Protecting Group Control of Hydroxyketone-Hemiketal Tautomeric Equilibrium Enables the Stereoselective Synthesis of a 1′-Azido C-Nucleoside

The synthesis of 1′-azido C-nucleosides is described to expand the set of azide-functionalized nucleosides for bioorthogonal applications and as potential antiviral drugs. Lewis acid-promoted azidation of a nucleoside hemiketal resulted in the formation of a tetrazole through a Schmidt reaction manifold. Conformational control to prevent ring-chain tautomerism enabled efficient 1′-azidation with complete β-diastereoselectivity. The unique reactivity and further derivation of the 1′-azido C-nucleosides are also reported.