The design and synthesis of gem-difluorinated sugar nucleosides were described. The key intermediate, 3-deoxy-3,3-difluoro-d-arabinofuranose 9, was first stereoselectively prepared from the chiral gem-difluorohomoallyl alcohol 12. The kinetic formation of single anti-14 in the benzylation of 12 could be accomplished by controlling the amount of sodium hydride used. The dihydroxylation of 14 (a mixture of anti and syn isomers) followed by deprotection and oxidation stereoselectively afforded furanose 9 with the arabino configuration at the C2 position. N(1)-(3-Deoxy-3,3-difluoro-beta-D-arabinofuranosyl)cytosine 6 was prepared from 9 by the glycosylation reaction. 4'-Thiofuranose 25 was easily synthesized from 9. The oxidation of 25 followed by the condensation with silylated N(4)-benzoylcytosine (Pummerer reaction) failed to give our desired protected nucleoside l-3'-deoxy-3',3'-difluoro- 4'-thiocytidine 27', but the regioisomer 27 was obtained. The regiochemistry of the Pummerer reaction was determined by the kinetic acidity of the alpha-proton of 4'-thiofuranose 25.

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Bis(tributyltin)-initiated atom transfer cyclization reactions of 3-butenyl iodoalkanoates in the presence of BF3.OEt2 as the catalyst afforded the 6-exo cyclization products as a mixture of 3,4-cis- and trans-substituted tetrahydro-2H-pyran-2-ones in 53-71% yield with the major isomers being the cis ones. Ab initio calculations at the B3LYP/6-31G level on the transition states of the radical cyclization and on the cyclized products revealed that the reactions are kinetically controlled and the transition states for the 6-exo radical cyclization are in boat conformations. Moreover, the cis-oriented transition states are of lower energy than the corresponding trans-oriented ones, which are in excellent agreement with experimental results.