Inversion of product selectivity in an enzyme-inspired metallosupramolecular tweezer catalyzed epoxidation reaction

Article abstract of DOI:10.1039/b908852k

This study describes a heteroligated, hemilabile Pt^II-P,S tweezer coordination complex that combines a chiral Jacobsen-Katsuki Mn ^III-salen epoxidation catalyst with an amidopyridine receptor, which leads to an inversion of the major epoxide product compared to catalysts without a recognition group. The Royal Society of Chemistry 2009.

Full text of DOI:10.1039/b908852k

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COMMUNICATION
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Inversion of product selectivity in an enzyme-inspired
metallosupramolecular tweezer catalyzed epoxidation reactionw
Pirmin A. Ulmann, Adam B. Braunschweig, One-Sun Lee, Michael J. Wiester,
George C. Schatz* and Chad A. Mirkin*
Received (in Cambridge, UK) 5th May 2009, Accepted 25th June 2009
First published as an Advance Article on the web 16th July 2009
DOI: 10.1039/b908852k
This study describes a heteroligated, hemilabile PtII–P,S tweezer
coordination complex that combines a chiral Jacobsen–Katsuki
MnIII-salen epoxidation catalyst with an amidopyridine receptor,
which leads to an inversion of the major epoxide product
compared to catalysts without a recognition group.
olefin will form a supramolecular complex with the catalyst,
thereby selecting and orienting the acid-functionalized olefin
with respect to the catalytic metal center. Indeed, Monte Carlo
conformation search simulations for a hydrogen bonded
supramolecular complex between 4 and the substrate molecule
4-vinylbenzoic acid 7 were performed in the gas phase with the
MM2 force field implemented in Macromodel,9 showing that
the global minimum structure (Fig. 1) exhibits a MnIII–olefin
distance of 3.9 A, which is appropriate for catalysis while
maintaining the hydrogen bonding interaction.2,3 Additionally,
a stabilizing p–p interaction between aryl groups on the
substrate and the catalyst that enhances binding was found.10
Complexes 4 and 5 (analogue without receptor group) were
synthesized under ambient conditions by a convergent route in
high yield from salen ligand 1, amidopyridine receptor ligand 2
(or ligand 3 without receptor group), NaBArF, a PtII metal
Recognition and catalysis allow enzymes to select a specific
substrate molecule from a large pool of potential reactants
with identical functional groups and convert it to a specific
product. For example, prostaglandin synthases1 bind
specifically to arachidonic acid, followed by the selective
oxidation of the C13 position in a step towards the desired
prostaglandin. Mimicking such substrate selectivity with
synthetic catalysts is among the goals motivating the field of
biomimetic chemistry.2 Supramolecular recognition, organic
linkers and rigid tweezer groups are strategically combined to
preorganize a structure capable of aligning a substrate
with respect to a catalytic site, thereby affecting product
distribution.3 While this strategy has led to numerous
examples of reactions with unique or otherwise unattainable
specificity, the synthetic effort to synthesize supramolecular
catalysts based on organic frameworks is cumbersome.
Recently, convergent, high-yielding methodologies have been
developed to create coordination complexes capable of
aligning functional groups or creating catalytically active
pockets.4 While such strategies have been used to create
libraries of complexes with heteroligated ligand coordination
modes around catalytically active metal centers, the alignment
of receptor and catalyst units in a tweezer fashion via a metal
coordination site has thus far not been reported.
precursor,
(Scheme 1). H NMR spectroscopic measurements for 4 and
a
MnIII precursor and 2,6-lutidinium-BArF
1
5
exhibit large upfield and downfield resonances that
are assigned to backbone protons on the MnIII-salen unit,
1
consistent with H NMR spectroscopic studies of analogous
(R,R)-[(salen)-MnIII-Cl]11 and (R,R)-[(salen)-MnIII-BArF]
6 complexes. As a result of the paramagnetic nature of these
complexes, their 31P{1H} NMR spectra exhibit broad
resonances, assigned to the k2-P,S-PtII chelating phosphine
ligands.6 High-resolution MS, 19F NMR, IR, UV/Vis spectro-
scopy, and elemental analysis are fully consistent with the
assigned structures (see ESIw for details).
The ability of the amidopyridine group in 4 to form a
hydrogen bonded, supramolecular complex with
7
By employing the weak-link approach (WLA)5 and the
halide-induced ligand rearrangement (HILR)6 reaction, two
different functional units can be oriented in a rigid, tweezer-
like fashion. Herein, we describe the rational design and
preparation of a novel, heteroligated, hemilabile PtII-phosphine
coordination complex
4 (Scheme 1) that combines a
catalytic metal center reminiscent of a Jacobsen–Katsuki
chiral MnIII-salen epoxidation catalyst7 with an amidopyridine
receptor.8 The idea is that in the presence of a pool of
olefin containing substrates, a carboxylic acid terminated
Department of Chemistry and the International Institute for
Nanotechnology, Northwestern University, 2145 Sheridan Road,
Evanston, IL 60208, USA. E-mail: schatz@chem.northwestern.edu,
chadnano@northwestern.edu; Fax: +1 847 467 5123
w Electronic supplementary information (ESI) available: Experimental
procedures, characterization, ITC data, and computational details.
See DOI: 10.1039/b908852k
Scheme 1 (i): [Pt(benzonitrile)2Cl2] (1 equiv.), NaBArF (2.1 equiv.),
CH2Cl2, filtration, (ii): Mn(acac)3 (2 equiv.), 2,6-lutidinium-BArF
(7 equiv.), MeOH, 24 1C. Yield: 4: 88%; 5: 89%. BArF:
B[3,5-(CF3)2(C6H3)]4; acac: acetylacetonate. Inset: analogous
(R,R)-[(salen)-MnIII-BArF]
coordinated to MnIII sites in apical position.7
6 complex. MeOH may be partially
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epoxides 9 and 10, respectively, in the presence of catalysts
4–6 (Scheme 2, Table 1).7 Reactions were carried out at 0 1C in
CH2Cl2, and high dilution (0.9 mM total olefin concentration)
was used to favor intramolecular reaction pathways. A limit-
ing quantity of iodosobenzene oxidant kept substrate concen-
trations close to equimolar levels until the reaction was
quenched with PPh3 after 2 h at a total conversion (9+10)
of 10 Æ 2%, in accordance with previous studies.3 4-Ethyl-
benzoic acid 12 was added in entries 2–4 as a competitive
inhibitor. 2-Acetamidopyridine 11 was added in entries 5 and 7
to equalize amidopyridine functionalities compared to entry 1.
Significantly, analysis of the product mixtures in entries 1
and 5 shows a 4.7 fold preference for epoxide product 9,
whose precursor 7 can form a supramolecular complex with
4, resulting in an inversion of the major epoxide product
depending on whether complex 4 or 5 is used for catalysis.
Competitive binding by 4-ethylbenzoic acid 12 to the receptor
(entries 2–4) gradually leads to diminished selectivity, suggest-
ing that the preferred formation of epoxide 9 in entry 1 is
indeed a consequence of the interaction between the amido-
pyridine group in 4 and the carboxylic acid group in substrate
7 and is not because of a general increase of steric bulk in
the catalyst from the amidopyridine receptor. In entries 6 and
Fig. 1 Global minimum structure obtained from conformation
search simulations of a hydrogen bonded supramolecular complex
between catalyst 4 and 4-vinylbenzoic acid 7.
Scheme 2 Catalytic competition experiment. (i) Catalyst (5 mol%),
PhIO (1 equiv.), n-hexadecane (standard), CH2Cl2, 0 1C, N2, 2 h. Total
olefin concentration: 0.9 mM. Inset: additives to catalytic experiments.
(Scheme 2) was confirmed by isothermal titration calorimetry
(ITC). The carboxylic acid 7 was added to a solution of
catalyst 4 to form a complex predominantly held together
via hydrogen bonding between the carboxylic acid and
the amidopyridine group (Ka (CH2Cl2, 25 1C) = 3090 Æ
360 MÀ1). Consistent with this observation, 2-acetamidopyridine
11 and 7 form a complex with a similar binding constant
(Ka (CH2Cl2, 25 1C) = 1440 Æ 110 MÀ1). Importantly, the
combination of complex 5 and 7 in CH2Cl2 does not result in
measurable binding via ITC. Addition of styrene 8 to a
solution of 2-acetomidopyridine 11 in CH2Cl2 also does not
result in measurable binding. These data all support the
hypothesis that a hydrogen bonded complex forms between
4 and 7 in CH2Cl2 as a consequence of interactions between
the carboxylic acid on 7 and the amidopyridine group on 4.
The influence of noncovalent interactions between 4 and 7
on the epoxide product distribution and enantioselectivity
from a two olefin pool of reactants was determined in a series
of catalytic epoxidation reactions. Equimolar amounts of
olefins 7 and 8 were oxidized to the corresponding chiral
7, (R,R)-[(salen)-MnIII-BArF]
6 shows similar epoxide
distributions and turnover as complex 5, confirming the
preference for styrene oxide formation by this catalytic moiety.
Significant variations in enantioselectivity are observed for
both epoxide 9 and 10 in the different catalytic runs, which are
attributed to a combination of hydrogen bonding and other
interactions that affect epoxide enantioselectivity.7
In conclusion, the assembly of a receptor and a catalyst in a
tweezer fashion via a highly convergent metal coordination
linker is reported for the first time, resulting in a supra-
molecular complex with a specific substrate that leads to its
preferential epoxidation compared to a substrate that does not
bind to the receptor. Use of triple-decker structures6 and a
larger pool of hemilabile P,S receptor, cofactor and catalyst
ligands should lead to improved catalytic selectivities.
We acknowledge the NSF, ARO, AFOSR, and DDRE for
financial support of this research and IMSERC (Northwestern U.)
for analytical services. C.A.M. is grateful for
a NIH
Director’s Pioneer Award. A.B.B. is grateful for a NIH
Postdoctoral fellowship (1F32CA136148-01). P.A.U. thanks
Dr Christopher Oliveri, Dr Hyojong Yoo and Dr Sebastian
Peter for helpful discussions.f
Table 1 Product distribution and enantiomeric excess (ee) of chiral
epoxides following catalytic epoxidation reactions. Catalytic reactions
were carried out in duplicate or triplicate. Conversion and the absolute
ee of 10 were determined via chiral gas chromatography (GC) after
carboxylic acid methylation. Standard deviations for conversion:
r0.7%; ee of 10: r2%; approximate accuracy for ee of 9: Æ 5%
(determined using a chiral 1H NMR shift reagent after purification).
Equiv., conversion and mol% are given with respect to total
olefin concentration
Notes and references
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