Ring Opening of 4‘,5‘-Epoxynucleosides: A Novel Stereoselective Entry to 4‘-<i>C</i>-Branched Nucleosides

Stereoselective synthesis of 4‘-α-carbon-substituted nucleosides has been accomplished through epoxidation of 4‘,5‘-unsaturated nucleosides with dimethyldioxirane (DMDO) and successive SnCl4-promoted ring opening of the resulting 4‘,5‘-epoxynucleosides with organosilicon reagents

Lithiation at the 6-Position of Uridine with Lithium Hexamethyldisilazide: Crucial Role of Temporary Silylation

Lithium hexamethyldisilazide (LiHMDS) can mediate silylation at the 6-position of uridine, although LiHMDS alone is not able to generate the C-6-lithiated uridine. Experimental results showed that temporary silylation of O-4 (or N-3) of the uracil ring triggers the C-6 lithiation with LiHMDS. This finding allowed us to develop an efficient intramolecular alkylation of 5‘-deoxy-5‘-iodouridine to furnish 6,5‘-C-cyclouridine

5-<i>Exo</i> versus 6-<i>Endo</i> Cyclization of Nucleoside 2-Sila-5-hexenyl Radicals: Reaction of 6-(Bromomethyl)dimethylsilyl 1‘,2‘-Unsaturated Uridines

The mode of cyclization of 2-sila-5-hexen-1-yl radicals generated from 6-(bromomethyl)dimethylsilyl-1‘,2‘-unsaturated uridines was investigated. In contrast to the case of the 2‘-unsubstituted 6-silicon-tethered substrate (4), which undergoes exclusive 6-endo-cyclization, reactions of the 2‘-substituted (Me, CO2Me, OBz, and Cl) derivatives (14, 20, 22, and 24) uniformly proceeded in preferential or exclusive 5-exo-mode. The Tamao oxidation of the resulting cyclized products was also carried out to synthesize the corresponding 1‘-C-hydroxymethyl derivatives