Pd-Catalyzed Enolate α-Arylation. Synthesis of Benzofurans

Significance

A convenient one-pot Pd-catalyzed enolate arylation followed by an intramolecular acid-catalyzed cyclization strategy for the synthesis of 2,3-disubstituted benzofurans is described. Among the screened biaryldialkylphosphines (including Buchwald’s bulky phosphines), racemic binaphthyl di-tert-Bu phosphine was established as the optimal ligand. Unusually, identical yields were observed for conventional heating and microwave reaction conditions. The application of the methodology has been demonstrated by the synthesis of a biologically active natural product, Eupomatenoid, in four steps. The substrate scope for ketones is fairly well studied (both cyclic and acyclic). In the case of unsymmetrical cyclic ketones, formation of single regioisomeric benzofurans was observed. Both EWGs and EDGs bearing o-bromophenols were studied.