Stereospecific Alkane Hydroxylation with H2O2 Catalyzed by an Iron(II)-Tris(2-pyridylmethyl)amine Complex

Full text of DOI:10.1021/ja9642572

5964
J. Am. Chem. Soc. 1997, 119, 5964-5965
Herein, we report the details of its reactivity and present
evidence for an [Fe(TPA)(OOH)]2+ intermediate.
Stereospecific Alkane Hydroxylation with H2O2
Catalyzed by an
Complex 1 is a low-spin six-coordinate Fe(II) complex.14
Under the syringe pump conditions used for the hydroxylation
of cyclohexane with [Fe2O(TPA)2(H2O)2]4+ (2) and tBuOOH,10
0.7 mM 1 reacts with 10 equiv of H2O2 and 1000 equiv of
cyclohexane in CH3CN to afford 3.0 equiv of cyclohexanol and
0.7 equiv of cyclohexanone in the course of 15 min (Table 1);
essentially the same results are obtained under Ar or in air. This
reactivity is comparable to that of [Fe(TTP)Cl]/PhIO6e (TTPH2
) meso-tetrakis(p-tolyl)porphyrin) but superior to those of other
nonheme iron catalysts with H2O2 as oxidant which afford lower
oxidant-to-product conversions and smaller A/K ratios.15,16 Even
more significant is the oxidation of cis- and trans-1,2-dimeth-
ylcyclohexane to afford tertiary alcohol products with >99%
retention of stereochemistry (Table 1). This high stereospeci-
ficity of hydroxylation is comparable to those found for [Fe-
(porphyrin)Cl]/PhIO6b-d and for stoichiometric organic peroxide
oxidants such as perfluorodialkyldioxiranes, perfluorodialky-
loxaziridines, and p-nitroperoxybenzoic acid,2 but is not ob-
served when hydroxyl radicals are involved.6c To our knowl-
edge, 1 is the first example of a nonheme iron catalyst/H2O2
combination capable of stereospecific alkane hydroxylation.17
Several lines of evidence suggest that the 1/H2O2 combination
generates an oxidant distinct from that typically associated with
Haber-Weiss chemistry: (1) the fact that alcohol is the major
oxidation product, (2) the insensitivity of the reaction to the
presence of O2, and (3) the stereospecificity of hydroxylation.
Furthermore, the oxidant is capable of oxygen atom insertion
into olefins, affording only epoxide products with complete
retention of stereochemistry (Table 1). Lastly, the kinetic
isotope effect for cyclohexanol formation is 3.5, a value
indicative of an oxidant more selective than the hydroxyl radical
(kH/kD ) 1-2).18 These observations implicate a metal-based
oxidant.
Iron(II)-Tris(2-pyridylmethyl)amine Complex
Cheal Kim, Kui Chen, Jinheung Kim, and
Lawrence Que, Jr.*
Department of Chemistry and Center
for Metals in Biocatalysis
207 Pleasant Street SE, UniVersity of Minnesota
Minneapolis, Minnesota 55455
ReceiVed December 10, 1996
The stereospecific functionalization of aliphatic C-H bonds
is an important goal for chemistry and biochemistry.1 While
such transformations can be carried out by organic peroxides
in a stoichiometric fashion,2 the prospect of using metal
complexes and cheap and environmentally friendly oxidants
(e.g., O2, H2O2) to carry out such reactions catalytically has
aroused considerable interest in these endeavors.3,4 The latter
has been inspired by metalloenzymes such as cytochrome P450,5
which utilize a heme center for catalysis. Iron porphyrin
complexes can be used as catalysts for stereospecific hydroxy-
lation of hydrocarbons;6 however, the susceptibility of the
porphyrin to oxidative self-degradation and the usual require-
ment for an expensive oxidant like PhIO have limited the utility
of this approach.7 Our long-standing interest in oxygen activat-
ing nonheme iron enzymes such as methane monooxygenase8
has stimulated our efforts to use nonheme iron complexes to
catalyze this chemistry.9,10 The combination of an iron complex
with peroxides is often considered to afford Haber-Weiss
chemistry,11 generating hydroxyl (or alkoxyl) radicals that
initiate radical chain autoxidation reactions.12,13 In these
reactions, alkanes typically afford alcohol (A) and ketone (K)
products with an A/K ratio of about 1, while alkenes yield
mostly allylic oxidation products. This pattern of reactivity does
not appear to hold for the combination of [Fe(TPA)(CH3CN)2]-
What is the nature of this iron oxidant? Among catalytic
nonheme iron systems that utilize H2O2 as oxidant, iron(III)-
peroxo species are often invoked as reaction intermediates, but
in only two cases has some spectroscopic evidence for such
species been reported.16b,c With this system, we are able to trap
a possible reaction intermediate (3) at -40 °C (70% yield) by
treatment of 1 with 10 equiv of H2O2 in CH3CN. Intermediate
3 exhibits UV-vis (λmax ) 538 nm, Figure 1a) and EPR
properties (S ) 1/2; g ) 2.19, 2.15, and 1.97; Figure 1b), similar
to those of previously reported for low-spin [FeIII(TPA)(H2O)(OOt-
14
(ClO4)2 (1, TPA ) tris(2-pyridylmethyl)amine) with H2O2.
(1) Ojima, I., Ed.; Catalytic Asymmetric Synthesis; VCH: New York,
1993.
(2) (a) Schneider, H.-J.; Muller, W. J. Org. Chem. 1985, 50, 4609-
4615. (b) Mello, R.; Fiorentino, M.; Fusco, C.; Curci, R. J. Am. Chem.
Soc. 1989, 111, 6749-6757. (c) DesMarteau, D. D.; Donadelli, A.;
Montanari, V.; Petrov, V. A.; Resnati, G. J. Am. Chem. Soc. 1993, 115,
4897-4898.
t
Bu)]2+ derived from reaction of 1 or 2 with BuOOH in CH3-
(3) Meunier, B. Chem. ReV. 1992, 92, 1411-1456.
(4) (a) Barton, D. H. R.; Doller, D. Acc. Chem. Res. 1992, 25, 504-
512. (b) Sawyer, D. T.; Sobkowiak, A.; Matsushita, T. Acc. Chem. Res.
1996, 29, 409-416.
CN at -40 °C.14,19 Electrospray ionization mass spectrometry
of 3 shows prominent ion clusters at m/z 478, 461, and 445,
which have mass values and isotope patterns consistent with
(5) Ortiz de Montellano, P. R., Ed.; Cytochrome P-450; Plenum: New
York, 1986.
(6) (a) Groves, J. T.; Viski, P. J. Am. Chem. Soc. 1989, 111, 8537-
8538. (b) Sorokin, A. B.; Khenkin, A. M. New J. Chem. 1990, 14, 63-67.
(c) Khenkin, A. M.; Shilov, A. E. New J. Chem. 1989, 13, 659-667. (d)
Lindsay Smith, J. R.; Sleath, P. R. J. Chem. Soc., Perkin Trans. 2 1983,
1165-1169. (e) Groves, J. T.; Nemo, T. E. J. Am. Chem. Soc. 1983, 105,
6243-6248.
(15) For comparison, we list the percent conversions of oxidant to alcohol,
the A/K ratios, and reaction times for other nonheme iron catalyst/H2O2
systems reported thus far: Fe(ClO4)3, 25%, 2, 6 h;13a Fe2O(bpy)2(O2CCH3)2-
Cl2, 4%, 1, 6 h;13a [Fe2O(tmima)2(O2CCH3)](ClO4)3, 4%, 1, 6 h;13a [Fe2O-
(bpy)4(H2O)2](ClO4)4, 12%, 1.5, 0.5 h;16a [Fe(PMA)]2+, 5%, 1, 0.5 h;16b
[Fe(N4Py)(CH3CN)](ClO4)2, 13%, 2.6, 0.5 h.16c
(16) (a) Me´nage, S.; Vincent, J.-M.; Lambeaux, C.; Fontecave, M. J.
Mol. Catal. A 1996, 113, 61-75. (b) Nguyen, C.; Guajardo, R. J.;
Mascharak, P. K. Inorg. Chem. 1996, 35, 6273-6281. (c) Lubben, M.;
Meetsma, A.; Wilkinson, E. C.; Feringa, B.; Que, L., Jr. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1512-1514.
(7) Traylor, T. G.; Hill, K. W.; Fann, W.-P.; Tsuchiya, S.; Dunlap, B.
E. J. Am. Chem. Soc. 1992, 114, 1308-1312.
(8) Waller, B. J.; Lipscomb, J. D. Chem. ReV. 1996, 96, 2625-2657.
(9) (a) Leising, R. A.; Kim, J.; Pe´rez, M. A.; Que, L., Jr. J. Am. Chem.
Soc. 1993, 115, 9524-9530. (b) Kojima, T.; Leising, R. A.; Yan, S.; Que,
L., Jr. J. Am. Chem. Soc. 1993, 115, 11328-11335.
(17) (a) The hydroxylation of the tertiary C-H bonds of trans-1,2-
dimethylcyclohexane by [Fe2O(L)4(H2O)2](ClO4)4/H2O2 (L ) substituted
bipyridine or phenanthroline) has been reported to afford 50-70% retention
of configuration (Kulikova, V. S.; Gritsenko, O. N.; Shteinman, A. A.
MendeleeV Commun. 1996, 119-120). (b) The hydroxylation of cyclohex-
anol by Fe(ClO4)2/H2O2 in CH3CN has been reported to afford mostly cis-
1,3-cyclohexanediol, but the conversion from H2O2 was only 1% (Groves,
J. T.; Van Der Puy, M. J. Am. Chem. Soc. 1976, 98, 5290-5297).
(18) Buxton, G. V.; Greenstock, C. L.; Helman, W. P.; Ross, A. B. J.
Phys. Chem. Ref. Data 1988, 17, 513-886.
(10) Kim, J.; Harrison, R. G.; Kim, C.; Que, L., Jr. J. Am. Chem. Soc.
1996, 118, 4373-4379.
(11) Walling, C. Acc. Chem. Res. 1975, 8, 125-131.
(12) Sheldon, R. A.; Kochi, J. K. Metal-Catalyzed Oxidations of Organic
Compounds; Academic: New York, 1981; Chapter 2.
(13) (a) Fish, R. H.; Konings, M. S.; Oberhausen, K. J.; Fong, R. H.;
Yu, W. M.; Christou, G.; Vincent, J. B.; Coggin, D. K.; Buchanan, R. M.
Inorg. Chem. 1991, 30, 3002-3006. (b) Arends, I. W. C.; Ingold, K. U.;
Wayner, D. D. M. J. Am. Chem. Soc. 1995, 117, 4710-4711.
(14) Zang, Y.; Kim, J.; Dong, Y.; Wilkinson, E. C.; Appelman, E. H.;
Que, L., Jr. J. Am. Chem. Soc. 1997, 119, 4197-4205.
(19) Kim, J.; Larka, E.; Wilkinson, E. C.; Que, L., Jr. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 2048-2051.
S0002-7863(96)04257-6 CCC: $14.00 © 1997 American Chemical Society

Communications to the Editor
Table 1. Stereospecific Hydrocarbon Oxidations by H2O2 Catalyzed by [Fe(TPA)(CH3CN)2]2+ (1)a
substrate product
cyclohexane
J. Am. Chem. Soc., Vol. 119, No. 25, 1997 5965
turnover numberb
cyclohexanol
3.0
0.7
0.1
3.6
1.2
trace
1.3
1.3
trace
2.1
2.3
2.2
cyclohexanone
cyclohexene
cis-1,2-dimethylcyclohexane
trans-1,2-dimethylcyclohexane
cis-1,2-dimethylcyclohexanol
2,3- and 3,4-dimethylcyclohexanolc
1,2- and 1,6-dimethylcyclohexene
trans-1,2-dimethylcyclohexanol
2,3- and 3,4-dimethylcyclohexanolc
1,2- and 1,6-dimethylcyclohexene
1,2-epoxyhexane
1-hexene
cis-2-hexene
trans-2-hexene
cis-2-hexene oxide
trans-2-hexene oxide
a Reaction conditions: 0.3 mL of a 70 mM H2O2 solution in CH3CN was delivered by syringe pump over 15 min at room temperature to a stirred
2.7 mL CH3CN solution containing 0.7 mM 1 and 700 mM substrate. All of the oxidant was consumed as indicated by iodometry. No products
were observed in the absence of catalyst. b Moles of product/moles of catalyst. Products listed were identified based on GC and NMR analysis and
comparisons with standards, and no other products were observed. c These were identified by comparison with commercially available mixtures of
the isomeric secondary alcohols and not individually assigned.
1,2-dimethylcyclohexane. Furthermore, unlike 1/H2O2, 2/t-
BuOOH cannot epoxidize olefins. The resemblance in reactivity
of 1/H2O2 to heme catalysts suggests that similar mechanisms
may apply to both types of catalysts. The heme paradigm for
alkane hydroxylation20 involves hydrogen atom abstraction from
substrate by a formally FeVdO species and rapid capture of
the nascent alkyl radical by oxygen rebound; the high-valent
iron-oxo species would also be responsible for oxygen atom
insertion into olefins. Since the nonheme ligand environment
of 1 may not support an FeV oxidation state, an alternative worth
considering is a mechanism involving direct oxygen atom
insertion by an (η2-peroxo)metal intermediate,21 as proposed
for early transition metal peroxides that carry out stereospecific
epoxidations.22 An [Fe(TPA)(η2-OOH)]2+ structure for 3 is
consistent with the spectroscopic data obtained thus far and
would account for its distinct reactivity from that of the related
[Fe(TPA)(H2O)(η1-OOtBu)]2+ 10,20
but more work is needed to
,
sort out these alternative mechanisms.
Figure 1. Spectroscopic properties of [Fe(TPA)(OOH)]2+ (3). (a) UV-
vis spectrum in CH3CN at -40 °C (solid line). For comparison, the
spectrum of [Fe(TPA)(CH3CN)2]2+ (1) is shown in dashed lines. (b)
EPR spectrum in CH3CN at -40 °C. (c) Electrospray ionization mass
spectrum.
Irrespective of the structure of 3, it is clear that 1 can catalyze
stereospecific hydrocarbon oxidations with H2O2. Chiral groups
may then be conveniently incorporated into the relatively simple
TPA framework23 to afford catalysts capable of enantiospecific
alkane hydroxylation.
the ions {[Fe(TPA)(OOH)](ClO4)}+, {[Fe(TPA)(O)](ClO4)}+,
and {[Fe(TPA)](ClO4)}+, respectively (Figure 1c). The latter
two ions derive from the respective loss of HO• and HOO•
fragments from {[Fe(TPA)(OOH)](ClO4)}+. Taken together,
the data indicate that intermediate 3 is best formulated as [FeIII-
Acknowledgment. This work was supported by the National
Institutes of Health (GM-33162). We thank Dr. Yan Zang for providing
the [Fe(TPA)(CH3CN)2]2+ complex.
JA9642572
(TPA)(OOH)]2+
.
(20) Groves, J. T. J. Chem. Educ. 1985, 62, 928-931.
(21) (a) Bach, R. D.; Andre´s, J. L.; Su, M.-D.; McDouall, J. J. W. J.
Am. Chem. Soc. 1993, 115, 5768-5775. (b) Jorgensen, K. A.; Wheeler, R.
A.; Hoffmann, R. J. Am. Chem. Soc. 1987, 109, 3240-3246.
(22) Finn, M. G.; Sharpless, K. B. J. Am. Chem. Soc. 1991, 113, 113-
126. (b) Al-Ajlouni, A. M.; Espenson, J. H. J. Am. Chem. Soc. 1995, 117,
9243-9250.
At present we cannot establish the mechanism of oxidation,
but it is clear that 1/H2O2 behaves differently from 2/tBuOOH.
The latter in alkane hydroxylation reactions has been shown to
generate a long-lived alkyl radical that can be trapped with O2;10
in agreement, we have found that 2/tBuOOH affords the two
epimeric tertiary alcohol products in the hydroxylation of cis-
(23) See, for example: Canary, J. W.; Allen, C. S.; Castagnetto, J. M.;
Wang, Y. J. Am. Chem. Soc. 1995, 117, 8484-8485.