Green Method for Constructing Phthalides via Oxidative Coupling of Aromatic Acids and Acrylates in Neat Water and Air

Phthalides represent an important class of bioactive heterocycle extensively found in pharmaceuticals and natural products, their syntheses have attracted extensively attention. A water-promoted and rhodium-catalyzed [3+2] tandem cyclization of aromatic acids and acrylates has been developed in air and neat water free of any additives, which provides an environmentally benign approach for constructing phthalide motifs. Compared with previous literatures, this methodology features quite simple reaction conditions, simple operation and additive-free. Mechanistic studies indicate that apart from the many other well-known oxidations of Rh(I) by external oxidant, hydrogen transfer with the acrylate being a hydrogen acceptor is involved to regenerate the active Rh species, which is different from documented metal-catalyzed phthalides syntheses. The application of this protocol is further demonstrated by the green synthesis of biologically active isoochracinic acid in one step.