and zinc gave the corresponding 2′- and 3′-difluoromethylene derivatives 3 and 11. Attempted removal of the 3′- and 2′-O-trimethylsilylethoxymethyl (SEM) groups from compounds 3 and 11, with tetrabutylammonium fluoride in tetrahydrofuran (THF), resulted in fluorination at the unsaturated difluoromethylene carbon with loss of the SEM group and formation of hitherto unreported 2′,3′-didehydro-2′,3′-dideoxy-5′-O-dimethoxytrityl-2′-trifluoromethyluridine (5) and 2′,3′-didehydro-2′,3′-dideoxy-5′-O-dimethoxytrityl-3′-trifluoromethyluridine (13). Detritylation of 5 and 13 gave 2′,3′-didehydro-2′,3′-dideoxy-2′ (3′)-trifluoromethyluridines 6 and 14. Finally, hydrogenation of 5 and 13 followed by detritylation provided 2′,3′-dideoxy-2′-trifluoromethyluridine (8a) and 2′,3′-dideoxy-3′-trifluoromethyluridine (16a).