A dynamic supramolecular system exhibiting substrate selectivity in the catalytic epoxidation of olefins

Article abstract of DOI:10.1039/b411978a

A dynamic supramolecular system involving hydrogen bonding between a Mn(III) salen catalyst and a Zn(II) porphyrin receptor exhibits selectivity for pyridine appended cis-β-substituted styrene derivatives over phenyl appended derivatives in a catalytic ep

Full text of DOI:10.1039/b411978a

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A dynamic supramolecular system exhibiting substrate selectivity in the
catalytic epoxidation of olefins{
Stefa´n Jo´nsson,a Fabrice G. J. Odille,a Per-Ola Norrbyb and Kenneth Wa¨rnmark*a
Received (in Cambridge, UK) 4th August 2004, Accepted 25th October 2004
First published as an Advance Article on the web 2nd December 2004
DOI: 10.1039/b411978a
all recognition motifs, both between catalyst subunits, and between
substrate and catalyst, are kinetically labile.4{
A dynamic supramolecular system involving hydrogen bonding
between a Mn(III) salen catalyst and a Zn(II) porphyrin
receptor exhibits selectivity for pyridine appended cis-b-sub-
stituted styrene derivatives over phenyl appended derivatives in
a catalytic epoxidation reaction.
The catalytic subunit 2 is a derivative of the successful
Jacobsen–Katsuki epoxidation catalysts;5 a Mn(III)Cl–salen com-
plex with 2-quinolone groups appended to the ligand framework.
The receptor subunit 3 is a Zn(II) tetraarylporphyrin with
peripheral 2-pyridone units. The hydrogen-bonding moieties are
positioned in space to favor the formation of the heterodimer 1,
from 2 and 3, disfavoring discrete homoassemblies. The com-
plementary 2-pyridone-2-quinolone framework6 in 1 provides
kinetically labile and relatively weak association between 2 and 3,
allowing the system to be dynamic in its operation.{ The receptor
subunit takes advantage of the frequently employed pyridine-
Zn(II) porphyrin association for substrate recognition.7
Enzymes are very powerful catalysts, capable of carrying out
reactions on specific substrates with high turnover numbers and
frequencies. It has been of a great interest in the last decades to
mimic such processes1 and supramolecular catalysis is one
approach.1b,1e Most supramolecular catalysts to date rely on rigid,
preorganized systems, and few are able to compete with their
natural counterparts. Sanders has pointed out that more flexible
systems, based on weaker, non-covalent interactions, might be the
way to solve some of the inherent problems.1e However, this point
has not been tested so far, mainly due to the difficult design and
the synthetic effort required. In recent examples of catalysts
assembled by hydrogen bonding,2 as well as metal–ligand
coordination,3,4e the non-covalent interactions are kinetically stable
or show slow exchange kinetics,3c and thus do not contribute to
the overall flexibility of the cavity.
There are potential advantages with such an approach
compared to a covalent or a kinetically stable one. Briefly: (a)
facilitated synthesis of the macrocyclic cavity. (b) The cavity is
flexible enough to accommodate all the different intermediates and
transitions states of the catalytic cycle. (c) The processes of
substrate binding and assembly/disassembly of the cavity should
not severely slow down the catalytic process or result in product
inhibition.
Following the discussion above, we herein present a self-
assembled macrocyclic epoxidation catalyst (1, Fig. 1),{ in which
To study the selectivity of system (2 + 3 = 1) as an epoxidation
catalyst, we designed and synthesized three substrates, 5–7
(Scheme 1).{ All three are cis-b-substituted styrene derivatives
appended by phenyl or 4-pyridyl groups and should have similar
reactivities at the double bond. Selectivity should arise from the
different abilities of the substrates to bind to 3 and the distance
between their binding and reacting functionalities. All three
possible pairs of substrates were subjected to competitive
epoxidation by system (2 + 3 = 1) (2 : 3 5 1 : 1) in CH2Cl2
using PhIO as the oxidant.8 The relative selectivity was determined
after 20% conversion.{ All reactions were run in the presence of a
rigid long pyridine N-oxide derivative (4-(4-tert-butylphenyl)-
pyridine N-oxide, 11), in order to compensate for potential
activation of the Mn(III) salen catalyst by pyridine substrates9 and
in an attempt to block the outside of 1 from participating in non-
selective catalysis. The results are summarized in Table 1.
Fig. 1 The supramolecular catalyst 1 (2 + 3).
{ Electronic supplementary information (ESI) available: analytical and
selected synthetic data for compounds 2–7 and 11; experimental data for
the epoxidations, selectivity and estimation of association constant;
derivation of eqn. 1. See http://www.rsc.org/suppdata/cc/b4/b411978a/
*Kenneth.Warnmark@orgk1.lu.se
Scheme 1
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Kassoc 5 2?103 M21 could also be obtained.10 Based on that value,
70% of 2 is bound as 1 under standard conditions. The term
k52/k51, representing the ratio of epoxidation rates of non-
coordinating substrate 5 by catalysts 2 and 1 respectively, was
found to be very close to 1, implying that the observed selectivity is
a result of an increase in the reactivity of catalyst 1 towards
substrate 6 rather than a decrease in reactivity towards 5 compared
to catalyst 2.
Table 1 The selectivity of the catalytic system (2 + 3 = 1) for
different substrate pairs
Selectivityc
Entrya,b
Description
GC
NMR
1
2
3
6 vs. 5
6 vs. 7
7 vs. 5
1.55 ¡ 0.16
—
1.28 ¡ 0.05
1.44 ¡ 0.12
1.18 ¡ 0.08
1.34 ¡ 0.09
a
General procedure: 2 (3 mmol), 3 (3 mmol), 2 substrates, 5, 6 or 7
(30 mmol each), PhIO (12 mmol), 11 (12 mmol), DCM (0.60 ml), rt.
b
c
Approx. 70% of 2 bound as 1. Relative selectivity.8
sel(obs) 5 (%1?sel(1) + %2?k52/k51)/(%1 + %2?k52/k51)
(1)
To validate the model represented by eqn. 1, the above obtained
values of sel(1), k52/k51 and Kassoc can be used to predict the
observed selectivity of entry 3 (Table 2). The predicted selectivity of
1.25 proves quite close to the experimental one, thus supporting
the model.
While the selectivities8 observed for 1 are modest, they deviate
clearly and consistently from those of 2. The system (2 + 3 = 1)
favors the pyridine containing substrates 6 and 7 over the non-
coordinating substrate 5. However, 5 still shows substantial
reactivity. To investigate the limiting behavior and to get an
insight into the mechanism of selectivity, we subjected the substrate
pair showing the highest selectivity, 6 and 5, to a variety of reaction
conditions (see Table 2). Comparing the results from entries 1–3 in
Table 2, we can conclude that under standard conditions (entry 1),
the system is already close to the selectivity limit; increasing
the concentration of 3 three times, resulting in a higher amount of
catalyst part 2 bound as 1, gives only a minor change in
selectivity (entry 2), whereas dilution, dissociating 1 to free 2 + 3 to
a larger extent, results in lower selectivity (entry 3). Moreover,
replacing 3 with the metal free porphyrin 4 or Zn(II)TPP resulted
only in insignificant selectivity, ruling out non-coordinative
involvement of the co-factor 3 (entries 4 and 5). 4-Ethylpyridine
was identified as a competitive inhibitor of 1 since the selectivity
dropped in the presence of this compound (entry 6), proving that
the pyridyl appended substrates 6 and 7 are epoxidized while
bound to the Zn-moiety of 1. Replacing 11 with the smaller
pyridine N-oxide did not result in a significant change in selectivity
(entry 7).
The results from the epoxidation studies clearly indicate that 1 is
the major catalytic species under the reaction conditions. The
remaining reactivity of 5 can be attributed either to a reaction on
the outer face of the catalyst, or by the ability of 5 to enter the
cavity without being coordinated to Zn.
To our knowledge, this is the first example where substrate
selectivity is imposed on a nonselective catalyst by formation of a
dynamic hydrogen bonded supramolecular assembly around the
catalytic center. Although the observed selectivities are not high,
they are a clear testament that the concept is working, and that
weak, kinetically labile interactions can in fact be successfully
applied to the design of supramolecular catalysts.
Encouraged by the initial results, further studies will be
conducted to increase the selectivity of the system by more
efficiently blocking the outer face of the assembly 1, to elucidate
the kinetics of the processes involved in the catalysis and finally to
address the potential advantages given earlier ((a)–(c)). Given the
versatility of metal-salen complexes as catalysts, other types of
reactions could also be adopted.11
Variation of the concentration of 3 allows for the estimation of
the inherent selectivity of 1, which cannot be directly observed.
Non-linear curve fitting of entries 1 and 2 (Table 2) to an
expression for the observed selectivity (eqn. 1),{ gave an estimate
of the upper limit for the selectivity of 6 vs. 5 (sel(1)) as 1.66.
Further, the mole fractions of 1 and 2 (%1, %2) are derived from
the equilibrium Kassoc 5 [1]/[2][3], and so a rough estimate of
We are grateful to Dr Karl-Erik Bergquist for his expert
assistance on quantitative NMR analysis. We thank the Swedish
Research Council as well as the Crafoord Foundation, the Lars-
Johan Hierta Foundation, the Magn. Bergvall Foundation, and
the Royal Physiographic Society for generous grants.
Stefa´n Jo´nsson,a Fabrice G. J. Odille,a Per-Ola Norrbyb and
Kenneth Wa¨rnmark*a
aOrganic Chemistry 1, Department of Chemistry, Lund University,
P.O. Box 124, SE-221 00 Lund, Sweden.
Table 2 The selectivity of 6 vs. 5 under various conditions
Selectivity of 6 vs. 5a
E-mail: Kenneth.Warnmark@orgk1.lu.se; Fax: (+46) 46 2224119;
Tel: (+46) 46 2228127
bDepartment of Chemistry, Technical University of Denmark,
Kemitorvet, DK-2800 Kgs Lyngby, Denmark
Entry Systemg
GC
NMR
1b
2c
3d
4
2 (3 mmol) + 3 (3 mmol)
1.55 ¡ 0.16 1.44 ¡ 0.12
1.57 ¡ 0.09 1.68 ¡ 0.21
1.30 ¡ 0.11 1.32 ¡ 0.13
1.14 ¡ 0.07 1.06 ¡ 0.08
— 0.97 ¡ 0.14
1.32 ¡ 0.18 1.29 ¡ 0.14
2 (3 mmol) + 3 (9 mmol)
2 (3 mmol) + 3 (3 mmol)
2 (3 mmol) + 4 (3 mmol)
2 (3 mmol) + Zn(II)TTP (3 mmol)
Notes and references
{ All interactions are fast on the NMR timescale; signals represent averages
of bound and unbound species, thus the term: ‘‘kinetically labile’’.
5
6b,e 2 (3 mmol) + 3 (3 mmol)
7b,f 2 (3 mmol) + 3 (3 mmol)
1.56 ¡ 0.25 1.49 ¡ 0.09
c
1 (a) R. Breslow, Acc. Chem. Res., 1995, 28, 146; (b) M. C. Feiters,
Supramolecular Catalysis, in Comprehensive Supramolecular Chemistry,
eds. J. L. Atwood, J. E. D. Davies, D. D. MacNicol, F. Vo¨gtle,
J.-M. Lehn and D. N. Reinhoudt, Elsevier Science, Oxford, 1996,
vol. 10, pp. 267–360; (c) A. J. Kirby, Angew. Chem., Int. Ed. Engl., 1996,
35, 707; (d) Y. Murakami, J. Kikuchi, Y. Hisaeda and O. Hayashida,
Chem. Rev., 1996, 96, 721; (e) J. K. M. Sanders, Chem.–Eur. J., 1998, 4,
Relative selectivity.8 Approx. 70% of 2 bound as 1. Approx.
95% of 2 bound as 1. DCM (6.0 ml): approx. 40% of 2 bound as
a
b
d
e
f
1. 4-Ethylpyridine (90 mmol). Pyridine N-oxide (12 mmol) instead
g
of 11. The general procedure was followed unless otherwise noted:
5 (30 mmol), 6 (30 mmol), PhIO (12 mmol), 11 (12 mmol), DCM
(0.60 ml), rt.
550 | Chem. Commun., 2005, 549–551
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1378; (f) W. B. Motherwell, M. J. Bingham and Y. Six, Tetrahedron,
2001, 57, 4663.
2 Examples include: J. Kang, J. Santamaria, G. Hilmersson and J. Rebek,
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6 Examples of 2-pyridone derivatives as building blocks in self-assembly:
Y. Ducharme and J. D. Wuest, J. Org. Chem., 1988, 53, 5787;
S. C. Zimmerman and B. F. Duerr, J. Org. Chem., 1992, 57, 2215;
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M. Nakash, Z. Clyde-Watson, N. Feeder, J. E. Davies, S. J. Teat and
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8 In each experiment, a series of reactions was run from the same stock
solution of substrates and internal standard, including a reference
reaction using only 2 as catalyst. Product ratios for all the reactions were
obtained by GC and NMR analysis and were normalized to that of the
reference reaction, to correct for small differences in reactivity and GC
response factors (see ESI{).
9 Pyridine N-oxides are known to increase stability, reactivity and
enantioselectivity of the catalyst by coordinating to Mn in Jacobsen–
Katsuki epoxidation. See for example: J. El-Bahraoui, O. Wiest,
D. Feichtinger and D. A. Plattner, Angew. Chem., Int. Ed., 2001, 40,
2073; N. S. Finney, P. J. Pospisil, S. Chang, M. Palucki, R. G. Konsler,
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catalyst but do not interact with Mn as strongly as N-oxides do, see:
K. Srinivasan, P. Michaud and J. K. Kochi, J. Am. Chem. Soc., 1986,
108, 2309.
3 Examples: (a) N. C. Gianneschi, P. A. Bertin, S. T. Nguyen,
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P. W. N. M. van Leeuwen and J. N. H. Reek, Angew. Chem., Int. Ed.,
2003, 42, 5619.
4 Other approaches to supramolecular epoxidation catalysts: (a)
D. R. Benson, R. Valentekovich, S.-W. Tam and F. Diederich, Helv.
Chim. Acta, 1993, 76, 2034; (b) L. Weber, R. Hommel, J. Behling,
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R. Breslow, X. Zhang, R. Xu, M. Maletic and R. Merger, J. Am. Chem.
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A. E. Rowan and R. J. M. Nolte, Chem. Commun., 2000, 2443; (e)
M. L. Merlau, M. del Pilar Mejia, S. T. Nguyen and J. T. Hupp, Angew.
Chem., Int. Ed., 2001, 40, 4239; (f) G. A. Morris, S. T. Nguyen and
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(h) P. Thordarson, E. J. A. Bijsterveld, A. E. Rowan and R. J. M. Nolte,
Nature, 2003, 424, 915.
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Chem. Soc., 1990, 112, 2801; R. Irie, K. Noda, Y. Ito, N. Matsumoto
and T. Katsuki, Tetrahedron Lett., 1990, 31, 7345; T. Katsuki, J. Mol.
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10 It is assuring that the estimated Kassoc is similar to that of an analogous
salen-porphyrin macrocyclic dimer assembly (see ESI{).
11 L. Canali and D. C. Sherrington, Chem. Soc. Rev., 1999, 28, 85–93;
M. Bandini, P. G. Cozzi and A. Umani-Ronchi, Chem. Commun., 2002,
919; T. Katsuki, Synlett, 2003, 281.
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