Synthesis of 4‐Formyl‐2‐arylbenzofuran Derivatives by PdCl(C₃H₅)dppb‐Catalyzed Tandem Sonogashira Coupling‐Cyclization under Microwave Irradiation ‐ Application to the Synthesis of Viniferifuran Analogues

Abstract

Herein we present the use of low catalyst loading of PdCl(C3H5)dppb (1 mol%) to directly prepare 4‐CHO‐2‐arylbenzofurans by copper‐free tandem Sonogashira coupling‐cyclization under microwave irradiation. The method was utilized to prepare highly substituted analogues of viniferifuran, a biologically active resveratrol dimer. Key transformations included the application of PdCl(C3H5)dppb (5 mol%) catalyzed direct arylation of C‐3 sterically congested C‐2 and C‐4 substituted benzofuran substrates. Finally, we demonstrated that BCl3/TBAI is superior to BBr3 for final demethylation.

Synthesis and Antimicrobial Activity of δ-Viniferin Analogues and Isosteres

“…Several troublesome efforts in the demethylation process confirmed that this step is an Achilles' heel in the synthesis of stilbenoids-derived compounds [6,10,14,22].…”

“…Over the last years, several efforts were made towards the synthesis of complex natural resveratrol oligomers, by biomimetic and de novo approaches [1,[5][6][7][8][9]. However, only few research groups have focused on the synthesis of new resveratrol-derived chemical scaffolds with improved pharmacodynamics and pharmacokinetics with respect to the natural precursors [6,[10][11][12][13][14]. In this scenario, we planned to set up a versatile and efficient synthetic strategy for the construction of dimeric resveratrol-derived benzofurans.…”

Last Decade of Unconventional Methodologies for the Synthesis of Substituted Benzofurans

“…In 2013, Larock proposed a one-pot three component MW assisted protocol to generate 2,3-disubstituted benzofurans [146]. MWs were used by Elofsson to assist the synthesis of benzofuran core of some natural products [147]. Furthermore, 2-TMS-benzofuran was used in the asymmetric synthesis of the natural product (+)(R)-concentricolide [148].…”

Recent Development in Palladium-Catalyzed Domino Reactions: Access to Materials and Biologically Important Carbo- and Heterocycles

“…They performed the Sonogashira coupling-cyclization between different aromatic alkynes and 2-bromo-or 2-iodo-3-hydroxybenzaldehydes using a lower catalyst loading of PdCl(C3H5)dppb (1 mol%) under microwave irradiation to obtain the corresponding 4-formyl-2-arylbenzofurans in moderate to good yields. 168 Scheme 110. Synthesis of 2-substituted benzofurans.…”