Epoxidation of olefins by cytochrome P-450 model compounds: mechanism of oxygen atom transfer.

Abstract

The mechanism of the Mn(III) porphyrincatalyzed epoxidation of olefins by lithium hypochlorite is examined. The active oxidant is thought to be a high-valent manganese-oxo complex. It is shown that a relatively stable intermediate is reversibly formed upon interaction of the olefin and the oxo complex. The decomposition of this intermediate to Mn(III) porphyrin and epoxide is the rate-determining step of the catalytic cycle. Some analogies to the biochemical epoxidation of olefins catalyzed by cytochrome P-450 are discussed.The cytochrome P-450 family of monooxygenase enzymes catalyzes the reaction of molecular oxygen with various small molecules, including alkanes and alkenes (ref. 1; Eq. 1).olefin + 02 + 2H+ + 2e -* epoxide + H20 [1] The active site of these enzymes contains an iron(III) protoporphyrin IX moiety. This is attached to the polypeptide chain through axial ligation of a thiolate anion contributed by a cysteine residue. The active state of cytochrome P-450 is thought to be an iron-oxo complex, with iron formally in the V oxidation state. Scheme I shows the reaction of activated cytochrome P-450 with 2-butene, where the parallelogram represents the dianion of protoporphyrin IX. Ortiz de Montellano and co-workers (2-4) and others (5,6) have shown that olefins also can act as suicide substrates. In one case, Walsh and co-workers (7) demonstrated that the frequency of the suicide event is about 1 in every 250 epoxidation events. This implies that suicide inactivation is a minor side reaction of the normal epoxidation scheme. Because of the potential physiological importance of this process, great interest has been generated in elucidating the molecular mechanism of oxygen atom transfer to olefins.We recently have reported a highly efficient synthetic model system that uses Mn(III) porphyrins and a substituted imidazole ligand to catalyze the transfer of an oxygen atom from hypochlorite to an olefin (8, 9). Epoxides are produced in good yields and at high rates. The postulated catalytic reaction cycle is shown in scheme II, where the oval represents TPP. This paper presents a kinetic investigation of oxygen atom transfer in this system. Such information may lead to a deeper understanding of the atom-transfer reactions of cytochrome P-450 itself. EXPERIMENTALInstrumentation. All NMR spectra were recorded on a Nicolet NMC-300 spectrometer. Analyses of kinetic experiments were performed on a Hewlett-Packard 5880A gas chromatograph fitted with an OV-101 column. Response factors for all compounds were determined by using solutions of known concentration. UV/visible spectra were recorded on a Cary model 219 spectrometer.Materials. Manganese(III) meso-tetraphenyl porphyrin chloride [meso-tetraphenylporphinatomanganese(III) chloride; Mn(III)TPPCl] was prepared as described (10, 11). All olefins were purchased from Aldrich and passed through a short column of neutral alumina immediately prior to reaction to remove trace peroxides. 4'-(Imidazol-1-yl)acetophenone (NAcPhIm) (Aldrich) was twice recrystallize...

Kinetics of (Porphyrin)manganese(III)‐Catalyzed Olefin Epoxidation with a Soluble Iodosylbenzene Derivative

“…CH 2 Cl 2 ) system, but the phase-transfer process and other side reactions complicated the interpretation of the kinetic data and led to controversial conclusions. [5] Montanari and co-workers demonstrated that by lowering the pH of the aqueous NaOCl solutions from 12.7 to 10.0 ± 0.5, HOCl can be extracted into the organic phase as a soluble terminal oxidant. [6] Under two-phase conditions in the absence of a phase-transfer catalyst, they also investigated the kinetic behavior of a (porphyrin)manganese-catalyzed olefin epoxidation system employing HOCl as the terminal oxidant and observed Michaelis-Menten saturation kinetics.…”

Biomimetic Oxidation of 2-Methylimidazole Derivative with a Chemical Model System for Cytochrome P-450.

“…[25][26][27] However, there is little information about the fate of the added imidazoles during the oxidation reaction, although they were used in excess molar amounts as compared to the metalloporphyrin catalyst. 28) Our present results indicate that in certain cases, not only the substrate itself, but also the added imidazole might be oxidized, affording both the desired product and the oxidized imidazole.…”

Observations and comments on the mechanism of epoxidation of alkenes by manganese(III) porphyrins with hypochlorite.

“…These observations were offered in support of the accumulation of a metallaoxetane intermediate (6)(7)(8)(9)(10). If the reactions were zero-order in epoxide formation, then the accumulation of a compound of alkene and manganese-oxo species would be required.…”

“…It has been reported (8,9,14) that at 200 to 890 turnovers of catalyst, when using initial rates: (i) epoxide formation was zero-order; (it) rates were dependent upon alkene concentration; (iii) rates were different for different alkenes; and (iv) one alkene inhibited the epoxidation of another. These observations were offered in support of the accumulation of a metallaoxetane intermediate (6)(7)(8)(9)(10).…”

“…Epoxidations in high yields were reported when the biphase was rapidly stirred. From studies with this system (6)(7)(8)(9)(10), it has been concluded (i) that high enough CIO-concentrations may be reached such that epoxide appearance is rate-determining and independent of CIOconcentration and (ii) that The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C.…”