Pd-Catalyzed Synthesis of Dibenzoxazo-cinones and Related Heterocycles

Significance

The regioselective synthesis of tricyclic lactams via an intramolecular cyclocarbonylation reaction catalyzed by solid-supported palladium is described. Treatment of substituted 2-(2-ethynylphenoxy) anilines 1 with catalytic palladium(II) and tosic acid under an atmosphere of CO gave the exo-methylene cyclic lactams 2 in excellent yields. After extensive optimization of catalyst, ligand, solvent and H₂ pressure, asymmetric hydro­genation of 2 to optically active lactams 3 was achieved using rhodium catalysis in excellent yields and high enantioselectivities. X-ray crystal structure analysis of one example proved the absolute configuration as (R)-3. A wide variety of functional groups including halide, ketone, nitrile and ester are tolerated in both reactions.