Solvent-dependent nuclearity, geometry and catalytic activity of [(SPhos)Pd(Ph)Cl]2

Article abstract of DOI:10.1039/c7dt01019b

The nuclearity and structures of the palladium complex [(SPhos)Pd(Ph)Cl]₂ in the solid and solution states are revisited using a combination of Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy, NMR spectroscopy, mass spectrometry,

Full text of DOI:10.1039/c7dt01019b

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PAPER
Joseph T. Hupp, Omar K. Farha et al.
Efficient extraction of sulfate from water using
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Solvent-dependent nuclearity, geometry and catalytic activity of
[(SPhos)Pd(Ph)Cl]2
John B. Brazier,a Mark A. Newton,b Elena M. Barreiro,a,‡ Luis A. Adrio,a,§ Leticia Nayac,Ψ and King
Kuok (Mimi) Hiia,*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
The nuclearity and structures of the palladium complex [(SPhos)Pd(Ph]Cl]2 in the solid and solution states are revisited
using a combination of Extended X-ray Absorption Fine Structure (EXAFS) spectroscopy, NMR spectroscopy, mass
spectrometry, DFT calculations and trapping experiments. The complex was tested for its catalytic activity in the coupling
reaction between chlorobenzene and n-hexylamine, where different deactivation behaviour were observed in toluene,
1,4-dioxane and DMF.
www.rsc.org/
sterically bulky phosphines that are known to activate aryl
chlorides in cross-coupling reactions, and are therefore
particularly relevant to the present discussion. It is worth
Introduction
The use of aryl chlorides (ArCl) precursors in cross-coupling
reactions is desirable, not only because they are generally
cheaper than their corresponding bromides and iodides, but
they also generate less waste per unit mass of product. In this
context, sterically bulky monophosphine (PR3) ligands have
been used extensively to promote Pd-catalyzed reactions of
ArCl with a wide range of nucleophilic reagents. The unique
reactivity is attributed to the ability of these ligands to
promote the formation of coordinatively unsaturated 12- or
14-electron [(R3P)Pd] or [(R3P)2Pd] complexes that are
particularly reactive towards cleavage of Ar–Cl bonds,1-5
forming an oxidative adduct which can be isolated as a dimer,
[(R3P)Pd(Ar)(Cl)]2, containing bridging chloro ligands.
Depending on the relative positions of the phosphine and aryl
ligands, these complexes can exist as two geometric isomers:
syn- or anti- (Fig. 1).
noting that even within this small number of examples, both
syn- and anti- configurations
PR3
Ar
Ar
X
X
R3P
Ar
R3P
Ar
Pd
Pd
Pd
Pd
X
X
PR3
1
1
Figure 1. Possible geometrical isomers of [(R3P)Pd(Ar)X]2 complexes.
syn-
anti-
Table 1. Reported X-ray crystal structures of complexes 1a-f with general formula
[(R3P)Pd(Ar)Cl]2.
MeO
OMe
P
A
survey of the CCDC database reveals 31 unique
P( -Bu)
t
2
structures of such dimers containing monodentate phosphine
ligands, with ꢀ2-chloro, bromo, iodo, and fluoro ligands (Table
II
I
S1, ESI). The seven crystal structures containing
ꢀ-chloro
–1c contain
ligands are summarised in Table 1, where 1a
Complex
PR3
SPhos, I
Ar
Config.
CCDC
code
ref
6
1a
1b
1c
1d
1e
1f
Ph
2-CF3C6H4
2-CF3C6H4
p-Tol
syn
syn
JIMMEY
UHUZON
UHUZUT
CIXQUX
PAJGIS
7
P(Ad)(t-Bu)2, II
P(t-Bu)3
PPhMe2
PPh2Me
PEt3
7
anti
anti
anti
anti
anti
8
9
Ph
9
p-Tol
(η6-Ph)Cr(CO)3
PAJGOY
KONMIJ
10
1g
PCy3
can be found, regardless of the electronic or steric nature of
the phosphine ligand. Therefore, the observation of a specific
isomer in the solid-state could be due to physical effects such
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as crystal packing and comparative solubility of each isomer in amination16-18 (a.k.a. Buchwald-Hartwig) reactions. Generally,
the solvent(s) used for the crystallization. Buchwald-Hartwig amination reactions work well in solvents of
With sterically congested coordination spheres, the dimers low polarity - toluene and 1,4-dioxane are two of the most
are prone to dissociate in solution into three-coordinate T- commonly employed solvents.16 Occasionally, DMF or DMA
shaped monomers [(R3P)Pd(Ar)X], which may be stabilised by are known to accelerate these reactions, often at the expense
having the fourth coordination site occupied by a solvent of selectivity.19
molecule, or by agostic interactions with the bulky phosphine
The coordination chemistry of the SPhos-palladium(II)
ligand cis to the vacant site.11 These monomers could adduct (1a) had been previously described,20, 21 where the X-
potentially exist in two geometric forms, cis- or trans-2 (with ray crystal structure of 1a was found to have a syn-
reference to the relative position of the anionic ligands Ar and configuration (Table 1, entry 1). In a toluene solution, the 31P-
Cl, Scheme 1). There is an inextricable link between NMR spectrum of the complex was reported to consist of two
stereochemistry of the dimer and their monomers: syn-
dissociate to give a heterogeneous mixture of isomers cis- and of monomeric rotamers, and a sharp singlet (
trans- , while anti- will dissociate to generate homogeneous assigned as the -chloro-bridged dimer, in the ratio of 72:25:3
mixtures of either cis- or trans-
1
will broad peaks (
δP +40.9 and +39.7 ppm), assigned as a mixture
δP +33.0 ppm),
2
1
ꢀ
2.
in dynamic exchange.21 Subsequent DFT calculations showed
that cis-2a has a lower ground state energy than trans-2a (by
5.2 kcal/mol);20 two conformers of cis-2a were identified to be
particularly stable due to favourable agostic interactions
between the Pd metal centre with the ipso carbon of the arene
(2.86 Å), or with an oxygen of the methoxy group (2.30 Å); the
latter being slightly more stable than the former by 0.8
kcal/mol. Subsequently, the broad resonances were assigned
to the low energy conformers of the monomeric complex,
while the sharp signal observed at +33 ppm was assigned to
the resonance of the dimeric complex
dominant species in CH2Cl2 (Scheme 2).
1, which became the
Scheme 1. Dissociation of 1 into monomeric species 2 (● = vacant coordinaꢀon site
occupied by a coordinating solvent or agnostic interaction).
Crystal structures and theoretical calculations have
consistently shown that monomers having the chloride trans
to the phosphine ligand (cis-2
) are favoured,5, 11-13 in accord
with the aryl ligand exerting a larger trans-effect than the
phosphine ligand (thereby destabilising the trans- isomer).14
However, only trans-2 is able to participate in the catalytic
cycle, as it allows a second substrate to occupy the position
adjacent to the aryl group and achieve the required geometry
for reductive elimination and/or bond formation. Thus,
understanding the dynamic exchange between these oxidative
adducts would aid understanding of the relative population of
off-cycle and catalytically active species that can affect
catalytic turnover. In this paper, we will report how different
solvents affect the exchange processes between dimeric and
monomeric geometrical forms of [(SPhos)Pd(Ph)Cl]x (x = 1 or
2). In this paper, we will show that the dimeric structure is
surprisingly stable, even in relatively polar solvents. We will
also show that choice of solvent used in the recrystallization of
Scheme 2. Previously proposed solution structures in toluene.21
EXAFS study. We have previously demonstrated the utility of
Extended X-ray Absorption Fine Structure (EXAFS)
spectroscopy in characterizing Pd species in solution,22,
including the nuclearity of Pd(OAc)2 in different solvents.24
23
A
similar approach was adopted in this work to study the dimeric
and monomeric structures of 1a, beginning with recording the
Pd K-edge spectrum of a solid sample at 24.35 keV. Fitting in
the high k region (>8.5) can be achieved by inclusion of Cl and
P, while fitting in the low k region was achieved by the
addition of a C to the primary coordination sphere and
imposing a square planar geometry around Pd. The bond
lengths returned from analysis of the Pd K-edge EXAFS match
those derived from X-ray crystallography to within an error of
ca. 1.5% (Table 2), which is acceptable for absolute bond
length determination by EXAFS. Further introduction of
extended Pd–Pd or Pd–O (apical O-coordination) contacts did
complex
1 has a profound effect on its catalytic activity in the
coupling reaction between chlorobenzene and hexyl amine.
Results and discussion
SPhos (I) is an early example of a dialkylbiarylphosphine
developed by the Buchwald research group, belonging to a
class of sterically-demanding ligands that have been shown to
have broad applications in Pd-catalysed Suzuki-Miyaura15 and
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not make any significant changes to the fit. Thus, the EXAFS and DMF revealed substantial differences in the primary
data of the powdered sample is in good agreement with the coordination sphere (Fig. 3). In the solid sample and toluene
structure determined by X-ray crystallography – of a chloro- solution, Pd–Cl and Pd–C/O contacts dominate the spectra. As
bridged dimeric Pd complex consisting of P, C and two Cl’s in may be expected for dissociation into a monomer, the Cl shell
the primary coordination sphere.
is substantially reduced in the DMF solution, while the Pd–P
contact becomes more dominant. The result obtained from
fitting the spectrum is consistent with the presence of a
monomeric entity (Table 3), where one of the coordinated Cl
atoms is replaced by O (oxygen), with a Pd‒O bond distance of
2.11 Å (see also Figure S2 and discussions in ESI). This could be
due to the coordination of either the OMe group of SPhos, or
the DMF solvent. In the earlier DFT calculation, the Pd···O
contact found in the most stable conformer of a chelated
structure is 2.30 Å (Scheme 2), which is significant greater than
the experimentally determined value, and beyond the
acceptable error (±1.5%) for bond length determination by
EXAFS.26 As such, the chelated structures (Scheme 2) can be
ruled out, in favour of a mono-solvated complex (this is further
supported by DFT work, vide infra).
Table 2. EXAFS parameters obtained for [(SPhos)Pd(Ph)Cl]2 in the solid state.
Ra/Å
DWb (2σ2)/Å2
0.012
Element
Cl
Cl
P
2.37 (2.41)
2.45 (2.43)
2.24 (2.26)
2.00 (2.00)
2.94 (2.97)
3.29 (3.51)
0.006
0.009
C
0.009
O
0.006
Pd
0.03
a
Distance of scatterer atom from central atom. X-ray crystallographic data
reported for JIMMEY6 are indicated in parenthesis; b Debye-Waller factor.
Having verified the solid-state structure as a dimer, spectra
of 1a were subsequently recorded with the sample dissolved in
three different solvents that are commonly used for Buchwald-
Hartwig coupling reactions (toluene, 1,4-dioxane and DMF).25
Based on previous reports,20,21 we were expecting the
dissociation of the dimer to occur in the solution phase, which
will be reflected by noticeable changes in the EXAFS spectra,
particularly in the higher k region where Cl coordination
features dominate the spectrum. Much to our surprise,
solution spectra recorded in toluene and 1,4-dioxane are
identical to that recorded for the solid- state sample (Figure
2A), i.e. the dimeric structure is largely retained (by at least
90%) in these solvents at the given concentration (40 mM). In
contrast, a very different EXAFS spectrum was obtained from a
solution of complex 1a dissolved in a polar aprotic solvent,
DMF (Fig. 2B); most notably in the highlighted k3-weighted
region between 5–9 Å–1.
Figure 3. k3-weighted FT spectra derived from the solid and toluene and DMF
‡
solutions of 1a. The red lines show fits to the data. Multiple scattering events
across the square planar complex. *An artefact that cannot be fitted in the FT.
Table 3. EXAFS parameters obtained for 1a in DMF.
Element
Cl
Ra (Å)
2.42
DWb (2σ2)/Å2
0.015
P
C
2.24
1.98
2.11
0.007
0.006
0.010
O
Figure 2. Comparisons of k3-weighted Pd K-edge EXAFS spectra of complex 1a, recorded
of a solid sample (pellet) toluene and 1,4-dioxane solutions (40 mM) (A); and with a
DMF solution (B). The red curves are derived from fitting of the k3-weighted data (Table
S2, ESI). The highlighted region of k-space emphasises regions that serve to fingerprint
dimeric or monomeric structures.
a Distance of scatterer atom from central atom; b Debye-Waller factor.
NMR spectroscopy. The unexpected result prompted us to re-
examine the solution structure of 1 in greater detail, by
comparing the 31P-NMR spectra of complex 1a in a number of
Comparison between the Fourier-transformed (FT)
spectrum of the solid sample and those recorded in toluene
solvents (Fig. 4). It is worth noting that NMR spectra can be
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recorded with more dilute solutions (ca. 10 mM) than EXAFS assigned as the thermodynamically more stable cis-isomer
spectra, and are therefore more relevant for catalytic (Scheme 3). The proposal is supported by previous
a
reactions. The spectrum recorded in toluene (Fig. 4, spectrum computational study, where it was suggested that, for
i) was consistent with that previously reported,21 revealing [(R3P)Pd(Ar)X]2 complexes containing relatively small
three resonance signals, whereas a single upfield signal was phosphine ligands (PR3), dimeric structures are favoured over
observed
(δP +34.5 ppm) in chloroform (spectrum iii). solvated complexes in THF, but this can be reversed in the
Subsequently, the NMR spectra of complex 1a were recorded presence of more coordinating molecules, such as phosphine
in five other solvents: THF, 1,4-dioxane, DMF, nitromethane and DMF.11 It is somewhat surprising to note that the dimeric
and tert-amyl alcohol. As shown in Figure 4, the appearance of structure is largely maintained in toluene at elevated
the spectra falls into either one of two types: In coordinating temperatures up to 65 °C (see Fig. 6 in reference 21).
solvents such as chloroform (iii), nitromethane (vi), and DMF
Further evidence supporting this reassignment of the
(vii) a relatively sharp singlet resonance at ca.
δ
P +35 ppm solution species was made by employing 1H-NMR Diffusion
dominates the spectra. Conversely, in solvents such as toluene Ordered Spectroscopy (DOSY) to study the two solvents
(i), 1,4-dioxane (ii) and THF (iv), additional broad downfield showing the most extreme differences in their 31P-NMR
peaks between 38–40 ppm are the dominant features. spectra: toluene and chloroform (Figures S4 and S5, ESI). Using
Following each experiment, the solvent was evaporated and the Stokes-Einstein equation the hydrodynamic radius of the
the residue was re-dissolved in CDCl3: Spectrum (iii) may be complex is calculated to be approximately three times larger in
regenerated in every case, thereby confirming that the toluene than CDCl3, verifying that: (i) the dimeric structure is
dissolution of the sample in these solvents did not cause any largely retained in toluene, even in dilute solutions; and (ii)
irreversible change to the complex. In tert-amyl alcohol (v) and chloroform act as a coordinating solvent to stabilise the
a 1:1 mixture of toluene and CDCl3 (viii), significant peaks in monomeric structure.
both regions were observed corresponding to the formation of
An important outcome of this study is to identify the
distinct species, thus ruling out the possibility of a solvent- presence of both syn- and anti-1a in rapid equilibrium in
induced chemical shift. The relative population of these solvents that are relevant for catalysis (toluene, 1,4-dioxane
species did not appear to be dependent on the dipole moment and DMF). Although only a single resonance signal (
(D) or dielectric constant ( r) of the solvent, but rather on the ppm) can be observed for the monomeric species (Fig. 5), both
presence (or absence) of a donor group that is able to cis-2a and trans-2a must be involved in the exchange process,
δP +33
ε
coordinate to the metal centre.
as mandated by the C2v and C2h symmetries of syn- and anti-
1a, shown in Scheme 1. In a non-coordinating solvent such as
toluene, where a dissociative mechanism dominates,11 syn-1a
can only be formed from a combination of cis and trans-2a
.
Cl
Cl
PR3
Ph
Cl
Ph
solv
Cl
R3P
R3P
R3P
Pd
Pd
Pd
Pd
Pd
Ph
Ph
Ph
PR3
Cl
1a
syn-
1a
anti-
2a.
cis- solvate
dominatesin coordinating
solvents
e.g. DMF, nitromethane,
chloroform
dominate in non- or weakly
coordinatingsolvents
e.g. toluene,dioxane,THF
Scheme 3. Revised assignment of solution structures of complexes 1a and 2a (PR3
=
SPhos).
Mass spectrometry. Further indirect evidence is provided by
ESI-MS of solutions of the complex in DMF and in toluene (see
Section 4 of ESI). Arylpalladium(II) complexes are known to
undergo labile and extensive fragmentation and ligand
Figure 4. 31P{1H}-NMR spectra of complex 1a recorded in different solvents, arranged in
order of increasing solvent polarity. εr
= dielectric constant; D = Debye (dipole
moment). All spectra were recorded of the same sample; solvent switching between scrambling in the solution and gas-phases;27 therefore, not all
different spectra. Variability in signal-to-noise is due to solubility or signal broadening.
observed mass ions could be readily assigned. Nevertheless,
with the sample dissolved in toluene, the most abundant
These findings led us to revise the solution structures for
complex 1a, and propose a new interpretation of the 31P-NMR
spectra: The broad signals at 38–40 ppm are attributed to
peaks were observed at high molecular weights, including the
dimeric fragment ion [(SPhos)2Pd2(Ph)2Cl]+. In contrast, for the
solution in DMF the principal isotopic mass distributions were
much lower; the most significant peaks in the mass spectrum
can be assigned to the monomeric form of the complex
interconverting syn- and anti- dimers of 1a, which are
indistinguishable by EXAFS spectroscopy, as they have the
same coordination environment. On the other hand, the sharp
singlet is assigned to a solvated monomer 2a, tentatively
[(SPhos)Pd(Ph)]+,
[(SPhos)Pd(Ph)(DMF)]+.
and,
notably,
its
monosolvate
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Addition of PPh3 (31P-NMR). An attempt was made to trap
the monomeric species by adding 2 equivalents of PPh3 to
solutions of complex 1a in toluene-d8 and complex 2a in CD2Cl2
at –60 °C.28 The temperature of the reaction mixture was then
gradually warmed up to 25 °C, during which time 31P-NMR
spectra were acquired after each successive temperature rise
of 10 °C (Fig.’s S6 and S7 in ESI, selected spectra are presented
in Fig. 5). In each case, irrespective of the starting structure, an
AX pattern (open circles,
δP +20.1, 41.8) was observed initially,
with
a
distinctive 2J(PP) coupling of 400 Hz. This is
commensurate with the formation of a square planar complex
containing inequivalent and trans-disposed phosphine ligands
[(SPhos)(PPh3)Pd(Ph)Cl],
relatively unstable in toluene, undergoing slow ligand
exchange at room temperature, displacing SPhos ( P –9.5
ppm) to form trans-[(PPh3)2Pd(Ph)Cl], , observed as a sharp
singlet at
P +23.2 ppm29 (closed circles). In toluene, complex
3 (Scheme 4). This complex is
δ
4
δ
4
is the major species observed after 24 h. In contrast, for the
reaction conducted in CD2Cl2, the binding of PPh3 to the
monomeric 2a is reversible. In this case, the intermediate
complex
complex
3
may either undergo ligand exchange to form
or dissociate PPh3 to reform complex 2a
4
,
,
generating an equilibrium mixture of all three species in the
solution.
The result shows that the cis-trans isomerization of the
monomeric complex 2a is energetically accessible at sub-
ambient conditions, even in the presence of
a strong
coordinating species such as PPh3. In this case, the equilibrium
Figure 5. Selected 31P{1H}-NMR spectra of reaction mixtures of 1a and PPh3 (2 equiv.) at
favours the coordination of PPh3 at the site trans to the SPhos
different temperatures in toluene-d8 (top) and CD2Cl2 (bottom). Different vertical
ligand, as this will avoid steric interactions between the two expansions were applied for clarity. *Internal reference (POCl3 in a sealed capillary
tube). Open circles = AX system of trans-[(SPhos)(PPh3)Pd(Ph)Cl], 3; closed circle =
phosphines. If PPh3 is replaced by an amine substrate, it will
trans-[(PPh3)2Pd(Ph)Cl], 4.
allow the complex to access the transition state required for
C–N bond formation. Indeed, earlier work by Buchwald and co-
+ PPh3
PPh3
Ph Pd Cl
SPhos
PPh3
slow
δP −5.9 ppm
Ph Pd Cl
1a
+ SPhos
in toluene-d8
PPh3
4
δP +23.2 ppm
δP −9.5 ppm
δP +32.8 (s),
3
38.6 (br), 40.1 (br)
δ
P +20.1, +41.8,
2J(PP) 400 Hz
(largely dimeric)
PPh3
PPh3
Ph Pd Cl
SPhos
+ PPh3
Ph Pd Cl
+ SPhos
2a
in CD2Cl2
PPh3
δP +34.0 ppm
3
4
(monomeric)
Scheme 4. Coordination of PPh3 to 1a in different solvents.
workers have also shown that the coordination of amines to
complex 1a is reversible (in the absence of a base), and the
monomeric species was reported to exist largely as a single
isomer in solution.6
The relative stability of complex
3 in the two different
solvents is noteworthy: the coordination of phosphine appears
to be more labile in the chlorinated solvent, as the final
reaction mixture comprises of a mixture of complexes
2 and 3
and 4. In contrast, complex 3 does not revert to 1a in toluene.
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DFT calculations. Given that all the species are able to (Scheme 5). Catalyst loading was kept low (1 mol%), such that
establish thermodynamic equilibrium under ambient differences in turnover number and frequency (TON and TOF)
conditions, DFT calculations were performed to determine the could be easily distinguished. As expected, the yield afforded
distribution of the isomers of 1a and 2a in different by toluene (>90%) is better than 1,4-dioxane (ca. 40%) and the
environments. An initial screen of three density functionals in worst result was obtained in DMF (<10%), where catalyst
the geometry optimisation of dimer syn-1a, established that decomposition was evident (formation of Pd black).
WB97XD offered the more accurate predictions (Table S3, ESI),
1a (1 mol%)
which was adopted in further calculations. Using this method,
the relative energies are listed in Table 5, with the energy of
anti-1a set to zero in each system. Despite the large number of
atoms and conformation flexibility in these systems, the
theoretical results are in good agreement with our
H
N
n-C6H13NH2
+
Ph Cl
Ph
t-AmONa
Scheme 5. Coupling between chlorobenzene and n-hexylamine catalysed by 1a.
experimental observations: For dimer 1a
,
the syn-
configuration was found to be more stable than anti- in the gas
phase (Table 4). In the presence of two explicit toluene
molecules, the dimeric form is still thermodynamically
favoured over the monomeric forms. However, in this
medium, the anti-configuration is more stable than the syn-
isomer. Last but not least, as expected, the monomeric
solvated complexes are favoured in the presence of
coordinating DMF molecules. In this case, it is interesting to
note that the energy difference between cis- and trans-2a is
very small (<1 kcal/mol). Importantly, no agostic interactions
can be found in any of these structures. Additionally, a Pd···O
distance of 2.20 Å is found in the solvated complex. While this
is longer than the experimental value of 2.11 Å (Table 3), it is a
much closer value than the chelate structure (2.30 Å); even Figure 6. Catalytic performance of 1a (from the same batch, crystallized from
toluene/pentane) for the coupling between chlorobenzene and n-hexylamine (Scheme
more so considering that the current method tends to over-
5) in three different reaction solvents: toluene, 1,4-dioxane and DMF.
estimate bond lengths by ca. 1.2% (Table S3, ESI).
Table 4. Relative energies of dimers and monomers in the absence and presence of
toluene or DMF (kcal/mol).a
Indeed, comparison of the reaction profiles (Fig. 6)
revealed that this is entirely due to catalyst stability (TON). In
1,4-dioxane and DMF, initial turnovers appear to be rapid, but
Solvent
gas-phase
toluene
DMF
syn-1a
–5.8
anti-1a
cis- & trans-2a
2 x cis-2a
–
is followed by an abrupt cessation of catalytic activity after 20
minutes. In contrast, the profile of the reaction conducted in
toluene is particularly interesting, where a relatively fast
turnover was initially observed in the first 90 minutes of the
reaction, followed by a slower, yet steady, rate of conversion.
This could suggest a shift in the turnover-limiting step during
the reaction.
0
0
0
–
+5.2
+23.8
–1.4
+26.1
–2.0
+0.44
a
Geometries were optimised using the WB97xd density functional, and the
Def2TZVP basis set on Pd. For calculations involving solvent, two explicit solvent
molecules were included in the calculation, along with application of the
appropriate solvent field (PCM).
A
catalytic cycle may be tentatively constructed to
Catalytic reactions. In the last part of this study, complex 1a
was employed as a catalyst for the coupling reaction between
chlorobenzene and n-hexylamine in the presence of sodium
tert-pentoxide as a base. Although 1a is unlikely to be used as
a catalyst in synthesis, it is nevertheless a good precursor to
employ in mechanistic studies. As the product of the initiating
step (oxidative addition reaction), it obviates induction periods
when a Pd precursor and the ligand react to form the active
catalyst (which may also be subject to solvent effects), thus
allowing direct comparisons to be made. Furthermore, it
affords ‘clean’ access to the catalytic cycle without introducing
extraneous ligands such as acetate and dba associated with
the common palladium precursors, which can alter the nature
of the catalytic intermediates.30-33
incorporate the involvement of monomeric and dimeric
species identified in this study (Scheme 6). Following the initial
oxidative addition, the dimer undergoes dynamic exchange
with monomeric amine-bound complexes6 which may have
two possible isomers, of which only one has the required
geometry to undergo C-N bond formation, enabled by a strong
base. This is often an alkali metal alkoxide (e.g. NaOt-Bu),
which have limited solubility in toluene, and slightly more
soluble in 1,4-dioxane. Such inhomogeneity is an important
issue for kinetic analysis, as mass-transfer between the solid-
liquid interfaces will need to be taken into account. In cases
where the turnover rate is limited by the solubility of the
inorganic base (for example, in toluene), syn- and anti-1 can
serve effectively as the resting state of the catalytic cycle,
particularly if the amine binding is weak. The ability of the
complex to adopt a dimeric structure can thus minimise
Based on the earlier studies, the reaction was performed in
three different solvents: toluene, 1,4-dioxane and DMF
6 | J. Name., 2012, 00, 1-3
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catalyst decomposition. In contrast, the dimeric intermediates calculations in these systems, and explicit solvent molecules
are unstable in DMF. In this case, rapid decomposition of must be included wherever possible. Given the largely number
monomeric species may be the reason for the low observed and variety of heteroatoms, further complicated by degrees of
TON.
conformational flexibility inherent within these systems (e.g.
the cyclohexyl ring), any quantitative studies will invariably be
computationally very costly.
In the last part of the work, the catalytic activity of complex
1a was assessed in three different solvents, in the coupling
reaction between chlorobenzene and n-hexylamine. The
choice of solvent is found to have a profound effect on the
TON, which is curtailed rather abruptly in DMF and 1,4-
dioxane, but not in toluene. A catalytic cycle has been
proposed to take into account the possible involvement of 1a
as the resting state of the catalyst cycle in toluene.
Confirmation of their involvement will warrant detailed
mechanistic and kinetic investigations, which will be pursued
in future work.
Experimental
Scheme 6. Key steps of the catalytic cycle (in non-polar solvents).
EXAFS spectroscopy.
The similarity in rates observed for the first ca. 35
turnovers in toluene and 1,4-dioxane (Fig. 6) is particularly
striking, as it shows that the solvent does not have significant
impact on the TOF, at least initially. Beyond this, catalysis
either ceases completely, or switches over to a different
kinetic regime, depending on which solvent is used. This could
be due to the accumulation of the secondary amine product,
which can conceivably bind to Pd and interfere with the
equilibrium process, and/or by difference in the effective
concentration of the alkoxide base that can cause the
formation of catalytically inactive species. Understanding the
reasons behind these differences will be important in
EXAFS measurements were made at B18 at the Diamond Light
Source, using a Si (111) double crystal monochromators and
Ion chambers for detection of X-ray absorption, normalisation,
and energy scale (Pd foil) calibration. Spectra were collected
between 24 to 25.5 keV. Complex 1a was pressed into a pellet
for the solid-state sample, and dissolved in toluene, 1,4-
dioxane and DMF as 40 mM solutions. Solution spectra were
recorded in a quartz cuvette with path length 10 mm. The
EXAFS data was processed using PAXAS34 and then analysed,
using full curved wave multiple scattering theory, with
EXCURV.35
identifying critical parameters for catalyst deactivation. In turn, NMR spectroscopy
31P-NMR spectra were recorded on a Bruker Avance400
this will lead to better process designs, allowing the lifetime of
the precious metal catalyst to be extended without
compromising productivity.
spectrometer operating at 161.9 MHz.
Figure 4: Complex 1a was dissolved in CDCl3 to give a solution
of approx. 10 mM in Pd. The 31P-NMR spectrum was recorded
at 293 K, and the solvent was evaporated to return the solid
sample. This sample was then re-dissolved in the next solvent
and a 31P-NMR spectrum recorded. After each solvent was
evaporated, the sample was re-dissolved in CDCl3 and a
spectrum recorded to verify no permanent change to the
sample had taken place. All CDCl3 spectra obtained from this
experiment were identical. For deuterated solvents, the signal
was locked to the deuterium signal of the solvent. Where
undeuterated solvents were used (e.g. Dioxane, THF, DMF, and
t-amyl alcohol), a sealed capillary tube of D2O was placed
inside the NMR tube to allow a lock to the deuterium signal.
Conclusions
In this work, EXAFS and NMR spectroscopy have been used in a
highly complementary way, to determine the solid and
solution structures of palladium complexes. It was found that
the dimeric structure of the SPhos complex 1a is largely
retained in solvents such as toluene and 1,4-dioxane even at
high dilution (10 mM), and exists predominantly as monomers
in DMF and chlorinated solvents. Subsequently, the dynamic
equilibrium process observed in toluene and 1,4-dioxane
solutions of 1a is ascribed to exchange between syn- and anti-
geometric isomers, which occurs rapidly in solution, via
monomeric intermediates 2a. The relative stability of these
species in different reaction media was examined by DFT
calculations, which suggest that while syn-1a may be favoured
in the gas phase, the anti-isomer is favoured in toluene and
the monomeric species preferred in DMF. This serves to
highlight the importance of applying solvent models in the DFT
Figure 5: 6 mg of 1a (4.8 ꢀmol) were dissolved in 0.3 mL of the
appropriate deuterated solvent (CD2Cl2 or toluene-d8) inside
an NMR tube containing a capillary tube filled with POCl3
(internal standard). The tube was cooled in a dry ice bath, and
a solution of 2.5 mg of PPh3 (9.6 ꢀmol, 2 equiv.) dissolved in
0.2 mL of the deuterated solvent was added. The NMR
experiment was recorded immediately.
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6
7
8
9
M. R. Biscoe, T. E. Barder and S. L. Buchwald, Angew. Chem.
Int. Ed., 2007, 46, 7232-7235.
F. Barrios-Landeros, B. P. Carrow and J. F. Hartwig, J. Am.
Chem. Soc., 2009, 131, 8141-8154.
K. R. Chaudhari, A. P. Wadawale, M. Kumar and V. K. Jain, J.
Organometallic Chem., 2014, 760, 55-59.
K. R. Chaudhari, A. P. Wadawale and V. K. Jain, J.
Organometallic Chem., 2012, 698, 15-21.
DFT calculations
Calculations were performed on the HPC cluster at Imperial
College, using Gaussian ’09 (version C.01 or D.01).36 Three
density functionals were evaluated (see discussion) with
Def2TZVP basis set applied at Pd and 6-31G** for all other
elements. The reported X-ray crystal structure of syn-1a6 was
used originally as an input. Solvent effects were accounted for
by the inclusion of two implicit solvent molecules (toluene or
DMF), in addition to applying a PCM correction. Outputs for
the calculations were deposited within a digital repository, and
can be accessed via the links provided in the ESI.
10 V. Dufaud, J. Thivolle-Cazat, J. M. Basset, R. Mathieu, J. Jaud
and J. Waissermann, Organometallics, 1991, 10, 4005-4015.
11 S. Moncho, G. Ujaque, A. Lledós and P. Espinet, Chem. Eur. J.,
2008, 14, 8986-8994.
12 J. P. Stambuli, M. Buhl and J. F. Hartwig, J. Am. Chem. Soc.,
2002, 124, 9346-9347.
13 J. P. Stambuli, C. D. Incarvito, M. Buhl and J. F. Hartwig, J.
Am. Chem. Soc., 2004, 126, 1184-1194.
Catalytic reactions (Figure 6)
14 F. Basolo and R. G. Pearson, in Progress in Inorganic
Chemistry, John Wiley & Sons, Inc., 2007, pp. 381-453.
15 D. S. Surry and S. L. Buchwald, Chem. Sci., 2011, 2, 27-50.
16 H. Christensen, S. Kiil, K. Dam-Johansen, O. Nielsen and M. B.
Sommer, Org. Proc. Res. Dev., 2006, 10, 762-769.
17 T. E. Barder, S. D. Walker, J. R. Martinelli and S. L. Buchwald,
J. Am. Chem. Soc., 2005, 127, 4685-4696.
18 D. S. Surry and S. L. Buchwald, Angew. Chem. Int. Ed., 2008,
47, 6338-6361.
19 N. C. Bruno and S. L. Buchwald, Org. Lett., 2013, 15, 2876-
2879.
A Radley’s reaction tube was charged with a magnetic stir bar
and t-AmONa (430 mg, 1.6 mol equiv.). A PTFE screw cap was
fitted and the reaction vessel purged with N2 before the
addition of dry toluene, 1,4-dioxane or DMF (5 mL, 0.5 M)
through the rubber septum using a syringe. Chlorobenzene
(250 µL, 1 mol eq.) and hexylamine (430 µL, 1.55 mol eq.) were
added and the tube was heated to 80 °C before complex 1a
was added (15 mg,
1 mol%). Product formation was
determined by GC (5 mM dodecane used as standard) for
reactions performed in toluene and 1,4-dioxane and by HPLC
(5 mM o-xylene used as standard) for reactions performed in
DMF (due to overlapping GC peaks).
20 T. E. Barder and S. L. Buchwald, J. Am. Chem. Soc., 2007, 129
12003-12010.
,
21 T. E. Barder, M. R. Biscoe and S. L. Buchwald,
Organometallics, 2007, 26, 2183-2192.
22 G. Guilera, M. A. Newton, C. Polli, S. Pascarelli, M. Guino and
K. K. Hii, Chem. Commun., 2006, 4306-4308.
23 B. N. Nguyen, L. A. Adrio, T. Albrecht, A. J. P. White, M. A.
Newton, M. Nachtegaal, S. J. A. Figueroa and K. K. Hii, Dalton
Trans., 2015, 44, 16586-16591.
24 L. A. Adrio, B. N. Nguyen, G. Guilera, A. G. Livingston and K.
K. Hii, Catal. Sci. Technol., 2012, 2, 316-323.
25 Concentrations of the solution samples were 40 mM,
conpared to 5 mM typically employed in catalytic reactions.
26 J. M. Corker, J. Evans, H. Leach and W. Levason, J. Chem.
Soc., Chem. Commun., 1989, 181-183.
Acknowledgements
The work was funded by an EPSRC project grant titled: “ELSEP
(Elucidate and Separate) - Palladium Catalysts in C–C and C–N
Coupling Reactions” (EP/G070172/1), with additional
contributions from the Pharmacat Consortium (AstraZeneca,
GlaxoSmithKline and Pfizer). EMB is recipient of a Fellowship
from Xunta Galicia. Pd salts used in this project were provided
by Johnson Matthey PLC through an academic loan scheme.
We are grateful to Science and Technology Facilities Council
(STFC) for the allocation of synchrotron beam time. We thank
Dr Diego Gianolio (beamline scientist, B18, Diamond Light
Source) for the acquisition of EXAFS data, and Mr Peter
Haycock (Imperial College) for assistance with the DOSY
experiments. MAN is extremely grateful for a visiting scientist
position at the department of Physics at Warwick. We thank
Professor S. L. Buchwald for his constructive and valuable
comments on this work.
27 D. Agrawal, E.-L. Zins and D. Schroeder, Chem. Asian J., 2010,
, 1667-1676.
5
28 These spectra cannot be treated quantitatively due to
limited solubility of certain individual species (particularly
PPh3 at low temperatures), as well as significant signal
broadening due to exchange processes.
29 W. A. Herrmann, C. Broßmer, T. Priermeier and K. Öfele, J.
Organometallic Chem., 1994, 481, 97-108.
30 I. J. S. Fairlamb, A. R. Kapdi, A. F. Lee, G. P. McGlacken, F.
Weissburger, A. H. M. de Vries and L. Schmieder-van de
Vondervoort, Chem. Eur. J., 2006, 12, 8750-8761.
31 I. J. S. Fairlamb, Org. Biomol. Chem., 2008, 6, 3645-3656.
32 C. Amatore, E. Blart, J. P. Genet, A. Jutand, S. Lemaireaudoire
and M. Savignac, J. Org. Chem., 1995, 60, 6829-6839.
33 C. Amatore, A. Jutand, F. Lemaitre, J. L. Ricard, S. Kozuch and
S. Shaik, J. Organometallic Chem., 2004, 689, 3728-3734.
34 N. Binsted, PAXAS: Programme for the analysis of X-ray
absorption spectra, University of Southampton, 1988.
35 N. Binsted, EXCURV98 CCLRC Daresbury Laboratory
computer program, 1998.
36 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.
Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci,
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.
Notes and references
1
2
3
E. Galardon, S. Ramdeehul, J. M. Brown, A. Cowley, K. K. Hii
and A. Jutand, Angew. Chem. Int. Ed., 2002, 41, 1760-1763.
A. Kurbangalieva, D. Carmichael, K. K. Hii, A. Jutand and J. M.
Brown, Chem. Eur. J., 2014, 20, 1116-1125.
B. U. W. Maes, S. Verbeeck, T. Verhelst, A. Ekomie, N. von
Wolff, G. Lefevre, E. A. Mitchell and A. Jutand, Chem. Eur. J.,
2015, 21, 7858-7865.
4
5
F. Proutiere, E. Lyngvi, M. Aufiero, I. A. Sanhueza and F.
Schoenebeck, Organometallics, 2014, 33, 6879-6884.
C. L. McMullin, N. Fey and J. N. Harvey, Dalton Trans., 2014,
43, 13545-13556.
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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. Kobayashi, J. Normand, K. Raghavachari, A.
Rendell, J. C. Burant, S. S. Iyengar, 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. Cioslowski, and D. J. Fox,
Gaussian, Inc., Wallingford CT, 2009.
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