Gold catalysts with polyaromatic-NHC ligands. Enhancement of activity by addition of pyrene

Article abstract of DOI:10.1021/acs.organomet.7b00172

Three Au(I) complexes with N-heterocyclic carbene ligands fused to polycyclic aromatic hydrocarbons (pyrene and phenanthrophenazine) have been obtained and fully characterized. The complexes were tested as catalysts in the hydroamination of terminal alkyn

Full text of DOI:10.1021/acs.organomet.7b00172

Article
pubs.acs.org/Organometallics
Gold Catalysts with Polyaromatic-NHC ligands. Enhancement of
Activity by Addition of Pyrene
Susana Ibanez, Macarena Poyatos, and Eduardo Peris*
́
̃
Institute of Advanced Materials (INAM), Universitat Jaume I, Avda. Vicente Sos Baynat s/n, Castellon
́
E-12071, Spain
*
S Supporting Information
ABSTRACT: Three Au(I) complexes with N-heterocyclic carbene ligands
fused to polycyclic aromatic hydrocarbons (pyrene and phenanthrophena-
zine) have been obtained and fully characterized. The complexes were tested
as catalysts in the hydroamination of terminal alkynes, where they showed
moderate to good activity. The addition of a catalytic amount of pyrene to the
reaction mixtures produced an improvement in the performance of the
catalysts. The study of the reaction order of the catalyst in this reaction
indicated that the order is 0.5, indicating that an off-cycle inactive catalyst
dimer is formed, as consequence of the self-association of the complex by π−π
stacking interactions. The reaction order in catalyst when pyrene is added to
the reaction mixture is 1 > n > 0.5, therefore being higher than that in the
1
absence of pyrene. Studies made by H NMR spectroscopy demonstrate that
an important self-association of the catalyst occurs at the concentrations used
in the catalytic reactions. The association of pyrene with the catalyst was also
1
observed and quantified by H NMR titrations. The studies allowed us to conclude that pyrene influences the activity of the
Au(I) catalysts due to reasons related to the modification of the reaction order in the catalyst rather than to allosteric issues.
6
7
8
9
INTRODUCTION
developed by Grela, Blechert, Collins, Verpoort, and
■
10
̈
Furstner and mostly refer to the investigation of olefin
Originally inspired by enzymatic catalysis, supramolecular
metathesis reactions catalyzed by modified Ru-Grubbs type
catalysts. An interesting example of the allosteric inhibition of
the activity of a Pt(II)-metallocage catalyst by an external
additive (pyrene) was described by Peinador, Quintela, and co-
catalysis utilizes reversible noncovalent interactions to accel1-
erate reaction rates and/or facilitate highly selective reactions.
The development of supramolecular catalysis has been
benefited by the advances achieved in the fields of
homogeneous catalysis and supramolecular chemistry. As
2
11
workers.
recently defined by Raynal and co-workers, supramolecular
catalysis refers to those reactions that involve supramolecular
interactions that do not form part of the basic catalytic
In order to study the influence of π-stacking additives on the
catalytic activity of NHC-based metal catalysts, we obtained a
series of NHC ligands with fused polycyclic aromatic
2
b
12
reaction. In these types of systems allosteric regulations play
an important role, because they determine how the addition of
an “effector” may result in an enhancing or inhibiting effect in
hydrocarbons. The presence of these extended polyaromatic
systems was used to magnify the π-stacking interactions of the
ligand with aromatic substrates and with external π-stacking
additives, thus boosting the supramolecular effects in the
catalytic performances of the catalysts. We observed that the
electronic properties of these ligands could be modified upon
using suitable π-stacking additives. In particular, we observed
that the electron-donating character of the ligands A−C shown
3
terms of the activation of a substrate by the catalyst. Inspired
by this, many efforts have been made to implement this
concept into artificial systems to control chemical reactivity and
catalysis. The incorporation of stimuli-responsive features into
homogeneous catalysts introduces a new level of control of
chemical transformations, allowing these modified systems to
−1
in Chart 1 could be increased by 3 cm Tolman Electronic
4
perform tasks that cannot be achieved by other means.
Parameter (TEP) units by simply adding pyrene to a solution
of the related metal complexes. On the basis of these results, we
performed a number of catalytic studies aiming to determine
the influence of the addition of pyrene on the catalytic
performances of our complexes bearing NHC ligands with
extended polyaromatic systems and, in all cases, we observed
Noncovalent interactions such as π-stacking may play an
important role in certain types of homogeneously catalyzed
reactions. This type of effect has been systematically studied for
the case of catalysts containing N-heterocyclic carbene ligands
5
(
NHCs). The reason may be that the fan shape of NHCs
makes them more prone for establishing effective π−π
interactions with substrates in comparison to cone-shaped
phosphines. Some early studies of the influence of π-stacking in
reactions catalyzed by NHC-based ligands include the works
Received: March 6, 2017
©
XXXX American Chemical Society
A
DOI: 10.1021/acs.organomet.7b00172
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Chart 1. NHC Ligands with Extended Polyaromatic Systems
that the addition of pyrene had an inhibition effect in the
5
activity of our catalysts.
Prompted by these findings, we became interested in
obtaining a series of Au(I) complexes with NHC ligands
bearing extended polycyclic aromatic systems and in studying
the influence of the addition of pyrene on their catalytic
properties.
RESULTS AND DISCUSSION
■
The Au(I) complexes that we obtained in this work were
synthesized according to the procedure depicted in Scheme 1.
The pyrene-imidazolylidene Au(I) complexes were obtained
from the reaction of the corresponding pyrene-imidazolium
iodides with silver oxide in methylene chloride to form the
corresponding silver-NHC complexes, which we did not isolate.
Further addition of [AuCl(SMe )] produced the desired Au(I)
2
complexes 1 and 2, in 63 and 85% yields, respectively.
Compound 3 was obtained by deprotonating the phenan-
throphenazine-imidazolium salt with NaOtBu and a catalytic
amount of NaH in THF at −78 °C. Subsequent addition of
Figure 1. Molecular structures of complexes 2 (above) and 3 (below).
Selected bond distances (Å) and angles (deg): complex 2, Au(1)−
Cl(1) 2.2766(8), Au(1)−C(1) 1.987(3), C(1)−Au(1)−Cl(1)
176.30(9); complex 3, Au(1)−Cl(1) 2.3495(19), Au(1)−C(1)
[
AuCl(SMe )] afforded 3 in 54% yield. The NMR spectra of
2
complexes 1−3 were in accordance with the 2-fold symmetry of
1
3
1
.982(7), C(1)−Au(1)−Cl(1) 179.10(2).
their predicted structures. The C NMR spectra revealed the
appearance of signals due to the metalated carbene carbons at
1
77.8, 177.3, and 173.7 ppm for 1−3, respectively.
and the coordination about the metal center is quasi-linear, as
shown by the C−Au−Cl angle of 179.1(2)°.
The molecular structures of 2 and 3 were confirmed by
single-crystal X-ray diffraction (Figure 1). The molecular
structure of 2 contains a pyrene-imidazolylidene ligand bound
Complexes 1−3 were tested as catalysts in the hydro-
amination of phenylacetylene, a process for which several
13
to an Au−Cl fragment. The Au−C
bond distance is
Au(I)-based catalysts have shown good activity. The reactions
carbene
1.987(3) Å. The Au atom slightly deviates from the plane
were carried out in acetonitrile at 90 °C, using a catalyst loading
formed by the extended polycyclic ligand, at a distance of 0.375
Å. Complex 3 contains a phenanthrophenazine-imidazolylidene
ligand bound to an Au−Cl fragment. The distance between the
Au center and the carbene carbon is 1.982(7) Å. The gold
center is on the plane formed by the extended polycyclic ligand,
of 1 mol %. AgBF was added as a chloride scavenger in order
4
to activate the catalyst. The results obtained under these
reaction conditions are given in Table 1. From the results
shown, it can be observed that catalyst 2 provides the highest
yields of the final hydroaminated imine product (product yields
Scheme 1. Synthesis of Au(I) Complexes
B
DOI: 10.1021/acs.organomet.7b00172
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a
5,11
Table 1. Hydroamination of Phenylacetylene
inhibitory, rather than beneficial.
In order to get a clearer
insight into the influence of pyrene on the reaction process, we
decided to monitor the reaction by studying the time-
dependent reaction profile of the coupling of phenylacetylene
with aniline. As can be seen from the profiles shown in Figure
2
, the addition of pyrene not only offers higher yields in shorter
b
entry
Ar
catalyst
yield
1
2
3
4
5
6
7
8
9
Ph
Ph
Ph
Ph
Ph
1
2
44
88
99
21
36
70
90
92
55
60
50
80
84
29
41
68
82
37
40
39
62
77
54
c
2
3
c
3
2-MeC H
1
2
6
4
4
4
4
4
4
4
4
4
2-MeC H
6
c
2-MeC H
2
6
2-MeC H
3
6
c
10
11
12
13
14
15
16
17
18
19
20
21
22
23
2-MeC H
3
6
4-MeC H
1
2
6
4-MeC H
6
c
4-MeC H
2
6
Figure 2. Time-dependent reaction profile of the hydroamination of
phenylacetylene with aniline using catalyst 2 (1 mol %) with (orange
dots) and without (blue dots) addition of pyrene. All reactions were
carried out under the same conditions described in Table 1.
4-MeC H
3
1
2
6
2,4,6-Me C H
3
6
2
2
2
2
2
2,4,6-Me C H
3
6
c
2,4,6-Me C H
2
3
6
2,4,6-Me C H
3
reaction times but also accelerates the reaction from the
beginning, thus indicating that the higher activity of the catalyst
is due to kinetic reasons, rather than to thermodynamic reasons
(i.e., stability of the catalysts).
3
6
c
2,4,6-Me C H
3
3
6
2,6-iPr C H
1
2
2
6
3
3
3
3
2,6-iPr C H
2
6
c
2,6-iPr C H
2
The study of the reaction profiles of the coupling of
phenylacetylene with aniline at different concentrations of the
catalyst allowed us to determine the reaction order with respect
to the concentration of the catalyst. We used the normalized
2
6
2,6-iPr C H
3
2
6
a
Reaction conditions unless specified otherwise: 0.5 mmol of
phenylacetylene, 0.55 mmol of amine, 1 mol % of [cat.], 2 mol % of
AgBF , 1 mL of MeCN, 90 °C, 6 h. Yields determined by GC using
anisole (0.5 mmol) as internal standard. Addition of 0.05 mmol of
b
15
4
time scale method for determining the order in catalyst. This
c
n
method uses a normalized time scale, t[cat] , where n is the
pyrene.
order in catalyst. Figure 3 shows the time-dependent reaction
profiles at different catalyst concentrations (Figure 3a),
together with a graphic in which the scale is normalized
assuming a reaction order of 0.5, which was the value giving the
best fit (Figure 3b). This reaction order is consistent with the
order that we obtained for other pyrene-functionalized
ranging from 62 to 90%). All in all, catalyst 2 is less active than
other NHC-Au(I)-based catalysts previously reported by us.
13f
An interesting observation that we can extract from the analysis
of the data is that catalyst 3 affords the lowest activity (product
yields in the range of 21−55%), a fact that contrasts with the
weaker electron-donating character of the phenanthrophena-
zine-imidazolylidene ligand in comparison to the pyrene-
imidazolylidene ligand, which should make us expect a higher
activity for 3, due to the more electrophilic character of its gold
center. Prompted by this result, we decided to perform
further studies in order to elucidate if supramolecular
interactions may have some influence over the catalytic
properties of these three catalysts, because catalysts with
NHC ligands with polyaromatic fragments are known to be
strongly influenced by supramolecular effects on their
12d
homogeneous catalysts that we recently reported
and is
suggestive of the formation of an off-cycle catalytic dimer that is
in fast equilibrium with the active monomer species. Owing to
this equilibrium, the concentration of monomer is not linearly
proportional to the total concentration of catalyst added, and
this explains why the order in catalyst is <1. A different
situation arises when pyrene is added to the reaction mixture.
In this case, the best fitting corresponds to a first order in
catalyst, as shown by Figure 3c. This result is very interesting,
because it suggests that pyrene associates with 2 and therefore
competes with the self-association process, thus partially
avoiding the formation of the nonactive dimer. It has to be
taken into account that the reaction order of 1 associated with
the process performed with the addition of pyrene has to be
taken as a crude estimate. A more accurate analysis should
indicate that for this case the reaction order “n” should be a
fractional number in the range 0.5 < n < 1, because it is highly
unlikely that under the reaction conditions used in these
experiments the addition of pyrene results in the 100%
formation of pyrene complex 2 aggregates, therefore completely
avoiding the self-association of the catalyst.
1
4
5
activities. First, we performed the catalytic reactions adding a
catalytic amount of pyrene (10 mol % with respect to the
concentration of the substrates) in order to study if the addition
of this molecule may have an influence over the outcome of the
process. For this study we decided to use catalysts 2 and 3,
these being the most and least active among the three
complexes described in this work. The results indicated that, in
all cases, the addition of pyrene produced a clear increase in the
activity of the catalysts, with benefits within the range of a 5−
1
5% increase in the product yields. This result is remarkable
because, in all other cases reported in which pyrene was added
into a catalytic reaction, its allosteric effect was always
In order to confirm that self-association of 2 is taking place in
acetonitrile, we performed a series of H NMR spectra in
1
C
DOI: 10.1021/acs.organomet.7b00172
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pyrene moiety is shifted upfield by 0.1 ppm upon an increase in
the concentration of the complex. The signal due to the
protons of the methylene group bound to the nitrogen atoms of
the imidazolylidene are also significantly upfield shifted (Δδ =
0
.13 ppm). This observation is a clear indication that the
complex shows significant self-association in the range of 1−20
mM, which is the concentration range used in our catalytic
experiments. The nonlinear regression analysis of the data of
this series of spectra indicated that the self-association constant
−1
is in the range of 3−5 M (a more accurate result could not be
given due to the precipitation of the complex at concentrations
higher than 20 mM, thus not allowing a study with a sufficient
1
wide range of concentrations). Then we performed H NMR
studies in order to determine if 2 associates with pyrene in the
range of concentrations used in the catalytic experiments. The
1
H NMR titrations were performed at constant concentrations
of 2 (1 mM) and with monitoring of the variation of the
chemical shifts of the signals of the ligand of the complex upon
adding increasing amounts of pyrene. The addition of the
1
solution of pyrene induced important perturbations in the H
NMR spectra of 2, indicating the formation of aggregates that
showed fast kinetics on the NMR time scale. We assumed that
these aggregates are formed by π−π stacking interactions
between the molecules of pyrene and the pyrene moiety of
complex 2. As can be observed from the series of spectra shown
in Figure 5, the signal due to one of the protons of the pyrene is
Figure 3. (a) Time-dependent reaction profile of the reaction of
phenylacetylene with aniline using catalyst 2. (b) Reaction profile with
normalized time scale assuming a catalyst order of 1/2. (c) Reaction
profile for the same reaction with addition of 10 mol % of pyrene and
with a normalized time scale assuming a catalyst order of 1. Reaction
conditions are the same as those shown in Table 1. In all three
graphics the evolution is shown as consumption of phenylacetylene.
CD CN at different concentrations of the complex. Figure 4
3
shows a series of spectra of the complexes at concentrations
ranging from 1 to 20 mM. The analysis of the spectra indicates
that one of the signals assigned to an aromatic proton of the
1
Figure 5. Representative region of the H NMR (400 MHz) spectra of
the titration of 2 with pyrene in CD CN. The spectra were recorded at
3
a constant concentration of 2 (1 mM). The inset plot is the resulting
binding isotherm, which returns an association constant of k = 12 ±
1
1
−1
2
M
(H = 2; G = pyrene).
shifted upfield by 0.26 ppm, while the signals due to the N−
CH protons are shifted by 0.31 ppm. The analysis of the
2
spectra also allowed us to determine that the stoichiometry of
the aggregate complex formed by association of pyrene and 2 is
1
:1. This assumption is based on the analysis of the binding
isotherm resulting from the titration experiment, which gave
16
the lowest residuals for this stoichiometry. A Job plot analysis
also supported the formation of the 1:1 complex (see the
16,17
Supporting Information). The nonlinear regression analysis
of the curve returned a non-negligible association constant of
1
−1
Figure 4. Selected region of a series of H NMR spectra (400 MHz) of
k = 12 ± 2 M , thus demonstrating the affinity of 2 to form
11
complex 2 in CD CN at different concentrations.
π-stacking aggregates with pyrene in milimolar concentrations.
3
D
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This result indicates that, under the reaction conditions that we
used for our catalytic experiments (1 mol % = 5 mM of 2, 50
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(
2
mM of pyrene, in CH CN), about 35% of the catalyst is
3
forming a host−guest complex with pyrene.
2
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CONCLUSIONS
■
Biol. 2008, 4, 474−482.
In summary, we prepared three Au(I) complexes bearing NHC
ligands with fused polycyclic aromatic hydrocarbons. The
complexes were used as catalysts for the hydroamination of
phenylacetylene, where they showed moderate to good
activities. The activities of the catalysts were significantly
enhanced by addition of a catalytic amount of pyrene. The
preliminary kinetic studies indicated that the addition of pyrene
produces an increase in the reaction order with respect to the
concentration of the catalyst. This increase is attributed to the
formation of π−π stacking aggregates between the molecules of
pyrene and the catalyst, which in turn partially avoids self-
association of the catalyst. The self-association of the catalyst
and the formation of supramolecular aggregates between the
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We believe that the results presented in this article are of
high importance for the development of new supramolecular
catalysts. Our work demonstrates that pyrene influences the
activity of a family of homogeneous catalysts of Au(I), due to
reasons related to the modification of the reaction order in the
catalyst rather than toprobably more intuitiveallosteric
issues (i.e., modification of the electronic properties of the
catalyst by perturbation of the orbitals of the ligand by π-
stacking interactions with the additive).
1
(
2
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ASSOCIATED CONTENT
Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.7b00172.
■
*
S
(e) Gaillard, S.; Bosson, J.; Ramon, R. S.; Nun, P.; Slawin, A. M. Z.;
Nolan, S. P. Chem. - Eur. J. 2010, 16, 13729−13740. (f) Gonell, S.;
Poyatos, M.; Peris, E. Angew. Chem., Int. Ed. 2013, 52, 7009−7013.
(
14) Iban
Organometallics 2016, 35, 2747−2758.
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(16) Thordarson, P. Chem. Soc. Rev. 2011, 40, 1305−1323.
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012, 24, 585−594.
̃
ez, S.; Poyatos, M.; Dawe, L. N.; Gusev, D.; Peris, E.
Description of synthetic procedures and characterization
details, catalytic experiments, spectra of the new
(
1
complexes, crystallographic data, and H NMR spectra
(
2
from host−guest titrations (PDF)
Crystallographic data (CIF)
AUTHOR INFORMATION
Corresponding Author
E-mail for E.P.: eperis@uji.es.
■
*
ORCID
Eduardo Peris: 0000-0001-9022-2392
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We gratefully acknowledge financial support from the
MINECO of Spain (CTQ2014-51999-P) and the Universitat
Jaume I (P11B2014-02 and P11B2015-24). We are grateful to
́
the Serveis Centrals d’Instrumentacio Cientıfica (SCIC) of the
́
Universitat Jaume I for providing with spectroscopic facilities.
REFERENCES
■
(
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