New method for the preparation of some 2′- and 3′-trifluoromethyl-2′,3′-dideoxyuridine derivatives

Reaction of 5'-O-dimethoxytrityl-3'-oxo-2'-O-trimethylsilylethoxymethyluridine (2) and 5'-O-dimethoxytrityl-3'-oxo-3'-0trimethylsilylethoxymethyluridine (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). (C) 1999 Elsevier Science Ltd. All rights reserved.