Synthesis of Ring-Fused Oxazolo- and Pyrazoloisoquinolinones by a One-Pot Pd-Catalyzed Carboxamidation and Aldol-Type Condensation Cascade Process

A three-component cascade process is described for the synthesis of ring-fused oxazolo- and pyrazoloisoquinolinones by a one-pot carboxamidation/aldol-type condensation reaction. The cascade process involves Pd-catalyzed carboxamidation of an aryl halide/active methylene compound with oxazolidinone or pyrazolidinone, and subsequent intramolecular base-catalyzed cyclization/dehydration through an aldol-type condensation process, to give ring-fused oxazolo- and pyrazoloisoquinolinones. This methodology provides an easy one-step approach to these important classes of nitrogen-containing heterocycles and can tolerate it wide array of functional groups, including ester, nitrile, methoxy, and halide.