The synthesis of new 3′-bis-c-substituted-3′-deoxy-3′-dehydro-[3.3.0]-α-fused thymidines by intramolecular radical trapping by tethered acetylenes

Article abstract of DOI:10.1016/S0040-4020(01)90436-3

The Michael addition reaction of propargyl alcohol with 3′-nitro-olefin 1 and subsequent Henry reaction at C-3′with electron deficient reagents has produced various diastereomeric mixtures of 2′-O-propynyl-3′-deoxy-3′-dehydro-3′C-substituted- 3′-nitro-thymidine derivatives 4 - 7 [α-substitution (major); β-substitution (minor)] in 55-80% yield. Subsequently, the intramolecular cyclization-trapping of carbon radicals by tethered acetylene in 4 - 7 by the treatment with Bu₃SnH and AIBN afforded 3′-bis-C,-substituted-[3.3.0]-cis-fused thymidines 8 - 11 in 86-90% yield. The results detailed here represent the first examples of title compounds using a three-step procedure: (1) Michael addition of the propargyl alcohol to nitro-olefin, (2) Henry reaction with electron-deficient reagents, and (3) subsequent inramolecular cyclization-trapping of tertiary carbon radicals by a tethered acetylene.