Multidimensional Screening Accelerates the Discovery of Rhodium Catalyst Systems for Selective Intra- and Intermolecular C–H Amidations

We report herein a series of tailored CpXRh(LX)Cl catalyst systems for the outer-sphere C–H amidations discovered by high-throughput experimentation. Using a diverse repertoire of Cp-tunable group 9 [CpXMCl2]2 precatalysts in combination with bidentate LX-type co-ligands, we have established a premixing protocol for the fast and convenient in situ generation of an array of half-sandwich metal complexes. Benefitting from the designed multidimensional approach to simultaneously screen the metal center, CpX, LX-type co-ligands, and nitrene precursors, optimal CpXRh(III)(LX) catalysts were quickly identified for intra- and intermolecular C–H amidations and also for an enantioselective transformation using N-tosyloxycarbamates as the nitrenoid precursor.