Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs.

A sequential strategy to access 10,11-dihydro-5 H -dibenzo[ b , e ][1,4]diazepinones (DBDAPs) is disclosed in this article through a palladium and copper-catalyzed amination (Buchwald-Hartwig (B-H) or Chan-Lam (C-L)) followed by a palladium-catalyzed intramolecular aminocarbonylation with Mo(CO) 6 as CO surrogate (to avoid toxic CO handling) of readily available o -phenylenediamines and either 1,2-dibromobenzene or 2-bromophenylboronic acid. The 10,11-dihydro-5 H -dibenzo[ b , e ][1,4]diazepinone could be synthezised in good yield using a sequential catalytic procedure, using both C-L and B-H approaches. Gratifingly, the use of the C-L reaction was more impressive, and afforded the dibenzodiazepinones in good yields (up to 45%; 2 steps) and much milder conditions using copper as the catalyst. The synthetic utility of this novel strategy was showcased by demonstrating a formal synthesis for the antipsychotic drug clozapine and to an anticancer triazole-DBDAP hybrid.