Efficient catalytic oxidation of primary and secondary alcohols using a non-heme dinuclear iron complex

Article abstract of DOI:10.1039/b009368h

A novel μ-oxo diiron(III) complex is capable of fast and selective oxidation of primary and secondary alcohols in the presence of H₂O₂ and a remarkable increase in reaction rate is achieved by addition of 1 eq. of CF₃SO

Full text of DOI:10.1039/b009368h

Efficient catalytic oxidation of primary and secondary alcohols using a
non-heme dinuclear iron complex
Alette G. J. Ligtenbarg,a Peter Oosting,a Gerard Roelfes,a René M. La Crois,a Martin Lutz,b Anthony L.
Spek,b Ronald Hage*a and Ben L. Feringa*a
a Department of Organic and Molecular Inorganic Chemistry, University of Groningen, Nijenborgh 4, 9747 AG
Groningen, The Netherlands. E-mail: b.l.feringa@chem.rug.nl
b Department of Crystal and Structural Chemistry, Utrecht University, Padualaan 8, 3584 CH, Utrecht, The
Netherlands
Received (in Cambridge, UK) 22nd November 2000, Accepted 18th January 2001
First published as an Advance Article on the web 8th February 2001
A novel m-oxo diiron(III) complex is capable of fast and
selective oxidation of primary and secondary alcohols in the
presence of H2O2 and a remarkable increase in reaction rate
is achieved by addition of 1 eq. of CF3SO3H.
Primary and secondary alcohols are oxidised rapidly (Table
1).∑
The oxidation of benzyl alcohol was monitored in time by
GC. In Fig. 1 the turnovers per iron centre are plotted against
time. Surprisingly, already 4 eq. of benzaldehyde have been
formed in a reproducible manner, 30 s after the reaction was
started by adding H2O2. The origin of this initial burst of activity
is unclear. After the initial oxidation, a lag phase was observed.
A significant increase in catalytic activity occurred after
approximately 40 min and after 75 min the catalytic activity
ceased because all the H2O2 was consumed. A total of 50
turnovers towards benzaldehyde was reached. Although a trace
of benzoic acid was obtained, no other side products were
produced according to GC. When another aliquot of H2O2 is
added after 90 min, the catalyst is immediately active and no lag
phase is observed. A value of 96 turnovers per iron centre can
be obtained after 180 min. This can be repeated at least 3 times
without significant loss of activity, showing a good stability of
the system during catalytic turnover.
In nature, a variety of non-heme metalloenzymes are present
which are capable of oxidation of substrates with high turnover
frequencies and excellent selectivity.1 An example is the
mononuclear copper enzyme galactose oxidase (GOase) which
catalyses the aerobic oxidation of benzylic and allylic alcohols
to their corresponding aldehydes with concomitant formation of
H2O2. The study of model complexes not only provides
invaluable information about metalloenzymes, but also can
result in the development of new generations of oxidation
catalysts.2 Beautiful examples are the GOase models developed
by the groups of Wieghardt and Stack, which are capable of
oxidation of alcohols to the corresponding aldehydes with high
yield and selectivity.3 An iron(II) complex of a pentadentate
ligand N4Py† was developed as a model system for Fe-
BLM.4,5† This system is capable of oxidising alkanes using
H2O2 via a radical type mechanism. To explore the effect of
ligand variations on the oxidation behaviour of the complex, we
prepared a ligand HL1† in which one of the pyridyl groups is
replaced by a phenolate moiety. The corresponding m-oxo
dinuclear iron complex of HL1 proved to be a selective and
efficient catalyst for the oxidation of alcohols to aldehydes and
ketones using H2O2 as the oxidant. Yields up to 65% based on
H2O2 can be reached.
The UV/Vis absorption of 1 at 540 nm was monitored
concomitantly with the oxidation of benzyl alcohol to benzalde-
hyde. During the lag phase the solution remains purple but after
45 min the colour changes to yellow. This colour change
coincides with the end of the lag phase, suggesting that the
yellow species is responsible for the oxidation activity.
The synthesis of HL1 is shown in Scheme 1. Complexation of
the ligand with Fe(II)(ClO4)2·x H2O in MeOH, in the presence of
1 eq. of Et3N followed by slow diffusion of ethyl acetate into the
methanolic solution yielded purple crystals of complex 1 (lmax
= 540 nm, eM = 5.6 103 M21 cm21) in 50% yield.‡ The
complex was characterised as an antiferromagnetically coupled
1
diiron(III) species based on its EPR silent nature and its H-
NMR spectrum, which exhibits paramagnetically shifted sig-
nals in the 0–40 ppm range. The ESI/MS spectrum shows a peak
at m/z 445 ([(L1)Fe(m-O)Fe(L1)]2+), which is consistent with the
formulation of 1 as {[(L1)Fe(m-O)Fe(L1)](ClO4)2}. Further
proof for this assignment was obtained from the crystal
structure of the corresponding m-oxo diiron(III) complex
[(L1)Fe(m-O)Fe(L1)](PF6)2 (2), depicted in Scheme 1, which
was synthesised by adding Fe(NO3)3·9H2O to a solution of the
ligand in methanol, followed by the addition of 1 eq. of Et3N
and 2 eq. of NH4PF6. Dark purple–blue crystals were obtained
by slow diffusion of ether into the solution of 2. Each iron(III
)
ion adopts a distorted octahedral coordination geometry
involving a tertiary amine, three pyridine nitrogens, a phenolate
oxygen atom and the bridging oxygen atom, with the Fe–O–Fe
angle being 151.22(10)°.§ The crystal structure of 2 gave no
indications that a proton is present at the phenolate moiety,
which is consistent with the ESI/MS results of 1 (vide supra).
Complex 1 was examined as a catalyst (0.1 mol%) in the
oxidation of various substrates using H2O2 as the oxidant.¶
Scheme 1 Synthesis of HL1 and 2 and crystal structure of the cation of 2
(displacement ellipsoid plot with 50% probability level in which hydrogen
atoms are omitted for clarity). Reagents and conditions: i, 2-pyridine
carbaldehyde, 2 h, 97%; ii, NaBH4, MeOH, 2 h, 90%; iii, 2-(bromo-
methyl)phenyl acetate, iPr2EtN, EtOAc, 3 d, 66%; iv, K2CO3, MeOH, 1 h,
89%; v, Fe(NO3)3, Et3N, NH4PF6, 29%; Selected interatomic distances (Å):
Fe–O: 1.93, Fe(1)–O(2) 1.79, Fe(1)–N(1) 2.26, Fe(1)–N(2) 2.17Å, Fe(1)–
N(3) 2.22, Fe(1)–N(4) 2.13.
DOI: 10.1039/b009368h
Chem. Commun., 2001, 385–386
This journal is © The Royal Society of Chemistry 2001
385

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Table 1 Turnover numbers (t.o.n.) of the catalytic oxidation experiments
with 1 using H2O2
effect (KIE, kH/kD = 4.0) that was observed in a competition
experiment between benzyl alcohol and benzyl alcohol-d7, it
can be concluded that oxidising species more selective than
hydroxyl radicals are present. When the KIE was determined
30 s after starting the reaction by addition of H2O2, i.e. after the
initial burst of activity, a value of 1.8 was obtained indicating
the presence of a highly reactive oxidising species in the initial
stage of the reaction. Finally, since the purple colour of 1 is
indicative of a LMCT transition between the phenolic part of the
ligand and the iron(III) center,7,8 it is most likely that the
phenolic moiety is no longer coordinated to the iron centre in
this yellow species, which is thought to be responsible for
oxidation activity.
In conclusion, a new Fe(III) containing catalyst has been
developed for selective oxidation of primary and secondary
alcohols using H2O2. A dramatic enhancement in the reaction
rate upon addition of acid has been observed, which is attributed
to accelerated formation of the active mononuclear catalyst.
Mrs C. M. Jeronimus-Stratingh is gratefully acknowledged
for performing the ESI-MS measurements. This work was
supported in part (A. L. S., M. L.) by the Council for Chemical
Sciences of the Netherlands Organization for Scientific Re-
search (CW-NWO).
Entry
Substrate
Product
Time/min t.o.n.a
1b
2c
3d
4e
5
6
7
8
9
Benzyl alcohol
Benzyl alcohol
Benzyl alcohol
Benzyl alcohol
Cyclohexanol
Cyclohexanol
Cyclooctanol
Octan-1-ol
Benzaldehyde
Benzaldehyde
Benzaldehyde
Benzaldehyde
Cyclohexanone
Cyclohexanone
75
15
90
180
60
60
50
50
15
96
28
65
11
11
50
Cyclooxtanone 180
Octanalf
180
60
sec-Phenylethyl Alcohol Acetophenone
a t.o.n. = mol product/mol catalyst. b In the absence of catalyst a negligible
amount of 0.004 mmol of benzaldehyde was formed under the standard
reaction conditions after 90 min, whereas in the presence of Fe(II)(ClO4)2
only 8 turnovers were reached. c In the presence of 1 eq. CF3SO3H. d With
100 eq. of substrate instead of 1000 eq. e Addition of another aliquot of
H2O2 after 90 min. f Octanoic acid was formed as side product.
Notes and references
† Abbreviations used: N4Py
=
N,N-bis(2-pyridylmethyl)-N-bis(2-pyr-
idyl)methylamine; HL1
=
2-({[di(2-pyridyl)methyl](2-pyridylmethyl)-
amino}methyl)phenol; Fe-BLM = iron bleomycin.
‡ Anal. calcd. for C48H42N8O11Fe2Cl2·H2O: C 52.07, H 4.01, N 10.13%;
found: C 52.17, H 3.80, N 10.03%.
§ Crystal data: [C48H42Fe2N8O3](PF6)2, Fw = 1180.54, dark blue needle,
0.45 3 0.24 3 0.15 mm3, monoclinic, C2/c (No. 15), a = 31.0660(6), b =
11.1832(2), c = 33.8507(7) Å, b = 100.6240(7)°, V = 11558.7(4) Å3, Z =
8, r = 1.357 g cm23. 83260 reflections were measured on a Nonius
KappaCCD diffractometer with rotating anode (l = 0.71073 Å) at a
temperature of 150(2) K. 10198 reflections were unique (Rint = 0.043). R-
values [I > 2s(I)]: R1 = 0.0416, wR2 = 0.1173. Molecular illustration,
structure checking and calculations were performed with the PLATON
package. CCDC 154063. See http://www.rsc.org/suppdata/cc/b0/
b009368h/ for crystallographic files in .cif format.
Fig. 1 Catalytic oxidation of benzyl alcohol to benzaldehyde using 1: (-)
time course of the turnovers, (5) time dependent decay of the UV band at
l = 540 nm and (:) oxidation in the presence of 1 eq. CF3SO3H.
¶ Oxidation reactions were performed in acetone, under an argon atmos-
phere in a water bath thermostatted at 25 °C. In a typical reaction, 3.5 mmol
of substrate (1000 eq.) was added to 4 ml of a stock solution of 1.75 mmol
of the catalyst (i.e. 3.5 mmol of iron) and a known amount of the internal
standard bromobenzene. The reaction was initiated by addition of 35 ml of
H2O2 (30% solution in water, 100 eq.) and monitored by GC.
∑ Alkenes and alkanes were also investigated, but these reactions are slow
(6–18 h), less selective and turnover numbers are lower (typically
10–20).
Several observations suggest that the active oxidising
complex is a mononuclear species. First, complex 1 is EPR
silent whereas upon addition of benzyl alcohol and H2O2, when
the solution becomes yellow, a strong EPR signal can be
observed at g = 4.3 which is characteristic for a mononuclear
high-spin iron(III) complex.6 Secondly, it was found that
alcohols, which are known to be capable of breaking up the oxo-
bridge of some dinuclear iron m-oxo complexes to form
monomeric structures by coordination to the metal centre,6 are
oxidised rapidly. In contrast, the active yellow species is formed
very slowly in the absence of substrate or with a non-
coordinating substrate like cyclohexene. Finally, we envisaged
that protonation of the oxo-bridge in 1 would facilitate the
formation of the mononuclear species and hence would speed
up the reaction. Upon addition of triflic acid (CF3SO3H) to 1 in
1 For reviews on iron based enzymes, see: E. I. Solomon, T. C. Brunold,
M. I. Davis, J. N. Kemsley, S.-K. Lee, N. Lehnert, F. Neese, A. J. Skulan,
Y.-S. Yang and J. Zhou, Chem. Rev., 2000, 100, 235; L. Que, Jr. and
R. Y. N. Ho, Chem. Rev., 1996, 96, 2607.
2 H. J. Krüger, Angew. Chem., Int. Ed., 1999, 38, 627.
3 Y. Wang, J. L. DuBois, B. Hedman, K. O. Hodgson and T. D. P. Stack,
Science, 1998, 279, 537; P. Chaudhuri, M. Hess, U. Flörke and K.
Wieghardt, Angew. Chem., Int. Ed., 1998, 37, 2217.
4 M. Lubben, A. Meetsma, E. C. Wilkinson, B. Feringa and L. Que, Jr.,
Angew. Chem., Int. Ed. Engl., 1995, 34, 1512; G. Roelfes, M. Lubben, K.
Chen, R. Y. N. Ho, A. Meetsma, S. Genseberger, R. M. Hermant, R.
Hage, S. K. Mandal, V. G. Young, Jr., Y. Zang, H. Kooijman, A. L. Spek,
L. Que, Jr. and B. L. Feringa, Inorg. Chem., 1999, 38, 1929; R. Y. N. Ho,
G. Roelfes, B. L. Feringa and L. Que, Jr., J. Am. Chem. Soc., 1999, 121,
264.
5 G. Roelfes, M. Lubben, R. Hage, L. Que, Jr. and B. L. Feringa, Chem.
Eur. J., 2000, 6, 2152.
6 J. Kim, E. Larka, E. C. Wilkinson and L. Que, Jr., Angew. Chem., Int. Ed.
Engl., 1995, 34, 2048.
7 S. Ito, M. Suzuki, T. Kobayashi, H. Itoh, A. Harada, S. Ohba and Y.
Nishida, J. Chem. Soc., Dalton Trans., 1996, 2579.
8 S. Yan, L. Que, Jr., L. F. Taylor and O. P. Anderson, J. Am. Chem. Soc.,
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1
acetone a blue colour appears. The H-NMR spectrum of this
solution shows broad signals in the 210 to 120 ppm range
consistent with the presence of mononuclear high-spin Fe(III
)
species. The ESI/MS spectrum shows prominent peaks at m/z
581 and 472, which corresponds to [L1FeIII-OTf]+ and
[(HL1)FeIII(OH)2]+, respectively. Indeed when CF3SO3H (1
eq.) was used, the reaction rate increased dramatically (Fig. 1).
The yellow species was formed immediately upon addition of
H2O2 and after 15 min already 50 turnovers are reached in the
oxidation of benzyl alcohol.
Although the exact reaction mechanism is not known yet,
some tentative conclusions can be drawn. The fact that benzene,
which can act as a hydroxyl radical trap,5 is not oxidised by this
system, combined with the large kinetic deuterium isotope
386
Chem. Commun., 2001, 385–386