Stereoselective Synthesis of 2'-Amino-2',3'-dideoxynucleosides by Nitrone 1,3-Dipolar Cycloaddition: A New Efficient Entry Toward d4T and Its 2-Methyl Analogue

An efficient access to 2'-( dimethylamino)-2', 3'-dideoxynucleosides is reported. The synthetic strategy relies on the 1,3-dipolar cycloaddition of C-alkoxycarbonyl nitrones to allyl acetate, followed by reductive ring opening to substituted lactones, DIBALH reduction to the corresponding 3-(dimethylamino)tetrahydro-2-furanols, and coupling with silylated thymine. The removal of the dimethylamino group by Cope elimination affords a new formal synthesis of d4T and analogous unsaturated 2',3'-dideoxynucleosides.