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

Abstract

We report herein a series of tailored (CpRh)-Rh-X(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 [(CpXCl2)-Cl-M](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, Cp-X, 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.