Synthesis of 1′,2′-<i>cis</i>-Nucleoside Analogues: Evidence of Stereoelectronic Control for S_N2 Reactions at the Anomeric Center of Furanosides

We are reporting a highly diastereoselective route to 1′,2′-cis-nucleoside analogues in the d-ribo, d-lyxo, d-xylo, and d-arabinoside series. Five-membered ring lactols undergo highly selective N-glycosidation reactions in the presence of dimethylboron bromide with different silylated nucleobases. Stereoelectronic control plays a crucial role for the observed induction, and the products are proposed to be formed through SN2 “exploded” transition states. This approach shows great potential considering its simplicity and selectivity for the synthesis of nucleoside analogues, an important class of molecules in medicinal chemistry.