46094-B1
Efficient Synthesis of Heterocycles with the Aid of Electrophilic Cyclizations and Fluorous Chemistry
Synthesis of furans via 5-endo-dig cycloisomerization of 1,4- and 1,2,4-, mostly aryl-substituted, but-3-yn-1-ones was investigated with the use of metal catalysts. A variety of zinc-containing compounds was screened. The best results were acquired with the use of a catalytic amount of zinc chloride etherate (10 mol %) in dichloromethane at room temperature (22°C). 2,5-Di- and 2,3,5-trisubstituted furans were obtained in high yields (85−97%). DSC studies confirmed that a solely thermal process does not take place. The μ-oxo-tetranuclear zinc cluster Zn4(OCOCF3)6O gave comparable results, but was not pursued for preparative reactions since it was not commercially available. To acquire mechanistic insight, the time/concentration dependence for the conversion of 1-phenyl-4-(4-methylphenyl)butynone to 2-(4-methylphenyl)-5-phenylfuran was investigated. The reaction displayed first-order kinetics with the rate dependent on catalyst concentration. The plot of ln kobs versus ln[ZnCl2] indicated first-order cycloisomerization, as referred to ZnCl2 concentration, using both NMR and UV−vis reaction monitoring with the rate constant k = (0.191 +/- 0.007) M−1s−1.
The crystal structure of 2-(4-bromophenyl)-5-(4-tert-butylphenyl)furan (monoclinic, P 21/n, a/b/c = 7.7441(5)/6.2696(5)/35.046(3) Å, Z = 4) was acquired and shows coplanar structure of the furan ring and its aryl substituents in crystalline form.
In an investigation of electrophilic reactions, a one pot cyclization/halogenation the 5-endo-dig chlorocyclization of 1,4-disubstituted alk-3-yn-1-ones with the use of trichloro-s-triazinetrione (trichloroisocyanuric acid, 0.4 equiv.) process was studied. This lead to 2,5-disubstituted 3-chlorofurans (toluene, room temperature, in the absence of base), in high yields (79-96 %). The reaction can be accomplished by using commercially available swimming pool sanitizer. Selected 3-chlorofuran was validated as a substrate for Suzuki-Miyaura coupling.
So far two undergraduate students were supported by this project and enjoyed summer research opportunity. One, after finishing his B.S., entered the graduate (Ph.D.) chemistry program at Ohio State University, while the other is at the midpoint of his B.S. studies.
I am grateful to participate in this program, since it provided me with the unique opportunity to carry out research with undergraduate students and to have an impact for their future careers.
