Monoaurated: Vs. diaurated intermediates: Causality or independence?

Article abstract of DOI:10.1039/c9sc05662a

Diaurated intermediates of gold-catalysed reactions have been a long-standing subject of debate. Although diaurated complexes were regarded as a drain of active monoaurated intermediates in catalytic cycles, they were also identified as the products of gold-gold cooperation in dual-activation reactions. This study shows investigation of intermediates in water addition to alkynes catalysed by [(IPr)Au(CH₃CN)(BF₄)]. Electrospray ionisation mass spectrometry (ESI-MS) allowed us to detect both monoaurated and diaurated complexes in this reaction. Infrared photodissociation spectra of the trapped complexes show that the structure of the intermediates corresponds to α-gold ketone intermediates protonated or aurated at the oxygen atom. Delayed reactant labelling experiments provided the half life of the intermediates in reaction of 1-phenylpropyne (～7 min) and the kinetic isotope effects for hydrogen introduction to the carbon atom (KIE ～ 4-6) and for the protodeauration (KIE ～ 2). The results suggest that the ESI-MS detected monoaurated and diaurated complexes report on species with a very similar or the same kinetics in solution. Kinetic analysis of the overall reaction showed that the reaction rate is first-order dependent on the concentration of the gold catalyst. Finally, all results are consistent with the reaction mechanism proceeding via monoaurated neutral α-gold ketone intermediates only.

Full text of DOI:10.1039/c9sc05662a

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Monoaurated vs. diaurated intermediates: causality
or independence?†
Cite this: DOI: 10.1039/c9sc05662a
Mariarosa Anania,a Lucie Jasıkova,a Jan Zelenka,b Elena Shcherbachenko,a Juraj Jasıka
All publication charges for this article
have been paid for by the Royal Society
of Chemistry
ˇ´
´
ˇ´
b
*
and Jana Roithova
´
Diaurated intermediates of gold-catalysed reactions have been a long-standing subject of debate. Although
diaurated complexes were regarded as a drain of active monoaurated intermediates in catalytic cycles, they
were also identified as the products of gold–gold cooperation in dual–activation reactions. This study
shows investigation of intermediates in water addition to alkynes catalysed by [(IPr)Au(CH3CN)(BF4)].
Electrospray ionisation mass spectrometry (ESI-MS) allowed us to detect both monoaurated and
diaurated complexes in this reaction. Infrared photodissociation spectra of the trapped complexes show
that the structure of the intermediates corresponds to a-gold ketone intermediates protonated or
aurated at the oxygen atom. Delayed reactant labelling experiments provided the half life of the
intermediates in reaction of 1-phenylpropyne (ꢀ7 min) and the kinetic isotope effects for hydrogen
introduction to the carbon atom (KIE ꢀ 4–6) and for the protodeauration (KIE ꢀ 2). The results suggest
that the ESI-MS detected monoaurated and diaurated complexes report on species with a very similar or
the same kinetics in solution. Kinetic analysis of the overall reaction showed that the reaction rate is first-
order dependent on the concentration of the gold catalyst. Finally, all results are consistent with the
reaction mechanism proceeding via monoaurated neutral a-gold ketone intermediates only.
Received 8th November 2019
Accepted 12th December 2019
DOI: 10.1039/c9sc05662a
rsc.li/chemical-science
pathways is complicated by a possible causality problem: dia-
Introduction
urated complexes B+ and X+ may be formed by a gold attach-
ment to the primary intermediates A, while the monoaurated
intermediates can be simultaneously formed by gold detach-
ment from either B+ or X+. Hence, the detection of either species
does not necessarily exclude alternative pathways.
We have developed a method for following the kinetics of
reaction intermediates in solution using mass spectrometry –
Delayed Reactant Labelling.9 This approach combines the
power of mass-spectrometry, in detecting minor species and in
analysing them individually, with the advantage of collecting
information on their solution kinetics. We used this method
here to monitor intermediates in a gold(I)-catalysed addition of
Gold cations have unique properties. They can act as large
protons, they can form strong bonds with carbon atoms, and
they strongly interact among themselves.1,2 All these properties
led to the current boom in the eld of gold catalysis.3 Mecha-
nisms of gold-catalysed reactions have been extensively
addressed.4 Gold-containing reaction intermediates have oen
been detected and characterised using several methods, such as
NMR, MS, or X-ray crystallography.5 However, the initial studies
indicated that some detected organogold complexes are not
necessarily the reactive intermediates, but rather off-cycle
species that react either sluggishly or not at all.6
Gold-catalysed nucleophile addition to alkynes was initially
postulated to proceed via monoaurated intermediates A that
can be trapped with another gold cation and form non-reactive,
geminally diaurated complexes X+ (Scheme 1).6 Conversely,
a subsequent study suggested that complexes X+ are not formed
by trapping A but rather in a dual activation pathway leading to
the primary diaurated intermediates B+, which can rearrange to
the geminal isomers X+.7,8 In fact, the analysis of these reaction
aDepartment of Organic Chemistry, Faculty of Science, Charles University, Hlavova
2030/8, 12843 Prague 2, Czech Republic
bInstitute for Molecules and Materials, Radboud University, Heyendaalseweg 135,
6525 AJ Nijmegen, Netherlands. E-mail: jana.roithova@ru.nl
Scheme 1 Intermediates in gold(I)-mediated nucleophile addition to
an alkyne. Red and blue code independent pathways to monoaurated
and diaurated intermediates, respectively.
† Electronic supplementary information (ESI) available: Supporting results
obtained by NMR, MS and DFT calculations. See DOI: 10.1039/c9sc05662a
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water to alkynes. This reaction was selected because both the ions detected by ESI-MS, we measured their helium tagging
monoaurated and diaurated complexes can be detected by infrared photodissociation (IRPD) spectra.12
electrospray ionisation mass spectrometry. We have supple-
The IRPD spectrum of monoaurated ions with m/z 719 shows
mented the obtained kinetic information on the intermediates the O–H stretching vibrations slightly above 3450 cmꢂ1 (Fig. 1).
with overall reaction kinetics measurements using gas chro- The inset shows a detail of the O–H stretching bands measured
matography approach. The obtained data give an answer to the with a maximum photon ux. We observe two O–H stretching
title dilemma for gold-catalysed water addition to alkynes.
bands, and the sum of their heights is higher than 0.9 that is,
more than 90% of the trapped ions have an OH group. These
ions are present as a mixture of isomers/conformers. The
position of the OH bands is consistent with the theoretically
predicted spectra of protonated a-gold ketones with R and R0
being methyl and phenyl or vice versa. The remaining <10% of
ions are probably gold complexes of the ketone products.
The lower wavenumber, nger-print region of the IRPD
spectrum is also consistent with the assignment of the detected
ions as protonated a-gold ketone intermediates. Especially, the
band at about 1560 cmꢂ1 (highlighted in red, in Fig. 1a) corre-
sponds to the C–C stretch of the central C]C bond. The C–O
stretching band should be found below 1400 cmꢂ1 among peaks
that mostly correspond to the vibrations of the IPr ligand. The
spectrum agrees well with the predicted IR spectrum of
protonated a-gold ketones, but it is not possible to distinguish
between the regioisomers of the intermediates (R and R0 being
methyl and phenyl or vice versa; see Fig. S25 in the ESI†).
The alternative assignment of the detected ions to the gold-
tagged ketone products can be excluded. The C]O stretching of
these ions would be expected in the range 1650–1700 cmꢂ1 and
the CO stretching band should have a large intensity (see the
spectrum of gold-tagged acetone in ref. 9c, in which the C]O
stretch is the dominant band at ꢀ1660 cmꢂ1). Probably, the
Results and discussion
One of the efficient gold catalysts for water addition to alkynes
is [Au(IPr)(CH3CN)(BF4)] (IPr ¼ 1,3-bis(2,6-diisopropylphenyl)
imidazol-2-ylidene).10 This catalyst forms digold hydroxide
([Au2(IPr)2(OH)]) in water (reaction (1)) which can be even iso-
lated upon addition of a base.11 Hence, next to the classical
activation of a substrate by cationic gold, we could expect
involvement of digold hydroxide.
KAu
*
in THF
Â
Ãþ
2½ðIPrÞAuꢁþ þ H2O )
ðIPrÞ Au2ðOHÞ þ Hþ
(1)
2
We have studied water addition to 3-hexyne and to 1-phe-
nylpropyne. Water addition to 3-hexyne yields only one product,
3-hexanone. 1-Phenylpropyne is transformed to either benzyl-
methylketone or ethylphenylketone in a 6 : 1 ratio (Fig. S1, S2
and Scheme S1 in the ESI†). Under our conditions (see below),
the reaction of 3-hexyne is rather fast – we can reach almost
complete conversion in about 1 hour. This is not convenient for
ESI-MS study, because the rapidly formed products interact
with the gold catalyst and form complexes with the same m/z
ratio as the monitored reaction intermediates. The reaction
with 1-phenylpropyne has suitable kinetics. Under our typical
conditions, we had about 10% conversion aer one hour at
room temperature (see the NMR kinetics in Fig. S2 in the ESI†).
Therefore, the reaction with 1-phenylpropyne is ideally suited
for monitoring reaction intermediates in a time span up to one
hour. We have also tested diphenylacetylene in the same reac-
tion. The hydration reaction was extremely slow and ESI-MS
detected only negligible signals of the aurated intermediates
(Fig. S12†). Hence, we continued the ESI-MS investigation with
1-phenylpropyne acknowledging the problem of dealing with
a mixture of regioisomers of the intermediates. For the
measurements of infrared spectra of the reaction intermediates,
we cooled the reaction down to ꢂ30 ꢃC in order to further
suppress the conversion to products.
Structure of the detected intermediates
Electrospray ionization mass spectra of the reaction mixture
with 1-phenylpropyne show signals corresponding to the mono-
and diaurated intermediates (Fig. S5†). The monoaurated
intermediate [Au(IPr)(PhCCCH3,OH)] (1) is detected in its
protonated form, i.e., 1H+ (m/z 719). This ion is isomeric with
a gold complex of the ketone product. The diaurated complex
([Au2(IPr)2(PhCCCH3,OH)]+, 2+) can have a structure of isomers
B+ or X+ in Scheme 1 (Nu ¼ OH), or it could be an isomer of B+ in
which a hydrogen atom migrated from the oxygen atom to the
Fig. 1 (a) IRPD spectrum of [Au(IPr)(PhCCCH3,OH)]H+ (m/z 719). The
insert shows the O–H stretching IR range measured with a high
photon flux. (b) Theoretical IR spectrum of the most stable isomer of
1H+ and its geometry parameters. Red colour highlights the important
bands corresponding to the characteristic bands found in the experi-
carbon atom (all m/z 1303). To assign the correct structures to mental spectrum.
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small peak at about 1680 cmꢂ1 indicates a minor abundance of
these gold-tagged products among the detected ions. However,
their co-detection should have only a negligible effect on the
kinetics associated with the intermediates which represent
more than 90% of the detected ions as the OH stretching bands
suggest (see above).
The DFT calculated structures of the protonated a-gold
ketone intermediates (1H+) suggest that the (Au–C–C) bonding
angle ranges between 82ꢃ and 90ꢃ, and the Au–C bonding length
˚
ranges from 2.21 to 2.24 A for different conformers and
regioisomers (Table S10, Fig. S23†). Hence, the detected ions
have a structure characterized by two mesomeric extremes: (1)
a gold complex of an enol and (2) protonated a-gold ketone. In
comparison to these ions, the (Au–C–C) angle in neutral inter-
mediate 1 is predicted to range from 102ꢃ to 106ꢃ, and the Au–C
˚
length is expected to range from 2.10 to 2.12 A (Table S10,
Fig. S23†). The values of the neutral intermediates imply that
the gold atom binds to an sp3 carbon atom and thus the neutral
intermediates can be assigned as a-gold ketones. We can
conclude that protonation occurring during electrospray ioni-
zation (see below) substantially weakens the Au–C bond and
Fig. 2 (a) IRPD spectrum of [Au2(IPr)2(PhCCCH3,OH)]+ (m/z 1303). The
blue colour highlights the additional band next to the bands originating
drives the geometry of the complex towards the enol form, as from vibration of the IPr ligand (compare with Fig. 1a). (b) Theoretical IR
spectrum of the most stable isomer of 2+ and its geometry parameters.
shown in Fig. 1a.13 In principle, this protonation mimics the
mechanism of protodeauration leading to the enol product of
the overall reaction.
Degradation of the intermediates in solution
An alternative explanation could involve 2-gold vinyl
alcohol intermediates (A in Scheme 1 with Nu ¼ OH). These
intermediates could be protonated during electrospray ioni-
zation at the carbon atom yielding also monourated proton-
ated complexes 1H+. However, DFT calculations suggest that
the enol form of the intermediates is 74 kJ molꢂ1 higher in
energy than the suggested a-gold keto-form (R ¼ R0 ¼ CH3, see
Fig. S24 in the ESI†). Hence, a fast tautomerization of the
initially formed enol-intermediates to the keto-intermediates
is expected. The suggested a-gold keto-form of the intermedi-
ates is also fully consistent with all other nding in this work
(see below).
The IRPD spectrum of the diaurated complexes (m/z 1303)
shows no O–H stretching band (Fig. 2) which means that
neither geminally diaurated complexes of the type X+, nor the
intermediates of the type B+ (Nu ¼ OH in Scheme 1) are
detected. Instead, the detected ions correspond to the inter-
mediates 2+ with one gold atom bonded to the carbon atom
and with the other gold atom bonded to the oxygen atom
shown in Fig. 2. The C–O stretching band is highlighted in
blue. This part of the composite band around 1500 cmꢂ1 does
not overlap with the vibrational bands originating from the IPr
ligand (compare with Fig. 1) and thus must correspond to the
C–O bond. The large red shi of the carbonyl vibration is in
agreement with DFT calculations. These calculations predict
that the Au–C–C bonding angle ranges from 99ꢃ to 101ꢃ and
Aer analysing the structure of the detected ions, we shied our
focus to the reaction kinetics associated with these intermedi-
ates in solution. The solution kinetics of the ESI-MS detected
species can be investigated by Delayed Reactant Labelling.9
Peak heights in an MS spectrum are unrelated to the concen-
trations of the given species in a solution. The concentrations
can be determined only by using internal isotopically labelled
standards. Obviously, such standards are unavailable for reac-
tion intermediates. Therefore, we formed the isotopically
labelled intermediates in situ with a time delay in relation to the
unlabelled intermediates, and we evaluated the relative evolu-
tion of the corresponding signals. The typical experiment began
by starting a reaction with unlabelled reactants (here: H2O, Ph–
CC–CH3, catalyst, solvent), which leads to a build-up of
a specic concentration of the unlabelled intermediates 1 and
2+. Aer a tD delay, an isotopically labelled reactant (here: Ph–
CC–CD3) was added to the reaction mixture. ESI-MS spectra of
this reaction mixture show the progression of the signals of the
unlabelled (1H+ and 2+) and labelled (D3-1H+ and D3-2+) reac-
tion intermediates reecting the relative changes in the
concentration of the intermediates in solution (Fig. 3).
The concentrations of intermediates in the steady state
equilibrium depend on the concentrations of the reactants. For
the conditions here, the equilibrium is reached aer about
40 min (the concentrations of the labelled and unlabelled
intermediates are about equal as the concentrations of Ph–CC–
CH3 and Ph–CC–CD3 are). The relative progression of the MS
signals of the labelled and unlabelled intermediates can be
tted using an exponential function derived from the steady-
state approximation for the intermediates (see the equation in
˚
a Au–C bonding distance is about ꢀ2.16 A (Table S10,
Fig. S23†). Hence, these geometry parameters fall between
those found for the neutral monoaurated intermediate 1 and
for its protonated ion 1H+ suggesting a substantial delocali-
sation of the p electrons, as shown by the mesomeric structures
in Fig. 2a.
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showed that 10.8 mol% TsOH in the reaction mixture
shortens the half-lives of the detected intermediates to
approximately 3 min.
We have also tried to detect the neutral monoaurated inter-
mediates 1 as adducts with sodium cations. Therefore, we
infused an acetone solution of NaSbF6 as a sheath liquid into
the ion source. Indeed, we detected [1(acetone)Na]+ ions, and
we were again able to follow the kinetics associated with 1 from
the unlabelled and labelled signals of the sodium complexes.
The [1(acetone)Na]+ signals were weak and only observable
under slightly harder ionisation conditions (Fig. S9†). The half-
lives determined from these experiments are: 1H+ (7.6 ꢄ
0.5) min, [1(acetone)Na]+ (7.0 ꢄ 0.4) min, and 2+ (6.6 ꢄ 0.3) min
(Table 1).
In addition, we have studied the reaction with D2O because
we wanted to assess possible kinetic isotope effects on the
degradation of the intermediates. The half-lives of the inter-
mediates detected as 1D+, [1(acetone)Na]+, and 2+ more than
doubled in the reaction with D2O, compared to the reaction
with H2O (Table 1). The corresponding kinetic isotope effects
are thus slightly above 2 (see Table 2). The values of the kinetic
isotope effects suggest that the degradations of the intermedi-
ates are connected to hydrogen/proton transfer and that the
mechanism is likely very similar or the same for all detected
species.
Fig.
3 Delayed reactant labelling method. (a) ESI-MS spectrum
recorded 5 and 45 min after adding PhCCCD3 to the reaction mixture
of PhCCCH3 with 5.4 mol% [Au(IPr)(CH3CN)(BF4)] in acetone/water
(5 : 1); the time-delay was 30 min. (b) Mutual time progression of the
integrated MS peak intensities of 1H+ and D3-1H+ (in red) and of 2+ and
D3-2+ (in blue). The solid lines are exponential fits of the relative
growth of the D3-1H+ and D3-2+ signals.
Fig. 3). The ts provide rate constants for the degradation (kdeg
)
and the half-life t1/2 ¼ ln(2)/kdeg of the intermediates in solution
(details can be found in the ESI† and in the ref. 9).
It should be noted that kinetics of complexes formed in a fast
equilibrium (t1/2 < 1 min), such as [(IPr)Au(PhCCCH3)]+ and
[(IPr)Au(PhCCCD3)]+ (in gray denoted by D0 and D3 in Fig. 3)
cannot be monitored by ESI-MS, because the equilibrium is
reached faster than the response of ESI-MS is. Hence, the signal
intensities show no mutual evolution. The same observation is
expected for complexes/ions formed as artefacts during the
electrospray ionisation. On contrary, the signals of product
complexes do show the evolution of the intensities, but they
never reach the steady-state concentrations in equilibrium with
the reactants (details are in the ref. 9). Therefore, we can exclude
that the signals of 1H+ and 2+ would originate from gold-tagging
of reaction products.
Table 2 Kinetic isotope effects in the formation and degradation of
the intermediates detected as [Au(IPr)(PhCCCH3,OH)]H+ (1H+), [Au2(-
IPr)2(PhCCCH3,HO)]+ (2+) and [Au(IPr)(acetone)(PhCCCH3,OH)]Na+
([1(acetone)Na]+)
Kinetic isotope effect 1H+
2+
[1(acetone)Na]+
Degradationa
Formationb
2.1 ꢄ 0.2
2.3 ꢄ 0.4 2.2 ꢄ 0.3
5.8 ꢄ 0.2 1.0 ꢄ 0.2 4.1 ꢄ 0.3 6.6 ꢄ 0.5
The half-life of the intermediate detected as 1H+ was
determined as (8.7 ꢄ 1.6) min, and the half-life of the inter-
mediate detected as diaurated 2+ was (6.9 ꢄ 1.0) min
(Table 1). The addition of an acid usually accelerates the
degradation of the organogold intermediates.14 Therefore, we
have assessed the effect of p-toluenesulfonic acid (TsOH) on
the half-lives of the intermediates detected here. The results
a
The solution of PhCCCD3 in acetone was added to the reaction mixture
of 1-phenylpropyne with 5.4 mol% [Au(IPr)(CH3CN)(BF4)] in acetone/
b
H2O (5 : 1) and in acetone/D2O (5 : 1).
H2O and D2O were
simultaneously added to the reaction mixture of 1-phenylpropyne with
5.4 mol% gold catalyst in acetone/(H2O + D2O) (5 : 1) (0.12 mmol
solution of NaSbF6 in 3 ml of acetone was infused as a sheath liquid
in the reaction mixture to trap neutral complexes in sodium cations).
Table 1 Half-lives of the intermediates detected as [Au(IPr)(PhCCCH3,OH)]H+ (1H+), [Au2(IPr)2(PhCCCH3,HO)]+ (2+) and [Au(IPr)(PhCCCH3,-
OH)(acetone)]Na+ ([1(acetone)Na]+) determined from Delayed Reactant Labelling experiments (the labelled reactant was PhCCCD3, and the time
delay was 30 min)
Additive/sheath
liquid
Nucleophile
1H+ t1/2 [min]
2+ t1/2 [min]
[1(acetone)Na]+ t1/2 [min]
H2Oa
H2Oa
H2Oa
D2Od
8.7 ꢄ 1.6
2.9 ꢄ 0.4
7.6 ꢄ 0.5
16.2 ꢄ 1.2
6.9 ꢄ 1.0
2.8 ꢄ 0.2
6.6 ꢄ 0.3
14.9 ꢄ 1.8
—
—
TsOHb
NaSbF6
NaSbF6
c
c
7.0 ꢄ 0.4
15.5 ꢄ 2.0
a
The solution of PhCCCD3 in acetone was added to the reaction mixture of 1-phenylpropyne with 5.4 mol% [Au(IPr)(CH3CN)(BF4)] in acetone/H2O
b
c
(5 : 1). 10.8 mol% p-toluenesulfonic acid was added to the reaction mixture. 0.12 mmol solution of NaSbF6 in 3 ml of acetone was infused as
a sheath liquid in the reaction mixture to trap neutral complexes in sodium cations. The solution of PhCCCD3 in acetone was added to the
d
reaction mixture of 1-phenylpropyne with 5.4 mol% [Au(IPr)(CH3CN)(BF4)] in acetone/D2O (5 : 1).
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intermediates at the oxygen atom. Accordingly, KIE1 ¼ 5.8 ꢄ 0.2
corresponds to the reaction pathway that leads to the introduc-
tion of H to the carbon-atom.
The sodium-tagged monoaurated complexes and the diau-
rated complexes have only one added hydrogen atom; therefore,
the dependence of H-2+/D-2+ and H-[1(acetone)Na]+/D-
[1(acetone)Na]+ on the H : D ratio can be tted using only one
KIE. The resulting kinetic isotope effects are 4.1 ꢄ 0.3 for the
formation of the diaurated complexes and 6.6 ꢄ 0.5 for the
formation of the sodiated monoaurated complexes.
Formation of the intermediates in solution
Aer collecting the data on the degradation of the intermedi-
ates, we gathered kinetic information on their formation. For
this purpose, we started the reactions in a mixture of H2O and
D2O (without any delay) and studied the ratios of H and D
incorporation into the intermediates detected as 1H+ and 2+
(Fig. 4). We performed the experiments with different ratios of
H2O vs. D2O to enable kinetic modelling and to improve the
accuracy of our results. The exact H : D ratio was determined
from the ratio of the [(IPr)2Au2(OH)]+ and [(IPr)2Au2(OD)]+
signals in the spectra.
The results again show that the kinetics associated with the
intermediates detected as diaurated complexes is slightly
different than that associated with the formation of the mon-
oaurated complexes. The values of the kinetic isotope effects
corresponds to the values expected for general-acid catalysed
processes in a mixture of H2O and D2O (KIE ꢀ 5).15 Hence, it is
consistent with concerted protonation/deprotonation of the
initially formed 2-gold vinyl alcohol intermediates (A or B+ in
Scheme 1 with Nu ¼ OH) to form the detected a-gold ketones.
In summary, the experiments with 1-phenylpropyne showed
that we can detect monoaurated and diaurated complexes by
ESI-MS with structures derived from neutral a-gold ketones
protonated or aurated at the oxygen atom. The kinetics associ-
ated with the formation and degradation of the intermediates in
solution detected as 1H+ or 2+ slightly differ and suggest that the
intermediates detected as 2+ have probably a higher turn-over
frequency. However, the results for the intermediates detected
as 1H+ and 2+ are not fundamentally different. The small
differences between the detected 1H+ and 2+ can be well
explained by other scenarios.16 Most relevantly, two possible
isomers (depending on R and R0) of only one type of the inter-
mediate might be present in solution and the detected differ-
ences might result from different capabilities of the isomers to
attach or detach the gold cation bound at the oxygen atom.
Hence, the results showed that the kinetics of the intermediates
in solution are very similar, but further experiments are
necessary to resolve whether only one type of the intermediates
is relevant in this reaction and which one it is.
The relative signal intensities of monoaurated complexes
(protonated a-gold ketones) depend on H : D ratios of the
hydrogen atoms at the a-carbon atom and at the oxygen atom.
This situation can be described by a simple kinetic scheme with
two rate constants k1 and k2 describing the introduction of each
hydrogen atom (Fig. 4, details of the model are in the ESI†).
Quantitatively, we can t only ratios of the isotopic mass-
spectrometry signals. It means that we tted kH1/kD1 and kH2
/
kD2; i.e., kinetic isotope effects for the introduction of the
hydrogen atoms to the a-carbon atom and to the oxygen atom,
respectively. An unconstrained t of the signal intensities of
H-1H+, (H-1D+ + D-1H+) and D-1D+ in dependence of the H : D
ratio provided the kinetic isotope effects KIE1 ¼ 5.8 ꢄ 0.2 and
KIE2 ¼ 1.0 ꢄ 0.2 (Fig. 4, see also Fig. S11 in ESI†).
Protonation/deprotonation reactions (or exchange of acidic
hydrogen atoms) are fast processes, therefore mass spec-
trometry detects protonated ions in equilibrium with the
concentrations of H+ and D+ in the solution. This is consistent
with the determination of the apparent kinetic isotope effect
KIE2 ¼ 1.0 ꢄ 0.2 for the protonation of the monoaurated
Experiments with a symmetric alkyne
In order to remove the ambiguity of working with isomers, we
have repeated the experiments with symmetric 3-hexyne. The
NMR experiments showed that the reaction is much faster than
that with 1-phenylpropyne (Fig. S3 and S4†). The ESI-MS exper-
iments detected monoaurated as well as diaurated complexes.
The kinetic proles of the complexes determined by delayed
reactant labelling experiments show that the detected complexes
are a mixture of intermediates and product complexes (see the
analysis in Fig. S14–S16†). More importantly, however, the
kinetics associated with both types of the complexes is identical
Fig. 4 Formation of intermediates detected as monoaurated and
diaurated complexes in the reaction of 1-phenylpropyne with
a mixture of H2O and D2O with variable H : D ratios (catalyst: 5.4 mol%
[Au(IPr)(CH3CN)(BF4)]). The ratio of “acidic” H and D (x-axis) was
determined from the ratio of [Au2(IPr)2(OH)]+ and [Au2(IPr)2(OD)]+ in within the experimental noise. This implies that the monoau-
each experiment. The graphs show the relative abundances of (a) H-
rated and diaurated ions detected by ESI-MS report on only one
species present in solution. We have further investigated the
kinetics of the overall reaction by gas chromatography.
Firstly, we have determined rate constants for the product
formation in dependence of the p-toluenesulfonic acid (TsOH)
AH+ (circles) vs. D-AH+ + H-AD+ (triangles), and vs. D-AD+ (squares)
and (b) H-B+ (blue circles) vs. D-B+ (blue squares) and H-[A(acetone)
Na]+ (violet circles) vs. D-[A(acetone)Na]+ (violet squares). The
experimental results were fitted with kinetic equations shown below
the graphs.
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concentration did not increase the overall rate (Fig. 5a). The rate
constant increased three-fold which is in a very good agreement
with a three-fold increase of the degradation rate of monoau-
rated as well as diaurated intermediates in the reaction of 1-
phenylpropyne described above (Table 1). Hence, we have
concluded that the addition of 4 or more equivalents of the acid
with respect to the concentration of the gold catalyst results in
a situation that protodeauration step is not anymore the rate
determining step.
Next, we have investigated the dependence of the kinetics of
the product formation on the concentration of the gold catalyst.
In the regime with a large excess of the TsOH acid, the rate
depended linearly on the concentration of [Au(IPr)(CH3-
CN)(BF4)] (Fig. 5c). This clearly suggests that the product is
formed in the reaction mechanism involving a single gold
cation. The negligible role of (di)gold hydroxide in the reaction
under these conditions is also expected from the effect of the
acid on the eqn (1).
Without the addition of TsOH, the rate dependence on the
concentration of the gold catalyst shows an initial phase with
very small rates, but with the concentration of the gold catalyst
above 2 mol%, the rate started to increase linearly (Fig. 5b). We
have tested this linear dependence by a small addition of
sodium hydroxide (1.12 mol%) and of TsOH (1.12 mol%),
respectively. The rate dependence on the concentration of the
gold catalyst was almost exactly the same as without the addi-
tives, but the lag phase was larger when NaOH was added and
smaller when TsOH was added (compare red, blue, and green
data in Fig. 5b). These results suggest that the lag phase is
associated with the lack of available protons in the reaction
mixture. We suspected that a glassware, silica capillary or other
experimental circumstances might affect the reaction rate at
small concentrations of the catalyst. To test this hypothesis, we
repeated the experiment in a plastic vial and the lag phase was
indeed somewhat smaller (Fig. S22 and details in the ESI†).
The results clearly show that the basic conditions suspend
the overall reaction rate (eqn (2)).17 Firstly, a base shis the
equilibrium of the reaction (1) to the right converting the gold
catalyst to the digold hydroxide complex that most probably
does not catalyse this reaction. Secondly, a base impairs the
protodeauration step. The accounting of this “background
Fig. 5 Rate of the ketone product formation in the reaction of 3-
hexyne (27.6 mM in 5 : 1 mixture of THF and H2O, respectively) with
water catalysed by [Au(IPr)(CH3CN)(BF4)]. (a) Dependence of the rate
on the concentration of p-toluenesulfonic acid (TsOH). The experi-
ment was done with 1.12 mol% of the catalyst. (b) Dependence of the
reaction rate on the concentration of the catalyst under the standard
conditions (in red) and with addition of 1.12 mol% of NaOH (blue) or
1.12 mol% TsOH (green). The lines are bimodal linear fits of the data. (c)
Dependence of the reaction rate on the concentration of the catalyst
under the standard conditions with addition of 4 equiv. (purple) and 8
equiv. (yellow) of TsOH with respect to the concentration of the
catalyst. The red, blue, and green lines are fits from (b). (d) Dependence
of the reaction rate on the concentration of the catalyst under the
standard conditions with addition of 1 equiv. of TsOH (blue solid
circles). The other solid lines are experiments from (b) and (c).
concentration. Indeed, we observed that the rate linearly
increases up to the concentration of TsOH being double of the
concentration of the gold catalyst. Further increase of the TsOH
Scheme 2 Reaction pathway for [(IPr)Au]+ mediated hydration of alkynes. The ESI-MS experiments revealed that the detected monoaurated and
diaurated complexes report on the identical intermediate in solution, a-gold ketone. Small differences in the measured kinetics are most
probably associated R and R0. The GC kinetic experiments showed that the rate of the formation of the product depends on the first order of the
gold catalyst concentration.
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base” effect at low concentrations of the catalyst is important, the concentration of the gold catalyst. The reaction is acceler-
because the rate dependence on the gold catalyst concentration ated by addition of an acid which correlates with the observed
could be incorrectly denoted as quadratic, especially if a smaller acceleration of degradation (protodeauration) of the ESI-MS
range of concentrations is explored (see Fig. 5b) or when the detected intermediates. In the absence of an acid, we
reaction is conducted in an intermediate regime e.g., with 1 observed a lag in reactivity at small catalyst concentrations, but
equiv. of added acid (Fig. 5d).
at larger concentrations the rate dependence on the catalyst
In summary, the kinetic experiments suggest that the reac- concentration was again linear. All these kinetic data clearly
tion rate is rst-order dependent on the gold catalyst concen- point towards reaction mechanism involving only monoaurated
tration. Adding of a base and thus promoting of the formation intermediates.
of digold hydroxide leads to suspending of the reaction rate. On
the other hand, adding of an acid increases the reaction rate,
because it accelerates the rate-determining step – proto-
Experimental
deauration. However, for the acid concentrations exceeding the The electrospray ionization mass spectra were measured with
concentration of the gold catalyst, the reaction rate is not a TSQ 7000 mass spectrometer or an LTQ linear ion trap
anymore dependent of the concentration of the acid. This instruments.19 The ions were generated from reaction mixtures
suggests that protodeauration is not the rate-determining step of 1-phenylpropyne with 5.4 mol% [Au(IPr)(CH3CN)(BF4)] in
under these acidic conditions, but instead the deprotonation of acetone/water (5 : 1) at so ionization (low potentials on the
the initial adduct between the gold-activated alkyne and water entrance ion optics and the temperature of the capillary was 200
becomes the rate-determining step. All these results are ꢃC). Compositions of all investigated reaction mixtures and MS/
consistent with the reaction mechanism involving just a single MS analysis of the selected ions can be found in the ESI.†
gold-cation as an active catalyst and the reaction pathway Details of kinetic analysis as well as derivation of the kinetic
shown in Scheme 2.
equations used can be also found in the ESI.†
The infrared photodissociation spectra were measured with
the ISORI instrument.20 ISORI is based on the combination of
a low-temperature ion trap with a commercial TSQ 7000
Conclusions
Gold(I) ([Au(IPr)(CH3CN)(BF4)]) catalysed water addition to instrument. It preserves the same ionization chamber (here the
alkynes proceeds most likely via monoaurated intermediates. electrospray ionization is used in exactly the same way as for the
We have shown that these intermediates are neutral in solution other MS experiments). The generated ions are mass-selected by
and can be detected by electrospray ionization mass spec- quadrupole and guided by a quadrupole bender and octopole to
trometry either as protonated complexes or tagged with another an ion trap. The trap has a linear quadrupole geometry and
gold cation. The structures of the detected complexes corre- operates at 3.4–3.6 K and at 1 Hz. Trapping and cooling of the
spond to a-gold ketones protonated or aurated at the oxygen ions is achieved by collisions with a helium buffer gas (rst 300
atom. Exploratory DFT calculations suggest the a-gold ketone ms of the trapping cycle). About 1–3% of the ions form helium-
intermediates are more than 70 kJ molꢂ1 more stable than the tagged complexes. The ions were irradiated during the 300–990
alternative, probably primarily formed 2-gold vinyl alcohol ms time interval (10 Hz repetition rate, OPO/OPA system from
intermediates.18
LaserVision pumped by Nd:YAG laser Surelite EX from
Kinetic experiments with the intermediates in the water Continuum, tuning range 700–4700 cmꢂ1, FWHM ꢀ 1.5 cmꢂ1
,
addition to 1-phenylpropyne showed differences in the forma- 10 ns pulse length). At 990 ms, the ions were extracted, mass-
tion and the degradation of the ESI-MS detected monoaurated analyzed by a second quadrupole and detected by a Daly type
and diaurated complexes. However, these differences are most detector operated in the ion-counting mode. The IRPD spec-
likely caused by different selectivities in protonation and aura- trum is constructed as wavenumber-dependent (1 ꢂ N(ni)/N0),
tion of the two possible isomers of the neutral a-gold ketone where N(ni) is the number of helium complexes surviving irra-
intermediates. In agreement, the differences in kinetics van- diation at the ni wavenumber and N0 is the total number of
ished, when we did the experiments with symmetric 3-hexyne helium complexes (obtained in the alternative cycles with
reactant. The results for the reaction involving 1-phenylpropyne a photon beam blocked by a mechanical shutter).
showed that the half-life of the neutral monoaurated interme-
Gas chromatography was performed with a Shimadzu GC-
diates in solution is on the order of 7 min. The protodeauration 2010 Plus instrument with split/splitless injection and
of the a-gold ketone intermediates is associated with the kinetic a ame-ionization detector. H2 was used as carrier gas at
isotope effect of about 2. The kinetic isotope effect for the a constant linear velocity of 40 cm sꢂ1. The total ow was 38.4
hydrogen introduction to the gold-bonded carbon atom is mL minꢂ1 and the column ow 1.42 mL minꢂ1. Compounds
isomer-dependent and is in the range of 4–6. These values are were separated on a 30 m ꢅ 0.25 mm AB-5MS capillary column
consistent with kinetic isotope effects expected for general-acid (5% phenyl/95% dimethyl polysiloxane). The injection port was
mediated reactions in H2O/D2O.15 Hence, it is in accordance held at 300 C and used in split mode with a split ratio of 2ꢂ51.
ꢃ
with the scenario of keto–enol tautomerisation of the initially The oven temperature started at 50 ꢃC, increasing 10 ꢃC min
formed 2-gold vinyl alcohol intermediates.
The overall reaction kinetics of water addition to symmetric 80 C min up to 250 C. The total time for one GC run was
3-hexyne revealed that the reaction is rst-order dependent on 6.88 min. The FID temperature was 300 C. The exact reaction
up to 100 ꢃC. The temperature was then set to increase
ꢂ1
ꢃ
ꢃ
ꢃ
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mixtures compositions and all measure data can be found in
the ESI (Tables S5–S9 and Fig. S17–S22†).
Chem. Soc., 2017, 139, 10302; (i) M. Lu, Y. Su, P. Zhao,
X. Ye, Y. Cai, X. Shi, E. Masson, F. Li, J. L. Campbell and
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Density functional theory (DFT) calculations have been per-
formed with the mPW1PW91 density functional21 and with the
LanL2DZ basis set for the gold atoms and the cc-pVDZ basis set
for the remaining elements as implemented in Gaussian 09.22
The geometries were fully optimized and the results were
controlled by Hessian matrix calculations. The computed
¨
¨
5 (a) A. S. K. Hashmi, I. Braun, P. Nosel, J. Schadlich,
M. Wieteck, M. Rudolph and F. Rominger, Angew. Chem.,
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¨
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´
´
vibrational frequencies were scaled by 0.97 in the nger-print
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.
The nal IR
9,23,24
spectra were convoluted with a Gaussian function with a full
width at half maximum of 3 cmꢂ1. The optimized geometries,
energies, and IR spectra are in the ESI (Tables S10 and S11,
Fig. S23–S26†).
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6 (a) G. Seidel, C. W. Lehmann and A. Furstner, Angew. Chem.,
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Conflicts of interest
There are no conicts to declare.
7 (a) J. Roithova, S. Jankova, L. Jasikova, J. Vana and
S. Hybelbauerova, Angew. Chem., Int. Ed., 2012, 51, 8378;
(b) Y. Oonishi, A. Gomez-Suarez, A. R. Martin and
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Acknowledgements
The project was funded by the European Research Council (ERC
CoG No. 682275).
´
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A.
Gomez-Suarez,
Y.
Oonishi,
A.
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Martin,
S. V. C. Vummaleti, D. J. Nelson, D. B. Cordes,
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8 The dual activation pathway was recently supported by
examples of cooperation of different metals: (a) F. Lazreg,
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