Mechanistic studies on gold-catalyzed direct arene c-h bond functionalization by carbene insertion: The coinage-metal effect

Article abstract of DOI:10.1021/acs.organomet.6b00604

The catalytic functionalization of the Csp2-H bond of benzene by means of the insertion of the CHCO2Et group from ethyl diazoacetate (N2= CHCO2Et) has been studied with the series of coinage-metal complexes IPrMCl (IPr = 1,3-bis- (diisopropylphenyl)imidazol-2-ylidene) and NaBArF 4 (BArF 4 = tetrakis(3,5-bis(trifluoromethyl)phenyl)borate). For Cu and Ag, these examples constitute the first use of such metals toward this transformation, which also provides ethyl cyclohepta-2,4,6-trienecarboxylate as a byproduct from the so-called Buchner reaction. In the case of methyl-substituted benzenes, the reaction exclusively proceeds onto the aromatic ring, the Csp3-H bond remaining unreacted. A significant coinage-metal effect has been observed, since the gold catalyst favors the formation of the insertion product into the Csp2-H bond whereas copper and silver preferentially induce the formation of the cycloheptatriene derivative. Experimental studies and theoretical calculations have explained the observed selectivity in terms of the formation of a common Wheland intermediate, resembling an electrophilic aromatic substitution, from which the reaction pathway evolves into two separate routes to each product.

Full text of DOI:10.1021/acs.organomet.6b00604

Article
pubs.acs.org/Organometallics
Mechanistic Studies on Gold-Catalyzed Direct Arene C−H Bond
Functionalization by Carbene Insertion: The Coinage-Metal Effect
Manuel R. Fructos,† Maria Besora,‡ Ataualpa A. C Braga,‡,§ M. Mar Díaz-Requejo,*,† Feliu Maseras,*,‡,∥
and Pedro J. Perez*,†
́
†Laboratorio de Catal
́
isis Homogen
́
ea, Unidad Asociada al CSIC, CIQSO-Centro de Investigacion
́
en Química Sostenible and
Departamento de Química “Prof. Jose Carlos Vílchez Martín”, Universidad de Huelva, Campus de El Carmen, 21007 Huelva, Spain
‡Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, Avda. Països Catalans 16,
43007 Tarragona, Spain
§Departamento de Química Fundamental, Instituto de Química, Universidade de Sao Paulo, Sao Paulo, Brazil
∥Departament de Química, Universitat Auton
̃
̃
̀
oma de Barcelona, 08193 Bellaterra, Spain
S
* Supporting Information
2
ABSTRACT: The catalytic functionalization of the Csp −H bond of
benzene by means of the insertion of the CHCO2Et group from
ethyl diazoacetate (N2CHCO2Et) has been studied with the
series of coinage-metal complexes IPrMCl (IPr = 1,3-bis-
(diisopropylphenyl)imidazol-2-ylidene) and NaBArF (BArF
=
4
4
tetrakis(3,5-bis(trifluoromethyl)phenyl)borate). For Cu and Ag,
these examples constitute the first use of such metals toward this
transformation, which also provides ethyl cyclohepta-2,4,6-triene-
carboxylate as a byproduct from the so-called Buchner reaction. In
the case of methyl-substituted benzenes, the reaction exclusively
3
proceeds onto the aromatic ring, the Csp −H bond remaining
unreacted. A significant coinage-metal effect has been observed,
since the gold catalyst favors the formation of the insertion product
2
into the Csp −H bond whereas copper and silver preferentially
induce the formation of the cycloheptatriene derivative. Experimental studies and theoretical calculations have explained the
observed selectivity in terms of the formation of a common Wheland intermediate, resembling an electrophilic aromatic
substitution, from which the reaction pathway evolves into two separate routes to each product.
3
For Csp −H bonds, mechanistic studies seem to favor a
concerted mechanism in which the metallocarbene carbon
atom interacts with the σ C−H bond (Scheme 1). Nakamura
and co-workers computed the mechanism for rhodium-based
catalysts,5 on the basis of the previously reported experimental
results,6 later followed by our group for the Cu- and Ag-based
coinage-metal catalysts.7 However, the mechanistic picture is as
INTRODUCTION
■
The formation of carbon−carbon bonds is probably among the
most studied processes that employ homogeneous catalysts.1
Amid the different strategies described for such goal, a quite
simple one consists of the formal insertion of a carbene CR1R2
group into a C−H bond (Scheme 1), a process that can be
2
yet unclear for the benzene (or arene) Csp −H bond
3
Scheme 1. Csp −H Functionalization by Metal-Catalyzed
Carbene Insertion from Diazo Compounds
functionalization with this strategy. First, this reaction competes
with the so-called Buchner reaction, in which a cyclo-
propanation-derived norcaradiene intermediate is formed that
further evolves toward a cycloheptatriene (Scheme 2a). With
Rh2(OAc)4 as the catalyst, Shechter and Livant separately
reported8 the metal-catalyzed functionalization of benzene by
means of the formal insertion of the carbene unit into the C−H
bond. The use of the formal term is related to the nature of the
product obtained, but the mechanism does not seem to occur
accomplished with the aid of metal-based catalysts and diazo
reagents as the carbene source.2,3 These transformations are
known to occur through the intermediacy of reactive
metallocarbene intermediates,4 generated by extrusion of
dinitrogen from the diazo molecule, which react with the
hydrocarbon.
Special Issue: Hydrocarbon Chemistry: Activation and Beyond
Received: July 27, 2016
© XXXX American Chemical Society
A
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2
coinage-metal effect has been found. With the support of DFT
studies, a complete mechanistic picture is proposed fitting the
experimental differences observed with the three metals. It is
worth mentioning that a recent theoretical work by Liu, Xia,
and co-workers have provided some light on this trans-
formation on the basis of the (PhO)3PAuC(Ph)CO2Me
species.13 Additionaly, Hashmi and co-workers have provided
interesting mechanistic studies on gold-based transformations
involving vinylidene intermediates in C−H bond functionaliza-
tion reactions.14
Scheme 2. (a) Arene Csp −H Functionalization by Metal-
Catalyzed Carbene Transfer from Diazo Compounds and
(b) the Wheland-Based Mechanism Proposed for that
Transformation
RESULTS AND DISCUSSION
Metal Effect. The series of complexes IPrMCl (M = Cu, Ag,
■
Au) have been employed as the catalyst precursor, along with 1
equiv of NaBArF , in the test reaction of EDA and benzene.
4
The reactions were performed using benzene as the solvent, at
room temperature, with the EDA added in one portion. The
results are shown in Table 1, where a significant influence of the
Table 1. Metal Effect in the Reaction of EDA with Benzene
a
using IPrMCl + NaBArF as Catalytic Precursor
4
through that precise insertion pathway, at variance with the
3
aforementioned Csp −H bond modification. From seminal work
with rhodium,8a,9 it was proposed that the metallocarbene
originates a Wheland intermediate that undergoes a 1,2-
hydrogen shift to give the final product (Scheme 2b).
Nearly a decade ago we discovered10 gold as a catalyst for the
transfer of the CHCO2Et group from ethyl diazoacetate (N2
CHCO2Et, EDA), using IPrAuCl (IPr = 1,3-bis-
(diisopropylphenyl)imidazol-2-ylidene) to several saturated
and unsaturated substrates, with NaBArF (BArF = tetrakis-
(3,5-bis(trifluoromethyl)phenyl)borate) as the halide scav-
enger. Benzene and other alkylarenes were modified (Scheme
3), providing mixtures of the products derived from the
a
Reaction conditions: catalyst loading 0.025 mmol, 0.5 mmol of EDA
b
in 3 mL of benzene, room temperature. Percentage of initial EDA
converted into products as determined by NMR. The remaining initial
EDA (up to 100%) was converted into diethyl fumarate and maleate.
4
4
metal center in the distribution of products has been found.
Thus, the gold-based catalyst provided a regioselectivity of
75:25 favoring the alkylated product. In contrast, the silver-
based catalyst only led to a very minor 5% of such product, the
cycloheptatriene being by far the major products derived from
benzene. The copper catalyst gave a 70:30 mixture favoring the
seven-membered ring. Interestingly, the formation of diethyl
fumarate and maleate as byproducts as the result of the carbene
homocoupling side reaction was not observed with the gold-
based catalyst, whereas both the Cu and Ag analogues led to
their formation to a certain extent. Also, blank experiments
carried out with pure cycloheptatriene demonstrated that under
the same reaction conditions no isomerization to the insertion
products was observed.15
Scheme 3. Gold-Based Catalytic System for Carbene
Transfer from Ethyl Diazoacetate and Subsequent Arene
Csp −H Functionalization
2
Toluene has also been employed as the model substrate for
substituted arenes containing potentially reactive Csp −H
2
3
functionalization of the Csp −H bond as well as cyclo-
heptatrienes derived from the Buchner reaction. Interestingly,
bonds. As shown in Table 2, two different behaviors were
observed. On one hand, the copper and silver catalysts
predominantly led to the formation of cycloheptatrienes
(88−90%), with minor amounts of the alkylated products
being detected. On the other, the gold catalyst gave a mixture of
both compounds, with the insertion product as the major one.
A mixture of the ortho, meta, and para isomers was observed, a
feature that will be commented on in the next section. It is
remarkable that the product derived from the functionalization
of the methyl group (that we had previously observed using
copper catalysts bearing trispyrazolylborate ligands)16 was not
detected in any of the three catalytic systems, supporting the
3
the Csp −H bonds of the R substituents of the aromatic ring
remained unreacted,11 in spite of the well-known activated
nature of benzylic sites. This finding paved the way to the use
of this metal for carbene transfer reactions from diazo
reagents.12
On the basis of the uncertainty of the mechanism of this
Csp −H bond functionalization, we decided to perform a
mechanistic study toward that end, mixing experimental data
and DFT calculations. With the series of complexes IPrMCl,
(M = Cu, Ag, Au), we have established the influence of the
metal center on the reaction outcome, from which a marked
2
B
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Table 2. Metal Effect in the Reaction of EDA with Toluene
Table 4. Functionalization of Monosubstituted Benzenes
a
a
using IPrMCl + NaBArF as Catalytic Precursor
with EDA in the Presence of IPrAuCl + NaBArF
4
4
a
Reaction conditions: catalyst loading 0.025 mmol, 0.5 mmol of diazo
b
compound in 3 mL of toluene, room temperature. Percentage of
initial EDA converted into products as determined by NMR. The
remaining initial EDA (up to 100%) was converted into diethyl
c
fumarate and maleate. Ortho:meta:para ratio.
a
b
See the Experimental Section for details. Percentage of initial EDA
great chemoselectivity of this [IPrM+] system toward arene
converted into products. The remaining initial EDA (up to 100%) was
c
converted into diethyl fumarate and maleate. As a mixture of isomers.
3
functionalization over Csp −H modification.
d
Ortho:meta:para ratio.
The propensity of these catalysts to attack the arene ring has
been reinforced using styrene as the substrate (eq 1 and Table
substituent induced a profound effect on the reaction outcome.
An electron-withdrawing group such as CF3 favored cyclo-
heptatrienes as the major products, a situation that is reversed
with electron-donating groups such as OMe. Interestingly, all
Csp −H bonds remained unreacted along the series of
experiments.
3
As mentioned above, a mixture of isomers derived from the
ortho, meta, and para relative positions is observed in all cases.
In an attempt to evaluate the electronic influence of the X
groups in the selectivity of this transformation, a fitting of these
values to the Hammett equation has been performed. For this
Table 3. Metal Effect in the Reaction of EDA with Styrene
a
using IPrMCl + NaBArF as Catalytic Precursor
4
2
purpose the ratio of the Csp −H functionalized and cyclo-
heptatriene products was calculated, and its log was plotted vs
σ.17
As shown in Figure 1, a good correlation with the Hammett
equation is found, with a value of ρ = −2.21
0.73. We
a
Reaction conditions: catalyst loading 0.025 mmol, 0.5 mmol of diazo
compound, and 50 mmol of styrene in 3 mL of CH2Cl2, room
b
temperature. Percentage of initial EDA converted into products. The
remaining initial EDA (up to 100%) was converted into diethyl
c
d
fumarate and maleate. Not detected. As a mixture of the ortho, meta,
and para isomers.
3). In addition to the expected cyclopropanes, some amounts of
cycloheptatrienes and/or the insertion products are observed
with the three metals. The gold catalyst provides, by far, the
most significant difference, with a higher yield of the arene
2
Csp −H functionalized product in comparison to that of
Figure 1. Hammett σ correlation for relative rates of functionalization
of monosubstituted benzene derivatives with EDA.
cyclopropanes.
Monosubstituted Benzenes as Substrates. The use of
toluene as the substrate along with the gold-based catalyst has
2
shown a slight increase of the Csp −H functionalized product in
comparison to that of benzene (80% vs 75%). We wondered
about the possible effect that other substituents might exert on
the selectivity. Thus, a series of monosubstituted benzenes were
employed as reactants. As shown in Table 4, the nature of the
interpret this value as the result of a substantial effect of the
electronic nature of the arene substituent in the distribution of
products, the more donating products favoring the formal
insertion reaction of the carbene group.
C
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A competition experiment carried out with benzene and
benzene-d6 provided the following information: (i) the
amounts of the products derived from both arenes were nearly
identical within experimental error and (ii) kinetic experiments
on nitrogen evolution gave also identical curves in both cases
(see Figure S1 in Supporting Information). From these data we
can conclude that the rate-determining step is located much
earlier than the C−H cleavage (probably the metallocarbene
formation).
Scheme 5. Postulated Mechanism for the Insertion Reaction
from Adduct A in the Case of Ag
a
All experimental evidence collected in this and previous work
3
seems to support a pathway which differs from that of the Csp −
H bonds (Scheme 1). At variance with that metallocarbene C−
2
H bond one-step interaction, the Csp −H bond functionaliza-
tion with this strategy displays features resembling an aromatic
electrophilic substitution. In order to find additional support for
such an alternative, we have carried out DFT studies that not
only must provide the reaction pathway but also explain the
selectivities observed regarding the effect of the metal in the
chemoselectivity (insertion vs addition products).
DFT Studies. We have computationally investigated the
reaction mechanisms for the reaction between the metal-
locarbene IPrMC(H)COOMe and benzene (M = Cu, Ag,
Au) in order to explain the different insertion/addition ratios
experimentally observed. The initial approach between the
metallocarbene and benzene leads to the formation of an
adduct with a new C−C bond (distance below 1.66 Å) between
the carbenic carbon and benzene (Scheme 4). This adduct,
a
Free energies are given in kcal/mol.
compound is now a well-known feature of many metal carbene
transformations of diazocarbonyl compounds.18,19 The con-
tribution of water in the long distance proton transfers has been
proposed even for a protodeauration step.20
The Buchner reaction (addition) pathway is summarized in
Scheme 6. First, a second C−C bond is made through
Scheme 6. Postulated Mechanism for the Buchner Reaction
from Adduct A in the Case of Ag
Scheme 4. Reaction of the Metallocarbene and Benzene to
Form the Wheland Intermediate and Fischer Projection of
a
the Three Main Conformers of this Intermediate
a
Free energies are given in kcal/mol.
transition state ATS1. In most cases, ATS1 evolves directly to
AInt1, where the metal coordinates to the aromatic ring.
Finally, the AInt1 undergoes an electrocyclic opening (ATS2)
to form the cycloheptatriene AInt2, the addition final product.
There is certainly no experimental evidence concerning the π
complexes we propose in this mechanism, but we assume they
are correct because of the overall agreement between
computational results and experiment. The proposed mecha-
nism is moreover in agreement with that previously reported
for the Echavarren (retro-Buchner) reaction, a gold-catalyzed
decarbenation (carbene extrusion from cycloheptatriene)
process.21 Schemes 5 and 6 correspond to the Ag species,
but the results are similar for the Cu and Au complexes. Some
minor differences exist, however; for instance, in the case of Au,
the final intermediates are better described as η1 complexes
rather than metallacyclopropenes.
a
Free energies in are given in kcal/mol.
which is reached without any barrier in the potential energy
surface, may be viewed as a Wheland intermediate. Three
conformers (A, B, and C) of the adduct are in principle
accessible depending on the relative orientation of substituents
with respect to the newly formed C−C bond (see Scheme 4).
The adducts can evolve toward either insertion or addition
products. Scheme 5 shows such evolution for the insertion
pathway for the particular case of conformer A of the silver
species. It starts with a proton transfer to the oxygen of the
carbonyl to form an enol intermediate (ITS1). The enol IInt1
assisted by two water molecules or another enol molecule
performs a keto−enol rearrangement (ITS2) to transfer the
hydrogen from the oxygen to the former carbenic carbon,
affording the final alkylated (“insertion”) product IInt2. An
analogous mechanism of insertion has been recently postulated
for a similar gold system.13 The proton transfer to a carbonyl
In most computational mechanistic studies, the predicted
product ratio could be obtained directly by comparing the
barriers associated with the competing transition states ITS1
and ATS1. However, the combined presence of the three
possible conformations for the adduct and its association to
D
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very shallow minima with at least two exit channels lead to a
rather more complicated picture. The importance of con-
formers into the study of reaction mechanisms has been
previously acknowledged.22 The complexity of the picture can
first be seen in Table 5. Here we attempt to collect the free
shallow intermediates and an excess of total energy.24−26 It is
possible that in our system, once the adduct is formed, the
subsequent step takes place before the energy redistribution
occurs.
To explore this, we have conducted Born−Oppenheimer
molecular dynamics (BOMD) calculations27 on the simplified
model of our system of interest: NHC-MCH(COOH) +
C6H6. This type of quantum dynamics has been previously used
with success.28 We centered our attention to the first part of the
reaction where the first C−C bond is formed with the
immediate evolution of this unstable intermediate toward one
of the products. We ran only 10 trajectories for each approach
and metal, a total of 90 trajectories.
Table 5. Relative Free Energies (kcal/mol) of the Key
Minima and Transition States for the Addition/Insertion
Pathways
metal
A
B
C
Cu
Ag
Au
a
a
adduct
ATS1
ITS1
−10.5
−8.4
−10.0
−10.7
−13.4
−10.0
−11.8
−7.8
a
a
The results of the BOMD calculations are summarized in
Table 6. We have counted the number of trajectories going
a
a
a
a
adduct
ATS1
ITS1
−15.1
−12.7
−14.2
−15.1
−17.1
−14.2
−14.1
−13.6
Table 6. Number of Trajectories Going through the
Addition/Insertion/Nonreactive Reaction Pathways,
Depending on the Metal Center (Cu, Ag, Au) and the
Considered Conformer (A, B, C)
adduct
ATS1
ATS2
ITS1
−13.5
−8.5
−7.0
−13.3
−8.1
−7.0
−14.3
−3.0
0.8
metal
A
B
C
Cu
Ag
Au
9/0/1
8/0/2
0/0/10
8/2/0
6/3/1
0/8/2
6/0/4
5/0/5
0/0/10
−12.2
−12.2
a
Energies corresponding to structures optimized with a frozen
parameter.
through addition/insertion/nonreactive reaction pathways. In
the trajectories labeled as nonreactive, the complex remains as a
Wheland intermediate or forms unstable intermediates that are
expected to revert to it. For the copper catalyst 23 of the 25
productive trajectories lead to the addition product and 2 of
them, all associated with path B, to the insertion product. The
case of silver is similar, with 19 out of 22 going to addition and
3 out of 22 leading to insertion. We note that for copper 23:2
would mean a proportion of 92:8 and for silver 19:3 translates
to 86:14. The numbers are reasonably close to the experimental
observations of 70:30 and 95:5, respectively. There are at least
two major problems in the translation of reacting trajectories to
total ratios: namely, the small number of trajectories and the
assumption that the three paths have an identical probability.
Therefore, we do not claim this as an accurate prediction.
However, we consider these results indicative that extensions
beyond transition state theory do improve the agreement with
experiment in this system. We finally admit that these results
can still not explain the experimentally reported 25:75 result in
the gold system, as calculations still suggest 0:100. Explanation
of this result may require a more accurate dynamic study, which
is out of the scope of the current work.
The calculations reported above show an unexpected
complexity in the system but can yet provide a reasonable
reproduction of the experimental results. The key to the
different behavior of the gold complex lies in the energetics of
addition for path B. The step is barrierless in the potential
energy surface for copper and silver but has a barrier of 5.2
kcal/mol for gold. The higher barrier may be associated with
the existence of a substrate rearrangement in the metal
coordination sphere along this pathway, which is a poor fit
for the limited stability of Au(I) compounds with coordination
numbers above 2.
energies of the key points for each metal complex and each
conformation. Not all points could be located as stationary
points, and we had to carry out constrained geometry
optimizations (freezing selected distances, structures marked
with the superscript a) to estimate their energies. This has
minor implications for some structures, such as ATS1 for Cu,
which has a higher energy than both the corresponding adduct
and ITS1 and likely means that in this case insertion is not
feasible. However, it is critical in other cases such as the B
conformers for both Cu and Ag. In this case, there is no
stationary point associated with the adduct and the constrained
transition state ATS1 has a lower energy than the adduct. The
straightforward interpretation is that in the complex-benzene
approach corresponding to conformation B there is a direct
path from the separated reactants to the AInt1 species.
Direct application of transition state theory to the results in
Table 5 would predict 100% of addition product for Cu and Ag,
as a barrierless process should be always preferred. In the case
of gold, insertion should be preferred also at nearly 100%
proportion, as the free energy differences between the
competing transition states are larger than 4 kcal/mol. The
experimental trend of addition (Buchner reaction) being
favored for copper and silver and insertion being favored for
gold is reproduced. However, the experimental ratios, with the
major product never being above 90%, are definitely not
reproduced. This is a serious disagreement between calculations
and experiment that throws into question the validity of our
computational analysis. In order to justify the validity of the
calculations, we have analyzed the validity of the underlying
computational approaches, and we provide below a qualitative
justification of the discrepancy. We think that the origin of the
discrepancy is in the limitations of the transition state theory
(TST), which does not apply properly to this situation.23 TST
assumes redistribution of internal energy among the vibrational
modes and internal rotations previous to any reaction step. This
is not always the case, as has been recently shown in cases with
CONCLUSIONS
■
In summary, we have found that the catalytic system formed by
complexes IPrMCl and NaBArF (M = Cu, Ag, Au; IPr = 1,3-
4
E
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bis(diisopropylphenyl)imidazol-2-ylidene; BArF = tetrakis(3,5-
bis(trifluoromethyl)phenyl)borate), benzene, and ethyl diazo-
kinetic energy was taken as the difference between the starting point
and the separate reactants in the potential energy surface, and the
initial velocities were obtained from a preliminary calculation with the
nsample keyword and provision of the mode number and vibrational
energy corresponding to the mode for the stretch between the
carbenic carbon and the closest carbon of the benzene. The
calculations were performed defining the phase for the transition
vector between the carbonic carbon and one of the benzene carbons,
for a rotational temperature of 300 K, performing Hessian updates
every 12 gradient points before doing a new analytic Hessian. For each
system 10 trajectories were considered reading in initial velocities. For
the more reactive Ag we performed 3000 steps which correspond to
approximately 2 ps. For Cu and Au we generated 6000 steps
corresponding to approximately 4 ps; some tests with 12000 steps
were run for selected systems.
4
acetate promotes the functionalization of the aromatic ring,
2
providing mixtures of products derived from direct Csp −H
bond modification as well as cycloheptatriene rings derived
from the Buchner reaction. The selectivity strongly depends on
the nature of the coinage metal: Cu and Ag favored ethyl
cycloheptatriene-1-carboxylate, whereas gold gave the alkylated
arene as the major product. With toluene as the substrate, a
similar behavior is observed, although the methyl group
remained unreacted, as a consequence of a high selectivity
toward the arene vs aliphatic C−H bond. Experimental data
and DFT calculations support the existence of a mechanistic
pathway in which a Wheland-type intermediate is first formed,
from which two alternative routes might occur. That of the
insertion product resembles the aromatic electrophilic sub-
stitution, at variance with the concerted, one-step mechanistic
A data set collection of computational results is available in the
IoChem-BD repository38 and can be accessed via http://dx.doi.org/
10.19061/iochem-bd-1-11.
3
view of the functionalization of Csp −H by carbene insertion.
ASSOCIATED CONTENT
* Supporting Information
■
S
EXPERIMENTAL SECTION
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.organo-
met.6b00604.
■
General Methods. All reactions were carried out under an oxygen-
free nitrogen atmosphere by using an MBraun-Unilab glovebox
containing dry argon or nitrogen or conventional Schlenk techniques.
Solvents were purchased from Aldrich and were rigorously dried
before use. The reagents were also purchased from Aldrich and were
employed without further purification. The complexes IPrMCl and
NaBArF4 were prepared according to the literature.29,30 NMR solvents
were stored over molecular sieves under nitrogen. NMR spectra were
measured on Agilent 400 MR and 500 DD2 spectrometers. GC data
were collected with a Varian GC-3900 spectrometer with an FID
detector.
Detailed experimental catalytic and mechanistic proce-
dures, including kinetic isotopic effect studies and
computational data including transition states geometries
and Cartesian coordinates and energies of all stationary
points reported in the text (PDF)
Cartesian coordinates of calculated structures (XYZ)
AUTHOR INFORMATION
Corresponding Authors
*E-mail for M.M.D.-R.: mmdiaz@dqcm.uhu.es.
*E-mail for F.M.: fmaseras@iciq.es.
*E-mail for P.J.P.: perez@dqcm.uhu.es.
■
General Catalytic Experiment. The precatalyst IPrMCl (0.025
mmol) was dissolved in 3 mL of the corresponding substrate, and
NaBArF4 (0.025 mmol) was added to the solution. After 15 min, EDA
(0.5 mmol) was added in one portion. After it was stirred at room
temperature for 72 h, the mixture was analyzed by GC and GCMS.
The volatiles were removed under reduced pressure, and the residue
was analyzed by NMR spectroscopy to identify the products. See the
Supporting Information for experimental details.
Notes
The authors declare no competing financial interest.
Computational Details. The DFT studies presented have been
performed with Grimme’s B97D31 functional including a D2 empirical
dispersion correction as implemented in Gaussian 09.32 6-31g(d) basis
sets33 were used for all atoms except for the three metals of the
catalysts (Cu, Ag, and Au) for which lanl2dz34 was used instead
together with the corresponding ECP and an additional polarization
function f with the exponents Cu (ζ(f) = 3.525), Ag (ζ(f) = 1.611),
and Au (ζ(f) = 1.050).35 Solvent effects have been taken into account
through the continuum model SMD for benzene.36 The model used
was the same metallocarbene used experimentally except for the ethyl
group of the COOEt, which was replaced by a methyl. The static
calculations presented correspond to minima or transition states as
confirmed by frequency calculations; however, due to the
particularities of the considered potential energy surface some of the
structures presented correspond to geometries with a frozen distance
between atoms. These energies should only be taken as orientative and
are marked with an F in the schemes and text. All energies presented
correspond to free energies in solution and are given in kcal/mol.
To achieve a better understanding of the reactivity of the system,
quantum dynamics under the Born−Oppenheimer molecular
dynamics (BOMD) model27 as implemented in Gaussian 0937 were
carried out. The system was simplified by pruning the diisopropyl-
phenyl groups of the metallocarbene IPr to hydrogens and the ethyl
group of the carbene also to hydrogen. The dynamics calculations
were initiated from geometries where the carbenic carbon and one of
the carbons of the benzene were set to 2.5 Å and the rest of the
molecule was optimized, as a calculation from the separate reactants
would be unfeasible in terms of computational effort. The initial
ACKNOWLEDGMENTS
■
We thank the Spanish MINECO for CTQ2014-52769-C3-1-R,
CTQ2014-57761-R, RED INTECAT CTQ2014-52974-REDC
and Severo Ochoa Excellence Accreditation 2014-2018 SEV-
2013-0319 and the ICIQ Foundation for financial support.
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