Synthesis Of Densely Substituted Benzofurans By One-pot Three-component Reactions

Benzofuran derivatives have been extensively investigated by chemists for its promising biological activity. Some physical scientists paid their attention to utilize carbazole derivatives because these compounds displayed also very promising optoelectronic. Therefore, the development of new and efficient preparative protocols for these heterocyclic components remains an urgent task in organic synthesis.A current trend in green organic chemistry is the development of highly integrated domino processes with the aid of multi-component reactions which were proved simple to operate, excellent performance, and atom-economic and great practical value. Recently, bifunctional aldo-X reagents, such as aldo-OH, aldo-acid, aldo-halide, and aldo-alkyne, have been widely used as building blocks in organic synthesis. With these reagents, many heterocycls, such as furan, pyrrole, and imidazole could be constructed by a simple step reaction. Phenylglyoxal monohydrate, a type of aldo-ketone reagent, has attracted the attentions of synthetic chemists for its unique reactivity.In this article, we developed a three-component reactions of phenylglyoxal, phenols and indoles with the aid of acid-catalyst, with which various densely substituted benzofurans could be produced in good to excellent yields. Further investigation revealed that phenylglyoxal can be replaced by methyl ketone as a“pseudo aldo-ketone reagent” to construct benzofurans in I2/DMSO system. For the less costly of methyl ketone, this method exhibited better practical compared to phenylglyoxal. Moreover, indole component can be replaced by some other nucleophiles, such as 1,2,4-trimethoxybenzene and thiophenol.