Catalytic coupling of 1-(2-(allyloxy)phenyl)-2-yn-1-ols and isonitriles for the synthesis of 2-(benzofuran-2-yl)acetamides: A combined experimental and theoretical study

A new catalytic approach to the synthesis of an important sub-class of benzofuran derivatives (namely, 2-(benzofuran-2-yl)acetamides, known to possess significant biological activities) has been developed. The new method is based on the use of Pd(PPh3)4 as simple and commercially available catalyst, readily prepared 1-(2-(allyloxy)phenyl)-2-yn-1-ols, and commercially available isonitriles. Formation of benzofuran-2-yl)acetamides derives from a mechanistic pathway involving an ordered sequence of steps, that are, oxidative addition of the phenoxyallyl moiety to Pd(0), isonitrile insertion, water attack to the ensuing (allyl)(imidoyl)palladium complex, β-H elimination from the H-O-C-Pd(allyl) moiety with formation of an allylpalladium hydride species and a 2-(3-hydroxybenzofuran-2(3H)-ylidene)acetamide intermediate, followed by reduction of the latter by (allyl)PdH and MeOH. This mechanistic proposal has been corroborated by DFT studies, while the structures of representative products have been confirmed by X-ray diffraction analysis.