A detailed study of acetate-assisted C-H activation at palladium(IV) centers

Article abstract of DOI:10.1021/ja401557m

This report describes a detailed investigation of acetate-assisted C-H activation at Pd^IV centers supported by the tris(2-pyridyl)methane (Py₃CH) ligand. Mechanistic information about this transformation has been obtained through the following: (i) extensive one- and two-dimensional NMR analysis, (ii) reactivity studies of a series of substituted analogues, and (iii) isotope effect studies. These experiments all suggest that C-H activation at [(Py₃CH)Pd^IV(biphenyl)Cl₂]⁺ occurs via a multistep process involving chloride-to-acetate ligand exchange followed by conformational and configurational isomerization and then C-H cleavage. The data also suggest that C-H cleavage proceeds via an acetate-assisted mechanism with the carboxylate likely serving as an intramolecular base. The viability of acetate-assisted C-H activation at high valent palladium has important implications for the design and optimization of catalytic processes involving this transformation as a key step.

Full text of DOI:10.1021/ja401557m

Article
pubs.acs.org/JACS
A Detailed Study of Acetate-Assisted C−H Activation at Palladium(IV)
Centers
Ansis Maleckis, Jeff W. Kampf, and Melanie S. Sanford*
Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor Michigan 48109, United States
S
* Supporting Information
ABSTRACT: This report describes a detailed investigation of acetate-
assisted C−H activation at PdIV centers supported by the tris(2-pyridyl)-
methane (Py3CH) ligand. Mechanistic information about this transformation
has been obtained through the following: (i) extensive one- and two-
dimensional NMR analysis, (ii) reactivity studies of a series of substituted
analogues, and (iii) isotope effect studies. These experiments all suggest that
C−H activation at [(Py3CH)PdIV(biphenyl)Cl2]+ occurs via a multistep
process involving chloride-to-acetate ligand exchange followed by conforma-
tional and configurational isomerization and then C−H cleavage. The data
also suggest that C−H cleavage proceeds via an acetate-assisted mechanism with the carboxylate likely serving as an
intramolecular base. The viability of acetate-assisted C−H activation at high valent palladium has important implications for the
design and optimization of catalytic processes involving this transformation as a key step.
than PdII-mediated C−H functionalization processes.9 Thus, it is of
INTRODUCTION
■
great importance to understand whether these differences are the
Over the past decade, palladium-catalyzed C−H bond function-
result of novel mechanistic pathways for C−H activation at PdIV,
alization reactions have emerged as valuable methods in organic
different ligand environments at octahedral PdIV versus square
synthesis.1 The vast majority of these transformations are believed
planar PdII complexes, or other factor(s).
to involve C−H activation at a PdII center.1a In these systems,
This paper describes the design of PdIV model complexes that
Pd(OAc)2 is typically used as the catalyst (often in conjunction
have enabled a detailed interrogation of C−H activation at a PdIV
with a carboxylate salt or carboxylic acid solvent), and the
center. We demonstrate the first characterized example of
carboxylate plays an intimate role in the C−H cleavage process.
carboxylate-assisted C−H cleavage at PdIV and propose a mechanism
Numerous studies have implicated cyclic transition states for C−H
for this transformation that is supported by a series of experiments.
activation at PdII, where the carbonyl group of the carboxylate
ligand acts as an internal base (eq 1, 1).2,3 This carboxylate-assisted
The studies and mechanistic insights obtained herein could ultimately
prove valuable in accelerating the design and optimization of catalytic
processes involving C−H activation at high valent Pd as a key step.
RESULTS AND DISCUSSION
■
A recent communication from our group described the first
example of C−H activation at a PdIV center.10 In that system, the
oxidation of PdII precursor 2 with PhICl2 at −35 °C afforded PdIV
C−H cleavage pathway is supported by extensive experimental
data as well as quantum-mechanical calculations.4,5 DFT suggests
complex 3 as a transient intermediate. Warming a solution of 3 to
that there is minimal charge buildup in transition state 1 and that
the association between PdII and the C−H bond can be described
as an agostic interaction rather than a π-delocalized Wheland-type
species.4,5 Recent work has shown that carboxylate-assisted C−H
cleavage can also occur at RhIII, IrIII and RuII centers.1b,6−8
While carboxylate-assisted C−H activation at PdII has been well
studied, the possibility of analogous pathways at high oxidation state
palladium (PdIII and/or PdIV) centers remains unexplored. This gap
is particularly noteworthy because C−H activation at transient PdIV
intermediates has recently been proposed as a key step in a number
of different catalytic transformations.9 In most of these cases,
palladium carboxylates were used as catalysts, suggesting the
possibility for acetate-assisted pathways. However, these trans-
formations often proceed with markedly different site selectivity
25 °C resulted in rapid C−H activation to generate cyclo-
palladated product 4 (eq 2). Coordinatively unsaturated cationic
Received: February 12, 2013
© XXXX American Chemical Society
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PdIV species like 5 or 6 (Figure 1) are likely intermediates in the
conversion of 3 to 4; however, the low stability of 3 hampered
more detailed mechanistic investigations of this transformation.
Figure 1. Putative cationic PdIV intermediates.
Design of Complexes for Mechanistic Study. We hypo-
thesized that replacing the bidentate 4,4′-di-tert-butylbipyridine
ligand with a tridentate supporting ligand would stabilize
analogues of 5 and 6, thereby enabling a thorough mechanistic
investigation of the C−H activation reaction. Use of multi-
dentate ligands is a common strategy to stabilize high-valent Pd
complexes.11−13 For example, Canty and co-workers have
previously reported several organometallic PdIV tris(2-pyridyl)-
methane (Py3CH) complexes that are stable to reductive
elimination at room temperature.14 This suggested that the
third pyridine arm of Py3CH might impart an appropriate
balance of stability and reactivity to enable C−H activation
at PdIV. The Py3CH ligand was prepared in one step from
α-picoline and 2-fluoropyridine (see Supporting Information
for complete details).
Figure 2. 1H/1H ROESY spectrum of 8 (CD3NO2; 25 °C; tmix = 300 ms).
Synthesis of PdII-σ-Aryl Complexes. Our initial synthetic
efforts targeted PdIV complexes of general structure [(Py3CH)Pd-
(biphenyl)Cl2]+ (eq 3). The treatment of (Py3CH)PdII(biphenyl)-
shielding of the aromatic protons H-1 and H-2 (to 5.9 and 6.6
ppm, respectively) as well as by NOE correlations between H-1
and H-10/H-11. An analogous conformation is observed in the
solid state (vide infra). This conformational preference is likely
due to favorable π−π interactions between the biphenyl and
tripyridylmethane ligands.
1
The H NMR spectra of 8−10 show a large dependence on
the counterion X. The spin−lattice relaxation times for 8 and 9
in CDCl3 at 25 °C show that both ICl2 and Cl− have close
−
interactions with H-8, H-12, and H-16 of the Py3CH ligand.15
This is likely due to equilibration of the counterions between
these three similar sites (eq 4). Remarkably, these interactions
(I) (7) with 2 equiv of PhICl2 in CH2Cl2 at room temperature
(eq 3, method A) afforded the desired cationic PdIV product 8 in
85% yield as the ICl2− salt. The corresponding chloride salt (9)
was obtained in 83% yield under slightly modified conditions
(eq 3, method B). Finally, the treatment of 8 with 2 equiv of AgOTf
resulted in smooth conversion to the triflate salt 10 in 90% yield. As
predicted, complexes 8−10 were significantly more stable than 3,
and they could be stored in the solid state at room temperature for
at least 4 weeks without detectable decomposition.
persist even in the polar solvent CD3NO2. In contrast, the
triflate in complex 10 does not have strong interactions with
the Py3CH ligand in either CDCl3 or CD3NO2.15 Related
binding of iodide, bromide and chloride to the ligand periphery
of cationic PdIV complexes has been documented previously.16
The structure of complex 8 was further confirmed by single crystal
X-ray diffraction analysis, and an ORTEP drawing of 8 is shown in
Figure 3. In the solid state, the ICl2− counterion has short contacts
with the methine hydrogen [Cl(3)−H(1) = 2.872 Å] as well as
with pyridine proton H-2 [Cl(3)−H(2) = 2.752 Å; I−H(2) =
3.354 Å]. Furthermore, the phenyl ring of the biaryl is positioned
closely underneath the Py3CH ligand, consistent with the π-stacking
interaction proposed on the basis of the solution NMR studies.17,18
High resolution ESI mass spectrometric analysis of 8−10
showed an intense peak with m/z = 576.022, corresponding to
the cationic PdIV core. The solution stereochemistry and
1
conformations of 8−10 were elucidated via 1D H NMR and
1
2D H/1H NOESY and ROESY NMR spectra. The ROESY
NMR spectrum and peak assignments for 8 are shown in Figure 2.
The most notable feature of this structure is the orientation of the
phenyl ring of the biaryl ligand underneath two of the pyridine
rings. This solution conformation was assigned on the basis of the
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The acidification of D2O solutions of 14 with aqueous HCl
resulted in rapid and near quantitative regeneration of 9.
The observation of reversible chloride for deuteroxide ligand
exchange prompted us to test the related ligand substitution
reaction of chloride for acetate. We reasoned that incorporation of
an acetate ligand might trigger acetate-assisted C−H activation at
PdIV. Gratifyingly, the treatment of a CDCl3 solution of 9 with 5%
aqueous KOAc resulted in a rapid color change from orange to
yellow within 5 min, and 1H NMR analysis of the separated CDCl3
layer showed clean conversion to the cyclometalated product 13.
When this reaction was performed on a preparative scale, 13 was
isolated in only 39% yield. However, optimization of the conditions
(through the use of anhydrous CHCl3 as the solvent and
substituting aqueous KOAc with AgOAc) led to the formation of
13 in 78% isolated yield after 5 min at 25 °C (eq 7).22
Figure 3. ORTEP drawing of complex 8. Thermal ellipsoids are drawn
at 50% probability. Only hydrogen atoms involved in short contact
with ICl2− are shown for clarity. Selected bond lengths (Å): Pd−C(1)
2.087(3), Pd−Cl(1) 2.2904(7), Pd−N(1) 2.184(3), Pd−N(2)
2.043(3), Cl(3)−H(1) 2.872(3), Cl(3)−H(2) 2.751(8), I−H(2)
3.353(8). Selected bond angles (deg): N(2)−Pd−Cl(1) 88.32(7),
Cl(1)−Pd−Cl(2) 90.12(3), Cl(2)−Pd−N(3) 89.82(7), N(3)−Pd−
N(2) 91.27(8), N(1)−Pd−C(1) 178.87(11).
Complex 13 is stable at room temperature in the solid state
and in CDCl3 solution for at least two weeks. This
cyclometalated compound was characterized using standard
1D and 2D NMR analysis as well as by single crystal X-ray
diffraction. The X-ray structure of 13 is shown in Figure 4. In
Reactivity of 8−10. On the basis of our previous work
(eq 2),10 we expected that heating complexes 8−10 would
result in C−H activation to form products like 13 (eq 5a).
However, instead, heating 9 at 90 °C for 2 h in CDCl3 resulted
in C−Cl bond-forming reductive elimination to afford PdII
complex 11 along with chlorobiphenyl 12 (eq 5b).
We next hypothesized that base might be necessary to promote
C−H activation in this system. However, the treatment of 9 with an
excess of triethylamine or pyridine in CH2Cl2 at room temperature
for 4 h returned only unreacted starting material (eq 6b).19
Figure 4. ORTEP drawing of complex 13. Thermal ellipsoids are
drawn at 50% probability. Only hydrogen atom involved in short
contact with chloride counterion is shown for clarity. Selected bond
lengths (Å): Pd−C(1) 2.1765(14), Pd−Cl(1) 2.2961(6), Pd−N(1)
2.1765(14), Pd−N(2) 2.049(2), H(1)−Cl(2) 2.238(17). Selected
bond angles (deg): N(1)−Pd−Cl(1) 91.95(4), Cl(1)−Pd−C(1)
88.51(5), C(1)−Pd−N(2) 90.58(6), N(2)−Pd−N(1) 88.96(5),
C(1)−Pd−C(1′) 81.47(9), N(1)−Pd−C(1) 179.14(6).
Complex 9 did react quantitatively with NaOD at 25 °C to form a
colorless D2O-soluble PdIV product that we propose to be the
deuteroxide complex 14 (eq 6a). Attempts to isolate 14 resulted in
decomposition; however, this complex was characterized in situ via
the solid-state, the chloride counterion is in short contact with
the methine hydrogen (Cl(2)−H(1) = 2.568 Å) as well as with
a cocrystallized water molecule.
Proposed Mechanism of C−H Activation. We next
sought to gain insights into the mechanism of this C−H
activation reaction. As noted in eq 6 and 7, acetate was the only
base examined that promoted this transformation. This strongly
suggests that the carboxylate is not simply serving as an exter-
nal base in the reaction. Furthermore, the observation of
1
13C{1H}, H/1H gCOSY, and NOESY NMR experiments as well
as 1H/13C HSQC and HMBC correlation experiments. We
formulate 14 as a monomer rather than an oxo or deuteroxo-
bridged dimer on the basis of internal reference diffusion-ordered
NMR (DOSY)20 spectroscopic analysis.21 Notably, the chloride-
to-deuteroxide ligand exchange was completely reversible.
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facile replacement of chloride with hydroxide (eq 6) indicates
the feasibility of ligand substitution to form a PdIV acetate
intermediate prior to C−H activation. On the basis of these
preliminary observations, we hypothesized that the observed
C−H activation reaction could proceed via the pathway depicted
in eq 8. This involves four distinct steps: (1) chloride-to-acetate
support the assignment of this species as a monoacetate complex.
Most importantly, the 1H NMR spectrum shows that this
intermediate lacks a plane of symmetry, suggesting that only one
chloride ligand has undergone ligand exchange with an acetate. The
observed substitution of only one of the chloride ligands is likely due
to the possibility of κ2 binding of the acetate to the cationic PdIV
center (eq 10).24 This binding mode would inhibit coordination of a
second acetate.
In order to gain further insights into ligand exchange processes
at 9, we examined substitution reactions with other nucleo-
philic anions. As shown in eq 11, complex 9 underwent facile
ligand exchange with both bromide and azide to generate stable
products 19−22.
ligand substitution, (2) rotation about the Pd−CAryl bond, (3)
pyridine ligand dissociation and configurational isomerization via
Berry pseudorotation, and (4) acetate-assisted C−H cleavage.
(Note that steps 2 and 3 could also occur in opposite order.) We
have conducted a variety of experiments to assess the feasibility of
each of the proposed steps. These studies are described in detail in
the sections below.
Ligand Substitution. The first step of the proposed
mechanism involves chloride to acetate ligand substitution at
cationic PdIV complex 9. This would be expected to proceed via
reversible dissociation of one pyridine arm of the Py3CH ligand
followed by binding of acetate to generate intermediate 18 (eq 9).
Complexes 19−22 were characterized using conventional 1D
and 2D NMR techniques as well as HRMS. All of these
compounds show CS symmetry, which indicates that both
1
chloride ligands have been exchanged. Notably, the H NMR
spectrum of 19 shows several equilibrating species, suggesting
that it exists as a mixture of conformational and configurational
1
isomers (vide infra for further discussion). In contrast, the H
NMR spectra of 20−22 are each consistent with the presence
of a single major isomer in solution. These latter spectra are
extremely similar to that of 8. The identity of complex 20 was
further confirmed by single crystal X-ray diffraction analysis,
and the structure is shown in Figure 5. Interestingly, in this case
Subsequent chloride dissociation and reassociation of the pyridine
arm would then yield 15.
We first sought to detect 15 at low temperature using
1H NMR spectroscopy. Treatment of a CD2Cl2 solution of 9 with
3 equiv of Bu4NOAc at −20 °C resulted in the formation of a new
species with spectroscopic features consistent with 15 (eq 10). This
Figure 5. ORTEP drawing of complex 20. Thermal ellipsoids are
drawn at 50% probability. Hydrogen atoms are omitted for clarity.
Selected bond lengths (Å): Pd−C(1) 2.092(3), Pd−Br(1) 2.4267(5),
Pd−N(1) 2.199(3), Pd−N(2) 2.070(3). Selected bond angles (deg):
N(2)−Pd−Br(1) 88.74(8), Br(1)−Pd−Br(2) 89.707(15), Br(2)−
Pd−N(3) 89.17(8), N(3)−Pd−N(2) 91.88(10), N(1)−Pd−C(1)
177.49(13).
compound was unstable to isolation and underwent rapid C−H
activation to form 13 upon warming to 0 °C. As such, 15 could only
be characterized in situ by 1D 1H NMR spectroscopy as well as 2D
1H/1H gCOSY and NOESY.23 Several diagnostic spectral features
−
the IBr2 counterion is not in short contact with the cationic
PdIV core.
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The chloride to bromide ligand exchange was readily reversible,
and 20−22 reacted rapidly (within 5 min at 25 °C) with aqueous
NaCl to regenerate 9 (eq 11a). The presence of bromide ligands
did not alter the reactivity of the PdIV center toward carboxylate-
assisted C−H activation. For example, the reaction of 22 with 4
equiv of AgOAc resulted in clean C−H cleavage to afford
cyclometalated product 23 in 53% isolated yield (eq 12a). In
Despite this complexity, the experiments showed that, under
otherwise identical reaction conditions, ligand substitution of Cl for
Br at 10 proceeds to completion more than 10-fold faster than the
analogous transformation at 24. This is consistent with our
predictions about the increased rigidity of Py3CCH3 compared to
Py3CH.
Rotation about the PdIV−CAryl Bond. As discussed above,
complexes 8−10 were obtained as a single conformer with respect
to rotation about the Pd−biphenyl bond. The favored conformation
has the biphenyl ligand positioned under the Py3CH group. We
hypothesize that this conformation is stabilized by π-stacking
between the electron-rich phenyl group of the biphenyl and the
electron deficient pyridines. In an effort to disrupt this π−π
interaction, we synthesized a complex containing three electron-
withdrawing fluorine substituents on the biphenyl ligand (26). As
anticipated, this compound exists as a mixture of two CS symmetric
conformational isomers 26a and 26b (26a:26b = 40:60 in CDCl3,
contrast, the equilibrium for chloride to azide exchange appears to
lie far to the left, as no reaction was observed upon treatment of
19 with a large excess of aqueous NaCl (eq 11b). In addition, the
treatment of azide complex 19 with AgOAc returned only
unreacted starting material (eq 12b).
1
eq 15). The identity of each isomer was established using 1D H
The proposed ligand substitution (step 1 in eq 8) as well as
the configurational isomerization (step 3 in eq 8) both involve
reversible dissociation of one arm of the Py3CH ligand. We thus
hypothesized that these two steps (and therefore potentially the
overall C−H activation process) would be slowed significantly
by replacing the Py3CH ligand with Py3CCH3 (complex 24
in eq 13). The additional methyl group in Py3CCH3 is expected
NMR and 2D 1H/1H ROESY NMR spectroscopy. In addition, an
EXSY experiment revealed that 26a and 26b interconvert on the
NMR time scale.26 Collectively, these results show that rotation
around the Pd−aryl bond is fast in 26 and that both conformations
are readily accessible at room temperature.27
As shown in eq 15, both complex 26 and its triflate
counterpart 27 participate in acetate-assisted C−H activation in
a similar fashion to 8−10. For example, the treatment of 27a,b
with 4 equiv of AgOAc in dry CHCl3 afforded product 28 in
66% isolated yield.28 Overall this series of experiments
demonstrates the feasibility of rotation about the PdIV−aryl
bond in complexes that undergo acetate-assisted C−H activation
(and that are closely related to the parent compounds 8−10).
Configurational Isomerization via Berry Pseudorota-
tion. The viability of the proposed configurational isomer-
ization process was first probed by EXSY NMR experiments in
complexes of general structure [(Py3CH)Pd(biphenyl)Y2]+.26
Only one isomer is observed in the 1H and 13C NMR spectra of
to render 24 more rigid than Py3CH, thereby hindering the
pyridine dissociation process.
Complex 24 was synthesized using a similar procedure to
that for 10. As predicted, this complex showed dramatically
reduced reactivity toward acetate-assisted C−H activation. The
treatment of 24 with AgOAc or aqueous KOAc at room
temperature did not lead to cyclometalation (eq 13). Instead,
these conditions resulted in slow (over 1 h) decomposition of
24 to generate a complex mixture of products.
To directly compare ligand substitution at 24 and 10, we studied
the reaction of both complexes with KBr (eq 14). The reactions
1
dichloride complexes 8−10; furthermore, H/1H ROESY and
NOESY experiments show that 8−10 are configurationally
1
stable on the NMR time scale. In contrast, the H/1H ROESY
spectrum of dibromide complex 20 (Figure 6) shows chemical
exchange cross peaks between the two equivalent pyridine rings
trans to the bromides and the one distinct pyridine ring trans to
the carbon.
It is well documented that six-coordinate complexes can undergo
inversion of configuration at the metal via bond-rupture and
generation of a configurationally labile five-coordinate intermedi-
ate.29 We propose that the observed exchange in complex 20 is the
result of such a pathway. As depicted in eq 16, initial dissociation of
one arm of the facial tridentate pyridine ligand (labeled N2 in eq 16)
were monitored via UV−vis spectroscopy based on the appearance
of an absorbance band at 480 nm. Because the overall
transformation shown in eq 14 involves multiple elementary steps,
the obtained reaction traces could not be fitted to simple rate laws.25
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(25) shows no analogous chemical exchange cross-peaks,
indicating that this exchange process is significantly slower than
in the corresponding Py3CH adduct 20. This provides additional
support for the exchange pathway involving reversible dissociation
of an arm of the pyridine ligand.
Acetate Assisted C−H Cleavage. A series of isotope
effect studies were conducted to gain insights into the nature of
the transition state for C−H cleavage as well as to establish
whether C−H bond activation is involved in the rate-determining
step of the overall transformation.34 Monodeuterated complex 31
was synthesized by analogy to the procedure shown in eq 3.35
Complex 31 was then treated with various carboxylate sources to
yield the cyclopalladated product 32 (eq 17). 1H NMR analysis of
32 showed that cleavage of the C−H bond occurs in preference to
cleavage of the C−D bond with all of the carboxylates examined.
Accurate values for the intramolecular isotope effect were obtained
via ESI mass spectrometric analysis. All of the carboxylate sources
tested [KOAc (aqueous), AgOAc, AgOPiv, AgO2CCF3, and
AgO2CC6H5] afforded product 32 with an intramolecular kH/kD
between 9 and 12 at 25 °C. Increasing the reaction temperature to
55 °C and lowering it to 0 °C had a relatively small influence on
the observed isotope effect. For example, with AgOAc, kH/kD = 10
at 0 °C and 7 at 55 °C. These latter results indicate that quantum
tunneling does not contribute significantly to the isotope effect in
this system.36 Overall, the observed large magnitude of the
intramolecular isotope effect is indicative of a central transition
state for C−H cleavage, suggesting that the proton is transferred
between two sites of similar basicity.37 The observed values are
similar to those reported for carboxylate-assisted C−H cleavage
at Pd(II)4d and Ir(III)7b centers (values in the literature vary
from 5 to 7).
The intermolecular KIE for this reaction was next determined
using substrates 33 and 36 (eq 18). The t-butyl group was
Figure 6. 2D 1H/1H ROESY NMR spectrum of 20. 1D trace and peak
assignments are provided above. The peaks marked with * are low
intensity resonances associated with an unknown species that is in fast
exchange with 20.
would afford the 5-coordinate complex 29, which could undergo
configurational isomerization to form 30 via Berry pseudorotation.30
Reassociation of N2 would then afford product 20a. Importantly,
complexes 20 and 20a are chemically equivalent, with the sole
difference that N2 has swapped places with one of the N1 groups.
The configurational isomerization pathway proposed in eq 16 is
further supported by the observation of broad, low intensity
resonances in the H NMR and H/1H ROESY spectra of 20
(labeled with asterisks in Figure 6). This species is in fast exchange
with 20 on the NMR time scale. Although the broad signals make it
difficult to characterize definitively, we propose that this could be an
intermediate like 29 or 30.31−33
1
1
As discussed above, the Py3CCH3 ligand was predicted to render
the Pd center less reactive toward ligand dissociation, the first step
of the configurational isomerization process in eq 16. Indeed, the
ROESY NMR spectrum of [(Py3CCH3)Pd(Br)2(biphenyl)]Br
introduced on the biphenyl ligand of 33 and 36 in order to
enhance solubility (essential for obtaining quantitative rate data).
The fluorine substituent was added to enable monitoring of the
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reaction rate using 19F NMR spectroscopy.38 The treatment of 33
and 36 with 3 equiv of AgOPiv resulted in smooth conversion to
cyclopalladated products 35 and 38. The progress of these
reactions was monitored by 19F NMR spectroscopy. After 5 min,
both substrates 33 and 36 underwent nearly quantitative
conversion to the monopivalate intermediates 34 and 37. Both
intermediates 34 and 37 then underwent relatively slow
conversion to 35 and 38, respectively. The overall reaction rates
for substrates 33 and 36 under these conditions were the same
within the error of measurement. These observations show that
the rate of the overall transformation is not limited by the rate of
the ligand exchange or the availability of the carboxylate ligand and
that either conformational or configurational isomerization is likely
the rate-limiting step in this transformation.
(2) Ryabov, A. D.; Sakodinskaya, I. K.; Yatsimirsky, A. K. J. Chem.
Soc., Dalton Trans. 1985, 2629−2638.
(3) Lafrance, M.; Gorelsky, S. I.; Fagnou, K. J. Am. Chem. Soc. 2007,
129, 14570−14571.
(4) (a) Lapointe, D.; Fagnou, K. Chem. Lett. 2010, 39, 1118−1126.
(b) Gorelsky, S.; Lapointe, D.; Fagnou, K. J. Org. Chem. 2012, 77,
658−668. (c) Gorelsky, S. I.; Stuart, D. R.; Campeau, L.-C.; Fagnou,
K. J. Org. Chem. 2010, 75, 8180−8189. (d) D. García-Cuadrado, D.;
Braga, A. A. C.; Maseras, F.; Echavarren, A. M. J. Am. Chem. Soc. 2006,
128, 1066−1067.
(5) Davies, D. L.; Donald, S. M. A.; Macgregor, S. A. J. Am. Chem.
Soc. 2005, 127, 13754−13755.
(6) For carboxylate-assisted C−H activation at RhIII, see: Rhinehart,
J. L.; Manbeck, K. A.; Buzak, S. K.; Lippa, G. M.; Brennessel, W. W.;
Goldberg, K. I.; Jones, W. D. Organometallics 2012, 31, 1943−1952.
(7) For carboxylate-assisted C−H activation at IrIII, see: (a) Davies,
D. L.; Donald, S. M. A.; Al-Duaij, O.; Macgregor, S. A.; Polleth, M. J.
̈
CONCLUSIONS
■
Am. Chem. Soc. 2006, 128, 4210−4211. (b) Li, L.; Brennessel, W. W.;
This paper describes a detailed investigation of carboxylate-assisted
C−H activation at PdIV centers. As discussed above, we propose a
pathway involving four steps: (1) ligand exchange, (2) Pd−CAryl
bond rotation, (3) configurational isomerization via Berry
pseudorotation, and (4) carboxylate-assisted C−H cleavage. The
feasibility of each of these steps is supported by the experiments
presented above. A key feature of the investigated [(Py3CH)Pd-
(biphenyl)Cl2]X system is the semilabile tridentate tris(2-pyridyl)-
methane ligand. This ligand stabilizes octahedral cationic PdIV
centers toward reductive elimination. However, coordinatively
unsaturated species can be accessed readily via dissociation of a
pyridine arm of the ligand. This ligand dissociation is believed to
facilitate the key ligand exchange and configurational isomerization
steps. Importantly, the extremely mild conditions necessary for
acetate assisted C−H cleavage at PdIV centers renders this process
attractive for applications in catalytic C−H functionalization
processes mediated by high oxidation state palladium. Ongoing
investigations are focused on expanding this reactivity to other
octahedral high valent group 10 metal centers and to conducting
detailed investigations of the factors governing site selectivity in
these transformations.
Jones, W. D. Organometallics 2009, 28, 3492−3500.
(8) For carboxylate-assisted C−H activation at RuII, see: Davies, D.
L.; Al-Duaij, O.; Fawcett, J.; Giardiello, M.; Hilton, S. T.; Russell, D. R.
Dalton Trans. 2003, 4132−4138.
(9) (a) Juwaini, N. A. B.; Ng, J. K. P.; Seayad, J. ACS Catal. 2012, 2,
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(10) Racowski, J. M.; Ball, N. D.; Sanford, M. S. J. Am. Chem. Soc.
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(11) Examples of PdIV complexes supported by neutral tridentate
(L3-type) ligands: (a) Klaui, W.; Glaum, M.; Wagner, T.; Bennett, M.
A. J. Organomet. Chem. 1994, 472, 355−358. (b) Bennett, M. A.;
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(12) Examples of PdIV tris(pyrazoyl)borate complexes: (a) Campora,
J.; Palma, P.; del Rio, D.; Lopez, J. A.; Alvarez, E. Organometallics 2005,
24, 3624−3628. (b) Canty, A. J.; Jin, H.; Penny, J. D. J. Organomet.
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Skelton, B. W.; White, A. H. Organometallics 1996, 15, 5713−5722.
(13) Examples of PdIV pincer complexes: (a) Vicente, J.; Arcas, A.;
Julia-Hernandez, F.; Bautista, D. Inorg. Chem. 2011, 50, 5339−5341.
(b) Vicente, J.; Arcas, A.; Julia-Hernandez, F.; Bautista, D. Angew.
Chem., Int. Ed. 2011, 50, 6896−6899. (c) Vicente, J.; Arcas, A.; Julia-
Hernandez, F.; Bautista, D. Chem. Commun. 2010, 46, 7253−7255.
(d) Canty, A. J.; Rodemann, T.; Skelton, B. W.; White, A. H.
Organometallics 2006, 25, 3996−4001. (e) Lagunas, M.-C.; Gossage, R.
A.; Spek, A. L.; van Koten, G. Organometallics 1998, 17, 731−741.
(f) Alsters, P. L.; Engel, P. F.; Hogerheide, M. P.; Copijn, M.; Spek, A.
L.; van Koten, G. Organometallics 1993, 12, 1831−1844.
(14) (a) Byers, P. K.; Canty, A. J.; Skelton, B. W.; White, A. H.
Organometallics 1990, 9, 826−832. (b) Byers, P. K.; Canty, A. J.;
Skelton, B. W.; White, A. H. J. Chem. Soc., Chem. Commun. 1987,
1093−1095.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental details and crystallographic (CIF) and spectro-
scopic data for new compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
mssanfor@umich.edu
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We thank the NSF (CHE-1111563) for support of this research.
We also acknowledge funding from NSF Grant CHE-0840456 for
X-ray instrumentation. A.M. is a Howard Hughes Medical Institute
International Student Research Fellow.
(15) See pages S231−S235 in Supporting Information Document 4
for full details.
(16) (a) McCall, A. S.; Wang, H.; Desper, J. M.; Kraft, S. J. Am.
Chem. Soc. 2011, 133, 1832−1848. (b) Brown, D. G.; Byers, P. K.;
Canty, A. J. Organometallics 1990, 9, 1231−1235.
(17) The phenyl ring and pyridine rings of the Py3CH ligand in
complex 8 are offset, which is known to be the most favorable π-
stacking geometry. For detailed discussion on π-stacking interactions
and geometries, see: Hunter, C. A.; Sanders, J. M. K. J. Am. Chem. Soc.
1990, 112, 5525−5534.
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Journal of the American Chemical Society
Article
(18) The interplane angles between the phenyl ring of the biphenyl
ligand and pyridine rings of the Py3CH ligand in complex 8 are 28.3
and 39.7 degrees. The distances between the centroid of the phenyl
ring of the biphenyl ligand and centroids of the pyridine rings of the
Py3CH ligand are 3.754 Å and 4.206 Å. Such centroid−centroid
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observation that the Pd-N1 bond in dibromide complex 20 is 0.014
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in 20 is 0.027 Å longer than in 8. This data indicates that the more π-
donating bromide has a stronger cis and trans influence than the
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trans effect in PdIV d6 complexes such as 8 and 20.
(33) Interestingly, no chemical exchange crosspeaks were detected in
the 1H/1H ROESY spectrum for [(Py3CH)Pd(biphenyl)Br2][TfO]
(22). This observation demonstrates the influence of the outer-sphere
counterion on the inner sphere Py3CH ligand. A possible explanation
for this observation is that hydrogen bonding of IBr2− with the Py3CH
ligand in complex 20 promotes dissociation of one pyridine ring and
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́
(19) When this reaction was conducted at 60 °C, complex 10
underwent decomposition to generate a complex mixture of
unidentified products. The desired product 14 was not detected.
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(21) See pages S170−S172 in Supporting Information Document 4
for full details.
(22) When complex 9 was treated with 10 equiv of AgBF4 in CDCl3
solution (sonication for 1 h and stirring at room temperature for 24 h),
only abstraction of the outer sphere chloride counterion occurred, and
no cyclopalladated product 13 was formed as determined by 1H NMR.
When AgSbF6 was used instead of AgBF4, the starting material 9
decomposed to a complex mixture of products, none of which was the
anticipated cyclopalladated product 13. These results show that acetate
rather than silver ions promotes the C−H cleavage reaction.
(23) We used 6 sterically and electronically distinct carboxylates to
promote C−H cleavage (vide infra). In addition to monocarboxylates
we have also tested several dicarboxylates such as oxalate, malonate,
succinate, and glutarate. None of these mono- or dicarboxylates
afforded an intermediate that was stable enough to be isolated and
completely characterized.
(36) (a) Anslyn, E. V.; Dougherty, D. A. Modern Physical Organic
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respectively. Competitive formation of unidentified side products
precluded the determination of reliable rate constants for C−H
activation under these conditions.
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N.; Amoroso, D.; Bell, A.; Protasiewicz, J. D. Organometallics 2005, 24,
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(27) Surprisingly, the isomeric triflate complexes 27a and 27b do not
interconvert on the NMR time scale. This observation indicates that
the counterion can influence flexibility of the cationic PdIV core.
(28) Complex 26 also undergoes acetate-assistated C−H activation
under analogous conditions. However, in this case, the isolated
product was contaminated with approximately 15% of an unidentified
side product that could not be removed by crystallization.
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(31) We disfavor formulation of this species as an octahedral
tribromide complex on the basis of the fact that the addition of 2−4
equiv of NBu4Br did not increase the equilibrium population of this
compound in solution.
(32) The exchange processes described above can be observed for
both complexes 19 and 20 using ROESY spectroscopy. In contrast,
analogous exchange does not occur on the NMR time scale for
chloride complex 8. This is likely due to the strong π-donor ability of
azide and bromide ligands as well as their larger size compared to
chloride. Strong π-donors such as bromide should decrease ligand-field
strength and ligand-field activation energy [which is relatively high for
d6 PdIV] and thereby facilitate dissociation of one pyridine arm of the
hemilabile Py3CH ligand. This proposal is supported by the
H
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