Zinc-catalyzed cycloisomerizations. Synthesis of substituted furans and furopyrimidine nucleosides

(Chemical Equation Presented) 5-Endo-dig cycloisomerization of 1,4- and 1,2,4- mostly aryl-substituted but-3-yn-1-ones in the presence of a catalytic amount of zinc chloride etherate (10 mol %) in dichloromethane at room temperature gave 2,5-di- and 2,3,5-trisubstituted furans in high yields (85-97%). DSC studies confirmed that a solely thermal process does not take place. A relevant catalytic process, employing μ-oxo-tetranuclear zinc cluster Zn₄(OCOCF₃)₆O, yielded bicyclic furopyrimidine nucleosides, when starting from acetyl-protected 5-alkynyl-2′-deoxyuridines (85-86%). Furopyrimidine was deprotected or simultaneously converted into pyrrolopyrimidine nucleoside. The time/concentration dependence for the reaction of 1-phenyl-4-(4-methylphenyl) butynone to 2-(4-methylphenyl)-5-phenylfuran displayed first-order kinetics with the rate dependent on catalyst concentration. The plot of In K_0bS versus In[ZnCl₂ indicated first-order cycloi-somerization, as referred to ZnCl₂ concentration, using both NMR and UV-vis reaction monitoring. The crystal structure of propyl furopyrimidine nucleoside (orthorhombic, P2₁2₁2₁, a/b/c = 5.684(2)/6.682(2)/36.02(2) Å, Z = 4) shows C2′-endo deoxyribose puckering, and the base is found in the anti position in crystalline form.