SYNTHESIS OF A NUCLEOSIDE ANALOG BEARING A BRANCHED DIFUNCTIONAL SIDE-CHAIN USING THE PALLADIUM-MEDIATED CYCLIZATION OF A GAMMA-OXOALLENE

The aldehyde 8 was synthesized in high yield and with excellent stereo selectivity by treating a protected 3-hydroxypropanal with Corey's chi ral B-propargyl boradiazoline reagent. Cyclization of this gamma-oxoal lene with palladium(II) in the presence of methanol and carbon monoxid e produced the furanoside 9 with excellent stereoselectivity for the D -deoxyribose geometry. The furanoside 9 was converted to the branched extended sidechain deoxythymidine analog 11 by reduction, protection, and beta-stereoselective Vorbruggen coupling. The hydroboration/oxidat ion of 10 to yield the deoxyribofuranoside analog 13, bearing two side chain hydroxyl groups, was also demonstrated.