Supramolecular control on chemo- and regioselectivity via encapsulation of (NHC)-Au catalyst within a hexameric self-assembled host

Article abstract of DOI:10.1021/ja111106x

The encapsulation of a Au(I) catalyst within a self-assembled, hydrogen bonded, hexameric capsule dramatically changes its catalytic activity, leading to unusual products due to the steric requirements of the host's cavity.

Full text of DOI:10.1021/ja111106x

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Supramolecular Control on Chemo- and Regioselectivity via
Encapsulation of (NHC)-Au Catalyst within a Hexameric
Self-Assembled Host
†
,†
‡
†
,§
Alessandra Cavarzan, Alessandro Scarso,* Paolo Sgarbossa, Giorgio Strukul, and Joost N. H. Reek*
†
0
Dipartimento di Scienze Molecolari e Nanosistemi, Universit ꢀa Ca Foscari di Venezia, Calle Larga S Marta 2137,
0123, Venezia, Italy
Dipartimento di Processi Chimici per l Ingegneria, Universit ꢀa di Padova, Via Marzolo 9, 35131 Padova, Italy
3
‡
0
§
Van’t Hoff Institute for Molecular Sciences, University of Amsterdam, Postbus 94720, 1090 GE Amsterdam, The Netherlands
S Supporting Information
b
systems operate in aqueous conditions where the hydrophobic
effect is a powerful driving force for holding the capsules together
and pushing the catalysts and substrates inside the capsule. In
contrast, the use of multimeric self-assembled capsules held toge-
ther by weak intermolecular forces acting as a solvation sphere for
an encapsulated organometallic catalyst in order to alter its
catalytic activity and selectivity has not thus far been reported.
Herein we report the first Au catalyst that is encapsulated into
ABSTRACT: The encapsulation of a Au(I) catalyst within a
self-assembled, hydrogen bonded, hexameric capsule dra-
matically changes its catalytic activity, leading to unusual
products due to the steric requirements of the host’s cavity.
6
a capsule which is self-assembled in organic media. Application
nzymes are supramolecular catalysts par excellence in which
in the hydration reaction of terminal alkynes yields products of
which the chemo- and regioselectivities are strongly affected by
the capsule. To this purpose we selected the hexameric assembly
E
supramolecular interactions between the active site and the
reagents effect the selection of substrates, facilitate their orienta-
tion into the required position for reaction, and promote the
subsequent covalent modification, leading to highly selective
product formation. As such, enzymes control the selectivity of a
reaction dominantly by the second sphere environment, which
contrasts with the general mechanism of transition metal cata-
lysis where the substrate interacts only with a limited portion of
the catalyst surface, the rest remaining in contact with the bulk
solution. Inspired by the efficiency displayed by enzymes,
capsular structures as reaction hosts represent an interesting
but challenging goal. Recent breakthroughs in supramolecular
chemistry have enabled the preparation of a diversity of such
capsules, and for several organic reactions, it has been demon-
strated that activity and selectivity can indeed be controlled by
obtained by resorcin[4]arene 1 as the largest and, at the same
7
time, simplest self-assembled capsule. The capsule 1 exists in
6
organic solvents like chloroform-d or benzene-d even at con-
6
8,9
centrations as low as nanomolar, but only in water saturated
solvents. We found (NHC)-Au complexes to be the most
suitable catalyst precursors for encapsulation.
3
The cavity of 1 is about 1375 Å , and this space is usually filled
6
with six to eight solvent molecules. Suitable guests are usually
10
cationic species such as tetraalkylammonium and phospho-
nium cations that, depending on their size, are coencapsulated
with residual solvent molecules (Scheme 1). The active gold
species is monoligated, and the reaction takes place opposite to
the ligand position.
1
the second sphere environment provided by the capsule. In
The neutral (i-Pr-NHC)AuCl complex [chloro[1,3-bis(2,6-
diisopropylphenyl)imidazol-2-ylidene]gold(I)] can be encapsu-
lated within the hexameric host by simple mixing with the
resorcin[4]arene in a 1:7 ratio in water saturated chloroform-d
where self-assembly takes place. Encapsulation of the complex is
evidenced by the appearance of a new set of signals in the
contrast, the number of organometallic catalysts enclosed in such
systems to control catalytic activity and selectivity is very limited.
Organometallic complexes encapsulated into nanoporous
2
solids have been investigated with observations of improve-
ments in selectivity. Obviously, the creation of such a well-
defined environment in solution is much more difficult. Several
successful examples of organometallic complexes accommodated
in open ended cavitand structures have been reported. Since
these supramolecular structures are based on robust interactions,
1
H NMR for the i-Pr residue of the Au complex that is signifi-
cantly upfield shifted compared to the free complex (Δδ =
1
-0.95 ppm; see Supporting Information). A H NMR spectrum
of the mixture using different stoichiometry shows the coex-
istence of signals for the free and bound complex, indicative of a
slow exchange rate between encapsulated and free species on the
NMR time scale.
3
such as metal-ligand interactions or intramolecular hydrogen
4
bonds, the shape of the host is retained, enabling remarkable
changes in selectivity for both catalytic hydroformylation and
hydrogenation reactions, respectively. The use of capsular hosts
in principle allows control of the substrate by selection based on
As the active species in catalysis is generally cationic in nature,
we prepared (i-Pr-NHC)Au(OTf) 2 as well and studied its
5
size. Raymond observed substrate size exclusion imparted by the
capsule in the Rh(I) catalyzed isomerization of allylic alcohols
and ethers to the corresponding carbonyl compounds. These
Received: December 10, 2010
Published: February 14, 2011
r 2011 American Chemical Society
2848
dx.doi.org/10.1021/ja111106x
|J. Am. Chem. Soc. 2011, 133, 2848–2851

Journal of the American Chemical Society
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Scheme 1. Resorcin[4]arene 1 Forms a Supramolecular
Hexameric Capsule 1 Which Encapsulates (NHC)-Au-OTf 2
6
or Ammonium Guest 3
1
binding properties. As shown by the H NMR spectra reported in
1
Figure 1. H NMR spectra in CDCl
(
3
at 298 K. (A) 2 (3.3 mM); (B) 1
Figure 1, this complex showed quantitative coordination in the
capsule when working with the same 1:7 stoichiometry reported
above. The H NMR spectrum clearly shows the upfield shifted
resonances of the i-Pr residues of the ligand at -0.26 and 0.37
ppm (Δδ = -0.99 ppm) as broad signals. Analogously, the vinyl
resonances of the encapsulated complex appeared between 5 and
24 mM); (C) 1 (24 mM), and catalyst 2 (3.3 mM).
1
complete displacement of the latter and encapsulation of the
organic cation (see Supporting Information).
3
Complex 2 has a molecular volume of about 400 Å and
consequently occupies about 30% of the volume of the cavity.
This means that two to four extra solvent molecules are coencap-
sulated to ensure stable complexation, in agreement with the
general 55% occupancy rule proposed by Rebek. Such solvent
molecules can be easily exchanged with substrate molecules of
comparable size and shape, suggesting the possibility that the
encapsulated complex is able to convert substrates while in the
cavity. NHC-Au complexes are known to efficiently catalyze a
7
ppm while the resonances for the free complex in solution
completely disappeared.
11
The encapsulated and free complex 2 showed very different
-
10
-9
2 -1
diffusion coefficients (7.9 ꢀ 10
vs 1.4 ꢀ 10 m s res-
pectively) as evidenced by DOSY experiments. On the other
hand, the similar diffusion coefficients observed for encapsulated
and the hexameric host indicate that complex 2 indeed resides
inside the capsule (see Supporting Information). The F NMR
signal of the triflate anion of the complex did not change upon
encapsulation which means that it probably remains excluded by
the encapsulation process.
2
19
12
variety of organic transformations. For these initial experi-
ments, we selected the hydration of alkynes as a test reaction to
investigate the supramolecular effect of the capsule on the activity
and selectivity of the catalyst, also because the presence of water
is required for capsule formation. 4-Phenyl-1-butyne 4 was chosen
as a substrate yielding two possible hydration products, 4-phenyl-2-
butanone 5 and 4-phenyl-butanal 6.
Recent literature has demonstrated that Au catalysts usually
give Markovnikov addition of water to terminal alkynes leading
to the almost exclusive formation of methyl ketones. Under
anhydrous conditions the same catalyst transforms this substrate
into 1,2-dihydronaphthalene 7 via an intramolecular rearrange-
1
Further evidence for the encapsulation was provided by the H
NOESY spectra; in addition to the expected intramolecular
contacts between different resonances of 2, the NOESY spec-
trum of the encapsulated complex showed clear cross peaks bet-
ween the i-Pr residues of the Au complex and both the hydroxyl
residues of the capsule and the aryl proton between the OH
groups of the aromatic moieties, confirming the presence of the
Au complex within the self-assembled capsule (see Supporting
Information). Similar spectra indicating both binding and close
contacts were obtained if the experiments were performed in
benzene-d instead of CDCl as solvent.
1
3
1
4
15
ment. Therefore, Au catalyst 2 was evaluated, in both its free
and encapsulated form, in the hydration of 4-phenyl-butyne in
benzene-d under identical experimental conditions (Scheme 2).
6
3
6
The process can be reversed, as the encapsulated catalyst can
be displaced by a guest with better binding capabilities, such as
cationic tetraethyl ammonium tetrafluoroborate 3. In fact, addi-
tion of 10 equiv of 3 to a solution of the encapsulated 2 led to
As expected the reaction carried out with free 2 in water
saturated benzene-d at 70 °C led to the almost exclusive and
6
quantitative formation of 5 as hydration product within 30 min,
with only traces of 6 and 7. As expected, once encapsulated in the
2
849
dx.doi.org/10.1021/ja111106x |J. Am. Chem. Soc. 2011, 133, 2848–2851

Journal of the American Chemical Society
COMMUNICATION
Scheme 2. 4-Phenyl-butyne 4 Provides Two Possible Hy-
dration Products 5 and 6 and One Cyclization Product 7
under Anhydrous Conditions
self-assembled capsule 1 , the catalyst was much slower and only
6
5
% conversion was observed after 30 min, indicating that the
reaction rate is controlled by the barrier provided by the capsule
to the approach of the substrate to the catalyst. The catalyst was,
however, sufficiently stable and continued to convert the sub-
strate, and after 400 min 28% of the substrate was converted.
Interestingly, the encapsulated catalyst gives rise to a different
product distribution than the free catalyst. In addition to product
Figure 2. Reaction profiles for 4 (66 mM) with catalyst 2 (3.3 mM) in
water saturated benzene-d at 70 °C in the presence of 1 (33 mM) with
6
addition after 400 min of 3 (33 mM). (b) 5, (O) 6, and (4) 7.
of size, shape, and attractive weak interactions between the cata-
lyst and capsule. The remaining space is sufficiently large to
coencapsulate alkynes that can be subsequently converted into
hydration products. The catalytic activity and selectivity of the
NHC-Au catalyst is controlled by the nanoenvironment pro-
vided by the self-assembled capsule as host, leading to unusual
regioselectivity in the hydration of 4-phenyl-butyne together
with an unusual cyclization product. Solvation of the catalyst
from bulk benzene to the hexameric host alters activity and selec-
tivity mimicking catalysis occurring in the active site of enzymes.
Further studies on selectivity aspects for encapsulated complexes
in the self-assembled hexamer are currently ongoing in our
laboratories.
5
(12%), also significant amounts of linear aldehyde 6 (4%) was
formed as the hydration product, which is unprecedented for Au
1
3
catalysts. This clearly demonstrates that the regioselectivity can
be steered to the opposite direction with respect to the natural
catalyst selectivity by putting it in a sterically constrained envi-
ronment. Furthermore, we observed also the formation of 1,2-
dihydronaphthalene 7 (12%), a product that is formed after
intramolecular rearrangement usually found only in the absence
of water. Apparently, the intramolecular reaction is favored when
taking place within the cavity due to unusual folding of the subs-
trate. Alternatively, the capsule may impose a barrier for the
entrance of water, making the intermolecular reaction relatively
slow compared to the intramolecular one.
’ ASSOCIATED CONTENT
The ammonium salt 3 binds better than the complex, provid-
ing a means to control the reactivity of the encapsulated catalyst
and evidence for the reaction taking place inside the capsule. In a
typical experiment 10 equiv of 3 were added after the reaction
had progressed for 400 min. As displayed in Figure 2, a rapid
increase of the yield in 5 was observed, while the amount of 6 and
S
Supporting Information. Experimental part and proce-
b
dures for this article. This material is available free of charge via
the Internet at http://pubs.acs.org.
’
AUTHOR INFORMATION
7
remained almost unchanged, providing clear experimental
Corresponding Author
alesca@unive.it; j.n.h.reek@uva.nl
evidence for the complete displacement of 2 from the capsule.
Once released to the bulk solvent, the catalyst exclusively pro-
duces 5 as the hydration product.
Substrate 4 did not show affinity for the free caspule 1 in the
’ ACKNOWLEDGMENT
6
absence of catalyst 2. Addition of 4 to 2@1 under reaction
0
6
A.S., P.S., and G.S. thank Universit ꢁa Ca Foscari di Venezia,
Universit ꢀa degli Studi di Padova, and “Consorzio Interuniversi-
tario Nazionale per la Scienza e Tecnologia dei Materiali” for
financial support and L. Sperni for GC-MS analysis.
conditions did not provide new signals directly attributed to the
encapsulated substrate, but new weak very broad upfield shifted
resonances appeared at 0.20 and -0.39 ppm close to the signals
attributed to the i-Pr residues of encapsulated catalyst 2 and are
attributed to i-Pr residues of new Au species derived by the
’
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dx.doi.org/10.1021/ja111106x |J. Am. Chem. Soc. 2011, 133, 2848–2851