Extreme Rate Acceleration by Axial Thiolate Coordination on the Isomerization of Endoperoxide Catalyzed by Iron Porphyrin

Abstract

A coordinated effort: The isomerization mechanism of prostaglandin H2 (PGH2), which is catalytically isomerized to prostacyclin or thromboxane A2 by cytochrome P450s, was investigated using a heme‐thiolate complex and an endoperoxide. Isomerization of endoperoxides proceeded very rapidly with this complex, whereas imidazole‐ or chloride‐ligated heme had slight or no catalytic activity (see scheme).

Efficient conversion of primary azides to aldehydes catalyzed by active site variants of myoglobin

“…Under identical conditions but at higher catalyst loading (0.2 mol%), free hemin gave only 95 TON (Entry 1, Table 1 ). Given the presence of a histidine-coordinated heme in Mb 12 and the impact of axial ligands in affecting the reactivity of metalloporphyrin systems 13 , the same experiment was repeated in the presence of imidazole (Entry 2, Table 1). The low catalytic activity observed also in this case further highlighted the critical role of the protein scaffold in endowing the hemoprotein with high azide oxidation reactivity.…”

Spectroscopic and Mechanistic Studies on Oxidation Reactions Catalyzed by the Functional Model SR Complex for Cytochrome P450: Influence of Oxidant, Substrate, and Solvent

“…The fact that the [ SR (Fe III )–OOC(O)Ar] intermediate cannot be detected by UV/Vis spectroscopy—[( SR .+ )Fe IV O] is the first observed intermediate under conditions involving an equivalent or even a sub‐equivalent amount of oxidant and at −35 °C—can be related to the very fast heterolytic OO bond cleavage (${k{{{\rm Acet}\hfill \atop 2\hfill}}}$ ). This reaction is known to be significantly accelerated by the presence of strong electron donor axial ligands on the iron(III) center13 (in the present case, the thiolate ligand13e). As an example, formation of relatively stable acylperoxo iron(III) intermediates has been observed by UV/Vis spectroscopy in acetonitrile with simple iron(III) porphyrins that do not possess strongly donating axial ligands 14.…”

Biogenesis‐Guided Synthesis and Structural Revision of Sarocladione Enabled by Ruthenium‐Catalyzed Endoperoxide Fragmentation

“…In the 1980s, Mihailović reported the thermal fragmentation of steroidal 5α,8α‐peroxides in refluxing diglyme to afford diketone products in low yields [13] . More recently, Higuchi and colleagues studied fragmentation of 2,3‐dioxabicyclo[2.2.1]heptane with catalysis by iron porphyrin to generate malondialdehyde and ethylene as products [14] . Despite this progress, a general method for endoperoxide fragmentation remains elusive, and we decided to explore this transformation in the context of the synthesis of sarocladione.…”