Bio-Inspired Iron-Catalyzed Olefin Oxidations: Epoxidation Versus Cis-Dihydroxylation

A number of nonheme iron complexes have recently been identified that catalyze the epoxidation and cis-dihydroxylation of olefins with H₂O₂ as oxidant. These catalysts have been inspired by a class of arene cis-dihydroxylating enzymes called the Rieske dioxygenases, the active sites of which consist of an iron center ligated by two histidines and a bidentate aspartate residue. The two remaining sites are cis to each other and are utilized for oxygen activation. The most effective biomimetic catalysts thus far have polydentate ligands that provide two such cis-oriented labile sites to activate the H₂O₂ oxidant. This chapter summarizes recent developments in this area of bio-inspired oxidation catalysis and discusses the evolution of the mechanistic pathways proposed to rationalize the new experimental results and the dichotomy between olefin epoxidation versus cis-dihydroxylation. The epoxidation and cis-dihydroxylation of olefins are important chemical transformations in both natural product and drug synthesis. While epoxidation typically involves either peracids or metal-based catalysts with H₂O₂, olefin cis-dihydroxylation involves the use of OsO₄. These nonheme iron catalysts therefore potentially offer an environmentally more benign alternative to peracid-mediated epoxidations and osmium-catalyzed cis-dihydroxylation reactions. The most extensively studied ones thus far are complexes composed of tetradentate N4 ligands that have cis-oriented available coordination sites, analogous to those observed for the Rieske dioxygenase enzymes. These complexes have been shown to catalyze both the epoxidation and cis-dihydroxylation of olefins, but many factors affect which of these products is favored, revealing a surprisingly complex reaction landscape for catalysis.