Participation of two distinct hydroxylating intermediates in iron(III) porphyrin complex-catalyzed hydroxylation of Alkanes

Article abstract of DOI:10.1021/ja0010554

We have obtained evidence that acylperoxo-iron(III) porphyrin complexes 1a are involved as reactive hydroxylating intermediates in the hydroxylation of alkanes by m-chloroperoxybenzoic acid (m-CPBA) catalyzed by electron-deficient iron(III) porphyrin complexes containing chloride as an anionic axial ligand in a solvent mixture of CH₂Cl₂ and CH₃CN at -40 °C. In addition to the intermediacy of 1a, oxoiron(IV) porphyrin cation radical complexes 2 are formed as the reactive hydroxylating intermediates in the alkane hydroxylations by m-CPBA catalyzed by the iron(III) porphyrin complexes containing triflate (CF₃SO₃^-) as an anionic axial ligand under the same reaction conditions. In line with the recent proposal by Newcomb, Coon, Vaz, and co-workers for cytochrome P-450 reactions, these results suggest that two distinct electrophilic oxidants such as 1a and 2 effect the alkane hydroxylations in iron porphyrin models, depending on the reaction conditions such as the nature of the anionic axial ligands of iron(III) porphyrin complexes.

Full text of DOI:10.1021/ja0010554

J. Am. Chem. Soc. 2000, 122, 10805-10809
10805
Participation of Two Distinct Hydroxylating Intermediates in Iron(III)
Porphyrin Complex-Catalyzed Hydroxylation of Alkanes
,†
†
†
‡
Wonwoo Nam,* Mi Hee Lim, Sun Kyung Moon, and Cheal Kim
Contribution from the Department of Chemistry and DiVision of Molecular Life Sciences,
Ewha Womans UniVersity, Seoul 120-750, Korea, and Department of Fine Chemistry,
Seoul National Polytechnic UniVersity, Seoul 139-743, Korea
ReceiVed March 27, 2000
Abstract: We have obtained evidence that acylperoxo-iron(III) porphyrin complexes 1a are involved as reactive
hydroxylating intermediates in the hydroxylation of alkanes by m-chloroperoxybenzoic acid (m-CPBA) catalyzed
by electron-deficient iron(III) porphyrin complexes containing chloride as an anionic axial ligand in a solvent
mixture of CH2Cl2 and CH3CN at -40 °C. In addition to the intermediacy of 1a, oxoiron(IV) porphyrin cation
radical complexes 2 are formed as the reactive hydroxylating intermediates in the alkane hydroxylations by
-
m-CPBA catalyzed by the iron(III) porphyrin complexes containing triflate (CF3SO3 ) as an anionic axial
ligand under the same reaction conditions. In line with the recent proposal by Newcomb, Coon, Vaz, and
co-workers for cytochrome P-450 reactions, these results suggest that two distinct electrophilic oxidants such
as 1a and 2 effect the alkane hydroxylations in iron porphyrin models, depending on the reaction conditions
such as the nature of the anionic axial ligands of iron(III) porphyrin complexes.
Introduction
Scheme 1
Elucidation of the structure of reactive intermediates respon-
sible for oxygen atom transfer in the catalytic hydroxylation of
alkanes by cytochrome P-450 enzymes and their iron(III)
porphyrin models has been the continuing interest in biological
1,2
and bioinorganic chemistry. It has been generally believed
for a long time that oxoiron(IV) porphyrin cation radical
intermediates 2 are the sole reactive species capable of activating
Considerable indirect evidence for the intermediacy of 2 in the
1
the energetically difficult C-H bonds of alkanes (Scheme 1).
catalytic hydroxylation of alkanes by iron porphyrin complexes
3
has been reported. Also, several oxoiron(IV) porphyrin cation
†
Ewha Womans University.
Seoul National Polytechnic University.
radical complexes generated at low temperature were directly
used in the reactivity studies of alkane hydroxylation reactions.4
In addition to the intermediacy of 2, it has been proposed
recently that hydroperoxo-iron(III) porphyrin intermediates 1
are able to hydroxylate alkanes prior to the formation of 2
‡
(1) (a) Ingold, K. U.; MacFaul, P. A. In Biomimetic Oxidations Catalyzed
by Transition Metal Complexes; Meunier, B., Ed.; Imperial College Press:
London, 2000; pp 45-89. (b) McLain, J.; Lee, J.; Groves, J. T. In
Biomimetic Oxidations Catalyzed by Transition Metal Complexes; Meunier,
B., Ed.; Imperial College Press: London, 2000; pp 91-169. (c) Watanabe,
Y. In The Porphyrin Handbook; Kadish, K. M., Smith, K. M., Guilard, R.,
Eds.; Academic: New York, 2000; Vol. 4, Chapter 30, pp 97-117. (d)
Stahl, S. S.; Lippard, S. J. In Iron Metabolism Inorganic Biochemistry and
Regulatory Mechanisms; Ferreira, G. C., Moura, J. J. G., Franco, R., Eds.;
Wiley-VCH: Weinheim, 1999; pp 303-321. (e) Sono, M.; Roach, M. P.;
Coulter, E. D.; Dawson, J. H. Chem. ReV. 1996, 96, 2841-2887. (f) Ortiz
de Montellano, P. R. Cytochrome P450: Structure, Mechanism, and
Biochemistry, 2nd ed.; Plenum Press: New York, 1995. (g) Traylor, T. G.;
Traylor, P. S. In ActiVe Oxygen in Biochemistry; Valentine, J. S., Foote, C.
S., Greenberg, A., Liebman, J. F., Eds.; Chapman and Hall: London, 1995;
pp 84-187.
5
,6
(Scheme 1). Notably, Newcomb, Coon, Vaz, and co-workers
reported elegant results consistent with the involvement of two
distinct electrophilic oxidants such as 1 (or iron(III)-hydrogen
III
peroxide (Fe -H2O2) intermediate) and 2 in the hydroxylation
of alkanes by cytochrome P-450 enzymes and their mutants
(3) (a) Groves, J. T.; Shalyaev, K.; Lee, J. In The Porphyrin Handbook;
Kadish, K. M., Smith, K. M., Guilard, R., Eds.; Academic: New York,
2000; Vol. 4, Chapter 27, pp 17-40. (b) Meunier, B.; Robert, A.; Pratviel,
G.; Bernadou, J. In The Porphyrin Handbook; Kadish, K. M., Smith, K.
M., Guilard, R., Eds.; Academic: New York, 2000; Vol. 4, Chapter 31, pp
119-187. (c) Nam, W.; Goh, Y. M.; Lee, Y. J.; Lim, M. H.; Kim, C. Inorg.
Chem. 1999, 38, 3238-3240. (d) Gross, Z.; Simkhovich, L. J. Mol. Catal.
A: Chem. 1997, 117, 243-248. (e) Song, R.; Sorokin, A.; Bernadou, J.;
Meunier, B. J. Org. Chem. 1997, 62, 673-678. (f) Higuchi, T.; Shimada,
K.; Maruyama, N.; Hirobe, M. J. Am. Chem. Soc. 1993, 115, 7551-7552.
(g) Sorokin, A.; Robert, A.; Meunier, B. J. Am. Chem. Soc. 1993, 115,
7293-7299.
(4) Goh, Y. M.; Nam, W. Inorg. Chem. 1999, 38, 914-920.
(5) (a) Newcomb, M.; Shen, R.; Choi, S.-Y.; Toy, P. H.; Hollenberg, P.
F.; Vaz, A. D. N.; Coon, M. J. J. Am. Chem. Soc. 2000, 122, 2677-2686.
(b) Toy, P. H.; Newcomb, M.; Coon, M. J.; Vaz, A. D. N. J. Am. Chem.
Soc. 1998, 120, 9718-9719.
(6) Pratt, J. M.; Ridd, T. I.; King, L. J. J. Chem. Soc., Chem. Commun.
1995, 2297-2298.
(2) Some selected papers: (a) Suzuki, N.; Higuchi, T.; Urano, Y.;
Kikuchi, K.; Uekusa, H.; Ohashi, Y.; Uchida, T.; Kitagawa, T.; Nagano,
T. J. Am. Chem. Soc. 1999, 121, 11571-11572. (b) Filatov, M.; Harris,
N.; Shaik, S. Angew. Chem., Int. Ed. 1999, 38, 3510-3512. (c) Harris, D.
L.; Loew, G. H. J. Am. Chem. Soc. 1998, 120, 8941-8948. (d) Collman,
J. P.; Chien, A. S.; Eberspacher, T. A.; Brauman, J. I. J. Am. Chem. Soc.
1
998, 120, 425-426. (e) Choi, S.-Y.; Eaton, P. E.; Hollenberg, P. F.; Liu,
K. E.; Lippard, S. J.; Newcomb, M.; Putt, D. A.; Upadhyaya, S. P.; Xiong,
Y. J. Am. Chem. Soc. 1996, 118, 6547-6555. (f) Newcomb, M.; Le Tadic-
Biadatti, M. H.; Chestney, D. L.; Roberts, E. S.; Hollenberg, P. F. J. Am.
Chem. Soc. 1995, 117, 12085-12091. (g) Grinstaff, M. W.; Hill, M. G.;
Labinger, J. A.; Gray, H. B. Science 1994, 264, 1311-1313. (h) Egawa,
T.; Shimada, H.; Ishimura, Y. Biochem. Biophys. Res. Commun. 1994, 201,
1
464-1469. (i) Groves, J. T.; Nemo, T. E. J. Am. Chem. Soc. 1983, 105,
6
243-6248.
1
0.1021/ja0010554 CCC: $19.00 © 2000 American Chemical Society
Published on Web 10/21/2000

10806 J. Am. Chem. Soc., Vol. 122, No. 44, 2000
Nam et al.
Scheme 2
lacking threonine in the active site.5 In addition, Lippard,
Newcomb, and co-workers recently provided compelling evi-
dence that a hydroperoxo-iron(III) species is a plausible hy-
droxylating intermediate in methane monooxygenase enzymes
7
as well. In iron porphyrin models, although a number of reports
appeared recently that 1 is a viable reactive species capable of
8
oxygenating easily oxidized substrates such as olefins, it has
not been shown clearly that 1 is able to activate the C-H bonds
of alkanes to give alcohol products in iron porphyrin-catalyzed
hydroxylation of alkanes.9 In the present study, we report
evidence for the first time that acylperoxo-iron(III) porphyrin
III
complexes [(Porp)Fe -OOC(O)R, 1a] hydroxylate alkanes to
yield the corresponding alcohols in iron(III) porphyrin-catalyzed
hydroxylation of alkanes by m-chloroperoxybenzoic acid (m-
CPBA) at low temperature. We also show in this study that, as
Newcomb, Coon, Vaz, and co-workers have proposed in
cytochrome P-450 reactions, two distinct electrophilic oxidants
such as 1a and 2 are involved as reactive hydroxylating
intermediates in iron porphyrin-catalyzed hydroxylation of
alkanes.
Figure 1. UV-vis spectral changes upon the addition of m-CPBA to
a reaction solution containing Fe(TPFPP)Cl in the absence and presence
-4
of cyclohexane. (A) m-CPBA (1.5 × 10 mmol, diluted in 50 µL of
CH CN) was added to a 0.1-cm UV cell containing Fe(TPFPP)Cl (5
3
-
5
× 10 mmol, s) in a solvent mixture (0.5 mL) of CH
2 2 3
Cl and CH CN
IV
(1:1) at -40 °C. The completion of the formation of (TPFPP)Fe dO
(- - -) took 10 min. Inset: UV-vis spectra of Fe(TPFPP)Cl (s)
and (TPFPP)Fe dO (- - -) taken in the reaction of Fe(TPFPP)Cl
IV
-
4
-4
(
5 × 10 mmol) with 3 equiv of m-CPBA (1.5 × 10 mmol). (B)
Results and Discussion
The reaction procedures were the same as described in (A) except that
cyclohexane (0.3 mmol) was present in the reaction solution.
We have shown recently that the reactions of electron-
deficient iron(III) porphyrin complexes containing chloride as
an anionic axial ligand such as Fe(TPFPP)Cl (TPFPP ) meso-
tetrakis(pentafluorophenyl)porphinato dianion) and Fe(TDFPP)-
Cl (TDFPP ) meso-tetrakis(2,6-difluorophenyl)porphinato di-
anion) with m-CPBA gave the formation of oxoiron(IV)
porphyrin complexes 3 in a solvent mixture of CH2Cl2 and
CH3CN at -40 °C [Scheme 2, pathway A; see Figure 1A for
the UV-vis spectral change upon the addition of m-CPBA to
in the m-CPBA reactions and this intermediate is not able to
hydroxylate alkanes. However, it has been often reported
previously that the Fe(TPFPP)Cl complex is an effective catalyst
in the hydroxylation of alkanes by peracids in aprotic solvent,
1
3
giving high yields of alcohol products. Therefore, we were
curious about how the alcohol products are produced in the
hydroxylation of alkanes by the iron(III) porphyrin complex and
m-CPBA. We therefore carried out the m-CPBA reactions with
Fe(Porp)Cl complexes in the presence of cyclohexane under
the identical reaction conditions described above. Interestingly,
we observed a complete inhibition of the formation of 3 (see
Figure 1B for the UV-vis spectral change upon the addition
of m-CPBA to a reaction solution containing Fe(TPFPP)Cl and
cyclohexane) with a high yield of cyclohexanol formation
(∼70% based on m-CPBA added). This result suggests that a
reactive species different from 3 was generated as a hydrox-
ylating intermediate in the reactions of the iron porphyrin
complexes and m-CPBA.
10
a reaction solution containing Fe(TPFPP)Cl]. The oxoiron(IV)
IV
porphyrin complexes such as (TPFPP)Fe dO and (TDFPP)-
IV
Fe dO were found to be incapable of hydroxylating alkanes
at the reaction temperature (Scheme 2, pathway B).1
1,12
These
results indicate that we would not expect to observe the
formation of alcohol products in the hydroxylation of alkanes
by the electron-deficient iron(III) porphyrin complexes contain-
ing chloride as an axial ligand and m-CPBA, since 3 is formed
(
7) Choi, S.-Y.; Eaton, P. E.; Kopp, D. A.; Lippard, S. J.; Newcomb,
M.; Shen, R. J. Am. Chem. Soc. 1999, 121, 12198-12199.
8) (a) Vaz, A. D. N.; McGinnity, D. F.; Coon, M. J. Proc. Natl. Acad.
(
Sci. U.S.A. 1998, 95, 3555-3560. (b) Lee, Y. J.; Goh, Y. M.; Han, S.-Y.;
Kim, C.; Nam, W. Chem. Lett. 1998, 837-838. (c) Kamaraj, K.; Bandyo-
padhyay, D. J. Am. Chem. Soc. 1997, 119, 8099-8100. (d) Vaz, A. D. N.;
Pernecky, S. J.; Raner, G. M.; Coon, M. J. Proc. Natl. Acad. Sci. U.S.A.
More interestingly, the formation of 3 and the amounts of
cyclohexanol formed in the m-CPBA reactions were found to
depend on the concentration of cyclohexane present in the
reaction solutions. As the concentration of the alkane increased,
the formation of 3 decreased, while the yield of cyclohexanol
product increased (Figure 2). In addition to the concentration
effect, the amounts of 3 and alcohol products formed in the
m-CPBA reactions were found to depend on the C-H bond
strength of alkanes. When the C-H bond strength of alkanes
was weak (e.g., cis-1,2-dimethylcyclohexane), the formation of
1
996, 93, 4644-4648. (e) Machii, K.; Watanabe, Y.; Morishima, I. J. Am.
Chem. Soc. 1995, 117, 6691-6697. (f) Nam, W.; Lim, M. H.; Lee, H. J.;
Kim, C. J. Am. Chem. Soc. 2000, 122, 6641-6647.
(9) (a) Primus, J.-L.; Boersma, M. G.; Mandon, D.; Boeren, S.; Veeger,
C.; Weiss, R.; Rietjens, I. M. C. M. J. Biol. Inorg. Chem. 1999, 4, 274-
2
83. (b) Sorokin, A.; Robert, A.; Meunier, B. J. Am. Chem. Soc. 1993,
1
15, 7293-7299.
(10) Nam, W.; Lim, M. H.; Oh, S.-Y.; Lee, J. H.; Lee, H. J.; Woo, S.
K.; Kim, C.; Shin, W. Angew. Chem., Int. Ed. 2000, in press.
11) No formation of cyclohexanol was observed when cyclohexane was
(
3
was not detected but a high yield of alcohol formation was
IV
added to reaction solutions containing in situ generated (TPFPP)Fe dO
and (TDFPP)Fe dO complexes.
IV
observed (Table 1 and Figure 3). As the C-H bond strength of
alkanes became stronger (e.g., cyclohexane-d12), the formation
of 3 was detected with a lower yield of alcohol formation (Table
(
12) It has been shown by Groves and co-workers that the reactivity of
IV
oxoiron(IV) porphyrin complexes [e.g., (TMP)Fe dO] is low and different
+
•
IV
from that of oxoiron(IV) porphyrin cation radicals [e.g., (TMP) Fe d
O]: Groves, J. T.; Gross, Z.; Stern, M. K. Inorg. Chem. 1994, 33, 5065-
072.
(13) Lim, M. H.; Lee, Y. J.; Goh, Y. M.; Nam, W.; Kim, C. Bull. Chem.
Soc. Jpn. 1999, 72, 707-713 and references therein.
5

Fe(III) Porphyrin Complex-Catalyzed Hydroxylation
J. Am. Chem. Soc., Vol. 122, No. 44, 2000 10807
Table 1. Dependence of the Yields of Oxygenated Products and the Formation of Intermediate 3 on the C-H Bond Energy of Alkanes in the
Hydroxylation of Various Alkanes by Fe(TDFPP)Cl and m-CPBA
yields (%)
of products
formation (%)
C-H bond energy
a,c
b,c
d
substrate
products
of 3
(kcal/mol)
cis-1,2-dimethyl-cyclohexane
cis-1,2-dimethyl-cyclohexanol
trans-1,2-dimethyl-cyclohexanol
72 ( 4
0
5 ( 1
70 ( 4
2 ( 1
40 ( 3
0
∼96
2
,3- and 3,4-dimethyl-cyclohexanol
cyclohexane
cyclohexanol
cycloohexanone
cyclohexanol-d12
4 ( 2
99.3
cyclohexane-d12
50 ( 3
100.6
a
b
See Experimental Section for detailed experimental procedures of hydroxylation reactions. See footnote in Figure 3 for detailed experimental
procedures of UV-vis spectroscopic studies. Based on m-CPBA added. d See Table 5 in ref 4.
c
Scheme 3
Scheme 4
Figure 2. Concentration effect of alkane on the formation of 3 and
alcohol product in the reaction of Fe(TDFPP)Cl and m-CPBA. Reaction
-
4
conditions: m-CPBA (6 × 10 mmol, diluted in 50 µL of CH
was added to a 0.1-cm UV cell containing Fe(TDFPP)Cl (5 × 10
mmol) and various amounts of cyclohexane in a solvent mixture (0.5
mL) of CH Cl and CH CN (1:1) at -40 °C. Spectral changes were
3
CN)
-
4
2
2
3
directly monitored by UV-vis spectroscopy, and the percent yields of
cyclohexanol (based on m-CPBA added) were determined by analyzing
the reaction solutions with GC.
CH3CN at -40 °C (Scheme 4, pathway A). When the identical
reactions were performed in the presence of cyclohexane, we
found that the formation of 2 was not inhibited by the presence
of the alkane (Figure 4). This result is different from that
observed in the reactions of Fe(Porp)Cl with m-CPBA, in which
the formation of 3 was inhibited by the presence of cyclohexane
(vide supra). Although 2 was relatively stable in the absence of
cyclohexane at the reaction temperature (t1/2 ) ∼5 min), 2
disappeared faster in the presence of the alkane (Figure 4, t1/2
)
∼0.7 min). GC analysis of the resulting solutions revealed
that good amounts of cyclohexanol were yielded (∼40% based
on m-CPBA used). On the basis of the results presented above,
we conclude that 2 is formed as a hydroxylating intermediate
in the hydroxylation of alkanes by Fe(Porp)(CF3SO3) complexes
and m-CPBA in a solvent mixture of CH2Cl2 and CH3CN at
Figure 3. Effect of C-H bond strength of alkanes on the formation
of 3 and alcohol products in the reactions of Fe(TDFPP)Cl and
-
4
m-CPBA. Reaction conditions: m-CPBA (6 × 10 mmol, diluted in
0 µL of CH CN) was added to a 0.1-cm UV cell containing
Fe(TDFPP)Cl (5 × 10 mmol) and alkanes (0.3 mmol) in a solvent
mixture (0.5 mL) of CH Cl and CH CN (1:1) at -40 °C. Spectral
changes were directly monitored by UV-vis spectroscopy, and the
percent yields of products in Table 1 were determined by analyzing
the reaction solutions with GC.
5
3
-
4
2
2
3
-
40 °C (Scheme 4).
To gain further evidence that 1a and 2 were generated as
reactive hydroxylating intermediates in the reactions of m-CPBA
with the Fe(Porp)Cl and Fe(Porp)(CF3SO3) complexes, respec-
tively, we carried out isotopically labeled water, H2 O, experi-
ments
18
1
and Figure 3). On the basis of the results that the formation
4
,15
in the hydroxyation of cyclohexane by m-CPBA
of 3 depends on the concentration and C-H bond strength of
alkanes, we conclude that the formation of 3 is inhibited by the
competitive reaction of an intermediate with alkanes. Since 1a
is presumed to be the sole intermediate present in the course of
the formation of 3 via O-O bond homolysis (Scheme 3,
pathway A), we suggest that 1a is the reactive species that
effects the hydroxylation of alkanes by Fe(Porp)Cl and m-CPBA
in a solvent mixture of CH2Cl2 and CH3CN at -40 °C (Scheme
(14) We rule out a possibility that the hydroxylation reactions proceed
via free radical mechanism with the following observations. The alkane
hydroxylations were highly stereospecific, in which the hydroxylation of
cis-1,2-dimethylcyclohexane afforded cis-1,2-dimethylcyclohexanol with no
formation of trans-1,2-dimethylcyclohexanol (Table 1) and the hydroxylation
of trans-1,2-dimethylcyclohexane gave trans-1,2-dimethylcyclohexanol
(12%) and 2,3- and 3,4-dimethylcyclohexanol (44%). No formation of cis-
1,2-dimethylcyclohexanol was detected in the latter reaction. Another
evidence that supports ruling out the involvement of radical chemistry is
the high alcohol-to-ketone ratio obtained in the hydroxylation of cyclohexane
performed in air (Table 1), since hydroxylation of alkanes via free radical
pathways usually affords equal amounts of alcohol and ketone products:
(a) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of Organic
Compounds; Academic Press: New York, 1981. (b) MacFaul, P. A.; Ingold,
K. U.; Wayner, D. D. M.; Que, L., Jr. J. Am. Chem. Soc. 1997, 119, 10594-
10598.
, pathway B).14
3
We then studied the m-CPBA reactions with iron(III) por-
-
phyrin complexes containing triflate (CF3SO3 ) as an anionic
axial ligand. As we have observed previously,10 2 was formed
in the reactions of m-CPBA with Fe(TPFPP)(CF3SO3) and
Fe(TDFPP)(CF3SO3) in a solvent mixture of CH2Cl2 and

10808 J. Am. Chem. Soc., Vol. 122, No. 44, 2000
Nam et al.
Scheme 5
Figure 4. UV-vis spectral changes upon the addition of m-CPBA to
a reaction solution containing Fe(TDFPP)(CF SO ) and cyclohexane.
m-CPBA (6 × 10 mmol, diluted in 50 µL of CH CN) was added to
a 0.1-cm UV cell containing Fe(TDFPP)(CF SO
) (5 × 10 mmol)
and cyclohexane (0.3 mmol) in a solvent mixture (0.5 mL) of CH Cl
CN (1:1) at -40 °C. The completion of the reaction took 4
3
3
-
4
3
-
4
3
3
of 1a. If the oxidizing power of 1a is high enough to activate
the C-H bonds of alkanes and the lifetime of 1a is long enough
to transfer its oxygen to alkanes prior to the O-O bond cleavage
of 1a, then 1a becomes the hydroxylating intermediate (Scheme
5, pathway B). If the oxidizing power of 1a is weak and/or the
lifetime of 1a is short, 1a cannot effect the hydroxylation of
alkanes. In this case, O-O bond cleavage of 1a takes place
and 2 becomes the reactive species (Scheme 5, pathway A).
Detailed studies to understand the effect of the anionic axial
ligands on the reactivities of 1a and 2 are actively in progress
2
2
and CH
min.
3
Table 2. Percentages of 18O Incorporated from H
Cyclohexanol Product
18O into
2
a,b
18O (%) in
cyclohexanol cyclohexanol
yield (%) ofc
entry
reactions
+
•
IV
1
2
3
4
(TPFPP) Fe dO
31 ( 3
33 ( 3
4 ( 1
43 ( 5
32 ( 4
65 ( 5
42 ( 5
3 3
Fe(TPFPP)(CF SO ) + m-CPBA
Fe(TPFPP)Cl + m-CPBA
Fe(TPFPP)OH + m-CPBA
1
8,19
in this laboratory.
d
2 ( 1
In conclusion, we have obtained evidence that an acylperoxo-
iron(III) porphyrin complex is a viable reactive intermediate
capable of activating the energetically difficult C-H bonds of
alkanes to yield the corresponding alcohol products in iron
porphyrin-catalyzed hydroxylation of alkanes by m-CPBA. We
also proposed that both 1a and 2 are involved as reactive
intermediates in alkane hydroxylation reactions, depending on
the reaction conditions such as the nature of the anionic axial
ligands bound to iron(III) porphyrin complexes. The observation
that two different electrophilic oxidants effect the hydroxylation
of alkanes in iron porphyrin models is relevant to the recent
proposal of Newcomb, Coon, Vaz, and co-workers for cyto-
a
See Experimental Section for detailed experimental procedures.
b
All reactions were run at least in triplicate, and the data reported
c
represent the average of these reactions. Based on the amounts of
m-CPBA used. The reaction of Fe(TPFPP)OH with m-CPBA affords
the formation of (TPFPP)Fe dO under the reaction conditions.
d
IV
10
catalyzed by Fe(TPFPP)X complexes. For comparison, the
labeled water experiment was performed with an in situ
generated oxoiron(IV) porphyrin cation radical complex
+
•
IV
4,16
[
(TPFPP) Fe dO] as well.
As the results are shown in
18
Table 2, the O percentages in the cyclohexanol product formed
in the hydroxylation of cyclohexane by Fe(TPFPP)(CF3SO3)
and m-CPBA and by the in situ generated [(TPFPP) Fe dO]
complex were similar (entries 1 and 2), demonstrating that 2
was formed as a hydroxylating intermediate in the catalytic
hydroxylation of cyclohexane by Fe(TPFPP)(CF3SO3) and
5
+
•
IV
chrome P-450 reactions. Finally, we are currently investigating
the following questions: (1) how is the oxygen atom of (Porp)-
III
5,7,20
Fe -OOR inserted into the C-H bond of alkanes?
and
(
2) what are the reactivity differences between oxoiron(IV)
18
porphyrin cation radical and oxidant-iron(III) porphyrin inter-
mediates?
m-CPBA. Also, the observation that only a trace amount of
O
18
was incorporated from H2 O into the cyclohexanol product
formed in the hydroxylation of cyclohexane by m-CPBA
catalyzed by Fe(TPFPP)Cl and Fe(TPFPP)OH17 complexes
Experimental Section
(
Table 2, entries 3 and 4) leads us to conclude that the reactive
Materials. Dichloromethane (anhydrous) and acetonitrile (anhy-
drous) were obtained from Aldrich Chemical Co. and purified by
distillation over CaH prior to use. All reagents purchased from Aldrich
2
Chemical Co. were the best available purity and used without further
purification unless otherwise indicated. m-CPBA purchased from
Aldrich Chemical Co. was purified by washing with phosphate buffer
pH 7.4) followed by water and then dried under reduced pressure. All
iron(III) porphyrin complexes were obtained from Mid-Century Chemi-
cals and used without further purification.
species generated in this reaction should be 1a, since 1a cannot
exchange its oxygen with labeled water in the course of the
oxygen atom transfer from 1a to alkanes.16
Then, how are two distinct hydroxylating intermediates such
as 1a and 2 formed depending on the anionic axial ligands of
the iron(III) porphyrin complexes? At this moment, we presume
that the axial ligands may affect the oxidizing power and lifetime
(
Instrumentation. UV-vis spectra were recorded on a Hewlett-
(
15) (a) Bernadou, J.; Meunier, B. Chem. Commun. 1998, 2167-2173
DN
Packard 8453 spectrophotometer equipped with Optostat variable-
and references therein. (b) Lee, K. A.; Nam, W. J. Am. Chem. Soc. 1997,
1
1
19, 1916-1922. (c) Groves, J. T.; Lee, J.; Marla, S. S. J. Am. Chem. Soc.
997, 119, 6269-6273. (d) Bernadou, J.; Fabiano, A.-S.; Robert, A.;
temperature liquid-nitrogen cryostat (Oxford Instruments). Product
analyses for alkane hydroxylation reactions were performed on either
Meunier B. J. Am. Chem. Soc. 1994, 116, 9375-9376.
(
16) Fujii, H. Chem. Lett. 1994, 1491-1494.
(18) (a) Gross, Z.; Nimri, S. Inorg. Chem. 1994, 33, 1731-1732. (b)
Gross, Z. J. Biol. Inorg. Chem. 1996, 1, 368-371. (c) Czarnecki, K.; Nimri,
S.; Gross, Z.; Proniewicz, L. M.; Kincaid, J. R. J. Am. Chem. Soc. 1996,
118, 2929-2935.
(19) (a) Selke, M.; Valentine, J. S. J. Am. Chem. Soc. 1998, 120, 2652-
2653. (b) Urano, Y.; Higuchi, T.; Hirobe, M.; Nagano, T. J. Am. Chem.
Soc. 1997, 119, 12008-12009. (c) Yamaguchi, K.; Watanabe, Y.; Mor-
ishima, I. J. Am. Chem. Soc. 1993, 115, 4058-4065.
(20) (a) Harris, N.; Cohen, S.; Filatov, M.; Ogliaro, F.; Shaik, S. Angew.
Chem., Int. Ed. 2000, 39, 2003-2007. (b) Groves, J. T. J. Chem. Educ.
1985, 62, 928-931.
18
(17) A reviewer suggested to investigate the O-labeled water experiment
18
18
with Fe(TPFPP)OH, since a small amount of O-incorporation from H2
into cyclohexanol observed in Fe(TPFPP)Cl-catalyzed hydroxylation of
cyclohexane by m-CPBA might be the result of the absence of a hydroxo
ligand trans to the iron-oxo group (i.e., “redox tautomerism”). The result
of only a trace amount of O-incorporation into the cyclohexanol product
obtained in the Fe(TPFPP)OH reaction (Table 2, entry 4) suggests that the
small amount of O-incorporation observed in the Fe(TPFPP)Cl reaction
was not due to the axial ligand effect on the oxygen exchange between an
iron-oxo and labeled water.
O
15d
1
8
1
8

Fe(III) Porphyrin Complex-Catalyzed Hydroxylation
J. Am. Chem. Soc., Vol. 122, No. 44, 2000 10809
cyclohexane (0.15 mmol) and H 18O (5 µL, 95% 18O enriched, Aldrich
a Hewlett-Packard 5890 II Plus gas chromatograph interfaced with
Hewlett-Packard model 5989B mass spectrometer or a Donam Systems
2
Chemical Co.) in a solvent mixture (0.2 mL) of CH Cl and CH CN
2
2
3
+
•
IV
6
200 gas chromatograph equipped with a FID detector using 30-m
(1:2) was added to a reaction solution containing (TPFPP) Fe dO,
capillary column (Hewlett-Packard, HP-1 and HP-5).
-3
which was prepared by reacting Fe(TPFPP)(CF
3
SO
3
) (2 × 10 mmol)
Reaction Conditions. Since the hydroxylation reactions were not
affected by molecular oxygen, all of the reactions presented in this
with 3 equiv of m-CPBA in a solvent mixture (0.5 mL) of CH
CH CN (1:6) at -40 °C. The reaction mixture was stirred for 30 min
at -40 °C and then directly analyzed by GC/MS.
Catalytic hydroxylation of cyclohexane by Fe(TPFPP)X and m-
2 2
Cl and
3
-
3
study were performed in air. m-CPBA (1.2 × 10 mmol, diluted in
0 µL of CH CN) was added to a reaction solution containing an
iron(III) porphyrin complex (1 × 10 mmol) and alkane (0.3 mmol)
in a solvent mixture (0.5 mL) of CH Cl and CH CN (1:1) at -40 °C.
2
3
-
3
18
CPBA in the presence of H
(
2
O was conducted as follows: m-CPBA
6 × 10 mmol, diluted in 20 µL of CH CN) was added to the reaction
solutions containing Fe(TPFPP)X (2 × 10 mmol), cyclohexane (0.15
mmol), and H O (5 µL, 95% O enriched) in a solvent mixture (0.5
mL) of CH Cl and CH CN (1:6) at -40 °C. The reaction mixtures
were stirred for 30 min at -40 °C, and then PPh (0.06 mmol, diluted
in 0.1 mL of CH Cl ) was added to quench the reaction. The resulting
2
2
3
-3
The reaction mixture was stirred for 30 min at -40 °C, and then PPh
3
3
-3
-
2
(
2.4 × 10 mmol, diluted in 0.1 mL of CH
2
Cl
2
) was added to quench
18
18
the reaction. The resulting solution was directly analyzed by GC and
GC/MS, and product yields were determined by comparison against
standard curves (decane was used as an internal standard).
2
2
2
3
3
UV-vis spectroscopic studies were carried out as follows: in a
typical reaction, a reaction solution containing an iron(III) porphyrin
2
2
solution was directly analyzed by GC/MS.
complex in a solvent mixture (0.5 mL) of CH
was cooled to -40 °C in a 0.1-cm UV cell. m-CPBA (1.2 equiv, diluted
in 50 µL of CH CN) was injected to the UV cell in one portion, and
2 2 3
Cl and CH CN (1:1)
Acknowledgment. Financial support for this research from
the Korean Research Foundation (KRF-99-042-D00068), Center
for Cell Signaling Research at Ewha Womans University, and
the MOST through the Women’s University Research Fund (99-
N6-01-01-A-07) is gratefully acknowledged. M.H.L. is the
recipient of Research Fellowship (Brain Korea 21 Program).
3
spectral changes were directly monitored by UV-vis spectroscopy (see
Figure captions for detailed reaction conditions).
1
8
O-Labeled Water Experiments. The O and 18O compositions
16
in cyclohexanol were determined by the relative abundance of mass
1
6
18
peaks at m/z ) 57 for O and m/z ) 59 for O.
Stoichiometric hydroxylation of cyclohexane by (TPFPP) Fe dO
+
•
IV
1
8
in the presence of H
2
O was performed as follows: a mixture of
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