Studies On The Synthesis Of Substituted Benzofurans By Intramolecular Carbon-Carbon Bond Cleavage/Cyclization

Benzofuran derivatives are important compounds, and the benzofuran moiety is abundant in both natural and artificial molecules possessing potent biological activities. So more and more efforts are devoted to explore new methods for the synthesis of substituted benzofurans. Herein, the general methods for constructing benzofurans are summarized, and a novel method is discribed to synthesize substituted benzofurans via intramolecular carbon-carbon bond cleavage and the subsequent cyclization.Firstly,α-aryl-β-ketonitriles are prepared by the condensation of the substituted aryl nitriles and esters, which contains activated methylene, could form homodimers by oxidative carbon-carbon coupling mediated by manganese dioxide. Further study indicate that when the 3,4 position of benzene ring are substituted with methoxy group, the homodimers could be transformed to benzofurans by carbon-carbon bond cleavage in the presence of ferric chloride. Whether the side chain is substitued by alkyl or aryl group, the reaction could occur in moderate to good yields. A series of substituted benzofurans were synthesized by this method, and a preliminary mechanism is proposed.The stereochemistry of the coupling reaction and the stereoisomer's influences on the constuction of benzofurans is also studied. The homodermers composed by both dl-isomer and meso-isomer with the inferior thermodynamical stabilisation of the latter one. Furthermore, it's found that the meso-isomer could be transformed to benzofurans rapidly while the dl-isomer need long reaction time under the identical optimized condition.