Transformation of tert-Butyl Amide Directing Groups to Nitriles in Iridium-Catalyzed C-H Bond Functionalizations

To overcome limitations of the directing group in IrCp* catalysis for C-H functionalization, we developed a directing group transformation strategy that was applied after obtaining the desired products. Well-established Ir-catalyzed alkenylation, alkylation, and arylation reactions were performed under mild conditions, and then the stable coordinating amide groups were efficiently converted to versatile nitrile groups by in situ treatment with Vilsmeier reagent at room temperature. Whereas the conversion of primary amides has been extensively studied with modified Appel protocol, nitrile formation from secondary amides is very limited. Various ortho-functionalized benzonitrile derivatives (31 examples) were synthesized using this simple methodology, and the subsequent oxidative cyclization of an ortho-alkenylated product was investigated to demonstrate the synthetic utility of this strategy. This simple and versatile methodology should be available under various transition metal catalysis with stable amide directing groups.