Metalloporphyrin Peroxo Complexes of Iron(III), Manganese(III), and Titanium(IV). Comparative Studies Demonstrating That the Iron(III) Complex Is Extremely Nucleophilic

Article abstract of DOI:10.1021/ic9612616

Peroxo Fe(III), Mn(III), and Ti(IV) porphyrin complexes were reacted with a variety of electron-rich and electron-poor organic substrates in order to compare their reactivities with those of other known metalloperoxide complexes. The peroxoiron(III) porphyrin complex was unreactive with electron-rich substrates such as tetramethylethylene, cyclohexene, triphenylphosphine, or butyllithium but was quite reactive with electron-poor substrates such as 2-cyclohexen-l-one and 2-methyl-l,4-naphthoquinone. The peroxomanganese(III) porphyrin complex was unreactive with these electron-poor olefms but did react with the strongly electron-deficient olefin tetracyanoethylene. The peroxotitanium(IV) porphyrin complex was unreactive with both electron-rich and electron-poor olefins, as well as butyllithium, but did quantitatively oxidize triphenylphosphine to triphenylphosphine oxide. These results lead to the conclusion that the peroxo Fe(III) porphyrin complex is significantly more nucleophilic than the analogous Mn(III) and Ti(IV) complexes and than several well-known nucleophilic non-porphyrin peroxometal complexes.

Full text of DOI:10.1021/ic9612616

Inorg. Chem. 1997, 36, 979-984
979
Metalloporphyrin Peroxo Complexes of Iron(III), Manganese(III), and Titanium(IV).
Comparative Studies Demonstrating That the Iron(III) Complex Is Extremely Nucleophilic
Marlene F. Sisemore, Matthias Selke, Judith N. Burstyn,1 and Joan Selverstone Valentine*
Department of Chemistry and Biochemistry, University of California, Los Angeles, California 90095
ReceiVed October 16, 1996X
Peroxo Fe(III), Mn(III), and Ti(IV) porphyrin complexes were reacted with a variety of electron-rich and electron-
poor organic substrates in order to compare their reactivities with those of other known metalloperoxide complexes.
The peroxoiron(III) porphyrin complex was unreactive with electron-rich substrates such as tetramethylethylene,
cyclohexene, triphenylphosphine, or butyllithium but was quite reactive with electron-poor substrates such as
2-cyclohexen-1-one and 2-methyl-1,4-naphthoquinone. The peroxomanganese(III) porphyrin complex was
unreactive with these electron-poor olefins but did react with the strongly electron-deficient olefin tetracyano-
ethylene. The peroxotitanium(IV) porphyrin complex was unreactive with both electron-rich and electron-poor
olefins, as well as butyllithium, but did quantitatively oxidize triphenylphosphine to triphenylphosphine oxide.
These results lead to the conclusion that the peroxo Fe(III) porphyrin complex is significantly more nucleophilic
than the analogous Mn(III) and Ti(IV) complexes and than several well-known nucleophilic non-porphyrin
peroxometal complexes.
Cytochrome P450 enzymes catalyze oxygenations of a wide
variety of organic substrates using dioxygen itself as the oxygen
atom source.1 Mechanisms proposed for these enzymes all
invoke initial formation of a ferric heme peroxo complex,
formulated as either [(porphyrin)FeIIIO2]- or its protonated form
(porphyrin)FeIIIOOH.2-6 After formation of the peroxo inter-
mediate, three distinctly different modes of reaction were
proposed to account for the different types of reactivity observed
for different P450 enzymes, i.e., (a) heterolytic O-O cleavage
to generate a (porphyrin)FeVdO or (oxidized porphyrin)FeIVdO
high-valent oxo species, (b) homolytic O-O cleavage to
generate a (porphyrin)FeIVdO species, and (c) direct nucleo-
philic attack by a ferric heme peroxo species on an enzyme-
bound substrate. The last mechanism has been proposed for
aromatase,7-9 cytochrome P450-2B4,10 and NO synthase.11
Synthetic metalloporphyrin peroxo complexes have been
synthesized in several laboratories, and it is expected that studies
of the reactivities of such complexes will ultimately lead to
insights into the details of the cytochrome P450 enzymatic
pathways. Several of these synthetic metalloporphyrin peroxo
complexes have been well characterized with respect to their
crystal structures, spectroscopic and magnetic properties,12-15
and, in certain cases, reactivities.16 The metalloporphyrin
peroxides [(TPP)MnO2]- and (TPP)TiO2 have been structurally
characterized; both complexes form the following side-on
geometry:
On the basis of EXAFS,17 magnetic susceptibility, Mo¨ssbauer,
and EPR studies,15 it is very likely that the analogous iron
complexes possess the same geometry. Studies of Fe(III) and
Mn(III) porphyrin peroxo complexes have demonstrated a high
degree of nucleophilic character in their reactions with acyl
halides,18,19 aldehydes,20,21 carbon dioxide,22 and electron-
deficient olefins.23 We recently reported that [(PPIXDME)-
X Abstract published in AdVance ACS Abstracts, February 1, 1997.
(1) Current address: Department of Chemistry, University of Wisconsin,
Madison, WI 53706.
(2) Ho, R. Y. N.; Liebman, J. F.; Valentine, J. S. In ActiVe Oxygen in
Chemistry; Foote, C. S., Valentine, J. S., Greenberg, A., Liebman, J.
F., Eds.; Blackie Academic and Professional, Chapman and Hall:
Glasgow, U.K., 1995; pp 1-23.
(3) Ho, R. Y. N.; Liebman, J. F.; Valentine, J. S. In ActiVe Oxygen in
Biochemistry; Valentine, J. S., Foote, C. S., Greenberg, A., Liebman,
J. F., Eds.; Blackie Academic and Professional, Chapman and Hall:
Glasgow, U.K. 1995; pp 1-36.
(4) Traylor, T. G.; Trayor, P. S. In ActiVe Oxygen in Biochemistry;
Valentine, J.S., Foote, C. S., Liebman, J., Greenberg, A., Eds.;
Chapman and Hall: New York, 1995.
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(15) Burstyn, J. N.; Roe, J. A.; Miksztal, A. R.; Shaevitz, B. A.; Lang, G.;
Valentine, J. S. J. Am. Chem. Soc. 1988, 110, 1382-1388.
(16) Miksztal, A. R.; Valentine, J. S. Inorg. Chem. 1984, 23, 3548-3552.
(17) Friant, P.; Goulon, J.; Fischer, J.; Ricard, L.; Schappacher, M.; Weiss,
R.; Momenteau, M. NouV. J. Chim. 1985, 9, 33-40.
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D. S., Eds.; Academic Press: New York, 1992; Vol. XX; pp 405-
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Chemistry; Liebman, J. F., Greenberg, A., Eds.; VCH: New York,
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1984, 1219-1220.
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(22) Schappacher, M.; Weiss, R.; Montiel-Montoya, R.; Trautwein, A.;
Tabard, A. J. Am. Chem. Soc. 1985, 107, 3736-3738.
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35, 206-208.
(8) Cole, P. A.; Robinson, C. H. J. Am. Chem. Soc. 1991, 113, 8130-
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S0020-1669(96)01261-X CCC: $14.00 © 1997 American Chemical Society

980 Inorganic Chemistry, Vol. 36, No. 6, 1997
Sisemore et al.
FeIIIO2]- (PPIXDME ) protoporphyrin IX dimethyl ester) is
also able to directly transfer an oxygen atom to electron-deficient
olefins such as 2-cyclohexen-1-one or 2-methyl-1,4-naphtho-
quinone.23,24 This nucleophilic oxygen transfer mimics the
direct nucleophilic attack on an enzyme-bound substrate pro-
posed for certain of the P450 enzymes.
was used for the GC-MS analyses. HPLC data were obtained using a
Beckman Model 344 equipped with a Model 165 variable-wavelength
detector. UV-vis spectra were recorded on a Cary 3 spectrophotometer
(Varian). 1H and 31P NMR spectra were recorded on a Bruker 360
MHz spectrometer using P(OMe)3 as an external standard for the 31P
measurements.
Reactions of the Metalloporphyrin Peroxide Complexes with
Triphenylphosphine. The reactions of the peroxo metalloporphyrin
complexes with triphenylphosphine were monitored by 31P NMR and
UV-vis absorption spectroscopies. In the reaction of the manganese
or iron peroxo porphyrin complex, (TPP)MIIICl, M ) Fe or Mn (10
mg, 11 µmol), was added to a solution of KO2 (2 equiv) and K222 (3
equiv) in CD3CN (total volume ) 1 mL, [peroxo metalloporphyrin
complex] ) 11 mM), and the mixture was stirred for 10-20 min. This
solution was titrated with 5 equiv of triphenylphosphine, and the
resulting 31P NMR spectra were recorded after 1 h. Aliquots for UV-
vis absorption analysis were removed after 15 min and analyzed using
0.1 mm cells. (TPP)TiO2 (5 mg, 7.2 µmol) was dissolved in THF-d8
(total volume ) 1 mL, 7.2 mM), the solution was reacted with 5 equiv
of triphenylphosphine, the mixture was analyzed as described above.
Reactions of the Metalloporphyrin Peroxide Complexes with
Butyllithium. Molybdenum(VI) pentoxide hexamethylphosphoramide
(MoO5HMPA) was prepared by literature methods.31 The peroxo
complexes either were dissolved (TPP)TiO2 or were prepared (Mn or
Fe) in THF (1.85 mM); to this solution was added g1 equiv of
butyllithium. After 5 min-1 h of stirring, excess acetic anhydride was
added and the resulting solution was stirred for another 1 h. This
mixture was then assayed for the formation of butyl acetate by GC.
Reactions of the Metalloporphyrin Peroxide Complexes with
Cyclohexene. The reactions of the peroxo metalloporphyrin complexes
with cyclohexene were monitored by GC and UV-vis absorption
spectroscopies. (TMP)MnCl (20 µmol) or (TMP)FeCl (20 µmol) and
a 5-fold molar excess of KO2 were combined with 2.0 equiv of 18-
crown-6 in CH3CN (10 mL, [peroxo metalloporphyrin complex] ) 2
mM), and the mixture was stirred for 30 min. The resultant mixture
was then filtered through a 0.45 µm filter to remove undissolved KO2,
and the filtrate was stirred rapidly with 120 equiv of cyclohexene (250
µL in 5 mL of CH3CN). The reaction of the titanium peroxo complex
was performed in the same manner by dissolving the appropriate amount
of the peroxo complex in tetrahydrofuran and stirring the solution with
cyclohexene. Samples were analyzed by GC for the formation of
cyclohexene oxide as well as cyclohexen-1-ol and cyclohexen-1-one.
For spectral titrations, solutions of (TPP)MIIICl, M ) Fe and Mn (1
mM), were diluted to a final concentration of 1.7 × 10-5 M. Two
equivalents of superoxide was added in each case, the formation of
the peroxo complexes was verified by UV-vis absorption spectros-
copy,32,33 and then cyclohexene was added. Spectra were recorded
several minutes after addition of the cyclohexene.
We report here a study of the relative reactivities of a series
of Fe(III), Mn(III), and Ti(IV) porphyrin peroxo complexes in
direct reactions with a variety of electron-rich and electron-
poor organic substrates. The dramatic differences in the
reactivities of these species allow us to rank these metallopor-
phyrin complexes with respect to their relative reactivities and
to compare them with some of the non-porphyrin transition
metal peroxo complexes. We find that the ferric porphyrin
peroxo complex is by far the most nucleophilic of these
complexes and therefore conclude that peroxo heme intermedi-
ates in enzymatic systems likewise have a high degree of
nucleophilic character and will react with an appropriate
substrate, if the substrate has unhindered access to the peroxo
ligand. We also propose a classification scheme for the relative
nucleophilic reactivity of a number of porphyrin and non-
porphyrin transition metal peroxo complexes.
Experimental Section
Materials and Methods. All reactions were performed under an
inert atmosphere of helium in a Vacuum Atmospheres glovebox.
Solvents were dried by distillation under an inert atmosphere from
appropriate drying agents: calcium hydride for dimethylacetamide
(DMA) and acetonitrile (CH3CN); sodium/benzophenone for tetrahy-
drofuran (THF). Dimethylacetamide and acetonitrile were then further
dried inside the glovebox by passage through neutral Woelm or Sigma
activity grade Super I alumina. The solvent was stirred for 30 min
with powdered potassium superoxide (KO2, Aldrich) and filtered
through more Super I alumina.25 Electron spin resonance (ESR) spectra
of the solvents showed no signal from dissolved superoxide. Tetra-
methylammonium superoxide ((TMA)O2) was prepared by literature
methods and determined to be greater than 95% pure by titration.26
Kryptate 222 (K222, MCB) was purified by recrystallization from
heptane in the glovebox or was used as received. 18-Crown-6 (Aldrich)
was recrystallized by literature procedures.27 (TPP)FeCl and (TPP)-
MnCl (TPP ) tetraphenylporphyrin) were prepared by metalation of
chlorin-free tetraphenylporphyrin (Mid-Century Chemical) by published
procedures.28 For the cyclohexene reactivity studies, (TMP)FeCl (TMP
) tetramesitylporphyrin) was prepared by a modification of a published
procedure29 and metalated by the method of Adler.28 All other studies
30
used (TMP)FeCl obtained from Mid-Century Chemical. (TPP)TiO2
Reactions of the Metalloporphyrin Peroxide Complexes with
Tetramethylethylene. To a 1 mM solution of (TMP)MO2-, prepared
as described above, was added up to 100 equiv of tetramethylethylene
by syringe. The mixture was then analyzed by UV-vis absorption
spectroscopy using 0.1 mm cells.
was the generous gift of Dr. J.-M. Latour. Triphenylphosphine (BDH,
analytical standard grade) was dried over phosphorus pentoxide and
stored in the drybox. Triphenylphosphine oxide (Chemalog) was used
as a standard in the identification of the oxidized substrate. Tetrameth-
ylethylene (Aldrich) was passed over basic alumina and checked for
purity by 1H NMR prior to use. Butyllithium (1.5 M in hexanes),
tetracyanoethylene (TCNE), tetracyanoethylene oxide (TCNE oxide),
and Pt(PPh3)4 were obtained from Aldrich. Deuterated chloroform and
acetonitrile were obtained from Cambridge Isotopes.
Reactions of the Metalloporphyrin Peroxide Complexes with
2-Cyclohexen-1-one, 2-Methyl-1,4-naphthoquinone, and 2-Methyl-
1,4-naphthoquinone Epoxide. [(TMP)FeO2]- and the Mn analog were
prepared as described above. (TPP)TiO2 was dissolved in THF as
described above. Two-equivalents of 2-cyclohexen-1-one (103 mM,
67 µL in CH3CN) was added to 3.44 mM peroxo metalloporphyrin
solutions (1 mL total volume), and the reactions were allowed to
proceed, during which time aliquots were removed after approximately
10 and 30 min for GC-MS analysis. Prior to use, formation of the
peroxo metalloporphyrin solutions was confirmed in each case by UV-
vis spectroscopy. Two-equivalents of 2-methyl-1,4-naphthoquinone
was added to the peroxo metalloporphyrin solutions, under inert
atmosphere, at both 1 mM (58.1 mM, 34 µL in CH3CN) and 0.1 mM
Instrumentation. A Hewlett Packard 5890A gas chromatograph
coupled with a Hewlett Packard Model 5970 mass selective detector
(24) Selke, M.; Sisemore, M. F.; Valentine, J. S. J. Am. Chem. Soc. 1996,
118, 2008-2012 and references therein.
(25) Burstyn, J. N. Ph.D. Thesis, University of California, Los Angeles,
1986.
(26) Sawyer, D. T.; Calderwood, T. S.; Yamaguchi, K.; Angelis, C. T.
Inorg. Chem. 1983, 22, 2577-2583.
(27) Valentine, J. S.; Miksztal, A. R.; Sawyer, D. T. Methods Enzymol.
1984, 105, 71-81.
(28) Adler, A. D.; Longo, F. R.; Kampas, F.; Kim, J. J. Inorg. Nucl. Chem.
1970, 32, 2445-2448.
(31) Mimoun, H.; Serre de Roch, I.; Sajus, L. Bull. Soc. Chim. Fr. 1969,
5, 1481-1492.
(29) Badger, G. M.; Jones, R. A.; Laslett, R. L. Aust. J. Chem. 1964, 17,
1028-1035.
(32) McCandlish, E.; Miksztal, A. R.; Nappa, M.; Sprenger, A. Q.;
Valentine, J. S.; Stong, J. D.; Spiro, T. G. J. Am. Chem. Soc. 1980,
102, 4268-4271.
(30) Guilard, R.; Latour, J.-M.; Lecomte, C.; Marchon, J.-C.; Protas, J.;
Ripoll, D. Inorg. Chem. 1978, 17, 1228.
(33) Valentine, J. S.; Quinn, A. E. Inorg. Chem. 1976, 15, 1997-1999.

Metalloporphyrin Peroxo Complexes
Inorganic Chemistry, Vol. 36, No. 6, 1997 981
(5.81 mM, 34 µL in CH3CN) concentrations to give total volumes of
1 mL. UV-vis spectra were taken 10 and 30 min after addition of the
substrate, and epoxide yields were determined by HPLC after 15 min
and 1 h. Reactions of the peroxometal porphyrin complexes with the
corresponding epoxide products was also investigated. 2-Methyl-1,4-
naphthoquinone epoxide was prepared by a published procedure.34 Two-
equivalvent amounts of the epoxide (5.3 mM, 34 µL in CH3CN) were
added to 0.1 mM solutions of the peroxo metalloporphyrin complexes
(total volume 1 mL). UV-vis spectra were taken 15 min and 1 h
after addition of the epoxide, and the loss of epoxide was monitored
by HPLC.
Reactions of the Metalloporphyrin Peroxide Complexes with
Tetracyanoethylene and Tetracyanoethylene Oxide. Two-equivalent
amounts of TCNE (29 µL, 78 mM in CH3CN) were added to solutions
of the peroxo metalloporphyrin complexes (1 mM, 1 mL total volume),
and the mixtures were stirred for 10 min prior to analysis by UV-vis
absorption spectroscopy. Reactions of the peroxo metalloporphyrin
complexes with 2-equiv samples of TCNE epoxide (1 mg) were carried
out analogously. Organic products were analyzed by GC-MS.
Reaction of Pt(PPh3)2O2 with 2-Methyl-1,4-naphthoquinone. Pt-
Figure 1. UV-vis spectra for the reaction of TiIV(TPP)O2 with
triphenylphosphine in THF. Spectrum 1 corresponds to the peroxoti-
tanium porphyrin complex, while spectrum 2 corresponds to the product
formed upon reaction with 5 equiv of triphenylphosphine. The UV-
vis absorption spectrum of the porphyrin product is identical to that of
TiIV(TPP)O.
(PPh3)2O2 was prepared in CDCl3 by a literature method,35 and its 31
P
NMR spectrum was recorded. To this solution was added 4 equiv of
2-methyl-1,4-naphthoquinone. The final concentration of the Pt
complex was 5 mM. The 31P NMR and 1H NMR spectra of the reaction
solution were recorded after approximately 10 min and 2 h.
after 1 h, in a solution containing either 20 mM [(TMP)FeO2]-
or 20 mM [(TMP)MnO2]- and 5 equiv of triphenylphosphine.
(b) Reactions with Butyllithium. According to the proce-
dure described by Regen and Whitesides,38 the peroxo com-
plexes were reacted with butyllithium, and the extents of the
reactions were assayed by gas chromatography. In this assay,
the butoxy anion formed by the oxidation of the butyl anion by
the peroxo complex reacts with acetic anhydride to give butyl
acetate. (TPP)TiO2 was reacted with butyllithium according
to the published procedure. When butyllithium was added, the
solution immediately turned from pink to dark green. Only trace
amounts of butyl acetate were seen when the reaction was
quenched with acetic anhydride. In none of the reactions was
the yield of butyl acetate more than 6%. The iron peroxo
complex was reacted with butyllithium and acetic anhydride in
a similar fashion. No butyl acetate was observed despite the
addition of a large excess of butyllithium, nor was it observed
when the reaction was followed for an extended period of time.
The reaction was also monitored by UV-vis spectroscopy,
which indicated that the butyllithium reduced the Fe(III) initially
to a species similar to the ferrous hydroxo complex.
Results
I. Reactions of (porph)TiIVO2, [(porph)MnIIIO2]-, and
[(porph)FeIIIO2]- with Electron-Rich Substrates. (a) Reac-
tions with Triphenylphosphine. The titanium peroxo por-
phyrin reacted rapidly and stoichiometrically with triphenylphos-
phine to give 1 equiv of triphenylphosphine oxide, identified
by HPLC and 31P NMR, and 1 equiv of (TPP)TiIVO, identified
by its UV-vis spectrum. It was previously reported that the
peroxotitanium porphyrin can be photochemically induced to
oxygenate a variety of organic substrates;36,37 therefore, we also
carried out the reaction with triphenylphosphine in the dark in
order to ascertain if the reaction observed was photochemically
driven. Again the spectrum indicated that the sole component
of the reaction mixture was the oxotitanium porphyrin, and the
yield of triphenylphosphine oxide was 87% ( 2% as measured
by 31P NMR. From these results, we conclude that the oxidation
of triphenylphosphine is a characteristic reaction of the peroxo-
titanium porphyrin complex and does not require light. The
reaction is illustrated in eq 1; UV-vis spectra of the peroxo Ti
porphyrin complex before and after the addition of phosphine
are shown in Figure 1.
The reactivity of the manganese peroxo complex was similar
to that of the iron; i.e., no butyl acetate was formed under the
reaction conditions. MoO5HMPA was used as a control and
was observed to yield 1 equiv of butyl acetate/equiv of peroxide
ligand under identical conditions.
(porphyrin)TiIVO2 + PPh3 f (porphyrin)TiIVdO + Ph3PO
(1)
(c) Reactions with Cyclohexene and Tetramethylethylene.
Cyclohexene has two different modes of reactivity with oxygen
transfer reagents, i.e., allylic oxidation and epoxidation. The
former is characteristic of a radical mechanism, producing
primarily the allylic oxidation products cyclohexen-1-ol and
cyclohexen-1-one, and the latter of a non-radical, or atom
transfer, pathway, which typically produces high yields of the
epoxide. No epoxide was detected in the [(TMP)FeO2]-
reaction with cyclohexene, and only a trace (<1%) was detected
in the (TPP)TiO2 reaction. [(TMP)MnO2]- produced 2.4% of
the epoxide over a period of 1 h, but no further increase in the
epoxide level occurred over time. The levels of 2-cyclohexen-
1-one and 2-cyclohexen-1-ol were also quite low in all cases
(<1% for Ti and not detectable for Mn and Fe). The UV-vis
spectra of the metalloperoxide porphyrin complexes were
In contrast to the titanium complex, the iron and manganese
peroxo porphyrins did not react with triphenylphosphine.
Spectrophotometric titrations demonstrated that the peroxo
complexes were unaffected by the addition of triphenylphos-
phine: when either the iron or the manganese peroxo complex
was titrated with 1-5 equiv of substrate, there was virtually no
UV-vis spectral change. This lack of reactivity was observed
in a variety of solvents, including DMSO, DMA, CH3CN, and
THF, and for both tetraphenyl- and tetramesityl porphyrins. In
addition, no triphenylphosphine oxide was detected by 31P NMR
(34) Felix, D.; Wintner, C.; Eschenmoser, A. Organic Syntheses; Wiley:
New York, 1988; Collect. Vol. 6, pp 679-682.
(35) Cook, C. D.; Jauhal, G. S. J. Am. Chem. Soc. 1968, 90, 1464.
(36) Hoshino, M.; Yamamoto, K.; Lillis, J. P.; Chijimatsu, T.; Uzawa, J.
Inorg. Chem. 1993, 32, 5002-5003.
(37) Boreham, C. J.; Latour, J.-M.; Marchon, J.-C.; Boisselier-Cocolios,
B.; Guilard, R. Inorg. Chim. Acta 1980, 45, L69-L71.
(38) Regen, S. L.; Whitesides, G. M. J. Organomet. Chem. 1973, 59, 293-
297.

982 Inorganic Chemistry, Vol. 36, No. 6, 1997
Sisemore et al.
spectrum of the resulting solution indicated that [(TMP)FeO2]-
reacted very rapidly with TCNE oxide to give unknown
products. Likewise, addition of 2 equiv of TCNE or TCNE
oxide to a 1 mM solution of [(TMP)MnO2]- immediately led
to dramatic changes in the UV-vis spectrum indicating the same
unknown products.
Table 1. Comparative Reactivities of Peroxo Fe(III), Mn(III), and
Ti(IV) Porphyrin Complexes with Electron-Deficient Olefins
yield,a %
peroxo
metalloporphyrin
complex
2-methyl-1,4-
naphthoquinone
epoxide
2-cyclohexen-1-
one epoxide
[FeIII(TMP)O2]- b
23 ( 2
<1
76 ( 8
5 ( 1
<0.5
Reaction of Pt(PPh3)2O2 with 2-Methyl-1,4-naphthoquino-
ne. Since Pt(PPh3)2O2 is a classic nucleophilic peroxometal
complex whose reactivity with tetracyanoethylene and related
electron-deficient olefins has been well characterized,39 we
investigated its reactivity with 2-methyl-1,4-naphthoquinone in
order to compare its nucleophilic reactivity with that of the
peroxo metalloporphyrin complexes. No 2-methyl-1,4-naph-
- b
[MnIII(TMP)O2]
c
TiIII(TMP)O2
<1
KO2 controlb
<3
8 ( 1
5 ( 1
H2O2/KHCO3 controlb
a Yields based on 3.44 mM porphyrin (or oxidant in the controls)
used to make the peroxo complexes. b These reactions were carried
out in CH3CN. c These reactions were carried out in THF.
1
thoquinone epoxide was detected (by H NMR) upon mixing
Pt(PPh3)2O2 with 4 equiv of 2-methyl-1,4-naphthoquinone in
CDCl3. The spectrum of the starting material did not change
after addition of the platinum peroxo complex: the 31P NMR
spectrum of the mixture showed the characteristic triplet of the
platinum peroxo complex [δ ) 15.3 ppm (t, J(195Pt-P) ) 4083
Hz); lit.40 16.4 ppm (t, J(195Pt-P) ) 4059 Hz)]; a small amount
of PPh3O was also present. The 31P NMR spectrum did not
change during a 2-h period, except that the peak for triphen-
ylphosphine oxide (29.2 ppm) increased somewhat, as would
be expected in a CDCl3 solution containing trace amounts of
water.40 Hence we conclude that the platinum peroxo complex
does not readily react with 2-methyl-1,4-naphthoquinone.
essentially unchanged after addition of either cyclohexene or
the more electron-rich olefin tetramethylethylene. No tetrameth-
ylethylene oxide was detected for any of the metalloperoxide
porphyrin complexes by GC-MS over a period of 30 min. Thus
none of the metalloporphyrin peroxo complexes we examined
demonstrated significant reactivity toward these electron-rich
olefins.
II. Reactions of Ti(IV), Mn(III), and Fe(III) Porphyrin
Peroxo Complexes with Electron-Deficient Substrates. (a)
Reactions with 2-Cyclohexen-1-one, 2-Methyl-1,4-naphtho-
quinone, and 2-Methyl-1,4-naphthoquinone Epoxide. Since
the metalloporphyrin peroxo complexes showed little tendency
to react with electron-rich substrates, the ability of these
complexes to react with electron-deficient olefins and quinones
was assessed. Addition of 2 equiv of 2-cyclohexen-1-one to
3.4 mM solutions of the Mn and Ti peroxo porphyrin complexes
(or 2 equiv of 2-methyl-1,4-naphthoquinone to 0.1 mM solutions
of these peroxo metalloporphyrin complexes) caused essentially
no change in the UV-vis spectra after 10 min. The yields of
the products, i.e., 2-cyclohexanone epoxide, determined by GC-
MS, and 2-methyl-1,4-naphthoquinone epoxide, determined by
HPLC, are shown in Table 1. No detectable level of 2-cyclo-
hexanone epoxide (i.e., <1%) was seen after 10 and 30 min. A
small amount of 2-methyl-1,4-naphthoquinone epoxide (5% (
1%) was observed for the [(TMP)MnO2]- reaction after 30 min,
but none was detected for (TPP)TiO2 (i.e., <0.5%). In contrast,
0.1 mM peroxoiron tetramesitylporphyrin gave much higher
yields of 2-methyl-1,4-naphthoquinone epoxide (76% ( 8%)
and was the only complex that epoxidized 2-cyclohexen-1-one
(23% ( 2%).23 When the peroxo Fe and Mn porphyrin
complexes were reacted with 2-methyl-1,4-naphthoquinone
epoxide (2 equiv) under the same conditions, the losses of
epoxide after 1 h were similar, i.e., 19% ( 2% for reaction
with the peroxo Fe porphyrin and 14% ( 2% for reaction with
the peroxo Mn porphyrin. (TPP)TiO2 was unreactive with
2-methyl-1,4-naphthoquinone epoxide. We conclude that the
large difference in epoxide yields (Table 1) observed is due to
inherent differences in reactivity with the olefin and not with
the epoxide product.
Discussion
Classification of Metalloperoxide Complexes According
to Their Reactivities with Electron-Rich vs Electron-Poor
Substrates. Peroxo complexes of transition metals can gener-
ally be classified as either electrophilic or nucleophilic with
respect to their reactivities with organic substrates.41-44 Elec-
trophilic species have been characterized by their ability to
oxidize the butyl anion to the butoxide anion38 and the sulfide
moiety of thianthrene 5-oxide (SSO) to sulfoxide.43,44 Reactivity
with triphenylphosphine to give triphenylphosphine oxide can
also be used to assess the electrophilicity of such complexes.45
The strongest electrophiles in such reactions are typically those
peroxo complexes of metal ions with low numbers of electrons
in d orbitals, such as Mo(VI), W(VI), and Cr(VI), which are
all d0. Complexes of metal ions with a high number of d
electrons, such as Pt(II) (d8) and Ir(III) (d6), are found to have
little electrophilic character. The electrophilic peroxo metal
complexes frequently are found to be more reactive with
electron-rich olefins.46,47
Sheldon and van Doorn39 have reported that some peroxo-
metal complexes derived from group VIII metal complexes are
nucleophilic: they react readily with the extremely electron-
poor olefin TCNE. Reactivity toward activated carbonyls, such
as acyl halides, also appears to be characteristic of nucleophilic
peroxo metalloporphyrin complexes.18,19 Our results indicate
that the reactivity of peroxo complexes with electron-deficient
(b) Reactions of of [(TMP)FeO2]- and [(TMP)MnO2]-
with Tetracyanoethylene and Tetracyanoethylene Oxide.
Addition of 2 equiv of TCNE to (TPP)TiO2 (1 mM) led to no
change in the UV-vis spectrum after 30 min; an immediate
change occurred, however, upon addition of TCNE to 1 mM
solutions of either [(TMP)FeO2]- or [(TMP)MnO2]-. Malono-
nitrile was the only organic product formed in the reaction, as
confirmed by comparison of the GC-MS fragmentation pattern
with that of a standard.
(39) Sheldon, R. A.; van Doorn, J. A. J. Organomet. Chem. 1975, 94, 115-
129.
(40) Sen, A.; Halpern, J. J. Am. Chem. Soc. 1977, 99, 8337-8339.
(41) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of Organic
Compounds; Academic Press: New York, 1981.
(42) Kitajima, N.; Moro-oka, Y. Chem. ReV. 1994, 94, 737-757.
(43) Adam, W.; Haas, W.; Lohray, B. B. J. Am. Chem. Soc. 1991, 113,
6202-6208.
(44) Ballistreri, F. P.; Tomaselli, G. A.; Toscano, R. M.; Conte, V.; Di
Furia, F. J. Am. Chem. Soc. 1991, 113, 6209-6212.
(45) Mimoun, H.; Postel, M.; Casabianca, F.; Fischer, J.; Mitschler, A.
Inorg. Chem. 1982, 21, 1303-1306.
(46) Chong, A. O.; Sharpless, K. B. J. Org. Chem. 1977, 42, 1587-1590.
(47) Mimoun, H. J. Mol. Catal. 1980, 7, 1-29.
To determine if TCNE oxide, if it were formed, would be
stable to the reaction conditions, we added 2 equiv of TCNE
oxide to a 1 mM solution of [(TMP)FeO2]-. The UV-vis

Metalloporphyrin Peroxo Complexes
Inorganic Chemistry, Vol. 36, No. 6, 1997 983
Table 2. Classification Scheme for Nucleophilic and Electrophilic
olefins such as 2-cyclohexen-1-one and 2-methyl-1,4-naphtho-
quinone can also be used to classify the reactivities of these
complexes. We have found that only those peroxo complexes
of extremely strong nucleophilic character react rapidly and in
high yield with 2-cyclohexen-1-one and 2-methyl-1,4-naphtho-
quinone. Thus these two substrates allow us to discriminate
between different degrees of nucleophilic character in the
peroxoiron and peroxomanganese porphyrin complexes. We
have classified the peroxotitanium porphyrin complex as a weak
electrophile, despite its lack of reactivity with the butyl anion25
and cyclohexene, because it is able to oxidize triphenylphosphine
and because it is completely unreactive with electron-deficient
olefins, including TCNE.
Neither the [(TPP)MnIIIO2]- nor the [(TPP)FeIIIO2]- complex
reacted with triphenylphosphine under conditions identical to
those used for the reaction with (TPP)TiO2. While the titanium
complex can form a stable oxo complex, this is not an option
for the manganese and iron complexes, since the corresponding
unprotonated oxo complexes of Fe(III) and Mn(III), if they were
formed as products, would be expected to be less stable than
the peroxo complees themselves. While hydroxo complexes
of manganese(III) and iron(III) porphyrins are stable, the
corresponding oxo complexes are not, because of the inability
of these metal ions to stabilize the oxide ligand through
π-bonding from filled oxygen p orbitals to empty d orbitals of
π symmetry on the metal.2,3 The absence of a favorable reaction
pathway presumably accounts for the lack of reactivity of
triphenylphosphine with either of these metalloporphyrin per-
oxides.
Ferrous porphyrins react with dioxygen to form µ-peroxo
dimeric porphyrin complexes which react with triphenylphos-
phine to give triphenylphosphine oxide.14,48 This sequence has
been shown to proceed not by a direct reaction of the peroxide
ligand but by prior O-O bond cleavage to give an Fe(IV) oxo
complex, PFeIVdO, which is the species responsible for the
transfer of an oxygen atom to the phosphine.
All of the metalloporphyrin peroxide complexes studied
reacted with butyllithium, but none of these reactions led to
the formation of lithium butoxide. Thus it appears that
butyllithium reacts with the Fe, Mn, and Ti metalloporphyrin
moieties faster than it does with the bound peroxo ligands.
Therefore no information regarding the inherent electrophilicity
of the peroxo ligand can be obtained in these cases. It is
interesting to note that, while butyllithium is a more exothermic
oxygen scavenger than triphenylphosphine thermodynamically
[∆Hf(LiBu) - ∆Hf(LiOBu) ) 390 ( 15 kJ/mol49 vs ∆Hf(Ph3P)
- ∆Hf(Ph3PO) ) 323.4 ( 4.9 kJ/mol],50 it fails to react with
the peroxo moiety of (TPP)TiO2, while triphenylphosphine does
react.
Peroxo Complexesa
rincreasing nucleophilicity
increasing electrophilicityf
class II class I
electrophile electrophiles
class I
class II
nucleophile
nucleophiles
[FeIII(porph)O2]- [MnIII(porph)O2]- TiIV(TPP)O2
MoVIO2
CrVIO2
VVO2
PtII(PPh3)2O2
Ir(CO)I(PPh3)2O2
TiIVO2
a Substrates oxidized by class I nucleophiles: TCNE, acyl halides,
CO2, enones, quinones. Substrates oxidized by class II nucleophiles:
TCNE, acyl halides, CO2. Substrates oxidized by class I electrophiles:
triphenylphosphine, electron-rich olefins. Substrates oxidized by class
II electrophiles: triphenylphosphine.
the d orbitals of the metal, as in the d8 metal complexes formed
by the group VIII metals such as Pt(II) and Pd(II). These
complexes are known to react with highly electron-deficient
substrates such as tetracyanoethylene38,39 and acyl halides.51 Our
studies indicate, however, that (Ph3P)2PtO2 does not react with
2-methyl-1,4-naphthoquinone. While the reactivity of the d6
complex (Ph3P)2Ir(CO)(O2)I has not been studied with class I
substrates, we place it in class II because it is known to react
38,39
with TCNE but to be less nucleophilic than (Ph3P)2PtO2.
Also included in this category is the d4 porphyrin complex
[(TMP)MnO2]-, which reacts with tetracyanoethylene (this
work) and acyl halides18 but does not react to any appreciable
extent with 2-cyclohexen-1-one or 2-methyl-1,4-naphthoqui-
none. All of the class I and class II nucleophiles are unreactive
toward electron-rich substrates such as cyclohexene, the butyl
anion, and triphenylphosphine.
Class I electrophiles react with butyllithium, at low temper-
ature, to give the butoxide anion; many also react with electron-
rich olefins such as cyclohexene to give the corresponding
epoxides. Examples of such electrophilic d0 peroxometal
complexes are those which contain Mo(VI) or W(VI),38,43,44,46,47
Cr(VI),]38 V(V),46,47 and Ti(IV).52,53 Class II electrophiles, such
as the d0 complex (TPP)TiO2, react neither with electron-
deficient nor with electron-rich olefins but do oxidize triphen-
ylphosphine to triphenylphosphine oxide.
Unusual Reactivity of Peroxo Fe(III) and Mn(III) Por-
phyrin Complexes with TCNE. Nucleophilic (dioxygen)metal
complexes such as (Ph3P)2MO2 (M ) Pd, Pt) readily add to
tetracyanoethylene to form cyclic peroxy adducts which have
been characterized by IR and NMR.39 Both [(TMP)Fe(O2]-
and [(TMP)MnO2]- react actively with tetracyanoethylene but
they react rapidly with tetracyanoethylene oxide as well, so we
are unable to determine if the epoxide is formed as an
intermediate in this reaction. Nevertheless, the known nucleo-
philic reactivity of [(TMP)FeO2]- and [(TMP)MnO2]- with
other electron-deficient olefins and the known reactivity of
TCNE with other nucleophilic metal peroxide complexes make
us confident that the initial step of the reaction involves
nucleophilic attack of the peroxometal complex on the electron-
deficient bond, as shown in eq 2.
Classification Scheme. Table 2 illustrates the classification
scheme that we have devised for metalloperoxide complexes
on the basis of their observed relative reactivities with electron-
rich and electron-poor substrates. Class I nucleophiles react
not only with extremely electron-deficient substrates, such as
tetracyanoethylene (this work) and acyl halides,19 but also with
enones and quinones.23 The only metalloperoxide complexes
known to transfer oxygen directly to these latter substrates are
those which contain a d5 iron(III) metal such as [(TMP)FeO2]-.23
Class II nucleophiles include those non-porphyrin metallo-
peroxide complexes that contain a high number of electrons in
The Remarkable Nucleophilicity of the Peroxoiron(III)
Complex. It has been proposed,54 on the basis of charge-
iterative extended Hu¨ckel (IEH) calculations, that the relative
energies of the orbitals of [(TMP)MnO2]- are unusual relative
(51) Chen, M. J. Y.; Kochi, J. K. J. Chem. Soc., Chem. Commun. 1977,
204-205.
(48) Chin, D.-H.; LaMar, G. N.; Balch, A. L. J. Am. Chem. Soc. 1980,
102, 4344-4350.
(49) Liebman, J. F.; Martinho Simoes, J. A.; Slayden, S. W. In Lithium
Chemistry: A Theoretical and Experimental OVerView; Sapse, A.-
M., Schleyer, P. v. R., Eds.; Wiley: New York, 1995; pp 173-193.
(50) Kirklin, D. R.; Domalski, E. S. J. Chem. Thermodyn. 1988, 20, 743.
(52) Williams, I. D.; Pedersen, S. F.; Sharpless, K. B. J. Am. Chem. Soc.
1984, 106, 6431-6433.
(53) Lu, L. D.; Johnson, R. A.; Finn, M. G.; Sharpless, K. B. J. Org. Chem.
1984, 49, 728-731.
(54) Van Atta, R. B.; Strouse, C. E.; Hanson, L. K.; Valentine, J. S. J. Am.
Chem. Soc. 1987, 109, 1425-1434.

984 Inorganic Chemistry, Vol. 36, No. 6, 1997
Sisemore et al.
nucleophilic of the known metalloporphyrin peroxo complexes
and that they are probably among the most nucleophilic of all
metal peroxo complexes, porphyrin or non-porphyrin. This
conclusion is supported by the observation by Rana and
Meares55,56 that non-porphyrin ferric peroxo EDTA complexes
tethered to proteins are highly reactive and cause cleavage of
peptides by a mechanism whose first step is nucleophilic attack
on a peptide carbonyl. The extraordinarily high nucleophilic
character of ferric porphyrin peroxo complexes demonstrated
here also lends strong support to mechanisms proposing
nucleophilic attack by peroxo heme intermediates in enzymes
such as aromatase,7,8 cytochrome P450-2B4,10 and NO syn-
thase11 and suggests that other examples of such enzymatic
reactions should be sought.
(2)
to other MnIII porphyrin complexes due to the large out-of-plane
metal displacement and strong d-O2 πg orbital mixing. The
lowest unoccupied molecular orbital in the d4 [(TMP)MnO2]-
complex is thought to be a 43% dyz + 47% O2 πgz hybrid.
However, in the d5 [(TMP)FeO2]- complex, this same orbital
would be occupied by a single electron, which would thus have
a high degree (47%) of peroxo orbital character. Occupancy
of this orbital by the fifth d electron may explain why the peroxo
Fe(III) porphyrin complexes are so extraordinarily nucleophilic
as compared to their Mn(III) analogs.
Conclusion. Determination of the relative reactivities of Fe-
(III), Mn(III), and Ti(IV) porphyrin peroxo complexes with
electron-rich and electron-poor substrates has allowed us to
classify these complexes and to compare them with several well-
characterized non-porphyrin metal peroxo complexes. We
conclude that the iron(III) peroxo complexes are by far the most
Acknowledgment. The authors thank Dr. Christopher S.
Foote, Dr. Jon M. Fukuto, and Dr. Joel F. Liebman for helpful
discussions throughout the course of this work, which was
funded by the National Science Foundation.
IC9612616
(55) Rana, T. M.; Meares, C. F. Proc. Natl. Acad. Sci. U.S.A. 1991, 88,
10578-10582.
(56) Rana, T. M.; Meares, C. F. J. Am. Chem. Soc. 1991, 113, 1859-
1861.