Competitive reaction of axial ligands during biomimetic oxygenations

Article abstract of DOI:10.1021/ic000071z

Nitrogenous bases have commonly been employed as axial ligands for metalloporphyrins in biomimetic model compounds and catalytic oxygenation chemistry. The addition of bases such as pyridines or imidazoles to metalloporphyrin-catalyzed hydrocarbon oxidation reactions is known to affect catalyst selectivity and turnover rate; this effect has been correlated with the electron-donor ability of the ligand. We have found that the role of pyridine in these reactions is far more involved than that of a simple axial ligand: Pyridine is a competitive substrate and is converted in high yield to the N-oxide. Subsequently, both of these species act as ligands to the metal center. Thus, catalytic systems containing oxidizable pyridines involve complex equilibria with multiple forms of ligated catalyst, and kinetic results should be interpreted with caution. Alternatives to free pyridine were tested, including a pyridine 'tail' which is covalently attached to the porphyrin.

Full text of DOI:10.1021/ic000071z

Inorg. Chem. 2000, 39, 4625-4629
4625
Competitive Reaction of Axial Ligands during Biomimetic Oxygenations
James P. Collman,* Allis S. Chien, Todd A. Eberspacher, Min Zhong, and John I. Brauman
Department of Chemistry, Stanford University, Stanford, California 94305-5080
ReceiVed January 21, 2000
Nitrogenous bases have commonly been employed as axial ligands for metalloporphyrins in biomimetic model
compounds and catalytic oxygenation chemistry. The addition of bases such as pyridines or imidazoles to
metalloporphyrin-catalyzed hydrocarbon oxidation reactions is known to affect catalyst selectivity and turnover
rate; this effect has been correlated with the electron-donor ability of the ligand. We have found that the role of
pyridine in these reactions is far more involved than that of a simple axial ligand: pyridine is a competitive
substrate and is converted in high yield to the N-oxide. Subsequently, both of these species act as ligands to the
metal center. Thus, catalytic systems containing oxidizable pyridines involve complex equilibria with multiple
forms of ligated catalyst, and kinetic results should be interpreted with caution. Alternatives to free pyridine were
tested, including a pyridine “tail” which is covalently attached to the porphyrin.
Introduction
Nitrogenous ligands are reported to lengthen and weaken the
M-O bond in the oxidized form of the catalyst by donating
Metalloporphyrins have long been employed as models of
heme proteins,1-10 and the use of nitrogenous bases as axial
ligands in these metalloporphyrin systems has extensive historic
precedent. Originally, these ligands were applied in biomimetic
chemistry as substitutes for the axial cysteine thiolate (P-450)
or histidine imidazole (horseradish peroxidase, hemoglobin,
myoglobin, cytochrome c oxidase) in the natural metalloproteins.
In metalloporphyrin systems which were designed to imitate
the oxygenation function of cytochrome P-450, the reported
benefits of nitrogenous bases included improvements in the
reactivities and selectivities of the catalysts, as well as protection
against the formation of µ-oxo dimers ((por)M-O-M(por)).
Marked improvements in selectivities and turnover rates have
resulted from the addition of nitrogenous ligands such as
pyridines or imidazoles to metalloporphyrin-mediated epoxi-
dations of olefins.11-13 In particular, manganese-based catalyst
systems are much improved by the use of such ligands.14-21
electron density into the M-O antibonding orbital, which can
account for the improved reactivity.22-27 Yields based on oxidant
consumed, however, typically have been low, especially for less
reactive substrates (vide infra).24,28-36
In monofaced model oxygen-binding and selective hydro-
carbon oxidation catalysts, bulky axial ligands were required
in order to block the open, nonselective face of the metallopor-
phyrin11,13,37 and to prevent the formation of µ-oxo dimers. Flat,
(19) Battioni, J. P.; Dupre, D.; Mansuy, D. J. Organomet. Chem. 1987,
328, 173-184.
(20) Guilmet, E.; Meunier, B. Tetrahedron Lett. 1982, 23, 2449-2452.
(21) Guilmet, E.; Meunier, B. NouV. J. Chim. 1982, 6, 511-513.
(22) Jorgensen, K. A.; Swanstrom, P. Acta Chem. Scand. 1989, 43, 822-
824.
(23) Gold, A.; Jayaraj, K.; Doppelt, P.; Weiss, R.; Chottard, G.; Bill, E.;
Ding, X.; Trautwein, A. X. J. Am. Chem. Soc. 1988, 110, 5756-
5761.
(24) Gunter, M. J.; Turner, P. J. Mol. Catal. 1991, 66, 121-141.
(25) Vandermade, A. W.; Nolte, R. J. M. J. Mol. Catal. 1984, 26, 333-
335.
(26) Vandermade, A. W.; Smeets, J. W. H.; Nolte, R. J. M.; Drenth, W. J.
Chem. Soc., Chem. Commun. 1983, 1204-1206.
(27) Razenberg, J.; Nolte, R. J. M.; Drenth, W. Tetrahedron Lett. 1984,
25, 789-792.
(28) Kellen-Yuen, C. J. Shape-selective and enantioselective epoxidation
catalyzed by manganese porphyrins: mimicking the selectivity of the
cytochrome P-450 enzymes. Ph.D. Thesis, Stanford University,
Stanford, CA, 1994.
(29) Lee, V. J. Enantioselective epoxidation of unfunctionalized olefins
catalyzed by threitol-strapped metalloporphyrins. Ph.D. Thesis, Stan-
ford University, Stanford, CA, 1992.
(1) Sono, M.; Roach, M. P.; Coulter, E. D.; Dawson, J. H. Chem. ReV.
1996, 96, 2841-2887.
(2) Ogoshi, H.; Mizutani, T. Compr. Supramol. Chem. 1996, 4, 337-
385.
(3) Momenteau, M. Perspect. Supramol. Chem. 1996, 3, 155-223.
(4) Chorghade, M. S.; Dezaro, D. A.; Hill, D. R.; Lee, E. C.; Pariza, R.;
Andersen, J. V.; Hansen, K. T.; Dolphin, D. H. Bioorg. Med. Chem.
Lett. 1994, 4, 2867-2870.
(5) Gunter, M. J.; Turner, P. Coord. Chem. ReV. 1991, 108, 115-161.
(6) Dawson, J. H.; Sono, M. Chem. ReV. 1987, 87, 1255-1276.
(7) Murayama, H.; Inoue, S. Kagaku (Kyoto) 1985, 40, 480-1.
(8) Baldwin, J. E.; Perlmutter, P. Top. Curr. Chem. 1984, 121, 181-220.
(9) Groves, J. T.; Nemo, T. E. NATO AdV. Study Inst. Ser., Ser. C 1983,
100, 329-341.
(10) Dolphin, D.; James, B. R. ACS Symp. Ser. 1983, 211, 99-115.
(11) Collman, J. P.; Brauman, J. I.; Fitzgerald, J. P.; Hampton, P. D.; Naruta,
Y.; Michida, T. Bull. Chem. Soc. Jpn. 1988, 61, 47-57.
(12) Gross, Z.; Ini, S. J. Org. Chem. 1997, 62, 5514-5521.
(13) Naruta, Y.; Maruyama, K. Tetrahedron Lett. 1987, 28, 4553-4556.
(14) Baciocchi, E.; Boschi, T.; Galli, C.; Lapi, A.; Tagliatesta, P.
Tetrahedron 1997, 53, 4497-4502.
(30) Meunier, B.; Guilmet, E.; Decarvalho, M. E.; Poilblanc, R. J. Am.
Chem. Soc. 1984, 106, 6668-6676.
(31) Collman, J. P.; Kodadek, T.; Raybuck, S. A.; Meunier, B. Proc. Natl.
Acad. Sci. U.S.A. 1983, 80, 7039-7041.
(32) Banfi, S.; Montanari, F.; Quici, S. J. Org. Chem. 1989, 54, 1850-
1859.
(33) Collman, J. P.; Chien, A. S.; Eberspacher, T. A.; Brauman, J. I. J.
Am. Chem. Soc. 1998, 120, 425-426.
(15) Mohajer, D.; Tangestaninejad, S. Tetrahedron Lett. 1994, 35, 945-
948.
(16) Konishi, K.; Oda, K.; Nishida, K.; Aida, T.; Inoue, S. J. Am. Chem.
Soc. 1992, 114, 1313-1317.
(17) Halterman, R. L.; Jan, S. T. J. Org. Chem. 1991, 56, 5253-5254.
(18) Mansuy, D. Pure Appl. Chem. 1987, 59, 759-770.
(34) Nolte, R. J. M.; Razenberg, A. S. J.; Schuurman, R. J. Am. Chem.
Soc. 1986, 108, 2751-2752.
(35) Razenberg, J.; Nolte, R. J. M.; Drenth, W. J. Chem. Soc., Chem.
Commun. 1986, 277-279.
(36) Razenberg, J.; Vandermade, A. W.; Smeets, J. W. H.; Nolte, R. J. M.
J. Mol. Catal. 1985, 31, 271-287.
10.1021/ic000071z CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/13/2000

4626 Inorganic Chemistry, Vol. 39, No. 20, 2000
Collman et al.
sterically unhindered metalloporphyrins are even more suscep-
tible to the formation of µ-oxo dimers38-44 which are inactive
in hydrocarbon oxidation. This dimerization is commonly
prevented by increasing the steric bulk of the porphyrin
ligand,45-47 or by the addition of an exogenous ligand, often
pyridine, imidazole, or various derivatives thereof, to the reaction
mixture.48-51
A drawback to the added ligand strategy is the well-
documented propensity of these metalloporphyrins to form
6-coordinate bis-ligated species in the presence of excess
exogenous ligand.52-55 Less well-documented is the susceptibil-
ity of these nitrogenous bases to oxidative degradation. Py-
ridines, in particular, have generally been regarded as reasonably
robust.28 Although pyridine is known to be oxidized by
potassium monopersulfate (KHSO5),56-58 pyridines were re-
ported to be stable toward oxidation in the Mn(por)/ClO-
catalytic system.20,21,59 Low yields in metalloporphyrin-catalyzed
hydrocarbon oxidations in the presence of pyridines or imida-
zoles were often attributed to the formation of the 6-coordinate
bis-ligated catalyst complex.12,41,60
use of a Mn(por)/H2O2 catalytic system as a mild synthetic
method for producing N-oxides from N-heterocycles.61)
In the oxidation of alkanes, which are far less reactive than
olefins, the undesirable side reaction of ligand oxidation is
nontrivial. We report here our observation that the oxidation of
pyridine is a significant competitive reaction pathway in iron
porphyrin catalyzed alkane hydroxylations employing iodosyl-
benzene as the terminal oxidant. This finding has major
consequences in the interpretation of kinetic and mechanistic
studies carried out in the presence of pyridine.33-36
Covalently attached axial ligand “tails” are commonly
employed in functional biomimetic modeling.62-72 This ap-
proach has also been used for alkene epoxidation catalysts,73-76
and in investigations of the effect of nitrogenous ligands on
manganese-based epoxidation catalysts.77 In alkane hydroxy-
lations, the use of a covalently attached axial ligand avoids the
problem of exogenous ligand oxidation competing with substrate
oxidation. A pyridine-tailed analogue of Fe(TPF5P)Cl has been
synthesized and evaluated as an alkane hydroxylation catalyst.
A later account of Mn(por)/ClO- mediated epoxidation
included an investigation into the fate of various nitrog-
enous ligands in the epoxidation of alkenes by manganese
porphyrins:32 N-hexylimidazole was oxidized to an unanalyzed
mixture of products, but 4-tert-butylpyridine and 3-phenylpy-
ridine were converted to their N-oxides, which were isolated in
high yields. This competitive reaction became increasingly
significant as less reactive olefins were employed, and as the
olefin concentration neared zero. (A recent report presents the
Experimental Section
Materials. Iron[5,10,15,20-tetra(pentafluorophenyl)porphyrin] chlo-
ride (Fe(TPF5P)Cl) was synthesized and metalated in a method
analogous to that found in the literature.78 Iodosylbenzene (PhIO) was
prepared from iodosylbenzene diacetate.79 Pyridine was dried over
KOH, then distilled from BaO, and stored in amber glass. Pyridine
N-oxide and cyclohexane were purified by standard procedures;80 after
removal of olefin contaminants, cyclohexane was dried, fractionally
distilled, and stored over 4 Å molecular sieves under argon. Methylene
chloride was dried and distilled from P4O10 under N2 and then stored
over 4 Å molecular sieves under argon. Other materials were purchased
in the highest possible purity and used as received, after confirming
purity by GC and/or GC-MS.
(37) Collman, J. P.; Zhang, X. M.; Lee, V. J.; Uffelman, E. S.; Brauman,
J. I. Science 1993, 261, 1404-1411.
(38) Ellis, P. E.; Lyons, J. E. Coord. Chem. ReV. 1990, 105, 181-193.
(39) Groves, J. T.; Nemo, T. E. J. Am. Chem. Soc. 1983, 105, 6243-6248.
(40) Groves, J. T. J. Chem. Educ. 1985, 62, 928-931.
(41) Iamamoto, Y.; Assis, M. D.; Ciuffi, K. J.; Sacco, H. C.; Iwamoto, L.;
Melo, A. J. B.; Nascimento, O. R.; Prado, C. M. J. Mol. Catal. A
1996, 109, 189-200.
(61) Thellend, A.; Battioni, P.; Sanderson, W.; Mansuy, D. Synthesis 1997,
1387-1388.
(42) The two following references concern the synthesis of µ-oxo dimers.
(43) Fleischer, E. B.; Srivastava, T. S. J. Am. Chem. Soc. 1969, 92, 2403-
2405.
(62) Collman, J. P.; Schwenninger, R.; Rapta, M.; Broring, M.; Fu, L. Chem.
Commun. 1999, 137-138.
(63) D’Souza, F.; Hsieh, Y. Y.; Deviprasad, G. R. Inorg. Chem. 1996, 35,
5747-5749.
(44) Kobayashi, H.; Higuchi, T.; Kaizu, Y.; Osada, H.; Aoki, M. Bull.
Chem. Soc. Jpn. 1975, 48, 3137-3141.
(64) Morgan, B.; Dolphin, D.; Jones, R. H.; Jones, T.; Einstein, F. W. B.
J. Org. Chem. 1987, 52, 4628-4631.
(45) Groves, J. T.; Haushalter, R. C.; Nakamura, M.; Nemo, T. E.; Evans,
B. J. J. Am. Chem. Soc. 1981, 103, 2884-2886.
(65) Saxton, R. J.; Wilson, L. J. J. Chem. Soc., Chem. Commun. 1984,
359-361.
(46) Traylor, P. S.; Dolphin, D.; Traylor, T. G. J. Chem. Soc., Chem.
Commun. 1984, 279-280.
(66) Momenteau, M.; Lavalette, D.; Mispelter, J.; Lhoste, J. M. Inorg. Chim.
Acta 1983, 79, 100-101.
(47) Bag, N.; Chern, S. S.; Peng, S. M.; Chang, C. K. Tetrahedron Lett.
1995, 36, 6409-6412.
(67) Collman, J. P.; Groh, S. E. J. Am. Chem. Soc. 1982, 104, 1391-
(48) Zhang, X. Synthetic analogues of cytochrome P-450 and dioxygen-
binding hemoproteins. Ph.D. Thesis, Stanford University, Stanford,
CA, 1992.
1403.
(68) Traylor, T. G.; Mincey, T. C.; Berzinis, A. P. J. Am. Chem. Soc. 1981,
103, 7084-7089.
(49) The newer polyhalogenated porphyrin ligands which contain halogens
on the â-pyrrolic positions as well as on the meso-aryl groups are not
susceptible to dimerization because the porphyrin macrocycle is ruffled
or saddle-shaped, rather than planar.
(69) Traylor, T. G. Acc. Chem. Res. 1981, 14, 102-109.
(70) Scheidt, W. R.; Reed, C. A. Chem. ReV. 1981, 81, 543-555.
(71) Mashiko, T.; Reed, C. A.; Haller, K. J.; Kastner, M. E.; Scheidt, W.
R. J. Am. Chem. Soc. 1981, 103, 5758-5767.
(72) Collman, J. P.; Brauman, J. I.; Doxsee, K. M.; Halbert, T. R.;
Bunnenberg, E.; Linder, R. E.; Lamar, G. N.; Delgaudio, J.; Lang,
G.; Spartalian, K. J. Am. Chem. Soc. 1980, 102, 4182-4192.
(73) Banfi, S.; Montanari, F.; Quici, S. Gazz. Chim. Ital. 1990, 120, 435-
441.
(50) Dolphin, D.; Traylor, T. G.; Xie, L. Y. Acc. Chem. Res. 1997, 30,
251-259.
(51) Senge, M. O.; Medforth, C. J.; Forsyth, T. P.; Lee, D. A.; Olmstead,
M. M.; Jentzen, W.; Pandey, R. K.; Shelnutt, J. A.; Smith, K. M.
Inorg. Chem. 1997, 36, 1149-1163.
(52) Walker, F. A.; Lo, M. W.; Ree, M. T. J. Am. Chem. Soc. 1976, 98,
5552-5560.
(74) Montanari, F.; Banfi, S.; Quici, S. Pure Appl. Chem. 1989, 61, 1631-
1636.
(53) Satterlee, J. D.; Lamar, G. N.; Frye, J. S. J. Am. Chem. Soc. 1976, 98,
7275-7282.
(75) Montanari, F.; Penso, M.; Quici, S.; Vigano, P. J. Org. Chem. 1985,
50, 4888-4893.
(54) Satterlee, J. D.; Lamar, G. N.; Bold, T. J. J. Am. Chem. Soc. 1977,
99, 1088-1093.
(76) Bortolini, O.; Momenteau, M.; Meunier, B. Tetrahedron Lett. 1984,
25, 5773-5776.
(55) Coyle, C. L.; Rafson, P. A.; Abbott, E. H. Inorg. Chem. 1973, 12,
2007-2010.
(77) Meunier, B.; Decarvalho, M. E.; Bortolini, O.; Momenteau, M. Inorg.
Chem. 1988, 27, 161-164.
(56) Robert, A.; Meunier, B. New J. Chem. 1988, 12, 885-896.
(57) Kennedy, R. J.; Stock, A. M. J. Org. Chem. 1960, 25, 1901-1906.
(58) Trost, B. M.; Braslau, R. J. Org. Chem. 1988, 53, 532-537.
(59) Collman, J. P.; Brauman, J. I.; Hampton, P. D.; Tanaka, H.; Bohle,
D. S.; Hembre, R. T. J. Am. Chem. Soc. 1990, 112, 7980-7984.
(60) Nappa, M. J.; Tolman, C. A. Inorg. Chem. 1985, 24, 4711-4719.
(78) Collman, J. P.; Tyvoll, D. A.; Chng, L. L.; Fish, H. T. J. Org. Chem.
1995, 60, 1926-1931.
(79) Saltzman, H.; Sharefkin, J. G. Org. Synth. 1963, 43, 60-61.
(80) Perrin, D. D.; Armarego, W. L. F.; Perrin, D. R. Purification of
Laboratory Chemicals, 2nd ed.; Pergamon Press: Oxford, England,
1980.

Competitive Reaction of Axial Ligands
Inorganic Chemistry, Vol. 39, No. 20, 2000 4627
Figure 2. Competitive oxidation of cyclohexane and pyridine: [,
iodobenzene (PhI); 9, pyridine N-oxide; 2, cyclohexanol. PhI is a
reaction byproduct which is used as a measure of PhIO consumption.
Reaction conditions: 0.5 mM Fe(TPF5P)Cl, 500 mM cyclohexane, 25
mM pyridine, 50 µmol of PhIO (would be 50 mM, if completely
dissolved), 5 mM PhCl (internal GC standard), 1 mL total volume in
CH2Cl2, 0 °C, Ar.
Figure 1. Plot of pyridine oxidation to pyridine N-oxide: [, pyridine
+ pyridine N-oxide; 9, pyridine; 2, pyridine N-oxide. Reaction
conditions: 0.5 mM Fe(TPF5P)Cl, 25 mM pyridine, 50 µmol of PhIO
(would be 50 mM, if completely dissolved), 5 mM PhCl (internal GC
standard), 1 mL total volume in CH2Cl2, 0 °C, Ar.
Product Analysis. Reaction products were detected and quantified
using a Hewlett-Packard 5890A gas chromatograph fitted with a (5%
phenyl)-methyl siloxane capillary column (DB-5, J&W Scientific, 0.32
mm ID x 30 m) and flame-ionization detector. All peaks were identified
by co-injection with the known compounds. Oxidation products were
quantified by comparison with an internal standard (chlorobenzene):
calibration plots for detector response were prepared for iodobenzene,
cyclohexanol, cyclohexanone, pyridine, pyridine N-oxide, and pen-
tafluoropyridine versus the internal standard, using known stock
solutions which approximated experimental concentrations.
Samples were sent to the University of California, San Francisco
Mass Spectrometry Facility, for MS analyses.
General Oxidation Procedure. A stock solution containing the
catalyst and GC internal standard (PhCl) in CH2Cl2 was prepared under
inert atmosphere conditions, such that 100 µL of the stock solution
contained 0.5 µmol of catalyst and 5 µmol of PhCl. PhIO (50 µmol,
11.05 mg) and a stir bar were placed in a 10 mL round-bottomed flask,
which was sealed with a SubaSeal septum. The flask was placed in an
ice bath, and the atmosphere in the flask was replaced with Ar.
Subsequently, the appropriate amounts of substrate(s) and solvent,
totaling 900 µL, were syringed into the flask.
To initiate the reaction, 100 µL of the catalyst stock solution was
injected. At appropriate intervals, 5 µL aliquots were removed, diluted
with 15 µL of CH2Cl2, and filtered through a microfiber glass plug.
Samples were analyzed immediately by GC.
Stability of Exogenous Ligands. Various concentrations of ligand
(pyridine N-oxide or pentafluoropyridine) were added to the reaction
flask containing oxidant and solvent. Controls were carried out both
in the presence and in the absence of 0.5 M cyclohexane. The catalyst
was added and reactions were monitored as above.
3-(3′-Pyridyl)propionyl Chloride Hydrochloride. 3-(3′-Pyridyl)-
propionic acid (0.1 mmol) was dissolved in 2 mL of freshly distilled
SOCl2 and stirred at room temperature for 4 h; the excess SOCl2 was
then removed and the residue was dried in vacuo. The residue was
dissolved in dry DMF and used for the acylation reaction without further
purification.63,81,82
Figure 3. Rate dependence of pyridine oxidation on pyridine concen-
tration. Reaction conditions: 0.5 mM Fe(TPF5P)Cl, 5-150 mM
pyridine, 50 µmol of PhIO (would be 50 mM, if completely dissolved),
5 mM PhCl (internal GC standard), 1 mL total volume in CH2Cl2, 0
°C, Ar.
the starting material was no longer observed by TLC, the reaction was
neutralized by bubbling with NH3(g). The mixture was washed
successively with saturated aqueous NaHCO3, water, and brine and
then dried with Na2SO4. The solvent was removed in vacuo, and the
residue was purified by column chromatography on silica gel with 1:1
CH2Cl2:hexanes (v/v) as the eluent, to give the corresponding amino
porphyrin.
Yield: 60%. UV-vis (λmax, CH2Cl2): 414, 510 nm. 1H NMR
(CDCl3): δ 8.93 (d, J ) 4.4 Hz, 2H), 8.86 (s, 4H), 8.78(d, J ) 4.4 Hz,
2H), 7.88 (d, J ) 1.8 Hz, 1H), 7.33 (d, J ) 1.8 Hz, 1H), 3.56 (s, 2H),
1.59 (s, 9H), -2.83 (s, 2H) ppm. LSIMS: calcd for C48H24F15N6O2
(M+ + H) 1001.2, found 1001.1.
meso-5-(4′-tert-Butyl-2′-nitro-6′-(3′′-(3′′′-pyridyl)propionamidophe-
nyl))-10,15,20-tris(pentafluorophenyl)porphyrin (H2(PyT-TPF5P))
(2). To a solution of 0.05 mmol of 1 in 5 mL of dry DMF was added
1 mmol of dry N,N-diethylaniline, followed by the dropwise addition
of a solution of 3-(3′-pyridyl)propionyl chloride hydrochloride in dry
DMF under N2. The resulting mixture was stirred at room temperature
for 3 h, after which time the reaction was quenched by the addition of
methanol. The solvent was removed in vacuo, and the residue was
redissolved in CH2Cl2, washed with saturated aqueous NaHCO3, water,
and brine, and then dried over Na2SO4. After evaporation of the solvent,
the residue was purified by preparative TLC on a silica gel plate with
1:1 CH2Cl2:hexanes (v/v) as the eluent.
meso-5-(2′-Amino-4′-tert-butyl-6′-nitrophenyl)-10,15,20-tris(pen-
tafluorophenyl)porphyrin (1). To a solution of 0.5 mmol of meso-
5-(4′-tert-butyl-2′,6′-dinitrophenyl)-10,15,20-tris(pentafluorophenyl)-
porphyrin83 in 1000 mL of N2-sparged CH2Cl2 was added 20 mmol of
concentrated HCl in one portion at 0 °C under N2 in the dark,
immediately followed by 3 mmol of SnCl2‚2H2O. The reaction mixture
was stirred at 0 °C and monitored by TLC. After several hours, when
Yield: 68%. UV-vis (λmax, CH2Cl2): 412, 510 nm. 1H NMR
(CDCl3): δ 9.03 (d, J ) 1.7 Hz, 1H), 8.88 (s, 4H), 8.78 (d, J ) 4.7
Hz, 2H), 8.74 (d, J ) 4.7 Hz, 2H), 8.22 (d, J ) 1.8 Hz, 1H), 7.80 (d,
J ) 4.3 Hz, 1H), 7.54 (s, 1H), 6.52 (d, J ) 7.6 Hz, 1H), 6.51 (s, 1H),
6.44 (dd, J ) 7.6, 4.4 Hz, 1H), 2.14 (t, J ) 7.7 Hz, 2H), 1.66 (s, 9H),
(81) Collman, J. P.; Broring, M.; Fu, L.; Rapta, M.; Schwenninger, R.;
Straumanis, A. J. Org. Chem. 1998, 63, 8082-8083.
(82) Bracher, F.; Papke, T. Monatsh. Chem. 1996, 127, 91-95.
(83) Rose, E.; Soleilhavoup, M.; ChristTommasino, L.; Moreau, G.;
Collman, J. P.; Quelquejeu, M.; Straumanis, A. J. Org. Chem. 1998,
63, 2042-2044.

4628 Inorganic Chemistry, Vol. 39, No. 20, 2000
Collman et al.
Figure 4. (a) Cyclohexane oxidation by Fe(PyT-TPF5P)Cl and (b) enlargement of the plot in Figure 4a, showing initial stages of the reaction: [,
iodobenzene (PhI); 2, cyclohexanol. Reaction conditions: 0.1 mM Fe(PyT-TPF5P)Cl, 500 mM cyclohexane, 50 µmol of PhIO (would be 50 mM,
if completely dissolved), 5 mM PhCl (internal GC standard), 1 mL total volume in CH2Cl2, 0 °C, Ar.
Scheme 1. Synthesis of Pyridine-Tailed Catalyst, Fe(PyT-TPF5P)Cl
1.46 (t, J ) 7.7 Hz, 2H), -2.90 (s, 2H) ppm. LSIMS: calcd for
C56H31F15N7O3 (M+ + H) 1134.2, found 1134.1.
zene (PhIO) as the oxygen donor is capable of oxidizing certain
pyridines to their N-oxides. Typical data for the oxidation of
pyridine is shown in Figure 1. As pyridine is consumed, pyridine
N-oxide is formed at the same rate. The reaction is virtually
quantitative. The total concentration of pyridine plus pyridine
N-oxide remains constant throughout the reaction, demonstrating
that pyridine is converted cleanly to the N-oxide, and that the
product is stable under the reaction conditions. In contrast, the
electron-deficient 2,3,4,5,6-pentafluoropyridine is not oxidized.84
Iron [meso-5-(4′-tert-Butyl-2′-nitro-6′-(3′′-(3′′′-pyridyl)propiona-
midophenyl))-10,15,20-tris(pentafluorophenyl)porphyrinato] Chlo-
ride (Fe(PyT-TPF5P)Cl). The free-base porphyrin 2 was metalated by
a procedure analogous to that reported for H2TPF5P.78 Yield: 82%. UV-
vis (λmax, CH2Cl2): 412 (Soret), 345 nm. LSIMS: calcd for
C56H28F15N7O3Fe (M+ - Cl) 1187.1, found 1186.9.
Oxidation Products of Iron [meso-5-(4′-tert-Butyl-2′-nitro-6′-(3′′-
(3′′′-pyridyl)propionamidophenyl))-10,15,20-tris(pentafluorophenyl)-
porphyrinato] Chloride, as Observed by LSIMS. Singly oxidized:
calcd for C56H28F15N7O4FeCl (MO+) 1238.1, found 1237.8. Doubly
oxidized: calcd for C56H28F15N7O5FeCl (MO2+) 1254.1, found 1253.9.
The µ-oxo dimer of the catalyst, [(TPF5P)Fe]2O, is a stable
compound which has been synthesized and isolated.38-41 Under
the oxidizing conditions of catalytic hydrocarbon oxidations,
the presence of an axial ligand was intended to prevent the
formation of these dimers. The use of nitrogenous ligands to
Triply oxidized: calcd for C56H28F15N7O6FeCl (MO3+) 1270.1, found
+
1270.7. Quadruply oxidized: calcd for C56H28F15N7O7FeCl (MO4
)
1286.1, found 1285.9. No attempt was made to identify the structures
of the higher oxidation products recovered from the reaction mixture.
(84) The concentration of pentafluoropyridine remains constant when mixed
in solution with the catalyst and iodosylbenzene, under reaction
conditions analogous to both those used for the oxidation of pyridine
and those used for the competitive oxidation of pyridine and
hydrocarbon substrate.
Results and Discussion
Oxidation of Pyridine. The iron chloride derivative of tetra-
(pentafluorophenyl)porphyrin (Fe(TPF5P)Cl) with iodosylben-

Competitive Reaction of Axial Ligands
Inorganic Chemistry, Vol. 39, No. 20, 2000 4629
block dimer formation in saturated hydrocarbon oxidation,
however, is problematic at best.
onstrated previously that the structure of this particular “tail”
does allow the pyridine to coordinate to the metal.81,86
The yield, based on oxidant consumed, of cyclohexanol with
Fe(TPF5P)Cl and 25 mM pyridine was 31%; this value increased
to 51% when the parallel reaction was run using Fe(PyT-TPF5P)-
Cl as the catalyst, without added exogenous ligand. However,
the rate of cyclohexanol production in the Fe(PyT-TPF5P)Cl case
was only half the rate with Fe(TPF5P)Cl as the catalyst. Also,
the oxidation rate with Fe(PyT-TPF5P)Cl began slowing at only
20% of oxidant consumption, suggesting the existence of
significant pathway(s) for catalyst decomposition or inactivation
(vide infra).
There is reason to believe that for the balance of a typical
alkane hydroxylation reaction, the active catalyst is in fact
coordinated by the N-oxide form of the intramolecular ligand,
which is produced from the original covalently linked pyridine
during the initial turnovers of the reaction. Figure 4 shows the
oxidation of cyclohexane using iodosylbenzene as the terminal
oxidant. The plots of cyclohexanol and PhI production are
sigmoidal, with a distinct rate change in the first few minutes.
In agreement with the previous study,32 which found that the
N-oxide ligands gave slightly faster turnovers than their non-
oxidized counterparts, the second rate in Figure 4 is greater than
the initial rate.
“Preoxidation” of the covalently linked pyridine by first
stirring Fe(PyT-TPF5P)Cl with PhIO in CH2Cl2 before the
addition of substrate eliminated the initial slow rate. Recovery
and analysis of catalyst recovered from the mixture revealed
the presence of a compound with a mass which is consistent
with a single oxygen addition. Unfortunately, significant further
oxidations and catalyst degradation were also indicated.
These findings are in accord with the suggestion22-24 that
pyridine N-oxide, with its formally negatively charged oxygen,
should make a better electron donor than pyridine,42,87 thus
further lengthening and activating the M-O bond. In situ
oxidation to the pyridine N-oxide tail is a simple, convenient
method by which to generate a more active catalyst. This
situation is reminiscent of the autoxidation of a chiral epoxi-
dation catalyst which resulted in improved enantiomeric selec-
tivities.88
The competitive oxidation of the axial ligand does not affect
alkene epoxidations as strongly as alkane hydroxylations, since
epoxidation is a much more facile reaction. Epoxidation is still
favored over N-oxidation, at equimolar concentrations of olefin
and pyridine.32 Hydroxylations, on the other hand, are dominated
by the oxidation of the axial ligand. Figure 2 plots the course
of a reaction in which cyclohexane and pyridine are both present
and act as competitive substrates. N-Oxidation is clearly
significant, even at a 20:1 ratio of alkane to pyridine.
A study of pyridine oxidation rates in the absence of
hydrocarbon substrate reveals a nonlinear dependence on
pyridine concentration (Figure 3). The reaction rate increases
rapidly from 5 to 50 mM pyridine and then falls off at higher
pyridine concentrations. This result is consistent with the
formation of a mono-ligated species at low pyridine concentra-
tions, and the bis-ligated species at higher concentrations.32 The
mono-pyridine adduct is a more potent oxidation catalyst than
Fe(TPF5P)Cl alone, which in turn, is a more effective catalyst
than the bis-ligated form.
Competitive reversible binding of the substrate, the added
ligand, and the ligand oxidation products greatly complicates
the mechanistic model by requiring the addition of numerous
equilibrium terms for the various ligation states of the catalyst.
(These equilibrium terms are further complicated by the dynamic
nature of the concentrations of these species.) Thus, the use of
an unreactive axial ligand would greatly simplify these reactions.
To this end, pyridine N-oxide (PyO) and 2,3,4,5,6-pentafluo-
ropyridine (F5Py) have proven to be stable under our reaction
conditions. In accordance with a previous report,32 an equimolar
amount of PyO results in enhanced reaction rates. Formation
of the bis-ligated catalyst seems to occur for the N-oxides as
well as for the pyridines: cyclohexane oxidation rates are lower
in the presence of excess PyO than with no added axial ligand.
This effect suggests that the formation of the (PyO)2Fe(TPF5P)
complex is more detrimental to the reaction rate than the
formation of µ-oxo dimers under our conditions. In fact, when
the catalyst concentration is lowered 10-fold to 0.05 mM and
run without additional axial ligand, no evidence of µ-oxo dimer
formation is detected during the initial stages of the reaction:
yields of alcohol and ketone (<1%) are quantitative, and UV-
vis analysis shows no sign of dimer formation.
Conclusion
Nitrogenous bases are known to be useful ligands in metal-
loporphyrin chemistry. However, many of these compounds are
also highly susceptible to oxidation and should be chosen
carefully: the oxidation of the axial ligand can become a major
consumer of terminal oxidant, which is problematic especially
when oxidizing less reactive substrates, employing a valuable
oxygen source, developing oxidation systems for practical use,
or studying the kinetics of a reaction. When exogenous ligands
are required, polyhalogenated pyridines are more oxidation-
resistant, although the protective halogens also reduce the donor
ability of the ligand. The amount of exogenous ligand employed
should be carefully optimized due to the concentration depen-
dence of the interactions between the catalyst and ligands.
A study of cyclohexane oxidation rates in the presence of
varying concentrations of exogenous F5Py42 yields a plot of rate
vs F5Py concentration which is similar in shape to but different
in scale from that of Figure 3: as with Py, the rate of
cyclohexane oxidation initially increases with increasing con-
centrations of F5Py. The maximum rate, which is nearly double
that of the F5Py-free reaction, occurs at 1 M F5Py; at higher
F5Py concentrations, the reaction rate declines. The high F5Py
concentrations which are required to observe the oxidation rate
dependence on [F5Py] are consistent with the reduced donor
ability of F5Py in comparison to that of Py.85
Pyridine-Tailed Catalyst. In order to reap the benefits of a
donor ligand without the drawback of the competitive oxidation
of excess ligand, we have synthesized a “pyridine-tailed” (PyT)
version of Fe(TPF5P)Cl, in which a pyridine is covalently linked
to the porphyrin by means of an amide bond to a meso-aryl
substituent (Fe(PyT-TPF5P)Cl) (Scheme 1). It has been dem-
Acknowledgment. We thank the NSF (Grant No.
CHE9123187-A4) for financial support.
IC000071Z
(86) Collman, J. P.; Rapta, M.; Broring, M.; Raptova, L.; Schwenninger,
R.; Boitrel, B.; Fu, L.; M, L. H. J. Am. Chem. Soc. 1999, 121, 1387-
1388.
(87) Gilmartin, C.; Smith, J. R. L. J. Chem. Soc., Perkin Trans. 2 1995,
243-251.
(88) Collman, J. P.; Wang, Z.; Straumanis, A.; Quelquejeu, M.; Rose, E.
J. Am. Chem. Soc. 1999, 121, 460-461.
(85) It should be noted that at 1 M, pentafluoropyridine comprises about
10% of the total reaction volume. Thus, a solvent effect may be an
alternate explanation for the change in reaction rates.