Silver comes into play: Henry reaction and domino cycloisomerisation sequence catalysed by [Ag(i)(Pc-L)] complexes

Abstract

We report herein the synthesis of new pyridine-containing macrocyclic ligands (Pc-L) bearing a non-innocent pendant arm, by exploiting both chiral and functional properties of natural amino acids. The obtained macrocyclic ligands were employed to synthesize well-defined cationic silver(I) complexes that were shown to be competent catalysts for the Henry (nitroaldol) reaction. Good to excellent yields and full selectivity in the β-nitroalcohol product were obtained starting from electron-poor aromatic aldehydes or other activated aldehydes such as furfural under mild reaction conditions. The straightforward synthesis of the macrocyclic ligands starting from cheap commercially available starting materials allowed the introduction of a suitable basic functionality into the ligand pendant arm, thus providing a bifunctional catalyst. Based on our previous experience in the [Ag(I)(Pc-L)] catalysed domino addition/cycloisomerisation reaction of o-alkynylbenzaldehydes and nucleophiles, the synthesis of isochromenes coupling the Henry reaction and the cycloisomerisation in a single step was subsequently explored. Although with low selectivity, [Ag(I)(Pc-L)] cationic complexes were able to promote such a cascade reaction and a possible mechanism based on experimental evidence has been proposed.