Stereoselective synthesis of alkynyl C-2-deoxy-beta-d-ribofuranosides via intramolecular nicholas reaction: A versatile building block for nonnatural C-nucleosides.

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 Co(2)(CO)(8), a catalytic amount of TfOH, Et(3)N, and iodine in one pot to give alkynyl C-3,5-di-O-benzyl-2-deoxy-beta-d-ribofuranosides with high beta-selectivities. The cobalt-mediated cyclization (intramolecular Nicholas reaction) is reversible; thus, thermodynamically more stable beta-anomers were obtained preferentially. The alkynyl C-deoxyribofuranosides were converted to a variety of C-deoxyribofuranoside derivatives.