Oligonucleosides with a Nucleobase-Including Backbone. Part 12

In contradistinction to the corresponding Grignard reagent, bis[(trimethylsilyl)ethynyl]zinc reacted with the 5′‐oxoadenosine 3 diastereoselectively to the β‐D‐allo‐hept‐6‐ynofuranosyladenine 5. Lithiation/iodination of the monomeric propargyl alcohol 5 and of the dimeric propargyl alcohol 22 provided the 8‐iodoadenosines 7 and 18, respectively, considerably shortening the synthesis of the dimeric O‐silylated 8‐iodoadenosine 25. The mixed uridine‐ and adenosine‐derived tetramers 21 and 32 were synthesised. The tetramer 21 was prepared by a linear sequence. Sonogashira coupling of 9 and 13 yielded the trimer 16 that was C‐desilylated to 17. A second Sonogashira coupling of 17 and 19 yielded the tetramer 21. Tetramer 32 was prepared in higher yields by a convergent route, coupling the acetylene 29 and the iodide 30. The uridine‐derived iodides proved more reactive than the adenosine‐derived analogues, and the N6‐unprotected adenosine‐derived alkynes were more reactive than their N6‐benzoylated analogues.