Synthesis of 3‘-Deoxynucleosides with 2-Oxabicyclo[3.1.0]hexane Sugar Moieties: Addition of Difluorocarbene to a 3‘,4‘-Unsaturated Uridine Derivative and 1,2-Dihydrofurans Derived from d- and l-Xylose¹

Syntheses of 3‘-deoxy analogues of adenosine, cytidine, and uridine with a 2,2-difluorocyclopropane ring fused at C3‘−C4‘ are described. Treatment of a 2‘,5‘-protected-3‘,4‘-unsaturated derivative of uridine with difluorocarbene [generated from (CF3)2Hg and NaI] gave a diastereomeric mixture of the 3‘,4‘-difluoromethylene compounds (α-l-arabino/β-d-ribo, ∼5:4). The limited stereoselectivity for addition at the β face results from competitive steric hindrance by an allylic 4-methoxybenzyloxy group at C2‘ on the α face and a homoallylic nucleobase at C1‘ on the β face. Protected uracil derivatives were converted into their cytosine counterparts via 4-(1,2,4-triazol-1-yl) intermediates. Treatment of 1,2-dihydrofurans derived from d- and l-xylose with difluorocarbene resulted in stereospecific addition at the β face (anti to the 1,2-O-isopropylidene group on the α face). Glycosylations with activated enantiomeric sugar derivatives with the fused difluorocyclopropane ring on the β face gave protected adenine nucleosides, whereas attempted glycosylation with an α-fused derivative gave multiple products. Removal of base- and sugar-protecting groups gave new difluoromethylene-bridged nucleoside analogues.