A new alkylation–elimination method for synthesis of antiviral fluoromethylenecyclopropane analogues of nucleosides

A new method for the synthesis of fluoromethylenecyclopropane nucleosides by alkylation–elimination procedure is described. Fluorination of methylenecyclopropane carboxylate gave fluoroester . Treatment of with phenylselenenyl bromide afforded the desired ethyl (E)-2-bromomethyl-1-fluoro-2-phenylselenenylcyclopropane-1-carboxylate in 85% yield. DIBALH reduction of gave , which after acetylation to was reacted with 2-amino-6-chloropurine to give the 9-alkylated product in 87% yield. Se-oxidation of with hydrogen peroxide afforded , which underwent smooth elimination in a mixture of THF–DMF at 60 °C giving rise to a Z,E mixture of protected nucleosides . Deacetylation gave and which were separated on a silica gel column. Both and were converted into the respective guanine analogues and .