A Palladium-Catalyzed Double Carbonylation Approach to Isatins from 2-Iodoanilines

A high-yielding procedure for the synthesis of isatins has been developed. Sequential Pd-catalyzed double carbonylation of 2-iodoanilines with near stoichiometric amounts of CO followed by acid-promoted cyclization readily affords an array of isatins. The conversion of 2-iodoanilines to isatins in good to excellent yields was found to proceed with good functional group tolerance. This protocol proved adaptable to C-13-isotope labeling of isatins, which was extended to the synthesis of the C-13-isotope labeled antiviral drug metisazone and the experimental anti-schizophrenia drug ML137.