C–H ACTIVATION WITH MANGANESE AND COBALT COMPLEXES

Abstract

Nature has evolved a panoply of metalloenzymes for the selective functionalization C-H bonds. They share common mechanistic features, often employing similar intermediates, such as metal-oxo/hydroxo species. Cytochrome P450s break strong C-H bonds using an oxoiron(IV) porphyrin cation radical. Despite many efforts that have been made to design small-molecule metal catalysts to mimic enzymes, strong C-H bonds remain a challenging goal. Over the past decade, (heteroatom) rebound catalysis with a manganese-based P450 model system has been established in our group and has emerged as a powerful tool for halogenations and pseudohalogenations. In this dissertation, this concept has been further developed for aliphatic C-H functionalizations using an electron-deficient fluorinated manganese porphyrin catalyst. In Chapters 2 - 4, the selective oxidation and bromination of aliphatic molecules using MnTPFPPCl (TPFPP = 5,10,15,20-tetrakis(pentafluorophenyl)porphyrinate) are presented. This system is capable of cleaving C-H bonds with bond dissociation energies exceeding 100 kcal/mol (e.g., in cubanes). Recalcitrant molecules, including amino acids, cyclobutane derivatives, polycyclic scaffolds, nitriles, and bioactive molecules, are well-tolerated in both systems. Diversifications of oxygenated and brominated products have led to the rapid access to medicinally important bioisosteres of benzene. Chapter 5 concentrates on the discovery of an unprecedented desaturation reaction by MnTPFPPCl, as evidenced by the isolated epoxides in the oxidation reactions. The rationale for this unexpected outcome is two sequential hydrogen atom transfers (HAT), and three classes of scaffolds are found to undergo this minor desaturation pathway, yielding epoxides. In contrast, hydroxo iron(III) or manganese (III) species are used to abstract hydrogen from allylic substrates in lipoxygenases, highlighting the capability of activating C-H bonds with mid-valent metal complexes. However, despite mid-valent metals including iron, manganese and copper, having been explored for HAT, mononuclear cobalt(III) complexes are yet to be investigated. In Chapter 6, we’ve achieved the first light-driven HAT using a cationic Co(III) porphyrin catalyst, as supported by kinetic isotope effects. Notably, photoreactive cobalt complexes are exceptionally rare among first-row transition metals. Moreover, in Appendix A, we contributed a complementary chemical approach for the synthesis of a Co(III) porphyrazine, which has previously been characterized as a highly reactive HAT catalyst in our group.