Mn(III) porphyrin and epoxide is the rate-determining step of the catalytic cycle. Some analogies to the biochemical epoxida- tion of olefins catalyzed by ...
Proc. Nati. Acad. Sci. USA Vol. 81, pp. 3245-3248, May 1984
Chemistry
Epoxidation of olefins by cytochrome P-450 model compounds: Mechanism of oxygen atom transfer (high-valent metal-oxo complexes/porphyrins/suicide inhibitors/metallacycles)
JAMES P. COLLMAN*, JOHN I. BRAUMAN*, BERNARD MEUNIERt, SCOTT A. RAYBUCK*, AND THOMAS KODADEK* *Department of Chemistry, Stanford University, Stanford, CA 94305; and tLaboratorie de Chemie de Coordination du Centre National de la Recherche Scientifique, 205 route de Narbonne, 31400 Toulouse, France
Contributed by James P. Collman, December 23, 1983
The mechanism of the Mn(III) porphyrinABSTRACT catalyzed 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. 0
+ \=/ IC C;yS-
'
@i~7 + CyS
Scheme I
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.
oc'
11
c
L
Lk |
I
Scheme 11
EXPERIMENTAL Instrumentation. 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 recrystallized from methylene chloride/heptane. Benzyldimethyltetradecylammonium chloride was purchased from Fluka and used without further purification. Methylene chloride was distilled
from CaH2. The hypochlorite solution was prepared as follows. LiOCl (3.5 g) (30%) purchased from Fluka was dissolved in 50 ml of deionized water. To this solution was added 1.15 g of anhydrous BaCl2 to remove sulfates. The BaSO4 was allowed to settle, and the solution was filtered away from the precipitate. The pH was 11.8. The concentration of LiOCI was 0.31 M as determined by thiosulfite titration. These solutions were always used within 0.5 hr. Deviation from these conditions can lead to irreproducible results. Kinetics. All kinetic experiments were performed as follows. Mn(III)TPPCl (0.007 mmol), NAcPhIm (0.62 mmol), benzyldimethyltetradecylammonium chloride (0.1 mmol),
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Abbreviations: TPP, dianion of meso-tetraphenyl porphyrin; NAcPhIm, 4'-(imidazol-1-yl)acetophenone.
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Proc. Natl. Acad. Sci. USA 81 (1984)
Chemistry: Collman et aL
olefin (2-6 mmol), and octane or dodecane (1 mmol) as an internal standard were dissolved in 10 ml of methylene chloride. Twenty milliliters of the hypochlorite solution (0.62 mmol of LiOCl per 20 ml of H20) was then layered over the organic phase. The reaction was initiated by vigorous stirring and monitored periodically by gas chromatography. (The reaction rate was not dependent upon the stirring rate as long as the aqueous and organic layers were visibly mixed.) Control experiments showed no difference between reactions done under nitrogen and those done in air. For each substrate, control experiments showed that no epoxidation had occurred in the absence of the manganese porphyrin. Rates of epoxidation are reported as mmol of olefin consumed per mmol of catalyst per sec (turnovers per sec) at early reaction times (
