Titanium Tetrachloride Promoted Cyclodehydration Of Aryloxyketones:Facile Synthesis Of Benzofurans And Naphthofurans With High Regioselectivity

Benzofuran core is highly versatile,presents in many important natural products and natural drugs.Many natural products containing the benzofuran moiety have been developed as clinical drug candidates for cancer,neurological disorders,diabetes,and so on.As a consequence,significant attention has been paid to the synthesis of benzofuran and its derivatives.At present,it has been reported to use various Lewis acids or Bronsted acids to promote the cyclization dehydration of aryloxyketones to obtain the corresponding benzofuran products.However,most of the reported methods require harsh reaction conditions and have limited substrate scope.Therefore,a mild and practical cyclodehydration procedure is still in demand.We have found an efficient method for the prepartion of a large range of benzofurans and naphthofurans via intramolecular cyclodehydration of aryoxyketones using titanium tetrachloride as the dehydrating agent.Cyclic and acyclic aryloxyketones were readily condensed to their corresponding benzofurans and naphthofurans in good to excellent yields with high regioselectivity.Importantly,most of these condensation reactions proceeded remarkably fast at room temperature.