Stereoselective synthesis of alkynyl C-2-deoxy-β-D-ribofuranosides via intramolecular Nicholas reaction: A versatile building block for nonnatural C-nucleosides

Figure presented The reaction of 3,5-di-O-benzyl-2-deoxy-D-ribofuranose with various alkynyllithium reagents afforded diastereomeric mixtures of the corresponding ring-opened alkynyldiols. The resulting diastereomeric mixtures were successively treated with Co₂(CO)₈, a catalytic amount of TfOH, Et₃N, and iodine in one pot to give alkynyl C-3,5-di-O-benzyl-2-deoxy-β-D-ribofuranosides with high β-selectivities. The cobalt-mediated cyclization (intramolecular Nicholas reaction) is reversible; thus, thermodynamically more stable β-anomers were obtained preferentially. The alkynyl C-deoxyribofuranosides were converted to a variety of C-deoxyribofuranoside derivatives.