Palladium-Catalyzed Carbonylative α-Arylation of tert-Butyl Cyanoacetate with (Hetero)aryl Bromides

A three-component coupling protocol has been developed for the generation of 3-oxo-3-(hetero)-arylpropanenitriles via a carbonylative palladium-catalyzed alpha-arylation of tert-butyl 2-cyanoacetates with (hetero)aryl bromides followed by an acid-mediated decarboxylation step. Through the combination of only a stoichiometric loading of carbon monoxide and mild basic reaction conditions such as MgCl2 and dicyclohexylmethylamine for the deprotonation step, an excellent functional group tolerance was ensured for the methodology. Through the use of C-13-labeled carbon monoxide generated from (13)COgen, the corresponding C-13-isotopically labeled beta-ketonitriles were obtained, and these products could subsequently be converted into cyanoalkynes and 3-cyanobenzofurans with site specific C-13-isotope labeling.