In 1979, Groves and co-workers published the first article on the use of a synthetic iron(III) porphyrin complex, Fe(TPP)Cl (TPPẳmeso-tetraphenylporphyrin), in catalytic olefin epoxida- tion and alkane hydroxylation reactions by iodosylbenzene (PhIO).23Olefins were preferentially oxidized to the corresponding epoxides, and alcohols were obtained as major products in alkane hydroxylations (Equations (3)and(4)):
O + PhIO Fe(TPP)Cl
+ PhI ð3ị
C H+ PhIO Fe(TPP)Cl C OH
+ PhI ð4ị
A remarkable feature of the Fe(TPP)Cl/PhIO system in olefin epoxidations was the stereospecific epoxidation of cis-stilbene and the high reactivity of cis-stilbene compared to trans-stilbene. With respect to the latter, cis-stilbene showed 15 times greater reactivity than trans-stilbene in intermolecular competitive epoxidation of cis- and trans-stilbenes by Fe(TPP)Cl and PhIO (Equation (5)).24 The preference of cis-stilbene over trans-stilbene was ascribed to nonbonded interactions between the phenyl groups of trans-stilbene and the phenyl groups of the Fe(TPP)Cl catalyst. In the same year, Chang and Kuo reported that a green intermediate,
generated in the reaction of Fe(OEP)Cl (OEPẳoctaethyl-porphyrin) and an iodosylbenzene derivative, hydroxylated CH bonds regiospecifically:25
Ph Ph Ph
+ Ph
O O
Ph Ph Ph
Fe(TPP)Cl/PhIO Ph CH2Cl2
ratio of cis-oxide : trans-oxide = 15:1
+ ð5ị
Other metalloporphyrins such as Mn(TPP)Cl and Cr(TPP)Cl were also investigated as catalysts in oxygenation reactions. Tabushi and co-worker were the first to use Mn(TPP)Cl as a catalyst in the oxygenation of hydrocarbons by molecular oxygen in the presence of sodium borohydride.26 In 1980, Hill, Groves, and Meunier reported independently that Mn(TPP)Cl was an efficient catalyst in olefin epoxidation and alkane hydroxylation reactions by PhIO and NaOCl.27–29 However, the chemistry of Mn(TPP)Cl was different from that of Fe(TPP)Cl. A significant amountof trans-stilbene oxide was obtained in cis-stilbene epoxidation by Mn(TPP)Cl, which was explained by the generation of a long-lived carbon radical.28 In the case of Cr(TPP)Cl, Groves and Kruper isolated a high-valent chromium oxo porphyrin intermediate in the reaction of Cr(TPP)Cl and PhIO, and the intermediate showed an ability to epoxidize and hydroxylate hydrocarbons.30 An important observation reported in the study was that the oxo ligand of the chromium oxo intermediate exchanged with labeled water, H218
O, and that when the intermediate reacted with an olefin in the presence of a small amount of H218
O, oxygen from the labeled water was incorporated into epoxide product.30In 1981, one of the most important papers in the history of metalloporphyrin chemistry was published by Groves and co-workers.31 When Fe(TMP)Cl (TMPẳmeso-tetramesitylporphyrin) was reacted withm-CPBA in CH2Cl2CH3OH at78C, a green intermediate was generated. On the basis of various spectroscopic measurements, this species was characterized to be an oxoiron(IV) porphyrin -cation radical complex, [(TMP)ỵFeIVẳO]ỵ, identical to the compound I of peroxidases. In addition, this intermediate was capable of oxygenating olefins to yield the corresponding epoxide products. Furthermore, when the intermediate was treated with H218
O prior to react with norbornene, the norbornene oxide productcontained 99% 18O (Scheme 1). The spectral similarity of the oxoiron(IV) por- phyrin-cation radical to the peroxidase compound I and the capability of oxygen atom transfer of the intermediate to organic substrates made this paper a milestone in the biomimetic studies of cytochromes P450.
8.12.2.2 First-, Second-, and Third-generation Metalloporphyrins
Metalloporphyrins containing the TPP ligand are called the first-generation metalloporphyrin catalysts. Although the first-generation metalloporphyrins associated with artificial oxidants such as PhIO, NaOCl, and KHSO5 mimicked much of the chemistry of cytochrome P450, their catalytic activities became rapidly diminished by the extensive oxidative destruction of the porphyrin ligand and the formation of an inactive -oxo dimer (e.g., (TPP)Fe-O-Fe(TPP)).
Such problems were overcome by introducing alkyl or halogen substituents on phenyl groups at themeso-positions of the TPP ligand, and these metalloporphyrins are called the second-generation metalloporphyrins. One important achievement of the second-generation metalloporphyrins was the increased catalytic activity toward substrate oxidation and the stability against oxidative destruction of porphyrin ligand.32Metalloporphyrins with halogenated substituents on the phenyl groups such as Fe(TPFPP)Cl (TPFPPẳmeso-tetrakis(pentafluorophenyl) porphyrin) and Fe(TDCPP)Cl (TDCPPẳmeso-tetrakis(2,6-dichlorophenyl)porphyrin) are particularly good examples (see Figure 3 for the structures).33–36 Based on the lesson that introducing electron- withdrawing substituents on the meso-aryl rings enhanced the reactivity of metalloporphyrin catalysts, the third-generation metalloporphyrins were synthesized by placing electron-withdraw- ing substituents such as F, Cl, Br, and NO2on the -pyrrole positions of the second-generation metalloporphyrins (Figure 3). Traylor and Dolphin reported independently that halogenation of the-pyrrole positions of Fe(TDCPP)Cl markedly increased the catalytic efficiency and stability of the iron porphyrin catalysts in oxygenation reactions.37,38 Ellis and Lyons also showed that these third-generation metalloporphyrins were efficient catalysts in the hydroxylation of alkanes
by air at room temperature and suggested that an oxoiron(IV) porphyrin was a reactive species responsible for alkane hydroxylations.39 However, subsequentstudies by Labinger, Gray, and co-workers demonstrated the involvement of a radical-chain mechanism in the alkane hydroxyla- tions.40Recently, Mansuy and co-workers published that Fe(TDCPP)þand Mn(TDCPP)þcom- plexes bearing-nitro substituents were efficient catalysts in the oxygenation of hydrocarbons by H2O2.41,42In addition to the high catalytic property, the perhalogenated iron porphyrins showed a large positive shift in the iron(III)/iron(II) redox couple as well as severe saddling of the macro- cyclic structure.40
FeIII X
FeIV
16O ArC(O)O16OH
X–
H218O
FeIV
18O
X–
18O
H216O ArC(O)OH
N
N N
N Fe O
+.
+
+.
+
Structure of [(TMP)+•FeIV=O]+
+ •
Scheme 1
N N
N N Ar
Ar
Ar M
Cl R1 R2
R3 R2
R1
Ar
X X pyrrole
Porphyrin
M = Fe, Mn, Cr
Pyrrole Ar group
TPP TMP TDCPP TPFPP TDCPβCl8P TDCPβBr8P TPFPβF8P
R1 H CH3 Cl F Cl Cl F
R2 H H H F H H F
R3 H CH3 H F H H F
X H H H H Cl Br F Figure 3 Structures of the first, second, and third-generation metalloporphyrins.
8.12.2.3 Metalloporphyrins as Catalysts in Oxidation Reactions
Synthetic metalloporphyrins of FeIII, MnIII, CrIII, and RuII,III,VI, especially with porphyrins bearing aryl-groups atmeso-positions, have been used in a variety of oxidation reactions (Figure 4), with the intention of developing biomimetic catalysts which show regio-, stereo-, shape-, and enantioselectivity with a high efficiency under mild conditions.5,43–47 Iron and manganese por- phyrins are the most often used metalloporphyrins in the oxidation reactions, and the catalytic activity of chromium porphyrins is much inferior to those of iron-, manganese-, and ruthenium porphyrins. Ruthenium porphyrins have shown a high catalytic activity in olefin epoxidation and alkane hydroxylation, and the hydrocarbons are stereospecifically oxygenated with complete retention of configuration.44 Although most of the metalloporphyrin-catalyzed oxidation reac- tions have been carried out in homogeneous solutions, polymer-supported metalloporphyrins such as metalloporphyrins anchored to organic or inorganic supports or encapsulated in zeolites have been used in heterogeneous oxidation reactions.48In addition to the oxidation reactions, metallo- porphyrins, especially water-soluble manganese porphyrins, have been the subject of extensive studies in oxidative DNA cleavage and their interactions with DNA.43
A variety of oxidants including iodosylbenzenes, peracids, hypochlorite, periodate, ozone, potassium monoperoxysulfate, monoperoxyphthalate, pyridine N-oxides, nitrous oxide (N2O), O2 plus reductants, hydrogen peroxide, and alkyl hydroperoxides have been used as oxygen atom donors in catalytic oxidation reactions. The last two are considered to be the most important oxidants, since these are biologically relevant and environmentally clean. Therefore, the reactions of these oxidants with iron porphyrins have been the topic of continuing interest over the past two decades. In 1989, Traylor and co-workers published the first article on the epoxidation of olefins by an electron-deficient iron porphyrin complex, Fe(TDCPP)Cl, and hydroperoxides in a solventmixture of CH2Cl2CH3OHH2O.49,50 An oxoiron(IV) porphyrin -cation radical intermediate, formed via OO bond heterolysis in protic solvents, was proposed as the epoxidizing intermediate. The authors also proposed that the absence of oxygenated products often encountered in hydrocarbon oxygenations by iron porphyrin catalysts and hydro- peroxides was the result of a fast reaction between oxoiron(IV) porphyrin-cation radicals and hydroperoxides (Scheme 2, pathway A). The proposal was confirmed by carrying out competitive reactions of hydroperoxides and organic substrates within situgenerated oxoiron(IV) porphyrin
Metalloporphyrin Catalysts
O
C H C OH
R R
OH
N
N+-O–
R C H O
R C O-H O N
N N H3C
+ HCHO H
N-dealkylation N-oxidation
S-oxidation
Aliphatic hydroxylation
Alkene epoxidation Aromatic hydroxylation
Aldehyde oxidation C OH
H C O
Alcohol oxidation S
S O
Figure 4 Metalloporphyrin-catalyzed oxidation reactions.
-cation radical complexes.51 In the reactions, oxoiron(IV) porphyrin -cation radicals of electron-rich porphyrins reacted fast with ROOH (i.e., catalase and peroxidase type of chemistry;
one-electron oxidation of ROOH) (Scheme 2, pathway A). On the other hand, oxoiron(IV) porphyrin -cation radicals of electron-deficient porphyrins reacted fast with olefins to yield epoxide products (i.e., cytochrome P450 type of chemistry; oxygen atom transfer) (Scheme 2, path- way B). These results demonstrated that electron-deficient iron porphyrin complexes are better catalysts in hydrocarbon oxygenations by hydroperoxides, since these complexes can avoid the facile decomposition of oxoiron intermediates by ROOH (Scheme 2, pathway A). Indeed, highly electron-deficient iron(III) porphyrin complexes efficiently catalyze alkane hydroxylations by H2O2in aprotic solvents.41,42,52
O
FeIV OH
FeIII FeIV +.
O
Electron-deficient porphyrin Electron-rich porphyrin
(A)
(B) +
ROOã + ROOH
Scheme 2
Since an enormous number of articles have been published on metalloporphyrin-catalyzed oxidation reactions, it is impossible to cover all the published work in this chapter. Consequently, readers are referred to the excellent review articles or book chapters given in references,1–7,43–47 especially a comprehensive review chapter by Meunier and co-workers.43
8.12.2.4 Labeled Water Experiments in Oxygenation Reactions
It is difficult to characterize reactive intermediates in catalytic oxygenation reactions by mono- oxygenase enzymes and their model compounds, since the intermediates are highly reactive and unstable in nature. Therefore,18O-labeled water experiments have been frequently carried out to obtain clues to identify the nature of reactive intermediates.6,53When labeled18O is incorporated from H218
O into products, high-valent metal oxo complexes have been suggested as oxygenating species since the oxygen of the metal oxo species is believed to exchange with labeled water at a fastrate (Scheme 3).30,31,54,55
LMn+ + oxidant(16O) substrate
product-18O H218O
H218O H216O
LM(n+2)+=16O LM(n+2)+=18O substrate
Scheme 3
Although the labeled water experiments have provided results in proposing the intermediacy of high-valent metal oxo complexes, this method led to an incorrect conclusion in the case of iodosylbenzene reactions.56 In the oxygenation of hydrocarbons by PhIO catalyzed by metal complexes, high-valentmetal oxo complexes were always proposed as reactive species because the source of oxygen in products was labeled water when the oxygenation reactions were carried outin the presence of H218
O. Even when a non-redox zinc complex was used as a catalyst, labeled oxygen from H218
O was fully incorporated into oxygenated products.56,57 On the basis of the latter result and the fact that the oxygen of iodosylbenzene coordinated to a manganese porphyrin
complex exchanges with labeled water,58 it was concluded that, in iodosylbenzene reactions, oxygen exchange does not have to involve high-valent metal oxo intermediates and the
18O-incorporation from H218
O into products cannot be the evidence for the intermediacy of metal oxo complexes. An alternative mechanism was proposed in which iodosylbenzene exchanges its oxygen with labeled water after solid iodosylbenzene is dissolved and coordinated to a metal complex, (8), but before the high-valent metal oxo is formed or the oxygen atom is transferred to the substrate (Scheme 4).
LMn+X + PhI16O LMn+ 16O IIII
Ph X
LMn+ 16O IIII
Ph H18O
LMn+
H16O IIII
18O Ph
LM(n+2)+=18O substrate
substrate
product-18O
HX H218O
–PhI/-16OH– (8)
–
Scheme 4
As alluded to above, the rate of oxygen exchange between the metal oxo species and H218O (Scheme 5, pathway D) was believed to be much faster than that of oxygen transfer from the intermediate to organic substrates (Scheme 5, pathway C). Therefore, in the reactions where no or only a small amountof 18O was incorporated from H218
O into oxygenated products, the inter- mediacy of high-valent metal oxo species has often been ruled out. However, it turned out that the rate of18O-exchange between metal oxo intermediates and H218
O (Scheme 5, pathway D) can be comparable or even slow relative to the reactions of the intermediates with substrates (Scheme 5, pathway C).59,60 In addition, the 18O-incorporation from H2
18O into oxygenated products was found to depend on reaction conditions such as the concentrations of substrate and H218
O,59the ease of substrate oxidation,51 the electronic nature of porphyrin ligand,51 the presence of axial ligandtransto the metal oxo moiety,59,61,62the oxidation state of high-valent metal(IV or V) oxo species,61,63and the temperature and pH of reaction solution.53, 59,64These factors affect the degree of18O-incorporation because:
(i) The reaction of a high-valent metal oxo intermediate with substrates (Scheme 5, pathway C) competes its exchange with isotopically labeled water (Scheme 5, pathway D).
(ii) The formation of a high-valent metal oxo intermediate from an oxidant-metal porphyrin adduct(Scheme 5, pathway B) competes with the oxygen atom transfer from the oxidant- metal porphyrin adduct to substrates (Scheme 5, pathway A).
(iii) The oxygen of metal oxo species exchanges with labeled water via ‘‘oxo-hydroxo tauto- merism.’’6,53
The ‘‘oxo–hydroxo tautomerism’’ was proposed by Meunier and co-workers on the basis of the observation that 50% of oxygen in oxide product came from bulk H2
18O in the epoxidation of carbamazepine (CBZ) by a water-soluble manganese porphyrin complex, MnIIITMPyP (TMPyPẳmeso-tetrakis(4-N-methylpyridiniumyl)porphyrin), and KHSO5 in aqueous solution (Equation (6)).65To explain the 50%18O-incorporation of labeled water into the oxide product, the authors proposed that an ‘‘oxo–hydroxo tautomerism’’ involves a rapid shift of two electrons and one proton from a hydroxo ligand to thetrans-oxo species, leading to the transformation of the hydroxo ligand into an electrophilic oxo entity on the opposite side of the initial oxo species (Scheme 6). The ‘‘oxo–hydroxo tautomerism’’ is supported by the fact that 18O-incorporation from H218
O into products is completely prevented when the axial position opposite to the oxo group of high-valent metal oxo complexes is blocked by an axial ligand in metalloporphyrins and a cysteine thiolate ligand in cytochromes P450.59,61,62,66
MnV O
•
MnV O
H •
H H+
H+ O from primary oxidant
from water
(50% O and 50% ) substrate product
•
•
Scheme 6
CO NH2
Mn(III)TMPyP/O3SO16OH– buffered H218O solution, pH 5
CO NH2
16O or 18O
CBZ CBZ-10,11-oxide
N
N N
N Mn
N
N
N
N
+
+ +
+
Mn(III)TMPyP
ð6ị
Very recently, Rietjens and co-workers proposed an alternative mechanism, ‘‘reversible com- pound I formation,’’ to explain more than 90% 18O-incorporation from bulk water into 4-aminophenol product in the hydroxylation of aniline by microperoxidase-8 (MP-8).67,68 Since MP-8 contains histidine as an axial ligand, such a high oxygen incorporation from solvent water
FeIII FeIII
16O
16O R
FeIV
16O
FeIV
18O H218O H216O
substrate product-16O
substrate product-16O
substrate product-18O
(A)
(B)
(C)
(D)
(E)
+ . + .
R16O16O– -R16O–
Scheme 5
into 4-aminophenol product cannot be explained by the ‘‘oxo–hydroxo tautomerism.’’ Thus, the authors proposed that the oxygen exchange occurs via OO bond formation between a high-valent metal oxo intermediate and a water molecule (Equation (7)):
FeIV
16O
FeIII
16O + .
H218O H+
18OH–
18OH
ð7ị