Hydroxylation metalloporphyrin-catalyzed

D. Mansuy, J. F. Bartoli, J. C. Chottard, M. Lange, Metalloporphyrin-catalyzed hydroxylation of cyclohexane by alkyl hydroperoxides pronounced efficiency of iron-porphyrins, Angew. Chem. Int. Ed. Engl. 19 (1980) 909. 

A new trend in the field of oxidations catalyzed by metalloporphyrin complexes is the use of these biomimetic catalysts on various supports ion-exchange resins, silica, alumina, zeolites or clays. Efficient supported metalloporphyrin catalysts have been developed for the oxidation of peroxidase-substrates, the epoxidation of olefins or the hydroxylation of alkanes. 

The metalloporphyrin-PhIO system catalyzes the oxidation of alkanes mainly to alcohols under mild conditions. High selectivity for the hydroxylation at the tertiary carbon is observed.132 Yields up to 40% based on the oxidant consumed are obtained. Acyclic alkanes usually exhibit very poor reactivity. A large isotope effect and retention of configuration in the oxidation of ds-decalin are additional important characteristics of the process. 

Among the oxidation catalyzed by heme enzymes, alkane hydroxylation is the hardest process to mimic with synthetic metalloporphyrins (7). This finding is also true for myoglobin mutants, even though the mutants are able to afford... 

Metalloporphyrins can catalyze the hydroxylations of solvent species such as cyclohexane. From our studies with cyclodextrin dimers, we concluded that by attaching cyclodextrin rings to metalloporphyrins we should be able to bind substrates in water and achieve selective hydroxylations directed by the geometries of the complexes. This was successful. 

An example of application of Fe(III) porphyrins is the hydroxylation of the anticancer drug cyclophosphamide to active metabolite 4-hydroxycyclophosphamide in yields similar or higher than those typically obtained by the action of liver enzymes in vivo [198]. This allows the development of novel anticancer drugs for the treatment of tumors with less toxic side effects to the patient. There are many other examples of metalloporphyrin-based systems for the synthesis of drugs or agrochemicals that mimic P450 catalyzed processes. 

D. Mansuy, J. F. Bartoli, M. Momenteau, Alkane hydroxylation catalyzed by metalloporphyrins-evidence for different active oxygen species with aUcylhydroperoxides and lodosobenzene as oxidants. Tetrahedron Lett. 23 (1982) 2781. 

The kinetics of product evolution in a typical reaction of adamantane hydroxylation showed an initial induction period followed by a fast, apparently zero-order phase with the maximum rate and highest efficiencies (Fig. 2). Deviation from linear behavior took place only after 90% oxygen donor and 80% of the substrate had been consumed. When Ru (TPFPP)(0)2, prepared by reaction of Ru"(TPFPP)(CO) with 3-chloroperbenzoic acid was used as the catalyst, no induction time was detected and zero-order kinetics were observed as well. The well defined and characteristic UV-vls spectra of metalloporphyrins provide an invaluable tool for the mechanistic studies. Thus, monitoring the state of the metalloporphyrin catalysts during the course of both model reactions by UV-vis spectroscopy revealed that the initial form of the catalyst remained the predominant one throughout the oxidation, i.e. in the Ru°(TPFPP)(CO) catalyzed reaction c.a. 80% of the porphyrin catalyst existed as Ru"(TPFPP)(CO) and in Ru (TPFPP)(0)2 catalyzed reaction more than 90% of... 

Although the mechanism of hydroxylation of C-H bonds by P-450 is surrounded by controversy [8], it is very likely that hydroxylation of activated C-H bonds catalyzed by synthetic metalloporphyrin complexes proceeds through radical intermediates. 

We were resigned not to get much sleep when an inspiration dawned on us Try a metalloporphyrin. It catalyzes regiospecific hydroxylation. Preliminary experiments were planned on one of the few available unused napkins. We landed in Zurich after the exhausting sojourn. We were weary but had the nucleus of an idea that was initially unsuccessful but was to play a very important role in our future research programs. 

Two kinds of systems based on Fe(III) or Mn(III) porphyrins are available now for the oxidation of hydrocarbons. The first ones involve such a metalloporphyrin catalyst and an oxygen atom donor like PhIO, H2O2 or O2 and a reducing agent 2-10 They reproduce quite well the reactions catalyzed by cytochrome P450-dependent monooxygenases and involve a high-valent metal-oxo active species which is able to epoxidize alkenes, hydroxylate alkanes and aromatic compounds and perform N- or S- oxidations. 

Iodosylbenzene has been used as an effective oxidant in hydrocarbon hydroxylation catalyzed by metal-loporphyrins [687-696]. In particular, various iron(III) and manganese(in) porphyrins can be used as catalysts in hydroxylations of cyclohexane, cyclohexene, adamantane and aromatic hydrocarbons [687,688, 692]. Breslow and coworkers have reported regioselective hydroxylations of several steroidal derivatives catalyzed by metalloporphyrins [689-691]. In a specific example androstanediol derivative 644 was... 

Guo, C.C., J.X. Song, X.B. Chen, and G.R Jiang (2000). A new evidence of the high-valent oxo-metal radical cation intermediate and hydrogen radical abstract mechanism in hydrocarbon hydroxylation catalyzed by metalloporphyrins. J. Mol. Cat. A 157, 31-40. 

Oxidations catalyzed by iron porphyrin complexes are not limited to hydroxylation of alkanes and epoxidation of alkenes. Many types of reactions catalyzed by heme enzymes such as P-450, peroxidases, and catalases have been modeled by synthetic metalloporphyrin complexes. 

Table 10. Cyclohexane hydroxylation by cumen hydrogenperoxide or PhIO catalyzed by various metalloporphyrins [284] ...

Suslick and his coworkers examined the shape selective oxidation of alkanes and alkenes catalyzed by the iron and manganese complexes of the bis-pocket porphyrin (Mn(TTPPP) and Fe(TTPPP) where TTPPP is tetrakis(2,4,6-triphenylphenyl)porphyrin) with a variety of oxidants such as mCPBA, PhIO, F5-PhIO [290]. The selectivities for terminal hydroxylation of n-alkanes are found to be very similar. While the details of the reactive intermediates are not clear, a peracid-Fe TTPPP adduct was obtained as a stable complex at -78°C to measure IR spectrum (Vc=o- 1744 cm l) [139]. However, an expected structure of an oxidant-metalloporphyrin complex could be too crowded to react with olefins. Uponwarming the solution temperature up to room temperature, the... 

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