| Abstract
| - A variant of the semipinacol rearrangement that was observed in our laboratory has been applied to thesynthesis of several furanose and pyranose derivatives. The process consists of an “orchestrated” [1,2]-hydride shift with departure of a leaving group from the opposite face. Transient formation of a COgroup is followed by rapid transfer of a hydride-equivalent from the same face from which the leavinggroup departed, which results in double inversion of stereochemistry at the two vicinal carbon atoms.Treatment of 2‘-O- and 3‘-O-tosyladenosine with lithium triethylborohydride in DMSO/THF gave therespective 2‘- and 3‘-deoxynucleoside analogues with β-d-threo configurations. Identical treatment of5‘-O-TPS-2‘-O-tosyladenosine gave 9-(5-O-TPS-2-deoxy-β-d-threo-pentofuranosyl)adenine. The same[1,2]-hydride shift and stereochemistry with the 5‘-OH and 5‘-O-TPS compounds demonstrated the absenceof remote hydroxyl-group participation. Application of this process to other nucleoside 2‘-O-tosylderivatives gave the 2‘-deoxy-threo compounds in good yields. The reaction-rate order was OTs ≈ Br ≫Cl for 2‘-O-tosyladenosine, 2‘-bromo-2‘-deoxyadenosine, and 2‘-chloro-2‘-deoxyadenosine (all with β-d-ribo configurations). Analogous results were obtained with mannopyranoside derivatives with either 4,6-O-benzylidene protection or a free OH group at C4. Deuterium labeling clearly defined the stereochemicalcourse as a cis-vicinal [1,2]-hydride shift on the face opposite to the original cis OH and OTs groupsfollowed by hydride transfer from the face opposite to the [1,2]-hydride shift. Synthetic and mechanisticconsiderations are discussed.
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