PdCl₂-catalyzed Cross-coupling Reaction Of Arylacetylene Halides With Arylboronic Acids

Suzuki cross-coupling reaction, which usually has high yield under the catalysis of palladium or nickel complexes, is very important in organic synthesis. It is the most powerful synthetic methodology for the formation of Csp2-Csp2 bonds. Desilylation reaction, which show high ipso rate factor, is very useful in organic synthesis, especially in regioselective synthesis of substituted aryl derivatives. When there are two silyl groups in arenes, the regioselectivity of substitution would be much more important.In this study,3,4-bis(trimethylsilyl)-1H-pyrrole was prepared through 1,3-dipolar addition of 2-aziridinecarbonitrile and bis(trimethylsilyl)acetylene according to a literature. From depyrrole building block of 21, two pyrrole derivatives 24 and 11 with two-TMS groups were obtained and their regioselectivity of mono-iodination were investigated. Then the mono-iodide pyrrole 11 can couple with p-methoxyphenylboronic acid to afford 2,3,4-trisubstituted pyrrole 15, which structure was confirmed by X-ray crystallography. The structure of 15 indicated that arylacetylene iodides could couple with arylboronic acids to form diarylacetylenes under typical Suzuki reaction conditions. As far as we know this is the first case of a 1-iodo-2-arylalkyne to couple with arylboronic acid to form a diarylacetylene under Suzuki-type conditions.Based on this unexpected result, we were interested to see if other substrates would be suitable for this coupling. We began to explore the conditions to optimize the reaction by using 4-iodoethynyl benzoic acid methyl ester and p-methylphenyl boronic acid as reaction partners in the reaction, modified the reaction conditions with respect to four key variables:the catalyst system, the solvent system, the base, and the amount of substrates. The best result (yield of 88%) was obtained when the structure simple, stable PdCl2 (1 mol%) was employed as catalyst, MeOH/toluene/H2O (3:3:1) as solvent, K2CO3 as base, and 1.5 equiv p-methylphenylboronic acid with refluxing at 80℃for 8 h. This catalytic system allows a diverse range of electron density around the aromatic rings either from arylacetylene iodides or aryl boronic acids with moderate to high yields between 69-92%. When arylacetylene bromides were employed in this system, the reaction could proceed smoothly when the arylacetylene bromides with electron-withdrawing group, the cross-coupling product yields were almost the same as arylacetylene iodides. But when the arylacetylene bromides with electron-donating group the reaction can not proceed, with only homo-coupling products of arylboronic acids. Heterocyclacetylene iodides could also couple with arylboronic acids under the catalysis of PdCl2. Four different 1-heteroaryl-2-arylacetylenes were prepared in yields between 82-91%, and these four compounds are not reported before.In most cases the yields obtained from this protocol are comparable to those obtained by the Sonogashira reaction; however, in some cases the yields from our protocol are superior. The change of the acetylene subunit from nucleophile to electrophile makes this method a supplement of the Sonogashira reaction to synthesize diarylacetylenes.