Quantitative description of structural effects on the stability of gold(I) carbenes

Article abstract of DOI:10.1002/chem.201403988

The gas-phase bond-dissociation energies of a SO₂-imidazolylidene leaving group of three gold(I) benzyl imidazolium sulfone complexes are reported (E₀=46.6±1.7, 49.6±1.7, and 48.9±2.1 kcalmol^-1) Although these energies are similar to each other, they are reproducibly distinguishable. The energy-resolved collision-induced dissociation experiments of the three [L]-gold(I) (L=ligand) carbene precursor complexes were performed by using a modified tandem mass spectrometer. The measurements quantitatively describe the structural and electronic effects a p-methoxy substituent on the benzyl fragment, and trans [NHC] and [P] gold ligands, have towards gold carbene formation. Evidence for the formation of the electrophilic gold carbene in solution was obtained through the stoichiometric and catalytic cyclopropanation of olefins under thermal conditions. The observed cyclopropane yields are dependent on the rate of gold carbene formation, which in turn is influenced by the ligand and substituent. The donation of electron density to the carbene carbon by the p-methoxy benzyl substituent and [NHC] ligand stabilizes the gold carbene intermediate and lowers the dissociation barrier. Through the careful comparison of gas-phase and solution chemistry, the results suggest that even gas-phase leaving-group bond-dissociation energy differences of 2-3 kcalmol^-1 enormously affect the rate of gold carbene formation in solution, especially when there are competing reactions. The thermal decay of the gold carbene precursor complex was observed to follow first-order kinetics, whereas cyclopropanation was found to follow pseudo-first-order kinetics. Density-functionaltheory calculations at the M06-L and BP86-D3 levels of theory were used to confirm the observed gas-phase reactivity and model the measured bond-dissociation energies.

Full text of DOI:10.1002/chem.201403988

DOI: 10.1002/chem.201403988
Full Paper
&
Carbenes |Hot Paper|
Quantitative Description of Structural Effects on the Stability of
Gold(I) Carbenes
David H. Ringger, Ilia J. Kobylianskii, Daniel Serra, and Peter Chen*[a]
Abstract: The gas-phase bond-dissociation energies of
a SO2–imidazolylidene leaving group of three gold(I) benzyl
imidazolium sulfone complexes are reported (E0 =46.6ꢀ1.7,
49.6ꢀ1.7, and 48.9ꢀ2.1 kcalmolꢁ1). Although these ener-
gies are similar to each other, they are reproducibly distin-
guishable. The energy-resolved collision-induced dissociation
experiments of the three [L]–gold(I) (L=ligand) carbene pre-
cursor complexes were performed by using a modified
tandem mass spectrometer. The measurements quantitative-
ly describe the structural and electronic effects a p-methoxy
substituent on the benzyl fragment, and trans [NHC] and [P]
gold ligands, have towards gold carbene formation. Evi-
dence for the formation of the electrophilic gold carbene in
solution was obtained through the stoichiometric and cata-
lytic cyclopropanation of olefins under thermal conditions.
The observed cyclopropane yields are dependent on the
rate of gold carbene formation, which in turn is influenced
by the ligand and substituent. The donation of electron den-
sity to the carbene carbon by the p-methoxy benzyl sub-
stituent and [NHC] ligand stabilizes the gold carbene inter-
mediate and lowers the dissociation barrier. Through the
careful comparison of gas-phase and solution chemistry, the
results suggest that even gas-phase leaving-group bond-dis-
sociation energy differences of 2–3 kcalmolꢁ1 enormously
affect the rate of gold carbene formation in solution, espe-
cially when there are competing reactions. The thermal
decay of the gold carbene precursor complex was observed
to follow first-order kinetics, whereas cyclopropanation was
found to follow pseudo-first-order kinetics. Density-function-
al-theory calculations at the M06-L and BP86-D3 levels of
theory were used to confirm the observed gas-phase reactiv-
ity and model the measured bond-dissociation energies.
Introduction
and the trapping of carbenes with styrene is a well-known re-
action model.[6]
Many reported homogeneous gold-promoted cyclopropana-
tion reactions of olefins proceed by multistep pathways and
presumably involve, as a key intermediate, a gold(I) carbene
with carbocationic behavior.[1] Direct evidence for the existence
of a gold(I) carbene intermediate has only very recently been
accomplished by the isolation of a Fischer-type gold carbe-
ne.[1b,2] The synthesis of the normally highly reactive intermedi-
ates are accomplished primarily through cascade cycloisomeri-
zation,[3] diazo-compound decomposition,[4] and retrocyclopro-
panation reactions[5] by using p-acidic gold(I) salts and com-
plexes. Many of these reactions work well, but the scope is
often less broad then would be desired. A more thorough un-
derstanding of the elementary reaction steps and intermedi-
ates can help in the pursuit of an alternative, and possibly
more versatile, route to the synthesis of positively charged
gold(I) carbenes. The inter- or intramolecular cyclopropanation
of alkenes to give cyclopropanes is reported in the literature
Electrospraying a charged complex in a tandem mass spec-
trometer (ESI-MS/MS) and performing collision-induced dissoci-
ations (CID) with an inert gas allows not only the detection of
charged reactive intermediates, but in the optimal case pro-
vides the means for bond-dissociation energy (BDE) measure-
ments. Such thermochemical data helps in the interpretation
of the steric and/or electronic effects of ligands, substituents,
and leaving groups on product formation, which, in the best
cases, is directly comparable to solution reactivity.[7] This
method allows for more extensive mechanistic thinking and
catalyst design, while decreasing the laborious trial-and-error
approach. Furthermore, the measured gas-phase BDEs are di-
rectly comparable to density-functional-theory (DFT) model-
ling, and thus can validate the choice of functional and give
confidence in its use for closely related complexes.[8]
Our group has been active in the application of ESI-MS/MS
to obtain thermochemical data for a number of organometallic
reactions, including olefin metathesis,[9] transmetalation,[10] pal-
ladium NHC-ligand dissociation,[11] cobaltꢁcarbon bond ener-
gies,[12] coinage metal carbene formation,[13] and the gas-phase
reactivity of an gold(I) carbene precursor complex, designated
here as C, generated from a phosphonium ylid. The latter,
however, proved unreactive in cyclopropanation reactions
under thermal conditions in solution, which we attributed to
a relatively strong carbonꢁphosphorus bond (51.7 kcalmolꢁ1,
[a] D. H. Ringger, I. J. Kobylianskii, Dr. D. Serra, Prof. Dr. P. Chen
Laboratorium fꢀr Organische Chemie, ETH Zꢀrich
Wolfgang-Pauli-Strasse 10, 8093 Zꢀrich (Switzerland)
Fax: (+41)44 632 1280
E-mail: peter.chen@org.chem.ethz.ch
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201403988.
Chem. Eur. J. 2014, 20, 14270 – 14281
14270
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
fragment and the trans [NHC] and [P] ligands have towards
gold carbene formation. These results were compared to the
obtained cyclopropane yields in the stoichiometric cyclopropa-
nation reaction, along with a kinetic decomposition study of
complex 1. The measured BDEs and activation energies were
also compared to DFT calculations at the M06-L and BP86-D3
level of theory.
The syntheses of the gold carbene complexes 1–3 were
facile and accomplished in overall good yields (Scheme 2).
1-Mesityl-1H-imidazole was treated with n-butyl lithium and
Scheme 1. Rational design of carbene precursors 1–3 based on previously
reported gold(I) complexes. CꢁS bond-dissociation energies, gas-, and solu-
tion-phase reactivity of gold carbene precursor complexes 1–3. IMes=1,3-
bis(2,4,6-trimethylphenyl)imidazole-2-ylidene, Mes=2,4,6-trimethylphenyl,
R=p-MeOC6H4 or H, DIPP=2,6-diisopropylphenyl.
Scheme 2. Synthesis of gold carbene precursor complexes 1–3. OTf=tri-
fluoromethanesulfonate, X=BF4 or SbF6, I-DIPP=1,3-bis(2,6-diisopropylphe-
nyl)imidazol-2-ylidene, JonPhos=(2-biphenyl)-di-tert-butylphosphine.
sulfur followed by the addition of an alkylating agent. The re-
sulting intermediates were oxidized and the addition of methyl
triflate yielded desired benzyl imidazolium sulfone salt 10. De-
protonation of 10 and addition of [L]–gold(I)–acetonitrile gives
the air-stable gold carbene precursor complexes 1–3. The start-
ing imidazole compound and alkylating agent can be varied
easily, and thus allows for structurally diverse benzyl imidazoli-
um sulfone salts. The corresponding anions of the complexes
1–3 are dependent on the gold starting material used. The
Scheme 1).[13a,b] We envisioned that appropriate modifications
in the leaving group of the gold complex would give access to
a gold carbene precursor complex that is reactive in catalytic
cyclopropanation in solution.
Preliminary gas-phase investigation of charged gold alkyl
complexes structurally analogous to B,[14] found that the
carbonꢁimidazolium bond of these complexes was much
stronger than the other bonds within the molecule. To weaken
this bond, an SO2 moiety was introduced to give a carbonꢁ synthesized gold complexes have a greater affinity to “soft”
SO2ꢁimidazolium configuration comparable to that of the neu-
tral and stable gold alkyl complex A.[15] The SO2ꢁimidazolyl-
idene moiety acts as a leaving group, which further dissociates
to give gaseous SO2 and imidazolylidene.[16] The imidazolium
function is desirable as it, not only provides the charge for
gas-phase detection of the complex, but, in solution, its basic
properties can be advantageous for a catalytic reaction during
which catalytic amounts of base is required. Based on these
considerations the gold complexes 1, 2, and 3 were synthe-
sized and their carbene formation capabilities were investigat-
ed in the gas phase and in solution (Scheme 1).
anions as described by the hard and soft acids and bases
(HSAB) principle.[18] X-ray crystallography of complexes 1 and 3
provided not only an unambiguous structural assignment, but
also located the associated anions. For more details, see the
Supporting Information.
It was suspected that complex 1 would be the best candi-
date for a catalytic cyclopropanation reaction due to the elec-
tron-rich trans [NHC] ligand and p-methoxy benzyl substituent.
In our previous report, a mixture of complex 1, the benzyl imi-
dazolium sulfone salt 10a, and p-methoxystyrene in CH2Cl2 at
1208C gave the desired cyclopropane 11 a with up to 4.3 turn-
overs. In the proposed cycle (Scheme 3), the gold carbene cy-
clopropanates p-methoxystyrene, and the SO2ꢁimidazolylidene
moiety further dissociates to give SO2 and imidazolylidene
12.[16] The latter acts as an in situ-formed base within the cycle
and deprotonates another molecule of 10a, which undergoes
auration to restore gold complex 1.[1a] This result is the starting
point for the present study.
Herein, we report the gas-phase energy-resolved collision-in-
duced dissociation experiments of the SO2ꢁimidazolylidene
leaving group, and the carbene cyclopropanation to an olefin
in solution, of three [L]-gold(I) (L=ligand) carbene precursor
complexes, 1–3. The experimentally obtained gas-phase BDEs
give an indication of whether the desired CꢁS bond breakage
would occur competitively under thermal conditions, given the
expected trends in solvation.[17] Additionally, these energies
provide quantitative information regarding the steric and/or
electronic effects a p-methoxy substituent on the benzylidene
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14271
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Figure 1. Relative intensity CID spectra of the gold carbene precursor com-
plexes 1–3 at 6 eV velocity (center-of-mass reference frame) and 80 mTorr
xenon. R=p-MeOC6H4 or H.
moiety could not be observed directly in the gas phase, but
has been shown in solution to further dissociate to give SO2
and imidazolylidene.[1a]
Taking into account that the gold carbene could, in princi-
ple, result from the rearranged gold complexes 7–9, the spray
settings were adjusted to generate what we presume to be 7–
9 in the ion source. Upon mass selection and CID (Figure 2),
Scheme 3. Proposed catalytic cycle of gold carbene precursor complex 1.
The [gold(I) carbene···styrene]° transition state drawing is not meant to
imply a preference for an inner-sphere over an outer-sphere carbene transfer
mechanism, or vice versa. Triflate anions are omitted for clarity. R and R’=p-
MeOC6H4.
Results
Gas-phase reactivity
The evaluation of potential gold carbene precursor complexes
was primarily accomplished by using an electrospray tandem
mass spectrometer (ESI-MS/MS) as an assay tool. This spec-
trometer enables the direct detection and manipulation of any
gold carbenes formed in the gas phase from potential precur-
sors and selection of the most promising precursor complexes
for a reaction in solution. The isolable and charged unimolecu-
lar gold carbene precursor complexes 1–3 are ideal for such
a gas- and solution-phase comparison study because carbene
formation presumably occurs by a single rate-determining
step.
Figure 2. CID spectra of gold complexes 7–9 generated in the ion source.
Spray voltage=4500 V, capillary temperature=1758C, capillary off-
set=200 V, tube lens offset=200 V.
Collision-induced dissociation (CID) of the electrosprayed
cationic [L]–gold(I) carbene precursor complexes 1, 2, and 3
(m/z=970, 940, and 880, respectively) in a ESI-MS/MS, fur-
nished two signals corresponding to 1) gold carbene 4, 5, and
6 (m/z=706, 676, and 616, respectively) by loss of SO2ꢁimida-
zolylidene and 2) gold complex 7, 8, and 9 (m/z=906, 876,
and 816, respectively), the latter being generated through the
extrusion of SO2 from the starting gold complexes 1–3
(Figure 1). Notably, no gold–carbene–SO2 adducts were ob-
served, indicating that only the benzylꢁsulfur bond is broken.
The fate of the neutral SO2ꢁimidazolylidene leaving-group
a range of signals were observed corresponding to ligand loss
and/or fragmentation. Only at very harsh collision conditions
were minor amounts of gold carbene 4–6 observed, indicating
that subsequent carbene formation from 7–9 has a much
higher barrier.
The detection of only two competing dissociation processes
stemming from the same reactant ion renders complexes 1–3
suitable for two-channel energy-resolved threshold experi-
ments. Thus, the benzylꢁsulfur BDEs for gold carbene forma-
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14272
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
tion and the activation energies of the SO2 extrusion can be
determined.
CID threshold measurements
Acetonitrile solutions (10ꢁ6 molLꢁ1) of the gold carbene precur-
sor complexes 1–3 were electrosprayed into a customized Fin-
nigan MAT TSQ-700 ESI-MS/MS spectrometer.[11] In a radiofre-
quency 24-pole ion guide, the reactant ions (1–3) were ther-
malized to the 708C manifold temperature with 10 mTorr
argon gas, followed by mass selection at low resolution, to
maintain a near-Gaussian kinetic energy distribution. Energy-re-
solved CID experiments were performed with low CID gas
pressures (20–110 mTorr) to minimize multiple collisions. The re-
actant and product ion (4–6, 7–9) intensities were recorded as
a function of the collision offset of ꢁ80 to +10 eV in the lab
frame energy, and the data curves fitted from 0 to up to 8.3 eV
in the center of mass reference frame (see the Supporting In-
formation for a full description of the experiment). The experi-
ments were repeated on three separate days to confirm repro-
ducibility. For each dataset, the signal intensities were convert-
ed to reactive collision cross sections,[11] and the single-collision
contributions were extracted by extrapolation to zero pressure
(Figure 1). The resulting curves were fitted with the L-CID pro-
gram[19] (see the Supporting Information) previously developed
within the group (Figure 3). To account for the correct treat-
ment of the kinetic shift and other fitting parameters, the L-
CID programrequires certain input assumptions, namely the
transition-state models: “loose”, if bond dissociation is rate lim-
iting, or “tight” if intramolecular rearrangement prior to disso-
ciation is rate limiting. Further input is the number of free
rotors in the parent ions 1–3.[20]
Figure 3. Top: Reactive cross sections (colored lines) and zero-pressure ex-
trapolations (black lines) of the formation of ions 4–6 and 7–9. Bottom:
Truncated zero-pressure extrapolated curves (red and green dots) and aver-
aged L-CID fitted curves (black lines). Inset: Kinetic-energy distribution (blue
dots) and Gaussian fit (red line).
The loose transition-state model is appropriate for gold car-
bene formation 4–6 and the tight transition-state model is ap-
propriate for the SO2 extrusion rearrangement. The five free
rotors consisting of the methyl groups and rotation about the
goldꢁbenzyl bond were determined by DFT analysis (only rota-
tions <10 kcalmolꢁ1 were considered) of the starting com-
plexes 1–3 vibrational modes.
Table 1. LCID fitted results for the tight SO2-extrusion rearrangement and
loose gold carbene formation processes. Estimate of E0 uncertainty of the
fit is included.
Varying the number of free rotors in the input file from 5 up
to 18, representing the lower and upper boundaries based on
the chemical structures (p-methoxy and tBu or iPr groups), in-
creases the absolute E0 energies by no more than 2–3 kcal
molꢁ1, but otherwise gives the same trends. The included error
bounds contains the uncertainty in the fit from L-CID due to
statistical scatter of the data points (see Table 1).
Processes 4–6 E0 [kcalmolꢁ1
]
7–9 E0 [kcalmolꢁ1
]
tight
loose
[L]=I-DIPP
R=OMe
[L]=I-DIPP
R=H
1!4+7 46.6ꢀ1.7
2!5+8 49.6ꢀ1.7
25.6ꢀ1.3
29.3ꢀ2.1
27.2ꢀ1.7
Although the absolute E0 energies, with the statistical error
bounds, for carbene formation 4–6 and rearrangement 7–9
overlap, the differences between them are distinct and repro-
ducible.
[L]=JonPhos 3!6+9 48.9ꢀ2.1
R=OMe
DFT calculations
tions were performed by using Gaussian 09[41] with M06-L/cc-
pVDZ, with no imposed symmetry, tight geometry conver-
gence criteria, tight SCF convergence criteria, and an ultrafine
integration grid. Frequency analyses were carried out to con-
firm the nature of each stationary point. Single-point calcula-
Theoretically calculated electronic energies (corrected for zero-
point energy), Eel+ZPE, were obtained to confirm the nature of
the observed species, and for comparison with the experimen-
tally determined activation energies E0. Geometry optimiza-
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14273
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
tions in Gaussian 09 with the cc-pVTZ basis set were per-
formed to improve the accuracy of the energies. Other func-
tionals were evaluated by single-point energy calculations
using the M06-L/cc-pVDZ geometries.
Table 2. Measured and calculated relative energies [kcalmolꢁ1] for the
formation of gold carbene (top) and rearranged (bottom) products.
Process
E0 loose
M06-L[a]
M06[b]
BP86[c]
BP86-D3[d]
For our investigation of the loose bond-dissociation process-
es, we mainly used the M06-L functional because it has been
designed to describe main-group and transition-metal thermo-
chemistry, kinetics, and attractive dispersion effects between
dissociating fragments.[21] Previously reported gas-phase and
DFT studies involving gold carbene formation and gold amino-
nitrene dissociation have shown that the M06 functionals
model the experimentally obtained data well.[13a,22] In particular,
these functionals found CꢁS bond homolysis to be rate deter-
mining.
1!4
2!5
3!6
46.6ꢀ1.7
49.6ꢀ1.7
48.9ꢀ2.1
39.7
48.6
41.9
40.4
47.8
42.5
19.8
25.2
19.8
45.4
53.4
47.2
Process
E0 tight
M06-L[a]
M06[b]
BP86[c]
BP86-D3[d]
1!7
2!8
2!9
25.6ꢀ1.3
29.3ꢀ2.1
27.2ꢀ1.7
38.8
40.8
42.8
40.8
42.1
44.8
40.8
42.1
44.8
31.5
33.2
35.2
[a] M06-L/cc-pVTZ//M06-L/cc-pVDZ single-point energies, including zero-
point energy corrections. [b] M06/cc-pVTZ//M06-L/cc-pVDZ single-point
energies, including zero-point energy corrections. [c] BP86/cc-pVTZ//M06-
L/cc-pVDZ single-point energies, including D3-dispersion and zero-point
energy corrections. [d] BP86-D3/cc-pVTZ//M06-L/cc-pVDZ single-point en-
ergies, including zero-point energy corrections.
The localization of the tight SO2 extrusion transition state re-
quired the evaluation of a few plausible reaction pathways.
The transition state depicted in Figure 4 was found to be
Performance of the DFT functionals without treat-
ment of dispersion effects can be described as poor
and cannot be recommended for the investigation of
similar systems. Inclusion of D3 treatment improves
agreement between different methods and gives
more accurate energy profiles with respect to experi-
mental gas-phase data (Figure 1) for the loose and
tight transition state. However, one should be careful
with the inclusion of D3 corrections because it can
mask other limitations of different functionals.
Solution-phase reactivity
The potential formation of gold carbenes 4–6 in solu-
tion was tested under conditions for the stoichiomet-
ric cyclopropanation of olefins.[1b–d] Heating com-
plexes 1–3 to 1208C in the presence of an excess of
p-methoxystyrene in CH2Cl2 gives the expected 11 cy-
clopropane with variable yields (Table 3).
Figure 4. M06-L/cc-pVTZ//M06-L/cc-pVDZ potential-energy diagram of gold complexes
1–3. Dashed lines denote dissociation reactions without reversible activation barriers. For
the SO2-rearrangement transition state and product, the ligands, hydrogen atoms, and p-
methoxy substituent are omitted for clarity.
To probe the reactivity of the presumably formed
gold carbene in solution, complex 1 was heated
under argon in the presence of cyclohexene, a less
reactive olefin (Scheme 4). The yield of cyclopropane
lowest in energy. However, M06-L appears to overestimate the
13 substantially decreased, but aside from the olefin, the only
side products detected by gas chromatography (GC) were
small amounts of benzaldehydes together with other unidenti-
fiable products and purple colloidal gold. Heating complex
SO2 extrusion activation energy and we decided to benchmark
other DFT functionals to assess their performance with respect
to the investigated systems.
Some common DFT functionals were screened for the cc-
pVTZ basis set, including the evaluation of Grimme’s D3 disper-
sion correction,[23] as suggested for complexes of such sizes
(Table 2).[24] For BP86, dispersion effects were found to affect
both fragmentation channels significantly, but by different
amounts. The starting complex 1 is stabilized by 25.6 kcal
molꢁ1 with respect to carbene formation, and the SO2 extru-
sion rearrangement transition state was found to be stabilized
by 9.3 kcalmolꢁ1 with respect to the starting complex (Fig-
ures 5 and 6).
Scheme 4. Stoichiometric cyclopropanation of cyclohexene with gold car-
bene precursor complex 1.
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14274
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
with the absence of p-methoxystyrene was conduct-
ed to probe the possible influence of the olefin.
Decomposition of complex 1 with and without the
presence p-methoxystyrene follows expected first-
order kinetics with a half-life of approximately 5.5–
7 min (Figure 7). During the course of the reactions
no other charged reactive intermediates were ob-
served.
To monitor the evolution of cyclopropane 11 a in
a stoichiometric cyclopropanation reaction, a setup
as described above was used, but instead of electro-
spraying the reaction mixture into an ESI-MS/MS
spectrometer, fractions were collected and analyzed
by GC with flame-ionization detection (GC-FID).[27]
The GC vials (in an automated fraction collector)
were prefilled with hexane, which served to cool the
reaction mixture to room temperature and immedi-
ately quench any subsequent chemistry. A Schlenk
tube, fitted with a fused silica capillary, was charged
with complex 1 in the presence of a large excess of
p-methoxystyrene to ensure pseudo-first-order condi-
tions, triphenylmethane (internal standard), and
chlorobenzene. The Schlenk tube was then placed
into a flask containing a boiling solvent to ensure
a much more stable temperature during the course
of the experiment. After collecting the fractions the
GC samples were placed into a centrifuge before in-
jecting them into the GC-FID (Figure 8). This experi-
ment was repeated twice for three different tempera-
tures using water, n-butanol, and chlorobenzene as
boiling solvents.
Figure 5. BP86/cc-pVTZ//M06-L/cc-pVDZ potential-energy surface diagram [kcalmolꢁ1] of
complex 1. The solid lines represent the D3-dispersion corrected energies. For the SO2-re-
arrangement transition state, ligand and hydrogen atoms are omitted for clarity.
It was found that the formation of cyclopropane
11 a follows pseudo-first-order kinetics with a rate
constant of ꢂ1.9ꢁ10ꢁ4–9.9ꢁ10ꢁ3 sꢁ1, consistent with
the slope of the exponential decay of gold complex
1. The Eyring equation was used to describe DG°,[28]
DH,° and DS°,[29] which were found to be 27.8ꢀ0.3,
36.0ꢀ2.7 kcalmolꢁ1, and 21ꢀ7 calmolꢁ1 Kꢁ1, respec-
tively.
The thermal decomposition of complexes 2 and 3
in CD2Cl2 at 1208C were studied by using 1H NMR
spectroscopy. After heating complex 2 for 97 h, small
amounts of starting complex, benzaldehyde, 3-mesi-
tyl-1-imidazolium, and substantial amounts of benzyl
Figure 6. BP86-D3/cc-pVTZ//M06-L/cc-pVDZ potential-energy diagram [kcalmolꢁ1] of
gold complexes 1–3. Dashed lines denote dissociation reactions without reversible acti-
vation barriers. For the SO2 rearrangement transition state and product, the ligand, hy-
drogen atoms, and p-methoxy substituent are omitted for clarity.
1 at 1208C for 16 h, in the absence of an olefin, provided ap-
proximately 45% p-methoxybenzaldehyde.[25]
imidazolium sulfone salt 10b were observed. In the case of
complex 3, the reaction was stopped after 3 h. After this time
the starting complex has completely disappeared and small
amounts of unidentifiable side products along with large
quantities of p-methoxybenzaldehyde and 3-mesityl-1-imidazo-
lium were observed. Further details are given in the Support-
ing Information.
To observe the expected unimolecular exponential decay of
the gold carbene precursor complexes, a Schlenk flask was
charged with 1, a large excess of p-methoxystyrene, tetraocty-
lammonium tetrafluoroborate (internal standard), and choloro-
benzene. The reaction mixture was then placed into a flask
containing boiling n-butanol (1188C) to ensure a much more
stable temperature during the course of the experiment. The
concentration of complex 1 was continuously monitored with
a Thermo–Finnigan TSQ Quantum ESI-MS/MS spectrometer by
using the pressurized infusion method setup as previously de-
scribed by Vikse et al.[26] Additionally, a control experiment
Discussion
Within L-CID the type of transition state (loose or tight) is a re-
quired input and either assumption gives statistically accepta-
ble fits for the two competing processes of carbene formation
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14275
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
Table 3. Stoichiometric cyclopropanation of gold carbene precursor com-
plexes 1–3.
Complex
Yield [%][a] cis/trans
Time [h]
3
1
2
3
[L]=I-DIPP
R=OMe
X=OTf
99 (14:1)
[L]=I-DIPP
R=H
X=OTf
[L]=JonPhos
R=OMe
X=SbF6
5 (12: 1)
80 (14:1)
16
3
[a] GC yields relative to an internal standard.
Figure 8. Ratio (cyclopropane/internal standard) (red symbols) versus time
(seconds), logarithmic product formation modelling (black line). Inset: Inte-
grated first-order rate graph ln[a-ratio] versus time (seconds). R=p-
MeOC6H4.
Figure 7. Normalized concentration of gold carbene precursor complex
1 (blue dots) versus time (seconds), exponential decay modelling (red line).
At tꢂ1400 seconds the Schlenk tube containing the reaction mixture was
placed into a flask containing boiling solvent, raising the temperature to
start the reaction. Inset: Integrated first-order rate graph ln[A] versus time
(seconds).
Figure 9. Recorded relative intensities as a function of the collision energy
of the reactants 4–6 (purple) and 7–9 (green) at low CID gas pressures rang-
ing from 110 to 20 mTorr. Inset: Statistical RRKM rate expression, and pictorial
description of competitive loose and tight pathways as a function of the in-
ternal energy E of the reactant.
and SO2 extrusion. However, based on chemical arguments
and the shapes of the recorded relative intensity curves of the
reactants (Figure 9), the appropriate transition-state models
can be assigned unambiguously.
Rice–Ramsperger–Kassel–Marcus (RRKM) theory (see Figure 9
inset). It defines the microcanonical rate constant of a process
as a function of the internal energy E, in which g is the reac-
tion degeneracy, W(E–E0) is the sum of states of the transition
Specifically, the spectrometrically observed product ratios of
the two competing processes can be explained by statistical
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14276
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
state with an energy less than or equal to E–E0, h is Planck’s
constant, and 1(E) is the density of states for the energized
starting ion at an energy E. The excess energy E–E0 applied to
the mass-selected ions is assumed to be statistically distributed
over the accessible vibrational/rotational modes. For a loose
dissociation transition state at the centrifugal barrier for the
treatment of the dissociation in an ion-molecule reaction is
modelled in L-CID. At the dissociation transition state, six vibra-
tions in the energized reactant ion become three rotational
and three translational modes, of which one translation is the
reaction coordinate. The rate of a reaction with a loose transi-
tion state increases with excess energy much more quickly
than that for a tight transition state. Consequently, the rate of
a dissociation can exceed the rate of a rearrangement even if
E0 for the loose process is higher than E0 of the tight process.
Based on these arguments, one can often infer general fea-
tures of the potential energy surface based on the observed
behavior of the reaction cross-sections even before the extrac-
tion of activation barriers and/or consulting DFT calcula-
tions.[11,30]
erature search reveals that ionized organic sulfonyl compounds
were also reported to extrude SO2 in the gas phase. This reac-
tion was suggested as a distinctive marker for the sulfonyl
group. Thorough mechanistic studies are scarce, however, and
it is difficult to make a direct comparison with our gold com-
plexes 1–3.[33] High resolution ESI-MS/MS of complexes 1–3
was conducted in order to validate the chemical formula of
the product ions 4–6 and 7–9 (see the Supporting Informa-
tion). The measured isotope patterns are in very good agree-
ment with calculated patterns and confirm their identity. Struc-
tural evidence for the existence of gold carbenes in the gas
phase has previously been reported by trapping experiments
using complex C.[13a,b] The structures of the rearranged com-
plexes 7–9 are DFT predictions.
With the reactive cross-section curves interpreted quantita-
tively, the measured thresholds energies were compared with
the DFT-calculated energy barriers for carbene formation and
SO2 extrusion. The computed reaction pathways (Figure 4 and
6) predict benzylꢁsulfur dissociation to proceed in a single
step without a definable transition state up until the centrifu-
gal barrier, whereas the SO2-extrusion rearrangement follows
a reaction with an initial tight transition state followed by SO2
extrusion. The depicted transition states and products 7–9 are
DFT predictions. It is also plausible that 7–9 further rearrange
to restore aromaticity and form a product analogous to com-
plex B (Scheme 1). However, experiments provide no evidence
for or against these structures. The energies of the simple dis-
sociation are in good agreement with the measured BDEs with
M06-L, M06, and BP86-D3. Adding Grimme’s D3-dispersion cor-
rection at the BP86 level greatly improved the calculations. In
the case of complex 1 (Figure 5), the dispersion corrections in-
creased the dissociation threshold by 25.6 kcalmolꢁ1 and de-
creased the rearrangement barrier by 9.3 kcalmolꢁ1. However,
in a solvation model the dispersion effects may be less pro-
nounced.[34] The M06-family calculations are also in good
agreement with the measured BDE of complex 2, but they
slightly overestimate the electronic contributions of the p-me-
thoxy benzyl substituents in complexes 1 and 3. Nevertheless,
the calculated BDE difference of approximately 2 kcalmolꢁ1 be-
tween 1 and 3 is in very good agreement with the measured
BDE difference, reproducing the overall trend of benzylꢁsulfur
bond strengths. For the SO2-extrusion activation energies, only
the BP86-D3 calculated energies are in acceptable agreement
with measurements, whereas M06 and M06-L consistently
overestimate the height of the activation energies.
Based on these arguments and on the inspection of the rela-
tive intensity of ions 4–6 and 7–9 as a function of collision
energy (Figure 9), the appropriate transition-state model is
loose for gold carbene formation 4–6 and tight for the SO2-ex-
trusion rearrangement 7–9 process (Table 1).
Having assessed the threshold CID curves qualitatively, and
fitted by using L-CID, the obtained BDEs (Table 1) for com-
plexes 1–3 allow the rationalization of the observed gas-phase
reactivity for the different para-substituents and different trans
[NHC] versus [P] ligand. The counterions can be ignored in the
comparisons because the complexes exist as naked cations in
the gas phase and there is no indication that the weakly coor-
dinating anion is important to the reactivity in the moderately
polar CH2Cl2 solution. Comparing complexes 1 and 2, the
formed carbene intermediate is stabilized by the donation of
electron density from the p-methoxy benzyl substituent by up
to 3 kcalmolꢁ1. The comparison of [NHC] and [P] ligand effects
on carbene stabilization is less straightforward as the overall
geometries are quite different. The approximately 2 kcalmolꢁ1
BDE difference between complex 1 and 3 can, however, be re-
garded as an upper bound for the stabilization of the carbene
owing to the electronic effects of the [NHC] ligand. It is gener-
ally accepted that [NHC] ligands are stronger s donors, also ex-
hibiting less d!p* backbonding in comparison with [P] li-
gands. This is consistent with the experimentally observed sta-
bilization of the electrophilic carbenes 4–6.[24,31] The activation
energies for the SO2-extrusion rearrangement (Table 1, 25.6–
29.3 kcalmolꢁ1) are surprisingly low when considering that aro-
maticity is disrupted, two CꢁS bonds are broken, and only one
CꢁC bond is formed. Other pathways, for example, a three-
membered cyclic transition state, have been considered, but
the computed transition-state energies were considerably
higher. An alternative, but higher energy transition state, is de-
scribed in the Supporting Information. The SO2-extrusion acti-
vation energies are, however, less interesting for our current
study because this reaction is not kinetically competitive with
the pathway leading to the cyclopropane in solution.[32,17] A lit-
A summary of the key gas phase and DFT results is present-
ed in Table 4, including the cyclopropanation yields observed
in solution.
Having measured the carbene formation and SO2-extrusion
rearrangement energies in the gas phase and having con-
firmed the results by DFT, we now turn our attention to the ac-
companying solution-phase experiments. For the comparison
of ease of carbene formation in terms of steric/electronic ef-
fects of the various structural modifications in both media, cer-
tain assumptions about the gold carbene precursor complexes
1–3 must be made. It is assumed that 1) carbene formation in
the gas phase, and cyclopropanation in solution, of the three
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14277
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
unlike what is commonly observed when using diazo com-
pounds as carbene precursors.[36] These findings suggest that
carbene formation is rate limiting for the overall cyclopropana-
tion reaction, implying that the gold carbene is present only in
small steady-state concentrations during the reaction, render-
ing homocoupling kinetically unfavorable. Consistent with this
kinetic picture, cyclopropanation follows pseudo-first-order ki-
netics (Figure 8). Comparison of the results from the different
kinetic-measurement techniques used in this study must be
done with caution, but the rates are nevertheless as consistent
with each other as one could expect. In any case, the first-
order and pseudo-first-order kinetics of carbene formation and
transfer are reproducible and unambiguous. The observed pos-
itive entropy of activation DS° (Figure 8, 21ꢀ7 calmolꢁ1 Kꢁ1) in
the GC-FID experiments is in accordance with the proposed
rate-limiting carbene formation transition state. For compari-
son, a negative DS° =ꢁ8.9 calmolꢁ1 Kꢁ1 for carbene formation
from ethyl diazoacetate and copper(I), measured by N2 evolu-
tion,[37] suggests that the rate-determining step in that reaction
could be coordination of the diazo compound to the metal, or
some rearrangement in the complex.
Table 4. Summary of the measured thermochemical data, DFT calcula-
tions, and cyclopropanation yields.
Complex
E0 4–6
M06-L[b]
39.7
BP86-D3[c]
45.4
11 Yield
[a]
[kcalmolꢁ1
]
[%][d]
1
2
3
[L]=I-DIPP
46.6ꢀ1.7
49.6ꢀ1.7
48.9ꢀ2.1
99
5
R=OMe
Xꢁ =OTf
[L]=I-DIPP
R=H
Xꢁ =OTf
[L]=JonPhos
R=OMe
Xꢁ =SbF6
48.6
41.9
53.4
47.2
80
[a] BDEs threshold for gold carbene formation in kcalmolꢁ1. [b] M06-L/cc-
pVTZ//M06-L/cc-pVDZ single-point energies, including zero-point energy
corrections. [c] BP86-D3/cc-pVTZ//M06-L/cc-pVDZ single-point energies, in-
cluding zero-point energy corrections. [d] GC yields relative to an internal
standard.
Having established that the assumptions 1–4 are very likely
to be correct, we turned our attention to assumption 5 and
compared the ease of gold carbene formation in solution,
measured by cyclopropanation yields, with the gas-phase BDEs
for carbene formation. The observed cyclopropanation yields,
resulting from precursor complexes 1–3, exhibit dependency
on the ligand trans to the carbene and on the para benzyl sub-
stituent (Table 4). The yields range from 5 to 99%, with com-
plex 1 giving the highest yields, followed by 3 and then 2. The
gas-phase BDE differences seem small, but in principle a small
increase of 2.3 kcalmolꢁ1 in BDE decreases the rate of carbene
formation by approximately 19 times[38] at the temperatures
used in the cyclopropanation in solution. Hence, if no other
competitive decomposition reactions are taking place, then
carbene formation is quantitative if the reaction time is pro-
longed accordingly. However, replacing the [NHC] with a [P]
ligand reduces the cyclopropane yields from 99 to 80%. In the
absence of the p-methoxy substituent on the benzylidene, the
yield drops further to 5%. The measured increase in BDE of
complexes 2 and 3 decreases the rate of carbene formation to
such an extent that eventually other decomposition pathways
become competitive. The rate of carbene formation and trans-
fer is most likely not influenced by the other decomposition
pathways, but the final cyclopropane yields and overall decom-
position rate of complexes 2 and 3 are. This effect is seen in
complex 2, which is slower in carbene formation, as evidenced
by the fact that the starting complex was not completely de-
composed after 97 h at 1208C. Consequently, the rate of the
dissociation of benzyl sulfone imidazolium moiety 10b from
[L]–gold(I) becomes competitive. Additionally, owing to the ab-
sence of an electron-donating p-methoxy substituent, the
goldꢁbenzyl bond is slightly weaker in complex 2 compared
with 1. This factor increases the rate of the dissociation of 10b
from complex 2 and makes the undesired decomposition path-
way even more competitive. These observations could explain
the absence of gold carbene formation for complex C in solu-
complexes 1–3 follow analogous transition states, 2) carbene
formation is the rate-determining step, 3) upon carbene forma-
tion, transfer to the electron rich p-methoxystyrene is quantita-
tive and very rapid, 4) cyclopropanation follows pseudo-first-
order kinetics with a steady-state olefin concentration and
5) solvation effects shift the absolute benzylꢁsulfur bond ener-
gies of the three complexes in the same direction with similar
magnitudes and the rate of carbene formation is reflected in
cyclopropane yields. If these assumptions hold true, then we
expect that the structural modifications are directly compara-
ble to the gas-phase measured BDEs for carbene formation.
The most reactive complex, 1, exhibiting no other observable
competitive decomposition pathways, was used to benchmark
the other complexes, and to examine the assumptions made
in points 2), 3), and 4).
To probe if the decay of the complexes 1–3 is rate limiting
and follows first-order kinetics, the ESI-MS/MS pressurized infu-
sion method described in Figure 7 was used to measure the
thermal decay of complex 1. The results revealed that carbene
formation follows clean first-order kinetics with a half-life of
5.5–7 min.[35] No other charged intermediates were observed in
the presence or absence of p-methoxystyrene. To confirm as-
sumption number 3, complex 1 was used in a stoichiometric
cyclopropanation reaction. This reaction gave the expected cy-
clopropane in quantitative yields (Table 4, 99%). Heating com-
plex 1 in the absence of an olefin yields small amounts of un-
identifiable products, but predominantly p-methoxybenzalde-
hyde. The aldehyde is most likely formed by oxidation of the
gold carbene by SO2.[25] The absence of 4,4’-dimethoxystilbene
indicates that no homocoupling of two gold carbenes occurs,
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14278
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
tion (Figure 1), for which the 51.7 kcalmolꢁ1 BDE is a further
1.8 kcalmolꢁ1 higher than in the worst case (complex 2) in the
current study. Although we cannot definitively exclude other
factors, the trend is correct.
method, and carbene transfer to the olefin was determined to
follow pseudo-first-order kinetics.
The measured BDEs are useful for benchmarking future en-
deavors in the search for gold carbene precursors, which may
be active in cyclopropanation. Further mechanistic investiga-
tion of the complexes 1–3 in cyclopropanation reactions will
be reported in due course.
It has been suggested that carbene transfer to olefins can
occur in a step-wise or concerted manner and may be depen-
dent on the olefin. It was proposed that the electron-rich styr-
enes follow a step-wise mechanism, whereas the less-polariza-
ble olefins follow a concerted pathway.[39] We used cyclohex-
ene not only to probe the cyclopropanation scope, but also
because different isomers might be observed if cyclopropana-
tion followed a concerted versus a step-wise reaction mecha-
nism (Scheme 4). If carbene transfer to cyclohexene followed
a step-wise mechanism, there might be a chance to form iso-
mers of cyclopropane 13 or polymerization products. However,
heating complex 1 in the presence of cyclohexene only yielded
55% of cyclopropane 13 and small quantities of p-methoxy-
benzaldehyde, which renders these results inconclusive for
such an argument. Other trapping experiments and DFT calcu-
lations are needed for the investigation of the carbene-transfer
transition state. The cis over trans and endo over exo selectivity
is intriguing because the more sterically demanding product is
observed. This phenomenon is, to date, unresolved and further
experiments and DFT calculations are needed.
Experimental Section
General Procedures
Unless stated otherwise, all reactions were carried out under an at-
mosphere of argon by using standard Schlenk techniques with
dried glassware and anhydrous solvents. Chromatographic purifica-
tions were carried out using neutral (pH 7.0) aluminum oxide. Thin-
layer chromatography was carried out by using 0.2 mm layer of
neutral aluminum oxide with UV254 indicator. NMR spectra were re-
corded on Mercury-vx 300, Amstrad DRX 400, and Avance III 600
spectrometers. Chemical shifts are given in ppm with respect to re-
sidual solvent resonances[40] and denoted by the following abbrevi-
ations: s (singlet), d (doublet), dd (double doublet), t (triplet), td
(double triplet), sept (septet), m (multiplet). The high resolution
ESI-MS/MS was performed by the MS service fꢂr Organische
Chemie, ETH Zꢂrich. The following chemicals were obtained from
commercial sources and used without further purification, unless
stated otherwise: 1,3-bis(2,6-di-iso-propylphenyl)imidazol-2-ylide-
ne(acetonitrile)gold(I) tetrafluoroborate, (2-biphenyl)di-tert-butyl-
phosphine(acetonitrile)gold(I) hexafluoroantimonate; p-methoxy-
styrene and cyclohexene were dried over CaH2 and fractionally dis-
tilled under vacuum.
The reported results complement our previously communi-
cated catalytic cyclopropanation reaction of complex 1 and
highlight how the difference of a few kcalmolꢁ1 in BDE can
have an order-of-magnitude effect on the solution-phase kinet-
ics for carbene formation and decomposition pathways.
Conclusion
The rationally developed gold carbene precursor complexes 1–
3 were studied by collision-induced dissociation threshold
measurements, along with DFT calculations and stoichiometric
cyclopropanation reactions in solution. The measured benzylꢁ
sulfur bond dissociation energies and SO2-extrusion barriers of
the three gold carbene precursor complexes were found to be
dependent on the ligand trans to the carbene and on the p-
methoxy benzyl substituent. The [NHC] ligand stabilizes the
gold carbene intermediate by 2 kcalmolꢁ1 and the p-methoxy
benzyl substituent by 3 kcalmolꢁ1. These results support chem-
ical intuition, which suggests that electron-donating groups on
gold will stabilize the electrophilic carbene. It is a rare example
of the quantitative assessment of reactive complexes without
the usage of surrogate complexes. The DFT calculations for the
BDEs at the M06-L and BP86-D3 level are in agreement with
experimental results, whereas the SO2-extrusion rearrangement
barriers could only be modelled reasonably by using the BP86-
D3 functional.
Synthesis of gold complexes 1–3
n-Butyl lithium (56 mmol) was slowly added to a solution of benzyl
imidazolium sulfone salt 10 (56 mmol) in THF (0.5 mL) at ꢁ788C.
The resulting yellow solution was stirred for 1 h at ꢁ788C before
a solution of [L]–gold(I)–acetonitrile (56 mmol) in THF (0.5 mL) was
added. The colorless solution was then stirred at ꢁ788C for 1 h
and subsequently allowed to warm to room temperature and
stirred for an additional 1 h. The mixture was then filtered through
Celite and the filtrate concentrated in vacuo. The colorless oil was
taken up in CH2Cl2 and purified by a short column chromatography
with neutral alumina oxide (hexane, followed by a mixture of ace-
tone/CH2Cl2 as eluent). The relevant fractions were combined and
concentrated in vacuo to give the product (ꢂ90%) as white solid.
Typical procedure for the stoichiometric cyclopropanation
reaction
A 5 mL Young Schlenk was charged, in a glovebox, with the gold
carbene precursor 1–3 (3 mmol), olefin (150 mmol), and CH2Cl2
(1 mL). The resulting reaction mixture was stirred overnight in an
oil bath at 1208C. The mixture was then allowed to cool to room
temperature and the internal standard (hexamethylbenzene) was
added. The organic solvents were removed under a flow of nitro-
gen. The resulting oil was suspended in ꢂ2 mL of CH2Cl2/hexane
9:1 and filtered through a syringe filter. The resulting colorless so-
lution was then injected into a GC-FID.
The ease of gold carbene formation in solution is reflected
in the obtained cyclopropane yields, ranging from 5 to 99%,
and follow the same trend as the measured gas-phase BDEs,
with complex 1 exhibiting the lowest BDE followed by 3 and
2.
The expected unimolecular first-order decay of complex
1 was confirmed by using an ESI-MS/MS pressurized infusion
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14279
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[5] a) C. S. R. Solorio-Alvarado, A. M. Echavarren, J. Am. Chem. Soc. 2010,
132, 11881–11883; b) C. s. R. Solorio-Alvarado, Y. Wang, A. M. Echavar-
ren, J. Am. Chem. Soc. 2011, 133, 11952–11955; c) Y. Wang, P. R. McGoni-
gal, B. Herlꢃ, M. Besora, A. M. Echavarren, J. Am. Chem. Soc. 2014, 136,
801–809.
[6] a) T. d. Hartog, J. M. S. Toro, P. Chen, Org. Lett. 2014, 16, 1100–1103;
b) D. F. Harvey, D. M. Sigano, Chem. Rev. 1996, 96, 271–288; c) M. P.
Doyle, Chem. Rev. 1986, 86, 919–939; d) É. Lꢃvesque, S. R. Goudreau,
A. B. Charette, Org. Lett. 2014, 16, 1490–1493; e) H. Lebel, J.-F. Marcoux,
C. Molinaro, A. B. Charette, Chem. Rev. 2003, 103, 977–1050; f) Y. Gai, M.
Julia, J.-N. Verpeaux, Bull. Soc. Chim. Fr. 1996, 133, 817–829; g) S.
Brandt, P. Helquist, J. Am. Chem. Soc. 1979, 101, 6473–6475.
[7] P. Chen, Angew. Chem. 2003, 115, 2938–2954; Angew. Chem. Int. Ed.
2003, 42, 2832–2847.
Procedure for the pressurized sample-infusion method
A 20 mL Schlenk was charged, in a glovebox, with complex
1
(1.2 mg, 1.0 mmol, 1.0 equiv), p-methoxystyrene (20 mL,
0.15 mmol, 150 equiv), and tetraoctylammonium tetrafluoroborate
(2.5 mg, 4.5 mmol) in chlorobenzene (1 mL). The resulting reaction
mixture was fitted with a fused silica tube (Ø=100 mm) connected
to a mixing T-piece, which was in turn connected to a syringe
pump (benzene as diluting solvent) and ESI-MS/MS spectrometer
that continuously recorded signal intensities of 1 and tetroctylam-
monium. The Schlenk was then placed into a preheated 1208C oil
bath and pressurized with 0.3 bar of N2.
[8] a) L. Operti, R. Rabezzana, Mass Spectrom. Rev. 2006, 25, 483–513;
b) P. B. Armentrout, Int. J. Mass spectrom. 2003, 227, 289–302; c) K. Eller,
H. Schwarz, Chem. Rev. 1991, 91, 1121–1177; d) V. J. F. Lapoutre, B. Red-
lich, A. F. G. van der Meer, J. Oomens, J. M. Bakker, A. Sweeney, A. Moo-
kherjee, P. B. Armentrout, J. Phys. Chem. A 2013, 117, 4115–4126.
[9] a) S. Torker, D. Merki, P. Chen, J. Am. Chem. Soc. 2008, 130, 4808–4814;
b) Y.-Y. Lai, M. Bornand, P. Chen, Organometallics 2012, 31, 7558–7565.
[10] a) M.-E. Moret, D. Serra, A. Bach, P. Chen, Angew. Chem. 2010, 122,
2935–2939; Angew. Chem. Int. Ed. 2010, 49, 2873–2877; b) D. Serra, M.-
E. Moret, P. Chen, J. Am. Chem. Soc. 2011, 133, 8914–8926.
[11] E. P. A. Couzijn, E. Zocher, A. Bach, P. Chen, Chem. Eur. J. 2010, 16, 5408–
5415.
Procedure for the GC-FID kinetic measurement
A 10 mL Schlenk was charged in the glovebox with complex
1 (2 mg, 1.5 mmol, 1.0 equiv), p-methoxystyrene (30 mL, 0.22 mmol,
160 equiv), and triphenylmethane (1.0 mg) in chlorobenzene
(2.5 mL). The resulting reaction mixture was fitted with a septum
and a fused silica tube (Ø=100 to 150 mm) connected to a fraction
collector. 400–600 mL hexane was added to the GC vials and frac-
tions were collected at a speed of 1–5 min depending on the tem-
perature. The Schlenk tube was then placed into boiling solvent
(water, n-butanol, and chlorobenzene) and pressurized with
ꢂ0.3 bar of N2.
[12] I. J. Kobylianskii, F. J. Widner, B. Kräutler, P. Chen, J. Am. Chem. Soc.
2013, 135, 13648–13651.
[13] a) A. Fedorov, M.-E. Moret, P. Chen, J. Am. Chem. Soc. 2008, 130, 8880–
8881; b) A. Fedorov, P. Chen, Organometallics 2009, 28, 1278–1281; c) L.
Batiste, A. Fedorov, P. Chen, Chem. Commun. 2010, 46, 3899–3901; d) A.
Fedorov, L. Batiste, A. Bach, D. M. Birney, P. Chen, J. Am. Chem. Soc.
2011, 133, 12162–12171.
[14] A. Fꢂrstner, M. Alcarazo, R. Goddard, C. W. Lehmann, Angew. Chem.
2008, 120, 3254–3258; Angew. Chem. Int. Ed. 2008, 47, 3210–3214.
[15] a) H.-J. Kneuper, K. Harms, G. Boche, J. Organomet. Chem. 1989, 364,
275–279; b) B. Djordjevic, K. A. Porter, S. Nogai, A. Schier, H. Schmid-
baur, Organometallics 2003, 22, 5336–5344.
[16] M. K. Denk, K. Hatano, A. J. Lough, Eur. J. Inorg. Chem. 2003, 224–231.
[17] a) D. K. Bohme, G. I. Mackay, J. Am. Chem. Soc. 1981, 103, 978–979;
b) E. D. Hughes, C. K. Ingold, J. Chem. Soc. 1935, 244–255; c) M. R. J.
Dack, J. Chem. Educ. 1974, 51, 231.
[18] R. G. Pearson, J. Songstad, J. Am. Chem. Soc. 1967, 89, 1827–1836.
[19] S. Narancic, A. Bach, P. Chen, J. Phys. Chem. A 2007, 111, 7006–7013.
[20] E. P. A. Couzijn, I. J. Kobylianskii, M.-E. Moret, P. Chen, Organometallics
2014, 33, 2889–2897.
Acknowledgements
The support from ETH Zꢂrich and Swiss Nationalfonds is grate-
fully acknowledged. We thank Dr. Bernd Schweizer, Dr. Nils
Trapp, and Michael Solar for the crystal structure determina-
tion; Louis Bertschi for the high resolution ESI-MS/MS; Dr. Erik
P. A. Couzijn, Dr. Tim den Hartog, and Dr. Krista L. Vikse for
useful discussions and Armin Limacher for synthetic support.
Keywords: bond-dissociation
carbocations cyclopropanation
calculations · gold
energies
·
carbenes
·
·
·
density functional
[21] a) Y. Zhao, D. G. Truhlar, J. Chem. Phys. 2006, 125, 194101; b) Y. Zhao,
D. G. Truhlar, Acc. Chem. Res. 2008, 41, 157–167; c) C. J. Cramer, D. G.
Truhlar, Phys. Chem. Chem. Phys. 2009, 11, 10757–10816; d) D. G. Gusev,
Organometallics 2013, 32, 4239–4243.
[22] a) A. Fedorov, E. P. A. Couzijn, N. S. Nagornova, O. V. Boyarkin, T. R. Rizzo,
P. Chen, J. Am. Chem. Soc. 2010, 132, 13789–13798; b) A. Fedorov, L. Ba-
tiste, E. P. A. Couzijn, P. Chen, ChemPhysChem 2010, 11, 1002–1005.
[23] a) S. Grimme, J. Antony, S. Ehrlich, H. Krieg, J. Chem. Phys. 2010, 132,
154104; b) S. Grimme, S. Ehrlich, L. Goerigk, J. Comput. Chem. 2011, 32,
1456–1465.
[24] T. Risthaus, S. Grimme, J. Chem. Theory Comput. 2013, 9, 1580–1591.
[25] C. A. Witham, P. Mauleón, N. D. Shapiro, B. D. Sherry, F. D. Toste, J. Am.
Chem. Soc. 2007, 129, 5838–5839.
[26] a) K. L. Vikse, M. P. Woods, J. S. McIndoe, Organometallics 2010, 29,
6615–6618; b) K. L. Vikse, Z. Ahmadi, C. C. Manning, D. A. Harrington,
J. S. McIndoe, Angew. Chem. 2011, 123, 8454–8456; Angew. Chem. Int.
Ed. 2011, 50, 8304–8306; c) K. L. Vikse, Z. Ahmadi, J. Luo, N. van der
Wal, K. Daze, N. Taylor, J. S. McIndoe, Int. J. Mass spectrom. 2012, 323–
324, 8–13.
[1] a) D. H. Ringger, P. Chen, Angew. Chem. 2013, 125, 4784–4787; Angew.
Chem. Int. Ed. 2013, 52, 4686–4689; b) G. Seidel, R. Mynott, A. Fꢂrstner,
Angew. Chem. 2009, 121, 2548–2551; Angew. Chem. Int. Ed. 2009, 48,
2510–2513; c) D. Benitez, N. D. Shapiro, E. Tkatchouk, Y. Wang, W. A.
Goddard, F. D. Toste, Nature Chem. 2009, 1, 482–486; d) A. M. Echavar-
ren, Nature Chem. 2009, 1, 431–433; e) A. S. K. Hashmi, Angew. Chem.
2008, 120, 6856–6858; Angew. Chem. Int. Ed. 2008, 47, 6754–6756.
[2] a) G. Seidel, B. Gabor, R. Goddard, B. Heggen, W. Thiel, A. Fꢂrstner,
Angew. Chem. 2014, 126, 898–901; Angew. Chem. Int. Ed. 2014, 53,
879–882; b) R. E. M. Brooner, R. A. Widenhoefer, Chem. Commun. 2014,
50, 2420–2423.
[3] a) E. S. Jimꢃnez-NfflÇez, A. M. Echavarren, Chem. Rev. 2008, 108, 3326–
3350; b) A. Fꢂrstner, L. Morency, Angew. Chem. 2008, 120, 5108–5111;
Angew. Chem. Int. Ed. 2008, 47, 5030–5033; c) W. Rao, M. J. Koh, D. Li,
H. Hirao, P. W. H. Chan, J. Am. Chem. Soc. 2013, 135, 7926–7932; d) P.
Nçsel, L. N. dos Santos Comprido, T. Lauterbach, M. Rudolph, F. Roming-
er, A. S. K. Hashmi, J. Am. Chem. Soc. 2013, 135, 15662–15666; e) E.
Merino, C. Nevado, CHIMIA 2013, 67, 663–668; f) E. Rettenmeier, A. M.
Schuster, M. Rudolph, F. Rominger, C. A. Gade, A. S. K. Hashmi, Angew.
Chem. 2013, 125, 5993–5997; Angew. Chem. Int. Ed. 2013, 52, 5880–
5884.
[27] The GC-FID was standardized by using independently prepared authen-
tic samples of 11 a. For more details, see the Supporting Information.
[28] DG was calculated from the measured rate constants by using the
Eyring equation and the calculated uncertainty corresponds to one
standard deviation.
[4] M. R. Fructos, T. R. Belderrain, P. de Frꢃmont, N. M. Scott, S. P. Nolan,
M. M. Díaz-Requejo, P. J. Pꢃrez, Angew. Chem. 2005, 117, 5418–5422;
Angew. Chem. Int. Ed. 2005, 44, 5284–5288.
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14280
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
[29] Plotting the six rate constants into an Eyring plot, the linear fit and
multiple regression analysis yielded the thermodynamic data, including
the one standard deviation error bands. For more details, see the Sup-
porting Information.
[30] a) A. G. Brenton, R. P. Morgan, J. H. Beynon, Annu. Rev. Phys. Chem.
1979, 30, 51–78; b) T. Baercor, P. Mayerfn, J. Am. Soc. Mass Spectrom.
1997, 8, 103–115.
[31] a) M. Alcarazo, T. Stork, A. Anoop, W. Thiel, A. Fꢂrstner, Angew. Chem.
2010, 122, 2596–2600; Angew. Chem. Int. Ed. 2010, 49, 2542–2546;
b) S. Fantasia, J. L. Petersen, H. Jacobsen, L. Cavallo, S. P. Nolan, Organo-
metallics 2007, 26, 5880–5889; c) D. Gatineau, J.-P. Goddard, V. Mouri›s-
Mansuy, L. Fensterbank, Isr. J. Chem. 2013, 53, 892–900.
[32] A difference in the activation barrier in solution versus gas phase results
from the differential solvation of the reactant and the transition states.
In agreement, we observe a decrease in DH for the carbene formation
transition state of ꢂ11 kcalmolꢁ1 in our solution phase measurements.
[33] a) Z. Wang, C. E. C. A. Hop, M.-S. Kim, S.-E. W. Huskey, T. A. Baillie, Z.
Guan, Rapid Commun. Mass Spectrom. 2003, 17, 81–86; b) N. Hu, P. Liu,
K. Jiang, Y. Zhou, Y. Pan, Rapid Commun. Mass Spectrom. 2008, 22,
2715–2722.
[37] R. G. Salomon, J. K. Kochi, J. Am. Chem. Soc. 1973, 95, 3300–3310.
[38] The relative rates of carbene formation were estimated by using the Ar-
rhenius equation and substituting Ea with the measured BDEs.
[39] a) M. J. Johansson, D. J. Gorin, S. T. Staben, F. D. Toste, J. Am. Chem. Soc.
2005, 127, 18002–18003; b) C. Obradors, A. M. Echavarren, Chem.
Commun. 2014, 50, 16–28.
[40] G. R. Fulmer, A. J. M. Miller, N. H. Sherden, H. E. Gottlieb, A. Nudelman,
B. M. Stoltz, J. E. Bercaw, K. I. Goldberg, Organometallics 2010, 29, 2176–
2179.
[41] Gaussian 09, Revision D.01, M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E.
Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Men-
nucci, G. A. Petersson, H. Nakatsuji, M. Caricato, X. Li, H. P. Hratchian,
A. F. Izmaylov, J. Bloino, G. Zheng, J. L. Sonnenberg, M. Hada, M. Ehara,
K. Toyota, R. Fukuda, J. Hasegawa, M. Ishida, T. Nakajima, Y. Honda, O.
Kitao, H. Nakai, T. Vreven, J. A. Montgomery, Jr., J. E. Peralta, F. Ogliaro,
M. Bearpark, J. J. Heyd, E. Brothers, K. N. Kudin, V. N. Staroverov, R. Ko-
bayashi, J. Normand, K. Raghavachari, A. Rendell, J. C. Burant, S. S. Iyen-
gar, J. Tomasi, M. Cossi, N. Rega, J. M. Millam, M. Klene, J. E. Knox, J. B.
Cross, V. Bakken, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,
O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. W. Ochterski, R. L. Martin,
K. Morokuma, V. G. Zakrzewski, G. A. Voth, P. Salvador, J. J. Dannenberg,
S. Dapprich, A. D. Daniels, Ö. Farkas, J. B. Foresman, J. V. Ortiz, J. Cio-
slowski, and D. J. Fox, Gaussian, Inc., Wallingford CT, 2009.
[34] S. Schmidt, G. Abkai, T. Rosendahl, F. Rominger, P. Hofmann, Organome-
tallics 2013, 32, 1044–1052.
[35] For the ESI-MS/MS pressurized infusion method the reaction mixtures
were heated by using an oil bath. To ensure a stable temperature
during the course of the GC-FID kinetic experiments, the reaction mix-
tures were heated in boiling solvents.
Received: June 16, 2014
[36] a) X. Dai, T. H. Warren, J. Am. Chem. Soc. 2004, 126, 10085–10094; b) W.
Baratta, A. Del Zotto, Chem. Commun. 1997, 2163–2164.
Published online on September 18, 2014
Chem. Eur. J. 2014, 20, 14270 – 14281
www.chemeurj.org
14281
ꢀ 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim