I. Studies towards catalytic site-selective carbon-hydrogen activation. II. A combinatorial approach to atom transfer catalyst discovery

I. A model system was developed for site-selective C-H oxidation catalysis. Exploration of tetradentate metal complexes led to the identification of a diamidomanganese(III) complex as a robust catalyst for alkene epoxidation and benzylic C-H bond oxidation. Installation of a rigid linker and covalent attachment of substrate molecules led to site-selective benzylic and aliphatic C-H bond activation in the presence of iodosobenzene. A secondary C-H bond of a cyclohexyl substrate was oxidized selectively despite an adjacent tertiary C-H bond and intrinsically more labile bonds elsewhere in the substrate. The system serves as a model for catalysts in which the covalent tether is replaced by a non-covalent interaction.; II. Fluorogenic diazoketone and alkene probes were developed for the high-throughput screening of metal complex libraries for carbene transfer and oxygen transfer catalysts, respectively. The probe was used to screen a ligand library in the presence of numerous transition metals. Copper(I) and rhodium(II) catalysts were identified that mediate the insertion carbenes into olefins and C-H bonds. Observation of pronounced and often surprising preferences for specific ligand environments led to the synthesis of two new libraries (containing 6,006 and 18,711 compounds, respectively) using a diverse set of 41 different building blocks. Screening of these libraries resulted in the identification of many active rhodium and ruthenium complexes; however, none competed well with known catalysts. Air-stable copper catalysts containing cysteine ligands were also identified, but irreproducible results prevented further exploration of these compounds. A screening of the new libraries for oxidation catalysts uncovered a highly active iron catalyst for epoxidation with hydrogen peroxide. Resynthesis and investigation of this catalyst revealed a high-spin Fe(III) complex with probable picolinamide and pyridyl ligands. The presence of a chiral turning unit in the ligand resulted in some degree of enantioselectivity; when a bis-proline unit was used, trans-β-methylstyrene was epoxidized in 15% ee. This result indicates oxidation within the ligand sphere rather than radical autoxidation.