Individual steps of the Mizoroki-Heck reaction and intrinsic reactivity of intermediate organopalladium complexes studied in the gas phase

Article abstract of DOI:10.1255/ejms.1310

The mechanism of the Mizoroki-Heck reaction (MHR) was analyzed by collision-induced dissociation (CID) tandem-mass spectrometry and gas-phase ion/molecule reactions (IMRs) as well as by DFT computational analysis. The MHR was performed in the gas phase and the intrinsic reactivity of important intermediates was examined individually. Kinetics and substituent effects of cationic palladium-PCy3-aryl complexes (Cy = cyclohexyl) with 2,3-dimethylbutadiene in the MHR were analyzed via IMRs and CID. The kinetics and ion structures of the species involved in the olefin insertion, i.e., the carbopalladation, were investigated. Moreover, linear free-energy correlations were applied and a concerted mechanism proceeding via a four-membered transition state for the carbopalladation step that exhibited only a minor charge separation was deduced.

Full text of DOI:10.1255/ejms.1310

L. Fiebig et al., Eur. J. Mass Spectrom. 21, 623–633 (2015)
623
Received: 8 December 2014
n
Revised: 6 February 2015 n Accepted: 10 February 2015 n Publication: 13 March 2015
EUROPEAN
JOURNAL
OF
MASS
SPECTROMETRY
Special Issue Celebrating the 20th Anniversary of EJMS—European Journal of Mass Spectrometry
Individual steps of the Mizoroki–Heck
reaction and intrinsic reactivity of
intermediate organopalladium complexes
studied in the gas phase
Lukas Fiebig,a* Joseph Held,b Hans-Günther Schmalza and Mathias Schäfera*
aDepartment of Chemistry, Institute of Organic Chemistry, University of Cologne, Greinstraße 4, 50939 Köln, Germany.
E-mail: lukas.fiebig@uni-koeln.de, mathias.schäfer@uni-koeln.de
bDepartment of Chemistry, Institute of Theoretical Chemistry, University of Cologne, Greinstraße 4, 50939 Köln, Germany
The mechanism of the Mizoroki–Heck reaction (MHR) was analyzed by collision-induced dissociation (CID) tandem-mass spectrometry
and gas-phase ion/molecule reactions (IMRs) as well as by DFT computational analysis. The MHR was performed in the gas phase and
the intrinsic reactivity of important intermediates was examined individually. Kinetics and substituent effects of cationic palladium-
PCy3-aryl complexes (Cy = cyclohexyl) with 2,3-dimethylbutadiene in the MHR were analyzed via IMRs and CID. The kinetics and ion
structures of the species involved in the olefin insertion, i.e., the carbopalladation, were investigated. Moreover, linear free-energy
correlations were applied and a concerted mechanism proceeding via a four-membered transition state for the carbopalladation step
that exhibited only a minor charge separation was deduced.
Keywords: gas-phase Mizoroki-Heck reaction, ion molecule reactions, Hammett relation, reaction mechanism
Introduction
Palladium-catalyzed coupling reactions, such as the Mizoroki– (Scheme 2).5–9 Initially, the aryl substrate and an (in situ formed)
Heck reaction (MHR) are extremely valuable synthetic tools
Pd(0) species undergo an oxidative addition (step I) that yields
an intermediate Pd(ii) aryl complex of the type [Pd(phosphine)
in modern organic chemistry.1 In the initial studies reported
by Mizoroki, Heck, and co-workers, aryl triflates or aryl halo- (Ar)(I)] and [Pd(phosphine)(Ar)(S)]+I–, respectively (S = solvent
genides were coupled with olefins in the presence of a palla- molecule). In the subsequent carbopalladation step, the Pd
dium(0) catalyst and a base (Scheme 1).2–4
aryl complex reacts with the olefin in a syn-insertion leading to
a s-Pd-alkyl complex (step II). Subsequent b-Pd hydride elimi-
nation (step III) yields the linear or branched coupling product
and a Pd–H complex that is finally transformed into the Pd(0)
starting complex by a base-mediated reductive elimination
(step IV).
The elementary steps of the MHR are widely accepted
and are similarly in both a neutral or an ionic catalytic cycle
Detailed kinetic analyses of the MHR revealed that the
rate-determining step strongly depends on the electronic
and steric properties of the reactants. However, many
Scheme 1. Pd(0)-catalyzed MHR.
ISSN: 1469-0667
doi: 10.1255/ejms.1310
© IM Publications LLP 2015
All rights reserved

624
Mizoroki–Heck Reaction Steps and Reactivity of Organopalladium Complexes in the Gas Phase
Scheme 2. Postulated neutral and ionic catalytic cycle of the MHR (S = solvent, Ar-X = aryl halide).5–9
studies consistently found that the oxidative addition of aryl
triflates and aryl iodides is usually fast and therefore not rate
limiting.8,10–13 Hence, in the MHR of these aryl substrates one
of the subsequent steps is the slowest of the reaction, i.e. the
reaction solution into the ESI-MS instrument and thereby the
monitoring and characterization of ionic reaction intermedi-
ates and products formed during the reaction.22–25 Especially,
the ionic catalytic cycle of the MHR is very suitable for an
kinetic bottleneck (Scheme 3). Extensive experimental inves- online-ESI-MS analysis, as a number of studies document. It
tigations suggest that either the olefin coordination, the olefin
insertion,11,12,14,15 or even the b-hydride elimination16,17 can
determine the overall reaction rate. However, an individual
was possible to study key intermediates of Mizoroki–Heck type
reactions,26 those of the Heck–Matsuda reactions (coupling
of arene diazonium salts with olefins),27,28 the tandem-Heck
examination of the carbopalladation or the b-hydride elimina- lactonizations,29 oxyarylations (Oxa–Heck),30 and the dehydro-
tion remains difficult as these reaction steps follow the oxida- genative MHR.31
tive addition.
Once transferred into the gas phase, collision-induced
The elucidation of reaction mechanisms governed by homo- dissociation (CID) experiments of the reaction intermedi-
geneous catalysts is a complex analytical problem, but elec- ates can afford characteristic fragmentation patterns that
trospray ionization mass spectrometry (ESI-MS)18–20 combined
with tandem mass spectrometry (MS/MS)21 proved to be a
powerful and versatile approach to transfer even labile and
reactive species from complex reaction solutions into the
gas phase for further analysis. This strategy benefits from
the facile coupling of a microreactor or a reflux apparatus to
the mass spectrometer allowing a continuous infusion of the
contain valuable pieces of information often enabling struc-
tural analysis. Furthermore, ion/molecule reactions (IMRs)
between stored ions and neutral reagents infused into the
buffer gas flow of the ion trap can be performed in an ion trap
mass spectrometer.32–34 In doing so, intrinsic structure–reac-
tivity relationships of the ionic reaction intermediates can be
studied in vacuo without the influence of solvent molecules
R
L
L
L
L
L
L
II
X
Pd
Pd
Pd
R
H
Ar
Ar
X
S
olefin
olef in insertion
(carbopalladation)
Ar
S
coordination
R
X
H
H
C-C-rotation
decomplexation
S
syn-ß-Pd-H-
elimination
L
L
L
L
L
L
II
Pd
Pd
Ar
X
Pd
H
H
H
R
S
R
R
H
Ar
X
X
Ar
H
Scheme 3. Stepwise C(sp2)-C(sp2) coupling following the ionic MHR mechanism, including olefin coordination, olefin insertion, and
syn-b-H-elimination (formation of the linear coupling product) (S = solvent, Ar = aryl moiety, X = halide).

L. Fiebig et al., Eur. J. Mass Spectrom. 21, 623–633 (2015)
625
Scheme 4. Oxidative addition of aryl iodides 1 and Pd(0) and transfer of complex ions 2 and 3·MeCN into the gas phase via (+)ESI-MS.
The complex ions [Pd(PCy3)(Ar)]+ (3) and [P(Ar)Cy3]+ (4) represent CID and ESI fragments of 3•MeCN and 2, respectively (see Figure S3,
SI; Cy = cyclohexyl)).
and counter ions, as numerous studies document.32,35–37 This
is particularly useful if the intermediates of interest tend to
form complex equilibria and aggregates in solution, which is
analysis, diluted solutions of the in situ formed aryl palladium
complex ions 2 and 3•MeCN were infused into the ion source
via a syringe pump (flow rate 5µL min–1, ESI heater tempera-
often the case in organometallic catalysis. Gas-phase IMRs, ture 50°C, capillary temperature 275°C). Typical spray volt-
for instance, allow us to investigate the nature of the coordi- ages were 3.0–3.5kV. Stable spray conditions were achieved by
nation sphere of organometallic complexes,38–41 to screen the
reactivity of potential catalysts in polymerization reactions,42,43
or to examine complete transition-metal catalytic cycles.44,45
Herein, we report a stepwise examination of the MHR
between aryl iodides and 2,3-dimethylbutadiene (DMB). After
solution-phase in situ preparation, the intermediate Pd aryl
complex ions [Pd(PCy3)(Ar)]+ were reacted with DMB under
the use of sheath and sweep gases (≥99.999% N2).
MSn experiments (collision gas helium, ≥99.999% He) were
conducted in the linear ion trap with a collision energy adjusted
to achieve extensive fragmentation.49–51 Exact ion masses
were measured in the Orbitrap analyzer [RFWHM = 30.000
(FWHM = full width at half height)], which was externally
calibrated with caffeine, trileucine, and thymopentin before
well-defined conditions in the gas phase (Cy = cyclohexyl). and after each measurement. The sum formulas of all the
The use of the P(Cy3) ligand and DMB in the gas phase allows
us to investigate the kinetics and substituent effects of the
presented ion structures were consistent with the experi-
mentally determined ion masses (Δm ≤ 3 ppm) and match
carbopalladation and b-hydride elimination reaction steps. the calculated isotope distributions (e.g., see Figure 1). Data
Especially, the selection of the P(Cy3) ligand excludes aryl
moiety scrambling processes in the respective [Pd(PCy3)
(Ar)]+, which substantially complicate such experiments in
the presence of triphenylphosphine ligands.46 Additionally,
the symmetric molecule DMB offers only olefinic protons on
carbons 1 and 4 for the b-hydride elimination reaction, which
exclusively leads to the linear MHR product with the formation
acquisition was performed with the Thermo Fisher LTQ Tune
Plus software. For data processing and analysis the Thermo
Fisher software Xcalibur 2.1.0 was used.
Oxidative addition of iodides and Pd(0)
In a flame-dried and argon-flushed Schlenk flask the respec-
tive iodide 1 (0.02mmol, 1.0equiv.), bis(dibenzylideneacetone)
of the branched regioisomer (see Schemes 1 and 5) excluded. palladium (23.0 mg, 0.04 mmol, 2.0 equiv.), and tricyclohex-
The identity of IMR product ions as well as all other relevant ylphosphane (0.04mmol, 11.2mg, 2.0equiv.) were suspended
ions is reliably confirmed by accurate mass measurements, in dry acetonitrile (8 mL) under an argon atmosphere. The
MS/MS and density functional calculations.
resulting solution was stirred at room temperature under an
inert-gas atmosphere until oxidative addition, i.e. the forma-
tion of the complex ions 2, 3, and 3•MeCN were observed in
the (+)ESI mass spectrum (0.5–4h).
Experimental section
Mass spectrometry
IMRs and determination of second-order
rate constants
All MSn experiments and gas-phase IMRs were performed on
an LTQ Orbitrap hybrid instrument (Thermo Fisher, Bremen, IMRs were performed inside the LTQ part of the mass spec-
Germany) equipped with a heated electrospray ionization
source, linear ion trap, octapole collision cell, and an Orbitrap
mass analyzer47,48 capable of measurements with a high mass
accuracy and an elevated resolving power. For (+)ESI-MS
trometer. To this end, the helium buffer-gas supply of the
LTQ was modified according to Gronert,32,52 O’Hair and
co-workers,33,44 and Harman and Blanksby,34 as described in
detail elsewhere.45,46 In brief, neutral reagents were injected

626
Mizoroki–Heck Reaction Steps and Reactivity of Organopalladium Complexes in the Gas Phase
Figure 1. Schematic view of the modified helium buffer-gas supply to a LTQ Orbitrap hybrid mass spectrometer that allows the
quantity-controlled introduction of neutral reagents into the linear ion trap. Illustration reproduced and modified with the kind
permission of the manufacturer.45,46
into the LTQ helium flow via a septum using a pump-driven
For the gas-phase carbopalladation reactions, DMB was
syringe (Figure 1). An open-split gas-flow divider that regu- introduced into the helium flow and reacted with Pd complex
lates the LTQ default pressure was replaced by a fused-silica
restriction capillary (inner diameter 0.2mm, length 25cm) to
prevent leakage of the gas mixture into the environment. As
a consequence, the LTQ pressure was adjusted to the default
trap pressure manually. Complete evaporation of the neutral
ions [Pd(PCy3)(Ar)]+ (3) isolated and stored in the ion trap
(isolation width 8 Da). Kinetics of the olefin insertion were
determined at reaction times of 0.03–20 ms. The reported
rate constants are the averages of four independent meas-
urements at different flow rates of DMB (0.5–1.0 µL min–1)
reagents was assured by heating of the gas flow with an elec- and of helium (195–215 sl h–1). Prior to each experiment,
tric tape wrapped around the stainless steel helium capillary
(ca. 130°C). To determine the molar neutral reagent/helium
ratio, the flow rates of both the neutral reagent and the helium
a delay time, typically of 10−20 min, was kept to ensure
constant-concentration conditions of neutral reagents inside
the ion trap (i.e., no observable change of the precursor ion/
were measured, the latter using a Swagelok gas-flow meter. product ion ratio at a specific reaction time). Further details
The experimental setup was validated using the gas-phase
nucleophilic substitution of a bromide anion and methyl iodide
and d3-methyl iodide, respectively, as a test reaction.34,44,53
regarding the determination of second-order rate constants
are given in the Supplementary Information (Figures S1 and
S2).
Figure 2. (+)ESI-MS spectrum of a reaction mixture of p-iodotoluene (1b, 1.0equiv.), Pd(dba)2 (2.0equiv.), and PCy3 (2.0equiv.) in
acetonitrile at room temperature under an inert gas atmosphere (inset: the theoretical isotopic distribution of [Pd(PCy3)(p-Tol)]+, 3b, is
compared to the experimental isotopic pattern to document the consistency).

L. Fiebig et al., Eur. J. Mass Spectrom. 21, 623–633 (2015)
627
Figure 3. IMR of the Pd complex ion 3b and DMB (5). The precursor ion is marked with an asterisk (isolation window 8Da, ca. 1011
molecules DMB versus 104 ions in the LTQ).32,45,46
All IMRs were performed without the application of addi- imaginary frequencies), vibrational frequencies were calcu-
tional collision-activation energy. Experimental and theoret- lated using the same functional and basis set as used for the
ical data evidence that ions stored in quadrupole ion traps
(QITs) were effectively thermalized by multiple collisions with
the surrounding buffer-gas atoms. Therefore, the stored ions
exhibited a Boltzmann energy distribution because the rapid
energy exchange between the stored ions and the buffer gas
outperformed the impact of the electric quadrupole field on
the internal energy of the ions.32,54 The effective temperatures
of ions stored in QIT instruments at room temperature are
geometry optimizations.
Results and discussion
To gain access to ionic Pd aryl complexes, the aryl iodides
1a were reacted with Pd(dba)2 (dba = dibenzylideneacetone)
and PCy3 in acetonitrile (Scheme 5). (+)ESI-MS analysis of the
in the range of 300–340K.52,55 As a result, the ion trap envi- reaction mixture showed the ionic products of the oxidative
ronment is perfectly suitable for the investigation of quasi- addition, i.e. the complex ions 2, 3, and 3•MeCN, after 2.5–4
thermal IMR.
h (Figure 1). According to the literature58–60 and to previous
studies in our group,46 the Pd complexes [Pd(PCy3)2(Ar)]
I und [Pd(PCy3)(MeCN)(Ar)]I are formed in solution under
these reaction conditions. During the ESI process, the loss
of iodide yields the observed ionic complexes 2 and 3·MeCN.
The detected ions 3 and 4 represent in-source fragments
of 3•MeCN and 2, respectively, and their formation is also
observed in the CID spectra of 3•MeCN and 2 (Figures S3).
Quantum chemical calculations
Theoretical calculations were carried out using the
TURBOMOLE 6.6 program package.56 For each of the ions
3a•DMB, 6a, and 7•(Ph)DMB, a range of conformations was
considered (data not shown). The most stable conformers we
identified are shown in Figure 3. All the reported geometries
were optimized at the DFT level of theory using the BP86 func- The product-ion spectrum of [Pd(PCy3)(Ar)]+ (3) is character-
tional. The cc-pVTZ basis set was used for carbon, hydrogen, ized by the extensive fragmentation of the phosphine ligand,
and phosphorus. The Stuttgart–Koeln MCDHF RSC ECP57
basis set was used for palladium. To identify the optimized
geometries as local minima of the potential energy surface (no
including the neutral losses of cyclohexene (C6H10) and
cyclohexane (C6H12), as well as the reductive elimination of
Pd(0), to yield the phosphonium ion [P(Ar)Cy3]+ (4). The latter
Scheme 5. Gas-phase carbopalladation via IMR followed by b-hydride elimination induced upon CID. The corresponding MHR products
are observed as neutral loss in the CID spectra of complex ions 6a–6i.

628
Mizoroki–Heck Reaction Steps and Reactivity of Organopalladium Complexes in the Gas Phase
Figure 4. MS3 product ion experiment of complex ion 6b. The precursor ion is marked with an asterisk and was isolated
monoisotopically.
dissociates by subsequently losing three cyclohexene units
(Figure S4).
precursor ion and is accompanied by a minor fragmentation
reaction to the phosphonium ion 4 [Figure S4(a)].
The Pd complex ions 2, 3, and 3•MeCN were isolated in the
linear ion trap part of the instrument and were allowed to react
with DMB (5) in the gas phase. However, only the complex ions
[Pd(PCy3)(Ar)]+ (3) reacted with DMB under the formation of
product ions 6, as Figure 4 illustrates. This IMR proceeds with
a mass increase of 82Da (C6H10) relative to the corresponding
Individual CID experiments of all nine IMR products 6a–6i
led to the formation of a common and characteristic product
ion at m/z 387, matching the Pd hydrido complex [Pd(PCy3)
(H)]+ (7). This ionic product indicates the release of the C–C
coupling product; in the exemplary case shown in Figure 5,
the para-tolyl-substituted DMB 8b (see also Scheme 5). The
Figure 5. Calculated relative electronic energies for the stepwise carbopalladation and b-H elimination (DFT level of theory using the
BP86 functional in a Stuttgart–Koeln MCDHF RSC ECP//cc-pVTZ basis).

L. Fiebig et al., Eur. J. Mass Spectrom. 21, 623–633 (2015)
629
Scheme 6. Supposed CID fragmentation pathway of complex ions 6 based on the CID fragmentation pattern of complex ion 7 and
of the fragment ions at m/z281, m/z385, and m/z467. The elemental composition of the ions matches the respective accurate ion
mass measured, but the depicted structures are not further verified and serve only to illustrate the proposed fragmentation pathway
(red. el. = reductive elimination).
identity of the Pd hydrido complex [Pd(PCy3)(H)]+ (7) ion was
The MS2-product ion spectra of all the s-complex ions
independently confirmed by an accurate ion-mass measure- [Pd(PCy3)s-(Ar-dimethylbutenyl)]+ (6a–6i) show the Pd hydrido
ment and by careful evaluation of its experimental isotopic
complex 7, aside from identical other fragment ions (Figure
distribution (Figures 4 and S5). The reversed addition reaction, S5). Based on MS4 product ion experiments of the fragment
i.e. a neutral loss of DMB, was not observed in the CID experi- ions at m/z281, m/z385, and m/z467 (Figure S6) as well as
ments of the complex ions 6a–6i. This observation, together
with the formation of the hydrido complex ion 7, evidences the
completion of the gas-phase MHR between [Pd(PCy3)(Ar)]+ (3)
and DMB. These experimental findings clearly document the
gas-phase olefin insertion via IMRs and the ultimate forma-
the observed fragmentation patterns of [Pd(PCy3)(Ar)]+ (3) and
P(Ar)Cy3 (4), these fragment ions are secondary fragmen-
tation products of the initially formed Pd hydrido species 7
(Scheme 6).
+
Secondary fragmentation reactions are only observed in QIT
tion of the s-complex ions of the type [Pd(PCy3)s-(Ar-dimeth- CID product-ion experiments when broadband activation61,62
ylbutenyl)]+ (6) which then undergo b-H elimination upon CID, or high activation energies are applied.63,64 The secondary
generating the palladium hydrido species 7 and the MHR
fragmentation processes observed in the present experi-
product, (Ar)DMB (8), as a respective neutral loss (Scheme 5). ment performed at low activation energies near the threshold
As the symmetric DMB molecule features olefinic protons
energy evidence the instability of the primarily formed product
for the b-hydride elimination reaction only on carbons 1 and
ion [Pd(PCy3)(H)]+ (7) (Figure 4). Since the Pd cation in the
4, only the linear MHR product 1-(para-aryl)-2,3-dimethylb- hydrido complex ion [Pd(PCy3)(H)]+ (7) receives only limited
utadiene can be formed, with the formation of the branched
regioisomer (see Schemes 1 and 5) excluded. However, the
stereochemistry of the gas-phase MHR product cannot be
addressed as the differentiation between the isobaric E-and
Z-conformers is not possible by means of MS.
stabilization by the PCy3-ligand and has a strong electron defi-
ciency (only 12 valence electrons), it immediately attaches a
DMB molecule still present in the gas phase of the QIT to gain
further stabilization or it dissociates to form more-stable frag-
ment ions, as shown in Figure 4. Thus, fragment ions 7·DMB

630
Mizoroki–Heck Reaction Steps and Reactivity of Organopalladium Complexes in the Gas Phase
Table 1. Second-order rate constants of the IMR between [Pd(PCy3)
(Ar)]+ (3a–3i) and DMB. The reported values are the averages of four
independent measurements at different flow rates of olefin and
helium. The presented error is the standard deviation.
(m/z469) and 9 (m/z281) result from another IMR process with
DMB still present in the QIT and reductive elimination of Pd(0),
respectively. The fragment ions at m/z301, 303, 383, 385, and
467 can be explained by a combination of cyclohexane neutral
loss and adduct formation with DMB, as Scheme 6 illustrates.
The identity of these ions was reliably confirmed by accurate
mass measurements, ruling out the possibility that these
signals represent Pd complex isotopologues.[1]
The MS/MS-based results provide essential pieces of infor-
mation on the identity of complex ions 6a–6i, but it is possible
that during the IMR both olefin insertion and b-H elimination
take place, leading to a complex ion [Pd(PCy3)(H)(Ar-DMB)]+;,
[7•(Ar)DMB], as the final IMR product. As it is impossible to
distinguish between the isobaric species 6 and 7•(Ar)DMB by
means of MS, we performed a detailed computational anal-
ysis of all the Pd complex ions relevant for olefin coordina-
tion, carbopalladation, and b-H elimination in the gas phase
Ar
k (10–9·cm3·s–1·molecule–1]
3.1 1.0
C6H5 (6a)
p-(C6H4)Me (6b)
p-(C6H4)OMe (6c)
p-(C6H4)Et (6d)
m-(C6H4)Me (6e)
p-(C6H4)F (6f)
p-(C6H4)COMe (6g)
p-(C6H4)CF3 (6h)
p-(C6H4)NO2 (6i)
1.8 0.2
1.5 0.1
2.2 0.1
1.9 0.2
1.5 0.2
2.0 0.4
1.6 0.3
2.0 0.2
(Figures 5 and S8). We report only the relative electronic ener- precursor ions (see Figure 3). The determined second-order
gies because of the enormous complexity of the ions under
investigation. For this reason we were unable to compute
rate constants are listed in Table 1. Each value is the mean of
four independent measurements using different olefin partial
transition states, although this would be highly desirable. pressures in the ion trap. A detailed description of the experi-
Figure 5 indicates that the DMB insertion, starting from the
ments and the measurements is given in the Supplementary
Information.45 We found rate constants for the carbopallada-
tion step of the gas-phase MHR of about 1–3 × 10–9·cm3·s–
1·molecule–1. Since the differences in the k values for the set of
aryl moieties lie in the range of the documented experimental
error of the method ( 20–30%)37,49, it is reasonable to assume
that the DMB insertion is not seemingly sensitive to the elec-
4
3a•DMB-h adduct complex, is an exothermic process. The
minimum enthalpy of association for a complex formed by an
IMR association reaction under the given circumstances to be
stable in a QIT has been roughly estimated to be about 25kcal
mol–1.45 These considerations and the fact that no loss of DMB
was observed in the CID experiments of complex ions 6 hints
toward the instantaneous carbopalladation after olefin compl- tronic effects of the aryl ligand. Consequently, the linear free
exation in the quasi-thermal conditions in the ion trap. On
energy correlation of the observed rate constants found for
the different aryl moieties versus their respective Hammett
the contrary, the b-H elimination, i.e. the transformation from
4
complex ion 6a to 7•(Ph)DMB-h , was found to be an endo- parameter yields an indifferent result with a substantial
thermic reaction. The critical energy required for this trans- dispersion of data points (Figure 6). A linear relationship is
formation to proceed is probably not covered by the enthalpy
of association. Hence, the DFT calculations suggest that the
IMR of the Pd precursor ion 3 and DMB will lead to the s-alkyl
complex ion 6. Only after the activation of this IMR product
ion upon collision activation is the MHR product formed by
b-H elimination and released as a neutral MHR product along
with the complementary Pd hydrido complex ion 7. Consistent
with this detailed computational analysis of the IMR process
obviously absent, suggesting no substantial charge formation
in the transition state of the particular reaction.
Other studies have suggested that the olefin insertion reac-
tion proceeds in a concerted manner via a four-membered
transition state (Scheme 7a).67–69 However, experimental find-
ings have been reported that point toward a carbopalladation
transition state with a positive charge concentration at the
olefin (Scheme 7b).70 In line with this result, Van Leeuwen
between the precursor ions 3 and DMB, we were able to inves- and co-workers found a Hammett plot with a negative slope
tigate the carbopalladation step individually.
of the linear regression (r = –1.5) for the MHR of para-substi-
For a kinetic analysis of the gas-phase carbopalladation, tuted iodobenzenes with styrene and the olefin coordination or
second-order rate constants of the IMR between [Pd(PCy3)(Ar)]+
insertion was determined to be the rate-limiting step in this
(3) and DMB were determined at reaction times of 0.03–20ms. case.11 Our kinetic analysis of the gas-phase carbopalladation
The intensities of both the precursor ion 3 and of the low- step suggests a DMB insertion proceeding through a transi-
abundance fragment ion [P(Ar)Cy3]+ (4) were summed to
compensate for differences in the fragmentation extent of the
tion state without substantial charge separation occurs (in
accordance with Scheme 7a and Figure 6).
[1]The kinetic examination of the b-hydride elimination combined with
the release of the MHR reaction product (Ar)DMB (8) induced by CID
indicates that the efficiency of these two steps does not depend on
the electronic properties of the aryl ligand (see Figure S7 and further
explanation in the Supplementary Information).
Conclusion
In the present study, a number of important individual steps of
the palladium-catalyzed MHR between aryl iodides and DMB
were investigated in the gas phase. The oxidative addition was

L. Fiebig et al., Eur. J. Mass Spectrom. 21, 623–633 (2015)
631
Figure 6. Log10 plot of the carbopalladation rate constants as a function of the Hammett parameter sP.65,66
performed in solution prior to the electrospray phase transfer
from solution to the gas phase, but both the carbopalladation
and the b-hydride elimination were conducted in a controlled
and defined manner in a linear QIT mass spectrometer. The
of the reaction product (Ar)DMB (8) requires a substantial
amount of activation energy to be fulfilled experimentally. The
kinetic analysis of the carbopalladation step by IMR of the
[Pd(PCy3)(Ar)]+ (3) complex ions with nine different aryl (Ar)
experimental strategy allowed the direct and isolated exami- substrates with DMB showed no trend and clearly evidenced
nation of the C–C coupling step by the IMR between [Pd(PCy3)
(Ar)]+ (3) and gaseous DMB and the collision-induced release
of the neutral product (Ar)DMB (8) from the IMR product ion
that the reaction rate is independent of electronic effects of
the aryl moiety.
This report underlines the great potential of gas-phase IMR
[Pd(PCy3)s-(Ar-dimethylbutenyl)]+ (6), leading to the respec- in combination with theory and MS/MS techniques for the
tive Pd hydrido complex ion (7). The identity and molecular
structure of the [Pd(PCy3)s-(Ar-dimethylbutenyl)]+ ion (6) was
closely probed by extensive MS measurements (accurate ion
detailed reaction mechanism studies of transition-metal-
mediated transformations, especially of those with homoge-
neous catalysts. The gas-phase strategy allows the selection
mass, isotopic distribution), as well as by DFT calculations. and investigation of individual reaction steps as well as the
Consistent with the experimental findings, theory indicated
that the olefin insertion is exothermic whereas the b-hydride
elimination is endothermic and therefore the rate-limiting step
of the gas-phase MHR under investigation. These proposals
are in agreement with the experimental findings that the
intermediate species of a catalytic cycle, which is usually very
difficult or even impossible because of their transient nature
and instability in complex reaction solutions. The presented
set of results encourages us to investigate further also the
influence of subtle electronic and steric effects of the olefin on
carbopalladation via IMR takes place without further activa- the outcome of MHR reactions in the gas phase.
tion and the b-hydride elimination combined with the release
Supplementary information
Additional mass spectra of CID experiments, kinetic data of
the gas-phase test reaction, and calculated complex ion struc-
tures are given in the Supplementary data associated with this
article and can be found in the online version at http://dx.doi.
org/10.1255/ejms.1310.
Acknowledgements
This work was generously supported by a doctoral fellowship
of the ‘Cusanuswerk’ to L.F. J.H. thanks Prof. Dr Michael Dolg,
Institute of Theoretical Chemistry, University Cologne for help-
full discussions.
Scheme 7. Carbopalladation via four-membered transition
states with (a) little charge separation67 and (b) polarization of
the olefin C–C double bond.70

632
Mizoroki–Heck Reaction Steps and Reactivity of Organopalladium Complexes in the Gas Phase
20. P. Kebarle and U.H. Verkerk, Mass Spectrom. Rev. 28, 898
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