Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5222568 | Tetrahedron | 2009 | 9 Pages |
Synthesis of 4â²-substituted thymidines was investigated based on nucleophilic substitution using organosilicon and organoaluminum reagents. Two substrates having a benzenesulfonyl leaving group at the 4â²-position were prepared for this purpose: 1-[4-benzenesulfonyl-3,5-bis-O-(tert-butyldimethylsilyl)-2-deoxy-α-l-threo-pentofuranosyl]thymine (8α) and the 4â²-(benzenesulfonyl)thymidine derivative (8β). The reaction of 8α with organosilicon reagents (Me3SiCH2CHCH2 and Me3SiN3) in combination with SnCl4 gave preferentially the 4â²-substituted β-d-isomer: the 4â²-allyl (12β) and 4â²-azido (15β) derivatives, respectively. The reaction of 8α with AlMe3, however, gave the 4â²-methyl-α-l-isomer (16α) as the major product, presumably through an ion pair mechanism. By employing the substrate 8β in this reaction, the 4â²-methylthymidine derivative (16β) was obtained exclusively in high yield. The 4â²-ethyl (20β) and 4â²-cyano (24β) derivatives were also synthesized by reacting 8β with the respective organoaluminum reagent.
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