Mechanistically Driven Development of an Iron Catalyst for Selective Syn-Dihydroxylation of Alkenes with Aqueous Hydrogen Peroxide

Abstract

Product release is the rate-determining step in the arene syn-dihydroxylation reaction taking place at Rieske oxygenase enzymes and is regarded as a difficult problem to be resolved in the design of iron catalysts for olefin syn-dihydroxylation with potential utility in organic synthesis. Toward this end, in this work a novel catalyst bearing a sterically encumbered tetradentate ligand based in the tpa (tpa = tris(2-methylpyridyl)amine) scaffold, [Fe(CFSO)(tpa)], 1 has been designed. The steric demand of the ligand was envisioned as a key element to support a high catalytic activity by isolating the metal center, preventing bimolecular decomposition paths and facilitating product release. In synergistic combination with a Lewis acid that helps sequestering the product, 1 provides good to excellent yields of diol products (up to 97% isolated yield), in short reaction times under mild experimental conditions using a slight excess (1.5 equiv) of aqueous hydrogen peroxide, from the oxidation of a broad range of olefins. Predictable site selective syn-dihydroxylation of diolefins is shown. The encumbered nature of the ligand also provides a unique tool that has been used in combination with isotopic analysis to define the nature of the active species and the mechanism of activation of HO. Furthermore, 1 is shown to be a competent synthetic tool for preparing O-labeled diols using water as oxygen source.

Theoretical Identification of the Factors Governing the Reactivity of C−H Bond Activation by Non‐Heme Iron(IV)‐Oxo Complexes

“…It is demonstrated that increasing Lewis acidity of metal ions boosts up the metal‐coupled‐electron‐transfer process. In a previous report, we have delineated the beneficial role of Lewis acidic Mg(ClO 4 ) 2 in reducing the high barrier for cis ‐diol release in the reaction of iron(III)‐hydroperoxo species with an alkene and enhancing the overall rate of the reaction . Addition of Brönsted acids like HClO 4 likewise deliver congruent variations in reaction mechanism.…”

“…Other non‐heme enzymes such as pterin‐dependent tyrosine hydroxylase also feature oxo‐iron(IV) ferryl systems to cleave C−H bonds in alkane substrates via a common mechanistic conduit . These enzymatic reactions have been inspirational for the development of efficient, inexpensive and “green” abiotic catalysts with high chemo‐, regio‐ and stereo‐selectivity towards valuable synthetic transformations (Scheme ) . In particular, much effort has been invested to design and develop non‐heme high‐valent iron complexes for efficient hydroxylation of C−H bonds, following Nature's design principles .…”

“…Consequently, hydrogen atom tunneling and kinetic isotope effects provide additional contribution to the reactive transition state [12,22] and exclusively directs target CÀ H oxidation of alkane substrates for highly chemo-selective and enantioselective transformations. [7] Since the reactivity of these metaloxygen complexes are not only limited to the oxidation of organic substrates, but has application in energy research and important biological processes, [23] they appear as attractive candidates for biochemical research and targets for the drug industry. Hence, an in-depth understanding of the factors which are responsible for selective CÀ H oxidation, appears significantly important and topical at present stage.…”

A Celebration of Science amidst Nature: The 54th Bürgenstock Conference

“…He also presented some recent applications of these systems for C−H bond oxidation along with approaches for the tuning of catalyst's site selectivity . Costas proposed a P450‐like reactivity for these systems, proving (by means of Mossbauer, XSAFS and EPR spectroscopy) the intermediacy of iron(V) species that mimic oxygenase activity . To conclude, recent investigations on alkene syn ‐dihydroxylation with aqueous hydrogen peroxide in “green” solvents were discussed (Figure ) …”

Ein Fest der Wissenschaft inmitten der Natur: Die 54. Bürgenstock‐Konferenz

“…Er stellte auch einige neuere Anwendungen dieser Systeme für die ##C‐H‐Bindungsoxidation vor, zusammen mit Ansätzen zur Anpassung der Positionsselektivität des Katalysators . Costas schlug eine P450‐ähnliche Reaktivität für diese Systeme vor und bewies (mittels Mößbauer‐, XSAFS‐ und EPR‐Spektroskopie) das Auftreten von Eisen(V)‐Spezies, die die Oxygenase‐Aktivität nachahmen . Abschließend wurden neuere Untersuchungen zur Alken‐ syn ‐Dihydroxylierung mit wässrigem Wasserstoffperoxid in “grünen” Lösungsmitteln diskutiert (Abbildung ) …”