Zinc-catalyzed cycloisomerizations. Synthesis of substituted furans and furopyrimidine nucleosides.
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 mu-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 ln k(obs) versus ln[ZnCl2] indicated first-order cycloisomerization, as referred to ZnCl2 concentration, using both NMR and UV-vis reaction monitoring. The crystal structure of propyl furopyrimidine nucleoside (orthorhombic, P2(1)2(1)2(1), a/b/c = 5.684(2)/6.682(2)/36.02(2) A, Z = 4) shows C2'- endo deoxyribose puckering, and the base is found in the anti position in crystalline form.
Sniady
Adam
A
Department of Chemistry, Oakland University, 2200 N. Squirrel Rd., Rochester, Michigan 48309-4477, USA.
Durham
Audrey
A
Morreale
Marco S
MS
Marcinek
Andrzej
A
Szafert
Slawomir
S
Lis
Tadeusz
T
Brzezinska
Krystyna R
KR
Iwasaki
Takanori
T
Ohshima
Takashi
T
Mashima
Kazushi
K
Dembinski
Roman
R
D002384:Catalysis; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry; D007536:Isomerism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D005663:Furans; D009705:Nucleosides; D011743:Pyrimidines; D015032:Zinc