Stereoselective Synthesis of Alkynyl C-2-Deoxy-β-D-ribofuranosides via Intramolecular Nicholas Reaction: A Versatile Building Block for Nonnatural C-Nucleosides

摘要

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_3N, 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.