Synthesis of 3-Aryl- and 3-Alkynylbenzofurans in the Presence of a Supported Palladium Catalyst

Abstract

Suzuki and Sonogashira coupling reactions of 3-iodo-2-phenylbenzofuran, leading to the corresponding 3-aryl- and 3-alkynyl derivatives, respectively, were carried out using a silica supported pyridinium ionic liquid based heterogeneous catalyst. Under optimized reactions conditions, arylboronic acids with either electron withdrawing or -donating substituents as well as terminal alkynes with aromatic or aliphatic groups could be coupled to the benzofuran skeleton efficiently. The application of this catalyst made it possible to carry out the reaction under phosphine-free and, in case of the Sonogashira coupling, under copper-free conditions. The catalyst retained its activity in at least 7 subsequent runs in both types of reactions. Palladium leaching of less than 1% of the original amount used in the catalytic reaction was observed under optimized conditions in most cases. The methodology was applied successfully in the synthesis of nine different 3-aryl- and ten different 3-alkynyl benzofuran derivatives in moderate to high yields.

Synthesis of Novel Ferrocene-Benzofuran Hybrids via Palladium- and Copper-Catalyzed Reactions

“…In the first step 4-ethynylaniline was used as the reagent to introduce the amine functionality. Intermediate 10 was produced with a high conversion (94%) and a good yield (83%) in the presence of catalyst CAT-1, according to our previous report [42]. The same heterogeneous catalyst has proved to be efficient in the second, carbonylation step starting from iodoferrocene and benzofuran 10.…”

“…It had been shown to be highly active, selective and reusable in aminocarbonylation as well as Sonogashira and Suzuki reactions. Amides and ketoamides with simple structures or even pharmacologically active molecules as well as diverse benzofuran derivatives were efficiently synthesized in the presence of this Pd-pyridinium-SILP [41,42].…”

“…Intermediate 10 was produced with a high conversion (94%) and a The efficiency of the heterogeneous palladium catalyst CAT-1 was also investigated in the Sonogashira reaction of ethynylferrocene and 2-phenyl-3-iodobenzofuran (1) (Scheme 6). Previous results [42] showed that DMF/KOAc solvent/base system could be efficiently applied in the Sonogashira reaction of benzofuran derivative 1. Similar to previous findings, full conversion was achieved, even using a catalyst/substrate ratio of 2.8 mol%, although in a more prolonged reaction (3 h) compared to the coupling carried out with a catalyst/substrate ratio of 5 mol% (1 h).…”

“…All other reactants were purchased from commercial sources and were used as received. The preparation of the heterogeneous palladium [41] and copper catalyst [43], as well as synthetic methodology to prepare 3-iodo-2-phenylbenzofuran (1) [42], azidomethylferrocene [51] and ferrocenylmethylamine [52] have been described before. All other reactants were purchased from commercial sources and were used as received.…”

“…After the evaporation of the solvent, the crude product was purified using column chromatography (silica, eluent: hexane/toluene 6:1) to obtain compound 9 as a dark orange solid: in 83% yield. 1 FT-IR (KBr, cm 3-((4-Aminophenyl)ethynyl)-2-phenylbenzofuran (10) was synthesized based on our previous report [42].…”