Syntheses and thermolysis of arylpalladium hydroxide complexes: Implications for C(sp2)-OH bond-forming reductive elimination to generate phenol derivatives

Article abstract of DOI:10.1021/om201142s

The decomposition of arylpalladium hydroxide complexes gave the corresponding phenolic products, which may form through a C(sp²)-OH bond-forming reductive elimination either by treatment of arylpalladium halide complexes with cesium hydroxide or by heating arylpalladium hydroxide complexes. Treatment of a p-nitrophenylpalladium iodide complex possessing a ^tBuXPhos ligand with cesium hydroxide formed a mixture of p-nitrophenol and 4,4′-di-p-nitrobiphenyl. The reaction of a D ^tBPP-ligated p-nitrophenylpalladium iodide complex with cesium hydroxide gave a mixture of p-nitrophenylpalladium hydroxide complex, cesium p-nitrophenoxide, and D^tBPP-bridged dinuclear Pd(0) complex. Gradual decomposition of p-nitrophenylpalladium hydroxide complex to cesium p-nitorophenoxide and a D^tBPP-bridged dinuclear Pd(0) complex suggested that the C(sp²)-OH bond-forming reductive elimination took place. While an isolated p-tolylpalladium hydroxide complex gave no phenolic product upon heating, thermolysis of an isolated trifluoromethyl-substituted arylpalladium hydroxide complex enabled us to observe p-trifluoromethylphenol directly. Although an ester-substituted hydroxide complex did not form free p-methoxycarbonylphenol, its invisibility enabled us to handle the kinetic equation to estimate the rate constant k₁ for reductive elimination. Polar solvents such as THF and DMF accelerated the reductive elimination with a large negative entropy of activation. Comparison of these results with those in the literature suggested direct C(sp²)-OH bond-forming reductive elimination with a concerted three-centered pathway. DFT calculations also predicted the hydrogen bond between the hydroxo ligand and the solvent molecule to stabilize the transition state.

Full text of DOI:10.1021/om201142s

Article
pubs.acs.org/Organometallics
Syntheses and Thermolysis of Arylpalladium Hydroxide Complexes:
Implications for C(sp2)−OH Bond-Forming Reductive Elimination To
Generate Phenol Derivatives
Yumi Hayashi, Shinji Wada, Makoto Yamashita,*,† and Kyoko Nozaki*
Department of Chemistry and Biotechnology, Graduate School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku,
113-8656 Tokyo, Japan
S
* Supporting Information
ABSTRACT: The decomposition of arylpalladium hydroxide
complexes gave the corresponding phenolic products, which may
form through a C(sp2)−OH bond-forming reductive elimination
either by treatment of arylpalladium halide complexes with cesium
hydroxide or by heating arylpalladium hydroxide complexes.
Treatment of a p-nitrophenylpalladium iodide complex possessing
t
a BuXPhos ligand with cesium hydroxide formed a mixture of p-
nitrophenol and 4,4′-di-p-nitrobiphenyl. The reaction of a DtBPP-
ligated p-nitrophenylpalladium iodide complex with cesium
hydroxide gave a mixture of p-nitrophenylpalladium hydroxide
complex, cesium p-nitrophenoxide, and DtBPP-bridged dinuclear
Pd(0) complex. Gradual decomposition of p-nitrophenylpalladium hydroxide complex to cesium p-nitorophenoxide and a
DtBPP-bridged dinuclear Pd(0) complex suggested that the C(sp2)−OH bond-forming reductive elimination took place. While
an isolated p-tolylpalladium hydroxide complex gave no phenolic product upon heating, thermolysis of an isolated
trifluoromethyl-substituted arylpalladium hydroxide complex enabled us to observe p-trifluoromethylphenol directly. Although an
ester-substituted hydroxide complex did not form free p-methoxycarbonylphenol, its invisibility enabled us to handle the kinetic
equation to estimate the rate constant k1 for reductive elimination. Polar solvents such as THF and DMF accelerated the
reductive elimination with a large negative entropy of activation. Comparison of these results with those in the literature
suggested direct C(sp2)−OH bond-forming reductive elimination with a concerted three-centered pathway. DFT calculations
also predicted the hydrogen bond between the hydroxo ligand and the solvent molecule to stabilize the transition state.
forming reductive elimination using Pt(IV) complexes
contained C(sp3)−OH bond-forming reductive elimination
from alkylmetal hydroxide complexes to produce aliphatic
alcohols.8c−f High-valent Pd(IV) complexes are also known to
undergo C(sp2)−OH bond-forming reductive elimination.7d
On the other hand, catalytic syntheses of phenol derivatives
from the corresponding aryl halide and hydroxide anion have
been reported by use of a palladium complex and a bulky
monophosphine ligand.9 The catalytic cycles of these reactions
were considered to include C(sp2)−OH bond-forming
reductive elimination as a product-forming step. However,
there has been no information about this process because
arylpalladium hydroxide intermediates possessing the bulky
monophosphine ligand were too unstable to be observed. Here
we report syntheses and thermolyses of arylpalladium
hydroxide complexes bearing a monophosphine or diphosphine
ligand to implicate C(sp2)−OH bond-forming reductive
elimination reactions.
INTRODUCTION
■
Carbon−heteroatom bond-forming reductive elimination re-
actions for C−P, C−S, C−N, and C−O are some of the most
important organometallic elementary reactions, studied as a
part of mechanistic investigations on transition-metal-catalyzed
reactions.1 It was indicated that the relative rate for these
reductive elimination reactions could be described as C−P >
C−S > C−N > C−O.2 Despite the slow rate of C−O bond-
forming reductive elimination reactions, these processes have
been carefully investigated because they may possibly be an
elementary reaction for designing difficult catalytic reactions
such as anti-Markovnikov hydration of alkene3 and direct
terminal oxidation of alkane.3a,4 Previous examples of directly
observed C−O bond-forming reductive elimination reactions
could be classified into several groups by the central metals and
their oxidation states, such as Pd(II),5 Ni(III),6 Pd(IV),7 and
Pt(IV).8 Detailed mechanistic studies generally suggested that
C−O bond-forming reductive elimination proceeded via a
concerted three-centered pathway induced by an oxidation of
the metal center,6 a dissociation of other ligand(s),5,7a−c or a
stepwise pathway containing dissociation of anionic oxygen
ligand from the metal center followed by its SN2-type attack at
the alkyl ligand.8a−d Some of these studies on C−O bond-
Received: November 16, 2011
Published: February 1, 2012
© 2012 American Chemical Society
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bearing DtBPP were synthesized from various palladium
precursors (Scheme 3). From the iodide-bridged dinuclear
RESULTS AND DISCUSSION
■
Synthesis of a Bulky Monodentate Phosphine Ligated
Arylpalladium Halide Complex To React with Hydrox-
t
Scheme 3. Syntheses of Arylpalladium Halide Complexes 4
Bearing a DtBPP Ligand
ide. Complexation of BuXPhos, which was reported to be a
good ligand for phenol synthesis,9a with CpPd(allyl)10 in the
presence of p-iodonitrobenzene afforded the three-coordinate
palladium complex (tBuXPhos)Pd(C6H4-p-NO2)I (1) in 78%
yield (Scheme 1). The 1H, 13C, and 31P NMR spectra of 1 were
Scheme 1. Synthesis of p-Nitrophenylpalladium Iodide
t
Complex 1 Bearing a BuXPhos Ligand
consistent with the expected structures. The whole structure
was confirmed by X-ray crystallography (Figure S15,
Supporting Information). A three-coordinate structure was
found in the solid state of 1 to have a relatively short contact
between the central palladium and 1-position of the
triisopropylphenyl ring (Pd1- - -C21 = 2.566(5) Å), as the
related monophosphine-ligated arylpalladium fluoride or bro-
mide complexes had a similar structure.11 Then, we attempted
to generate an arylpalladium hydroxide complex by the
treatment of 1 with cesium hydroxide hydrate (Scheme 2).
Scheme 2. Attempted Synthesis of Arylpalladium Hydroxide
Complex from Arylpalladium Iodide 1 with CsOH
a
complex [(o-tol)3PPd(C6H4-p-NO2)I]2, replacement of (o-
tol)3P with DtBPP gave (DtBPP)Pd(C6H4-p-NO2)I (4-NO2)
in 67% yield. A ligand exchange reaction of (tmeda)Pd(p-tol)I
with DtBPP gave the corresponding (DtBPP)Pd(p-tol)I
complex (4-Me) in 54% yield. Mixing of DtBPP, aryl halide,
and CpPd(allyl)10 afforded (DtBPP)Pd(C6H4-p-CF3)Br (4-
CF3) and (DtBPP)Pd(C6H4-p-CO2Me)I (4-CO2Me) in 89%
and 86% yields, respectively.
Three of the four complexes were structurally characterized
by X-ray analysis (Figures S16−S18, Supporting Information).
A THF molecule was cocrystallized with 4-Me to cause
disorder of the whole molecule. All complexes showed a typical
square-planar four-coordinate structure with a cis-chelate of the
DtBPP ligand having a wide bite angle of around 98°.
a
1
Yields were estimated from the H NMR spectrum.
Instead of detecting any arylpalladium hydroxide complex,
however, p-nitrophenol 2-NO2 and biaryl 3-NO2 were observed
after quenching with proton. The Pd counterpart may form
metallic Pd(0) in the absence or presence of an additional
Reactions of Bidentate Phosphine-Ligated Arylpalla-
dium Halide Complexes with CsOH. Reaction of 4-NO2
with an excess amount of solid cesium hydroxide in THF-d8
was monitored by 1H NMR spectroscopy (Scheme 4). Leaving
the reaction mixture at room temperature for 3 h led to a
complete consumption of 4-NO2 and formation of cesium p-
nitrophenoxide 7-NO2 and dinuclear palladium(0) complex 8.
t
amount of BuXPhos, because a large amount of black
precipitate was observed. Beller et al. reported a similar
observation for generation of phenol from arylpalladium
bromide possessing a P−N bidentate ligand and tetrabuty-
lammonium hydroxide via a rapid reductive elimination.9c The
formation of biaryl could be explained by the C−C bond-
forming reductive elimination from the diarylpalladium
complex, which may be generated by intermolecular aryl
exchange reaction of 1.12
Syntheses of Bulky Bidentate Phosphine-Ligated
Arylpalladium Halide Complexes. To synthesize isolable
arylpalladium hydroxide, which can undergo C(sp2)−OH
bond-forming reductive elimination, the bulky bidentate ligand
DtBPP (1,3-bis(di-tert-butylphosphino)propane) was used as a
supporting ligand. A series of arylpalladium halide complexes
1
The H NMR spectrum measured 1.5 h before the complete
consumption of 4-NO2 showed the formation of the thermally
unstable arylpalladium hydroxide complex 5-NO2, character-
ized by NMR spectroscopy as a mixture of 7-NO2 and 8 (see
1
the Supporting Information). On comparison of the H NMR
spectrum of the mixture with those of the isolated 4-NO2, 7-
NO2, and 8, characteristic signals for the p-nitrophenyl moiety
and two distinct tBu groups were observed for 5-NO2. Gradual
decomposition of 5-NO2 to 7-NO2 and 8 supported the notion
that the C(sp2)−OH bond-forming reductive elimination
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1
a disappearance of hydroxide proton in their H NMR spectra
and by an observation of a νOH vibration (3422 cm−1 for 5-Me,
3422 cm−1 for 5-CF3, 3410 cm−1 for 5-CO2Me) in their IR
spectra.
Scheme 4. Generation of Arylpalladium Hydroxide Complex
5-NO2 and Subsequent Reactions
Structures of isolated arylpalladium hydroxide complexes 5
were unambiguously characterized by X-ray crystallography
(Figures 1−3). Hydrogen atoms of hydroxo ligands were
occurred from 5-NO2. The product 8 was independently
synthesized and fully characterized, as illustrated in Scheme 5.13
Scheme 5. Independent Synthesis of Dinuclear Palladium(0)
Complex 8
Figure 1. ORTEP drawing of 5-Me (50% thermal ellipsoids).
Hydrogen atoms, except the hydroxide proton, and one of the two
independent molecules are omitted for clarity; R1 = 0.0386, GOF =
1.121. Selected bond distances (Å) and angles (deg)s: Pd1−C1,
2.046(3), 2.045(3); Pd1−O1, 2.046(2), 2.038(2); Pd1−P1,
2.2853(12), 2.2870(12); Pd1−P2, 2.4215(13), 2.4005(12); C1- - -
O1, 2.707, 2.703; P1−Pd1−P2, 98.10(4), 98.10(4); C1−Pd1−O1,
82.82(12), 82.89(12); P1−Pd1−C1, 92.53(10), 93.34(10); P2−Pd1−
O1, 86.58(8), 85.59(8).
Formation of phenoxide 7-NO2 may come from a deprotona-
tion of the reductively eliminated phenol 2-NO2 by cesium
hydroxide. The resulting DtBPP-ligated palladium(0) complex
6 may dimerize to form 8 in moderate yield. The addition of
trifluoroacetic acid to the reaction mixture liberated p-
nitrophenol 2-NO2 in high yield. Thus, it was difficult to
isolate arylpalladium hydroxide complex 5-NO2 probably due
to the rapid C(sp2)−OH bond-forming reductive elimination.
Treatment of the arylpalladium halide complexes 4-Me, 4-
CF3, and 4-CO2Me with cesium hydroxide in THF enabled us
to isolate the corresponding arylpalladium hydroxide complexes
5-Me, 5-CF3, and 5-CO2Me (Scheme 6). In the case of 5-CF3
placed by peaks in the differential Fourier maps. Each complex
has no intermolecular hydrogen bond through the hydroxo
ligand, probably due to the steric bulkiness of the DtBPP ligand.
The hydroxo ligand is coplanar with the square plane of the
central palladium atom. Bite angles of the DtBPP ligand were
similar to those of the arylpalladium halide precursors 4. The
C1−Pd1−O1 angles of 82−83° were slightly larger than the
C−Pd−X (X = halogen) angles of arylpalladium halide
precursors 4.
Scheme 6. Syntheses of Arylpalladium Hydroxide Complexes
Bearing a DtBPP Ligand
Thermolysis of Bidentate Phosphine-Ligated Arylpal-
ladium Hydroxide Complexes. To observe the C(sp2)−OH
bond-forming reductive elimination, thermolysis of the
arylpalladium hydroxide was examined. Heating 5-Me induced
decomposition of the complex; however, no phenolic product
was obtained. Instead, the reaction afforded the biaryl product
3-Me (36%; 18% of the p-tolyl group is included), the dinuclear
complex 8 (92%), and a significant amount, at least five kinds,
of unidentified compounds containing a p-tolyl group (Scheme
7).
Considering that the p-nitrophenylpalladium hydroxide 5-
NO2 underwent rapid phenoxide formation and that heating 5-
Me did not give any phenolic product, one can expect that the
C(sp2)−OH bond-forming reductive elimination follows the
tendency for other C(sp2)−heteroatom bond-forming reduc-
tive eliminations, where the electron-poor aromatic ring
and 5-CO2Me, addition of a catalytic amount of 18-crown-6
was effective for improvement of the yield. These complexes
were fully characterized by NMR and IR spectroscopy and
elemental analysis. Isolated arylpalladium hydroxide complexes
2
showed two doublet 31P signals accompanied by JPP cis
coupling, indicating an unsymmetrically coordinating bi-
sphosphine moiety. The existence of the hydroxo ligand was
confirmed by a treatment of their solutions with D2O to lead to
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Scheme 7. Thermolysis of 5-Me
Scheme 8. Thermolysis of 5-CF3
Figure 2. ORTEP drawing of 5-CF3 (50% thermal ellipsoids).
Hydrogen atoms, except hydroxide proton, are omitted for clarity; R1
= 0.0271, GOF = 1.128. Selected bond distances (Å) and angles (deg):
Pd1−C1, 2.044(2); Pd1−O1, 2.0698(16); Pd1−P1, 2.2927(7); Pd1−
P2, 2.3998(8); C1- - -O1, 2.716; P1−Pd1−P2, 97.98(2); C1−Pd1−
O1, 82.63(8); P1−Pd1−C1, 93.23(6); P2−Pd1−O1, 86.09(5).
a
b
Estimated from 31P NMR spectrum. Not detected.
consumption of all 5-CF3 and conversion of 2-CF3 to 9-CF3,
indicating that 9-CF3 may form by a condensation reaction
between 5-CF3 and 2-CF3. Observation of a gradual increase of
1
the signal for water in H NMR spectra also supported the
condensation reaction. This is the first example for direct
observation of the C(sp2)−OH bond-forming reductive
elimination from Pd(II) species. The side product 9-CF3 was
independently synthesized and fully characterized (Scheme 9
Scheme 9. Independent Synthesis of Arylpalladium
Aryloxide Complex 9-CF3
Figure 3. ORTEP drawing of 5-CO2Me (50% thermal ellipsoids).
Hydrogen atoms, except hydroxide proton, and the cocrystallized ether
molecule are omitted for clarity; R1 = 0.0407, GOF = 1.087. Selected
bond distances (Å) and angles (deg): Pd1−C1, 2.049(4); Pd1−O1,
2.042(3); Pd1−P1, 2.2782(16); Pd1−P2, 2.3911(17); C1- - -O1,
2.691; P1−Pd1−P2, 98.92(4); C1−Pd1−O1, 82.28(14); P1−Pd1−
C1, 95.09(11); P2−Pd1−O1, 83.64(9).
and Figure 4). Thus, thermolysis of 5-CF3 in THF-d8 contains
two reactions, the C(sp2)−OH bond-forming reductive
elimination and subsequent condensation.
accelerates the reaction.1,2 Therefore, thermolysis of arylpalla-
dium hydroxide bearing a moderately electron-poor aromatic
ring was next examined to observe the C(sp2)−OH bond-
forming reductive elimination.
Reaction of the arylpalladium hydroxide complex 5-CF3 in
THF-d8 at 90 °C for 15 min gave a mixture of four species:
namely, p-trifluoromethylphenol 2-CF3, dimeric palladium(0)
complex 8, arylpalladium aryloxide complex 9-CF3, and water
(Scheme 8). A prolonged reaction time (60 min) allowed the
On the other hand, thermolysis of 5-CO2Me in THF gave 8
and arylpalladium aryloxide complex 9-CO2Me with no
appearance of the phenolic intermediate 2-CO2Me over the
course of the reaction in the NMR probe (Scheme 10). The
side product 9-CO2Me was independently synthesized and fully
characterized (Scheme 11 and Figure 5). It was confirmed that
5-CO2Me could react with 2-CO2Me rapidly in THF at room
temperature. Thus, similarly to the case of 5-CF3, heating
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Figure 4. ORTEP drawing of 9-CF3 (50% thermal ellipsoids).
Hydrogen atoms and a minor part of the disordered fluorine atoms are
omitted for clarity; R1 = 0.0333, GOF = 1.052. Selected bond
distances (Å) and angles (deg): Pd1−C1, 2.040(4); Pd1−O1,
2.076(3); Pd1−P1, 2.2798(10); Pd1−P2, 2.4060(10); C1- - -O1,
2.795; P1−Pd1−P2, 99.15(3); C1−Pd1−O1, 85.54(16); P1−Pd1−
C1, 93.60(13); P2−Pd1−O1, 82.05(9).
Figure 5. ORTEP drawing of 9-CO2Me (50% thermal ellipsoids).
Hydrogen atoms and the cocrystallized hexane molecule are omitted
for clarity; R1 = 0.0748, GOF = 1.172) Selected bond distances (Å)
and angles (deg): Pd1−C1, 2.037(6); Pd1−O1, 2.086(4); Pd1−P1,
2.2901(15); Pd1−P2, 2.4280(16); C1- - -O1, 2.796; P1−Pd1−P2,
98.21(5); C1−Pd1−O1, 85.4(2); P1−Pd1−C1, 90.60(16); P2−Pd1−
O1, 85.12(12).
Scheme 10. Thermal Decomposition of 5-CO2Me (A =
CO2Me)
1 + 2
d[5]
dt
d[2]
dt
−
= 2k [5] −
1
(3)
(4)
k
= 2k
1
obs
Taking advantage of the invisibility of 2-CO2Me during the
reaction, a steady-state approximation for d[2]/dt = 0 was
applied to eq 3. Under this condition, consumption of 5-
CO2Me obeys a first-order rate equation with the rate constant
kobs = 2k1 (eq 4). The rate constants in C6D6, THF-d8, and
DMF-d7 at 60 °C were estimated by monitoring the
1
consumption of starting complex 5-CO2Me in the H NMR
spectra with the use of 1,3,5-trimethoxybenzene as an internal
standard. CD3CN could not be used, because a significant
amount of unknown compounds having two doublets in the
aromatic region was observed to interfere with the kinetic
analysis. The consumption of 5-CO2Me obeyed first-order
kinetics over 3 half-lives in all three cases. The obtained first-
order rate constants k1 are summarized in Table 1. Solvent
Scheme 11. Independent Synthesis of 9-CO2Me
Table 1. First-Order Rate Constants of k1 (60 °C) with
Various Solvents and Their Relative Values for Reductive
Elimination of Phenol 2-CO2Me from 5-CO2Me
arylpalladium hydroxide complex 5-CO2Me may induce the
C(sp2)−OH bond-forming reductive elimination, although the
reaction could not be directly observed due to rapid
condensation of the phenolic product with starting 5-CO2Me.
However, the invisibility of 2-CO2Me enabled us to perform a
kinetic analysis as follows.
solvent
k1 (s−1
)
krel
C6D6
(2.16 0.07) × 104
(4.73 0.23) × 104
(1.68 0.09) × 103
1
THF-d8
DMF-d7
2.19
7.78
Kinetic Studies on the C(sp2)−OH Bond-Forming
Reductive Elimination from 5-CO2Me. Based in Scheme
10, the following eqs 1-4 could be derived.
effects on the reaction rate showed that more polar solvents
accelerated the reductive elimination. Addition of the DtBPP
ligand (3 equiv) to the C6D6 solution of 5-CO2Me did not
change the reaction rate (2.08 × 104 s−1), indicating there may
be no associative pathway via a five-coordinate complex. On the
other hand, treatment of 5-CO2Me with CsOH·H2O at 60 °C
for 3.5 h induced a formation of cesium p-methoxycarbonyl-
phenoxide (7-CO2Me) in 66% yield after full conversion;
d[5]
−
−
= k [5] + k [5][2]
1 2
(1)
(2)
dt
d[2]
dt
= k [5] − k [5][2]
1
2
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however, the rate constant in the presence of additional CsOH
could not be estimated, due to the moderate yield of 7-CO2Me,
reflecting the formation of a significant amount of unidentified
byproducts and overlapping the signals of 7-CO2Me with the
byproducts. Variable-temperature experiments (C6D6, 50−75
°C; THF-d8, 35−60 °C) afforded activation parameters of
C(sp2)−OH bond-forming reductive elimination step via an
Eyring plot (Figure 6, Table 2).
involves a partial dissociation of the DtBPP ligand and
subsequent reductive elimination from the three-coordinate
complex. Direct reductive elimination from four-coordinate
species is shown as path B. Path C contains a formation of a
separated ion pair by a reversible dissociation of the hydroxide
ligand and subsequent outer-sphere ipso attack of hydroxide. A
C−F bond-forming reductive elimination from the Pd(IV)
complex (Scheme 13) was reported to involve a dissociation of
Scheme 13. C−F Bond-Forming Reductive Elimination from
a
Pd(IV) Species via Dissociation of Chelate Ligand
a
ΔS⧧ = 12.4 1.3 cal/(mol K).
chelate ligand with a positive entropy of activation (12.4 1.3
cal/(mol K)).14 Our observation of a negative entropy of
activation could argue against path A having a similar
dissociative pathway. On the other hand, ionic path C may
also be excluded by the observed negatively large entropy of
activation by comparison to the literature as follows. (1)
Reductive elimination of iodomethane from a Pt(IV) complex
having a diphosphine ligand was induced by the dissociation of
iodide followed by an outer-sphere attack of I− at the Pt-bound
methyl group in an SN2 fashion (Scheme 14a).15 The reported
Figure 6. Eyring plot for reductive elimination of 5-CO2Me in C6D6
or THF-d8.
Table 2. Activation Parameters ΔH⧧ and ΔS⧧ for Reductive
Elimination of Phenol 2-CO2Me from 5-CO2Me
Scheme 14. Reported Mechanisms for Reductive
Elimination Involving Dissociation of the Anionic Ligand
and Its Attack from the Outer Sphere
solvent
ΔH⧧ (kcal/mol)
ΔS⧧ (cal/(mol K))
C6D6
18.5 0.8
18.6 0.9
−19.9 2.5
−18.0 3.0
THF-d8
Mechanistic Considerations on the C(sp2)−OH Bond-
Forming Reductive Elimination from 5-CO2Me. Six
possible reaction pathways for C(sp2)−OH bond-forming
reductive elimination are illustrated in Scheme 12. Path A
Scheme 12. Six Possible Pathways for C(sp2)−OH Bond-
Forming Reductive Elimination from 5-CO2Me (A =
CO2Me)
near-zero entropy value (−2.9
0.2 cal/(mol K)) was
explained by a cancellation of positive entropy for dissociation
of I− and negative entropy for association of I− to construct a
C−I bond. (2) The reported CH3−OAr bond-forming
reductive elimination from a Pt(IV) complex was also shown
to have the same mechanism, where C6D6 and THF-d8 afforded
similar reaction rates (Scheme 14b).8b The obtained data in the
present study showed a large negative entropy of activation and
the acceleration of the reaction by the use of more polar
solvents (THF-d8, krel = 2.19; DMF-d7, krel = 7.78), indicating
dissociative path C may be unlikely. Path D involves ligand
exchange to form the dimeric Pd(II) species 10 with a bridging
DtBPP ligand. However, first-order kinetics for the con-
sumption of 5-CO2Me and the trans regiochemistry of the
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phosphine ligand, not appropriate for reductive elimination,
would argue against this mechanism. The remaining two
mechanisms are induced by a homolytic cleavage of the Pd−Ar
(path E) or Pd−OH bond (path F). However, previously
calculated bond dissociation energies (BDE) of Pd−C (39
kcal/mol)16 and Pd−OH (45 kcal/mol)17 bond are larger than
the experimentally obtained ΔH⧧ values for C(sp2)−OH bond-
forming reductive elimination (18−19 kcal/mol) in this study.
Thus, path B is the most probable mechanism for C(sp2)−OH
bond-forming reductive elimination.
The electronic character for the transition state in path B was
estimated as follows. One can imagine that the concerted path
B has a neutral or charged transition state with a strong
interaction between carbon and oxygen atoms, as illustrated in
Figure 7. A neutral TS such as that in Figure 7a is sometimes
Figure 8. Models for solvent ordering with polar TS to induce a large
negative entropy of activation (s = solvent).
Figure 7. Possible characters of the transition state for path B.
assumed for C−C bond-forming reductive elimination.1
However, the present C(sp2)−OH bond-forming reductive
elimination may involve a charged TS because of the difference
in electronegativity between carbon and oxygen atoms.
Acceleration by more polar solvents also supports the existence
of a charged TS. We can expect two types of structures for the
charged TS. One has a three-centered structure with a
positively charged oxygen atom (Figure 7b), and the other
has an opened structure without a Pd−O bond (Figure 7c),
where the palladium atom is cationic. The latter corresponds to
a model for C(sp2)−OR bond-forming reductive elimination
suggested by Widenhoefer and Buchwald.5b,c Since both of
them have a delocalized negative charge over the aromatic ring,
solvent molecules may have interactions with these charged
TSs. Considering the delocalization of negative charge, a basic
solvent or aromatic solvent may interact with the positively
charged hydroxo ligand on the palladium atom through
hydrogen bonding or an OH- - -π interaction18 because of
their localized charge density. If we could imagine a strong
interaction between the charged TS and solvents to provide a
large negative entropy of activation, as discussed for C−C
bond-forming reductive elimination from a Pt(IV) complex
(Figure 8a),19 solvent ordering may occur with a three-centered
structure due to the presence of a hydrogen donor hydroxide
ligand (Figure 8b). Therefore, we have decided to examine
DFT calculations to clarify the nature of the charged TS.
Theoretical Studies on the C(sp2)−OH Bond-Forming
Reductive Elimination from 5-CO2Me. The arylpalladium
hydroxide 5-CO2Me or its solvates were optimized by
B3LYP//LanL2DZ/6-31G* with IEFPCM solvation model
with C6H6, THF, or DMF solvent (Figure 9). The obtained
ground-state structure of 5-CO2Me without solvent could
reproduce the crystal structure, where the hydroxo ligand was
coplanar with the square plane of palladium. Addition of one
THF or DMF molecule to 5-CO2Me led to a formation of a
hydrogen bond between the proton of the hydroxo ligand and
the oxygen atom of the solvent molecule; however, addition of
Figure 9. Calculated structures of ground, transition, and product
states (Pd = (DtBPP-Pd), A = CO2Me), their free energy changes, and
activation parameters ΔH⧧ and ΔS⧧ for C−OH reductive elimination
from 5-CO2Me without solvent (black), with THF (blue), and with
DMF (red) using the B3LYP method with the LanL2DZ/6-31G*
basis set and the solvation model of IEFPCM (C6H6 (black), THF
(blue), or DMF (red)).
a C6H6 molecule did not give any stable structure with a OH- - -
π interaction. All obtained transition states show a close contact
between the hydroxo ligand and the palladium-bonded carbon
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Organometallics
Article
atom (∼1.8 Å), supporting the three-centered TS. This C−O
contact corresponds to a vibration possessing an imaginary
frequency in each transition state. The Pd−O bond in the
transition state (2.13−2.14 Å) was slightly elongated, compared
to that (∼2.05 Å) in the ground state. In the transition states,
the hydroxo ligand was rotated along with the Pd−O bond, in
comparison to the ground state, as suggested by changes in
dihedral angles of C(sp2)−Pd−O−H (<5° for ground states;
>97° for TSs). The structure of the product obtained without
solvent had an interaction between the Pd(0) center of 6 and
the phenolic proton of 2-CO2Me. In the presence of THF or
DMF, the Pd(0) center of 6 interacted with the α-proton of
THF or the N-methyl proton of DMF, together with a
hydrogen bond from the oxygen atom of the solvent molecule
to the phenolic proton of 2-CO2Me. A diagram of the relative
free energies without or with solvent showed that transition
states were more stabilized by a hydrogen bond between the
hydroxo ligand and the polar solvent molecule. Because the
hydroxo ligand can easily interact with solvent molecules,
absolute values of activation entropy were larger than those
obtained from C(sp2)−OR (R = CH2CMe3) bond-forming
reductive elimination from an arylpalladium neopentoxide
complex (−9.3 0.3 cal/(mol K)).5b The smaller calculated
ΔH⧧ values with more polar solvents and the order of ΔH⧧
values reflected the order of rate constant for each solvent. The
reason for the discrepancy between experimental and calculated
ΔH⧧ values may come from the lack of a C6H6 molecule
affording a weak OH- - -π interaction in the calculation.
Similarly, calculated ΔS⧧ values did not match with
experimental values probably because only one solvent
molecule was considered, while large numbers of solvent
molecules should be involved in the real solution.
CONCLUSION
■
The decomposition of arylpalladium hydroxide complexes gave
the corresponding phenolic products, which may form through
a C(sp2)−OH bond-forming reductive elimination, either by
treatment of arylpalladium halide complexes with cesium
hydroxide or by heating arylpalladium hydroxide complexes.
Treatment of nitrophenylpalladium iodide 1, possessing a
tBuXPhos ligand with cesium hydroxide, formed a mixture of
nitorophenol 2-NO2 and 4,4′-dinitrobiphenyl 3. The reaction of
DtBPP-ligated nitrophenylpalladium iodide 4-NO2 with cesium
hydroxide gave a mixture of arylpalladium hydroxide complex
5-NO2, cesium phenoxide 7-NO2, and dinuclear Pd(0)
complex 8. Gradual decomposition of 5-NO2 to 7-NO2 and
8 suggested that the C(sp2)−OH bond-forming reductive
elimination took place from 5-NO2. Heating p-tolylpalladium
hydroxide 5-Me gave no phenolic product. Thermolysis of the
trifluoromethyl-substituted arylpalladium hydroxide 5-CF3
enabled us to observe phenol 2-CF3 directly. In the case of
ester-substituted hydroxide complex 5-CO2Me, no formation of
phenol 2-CO2Me was observed. However, the invisibility of 2-
CO2Me enabled us to establish the kinetic equation with a
steady-state approximation to estimate the rate constant k1 for
reductive elimination. The kinetic study showed that polar
solvents such as THF and DMF accelerate the reductive
elimination and there is a large negative entropy of activation.
Comparison of these results with those in the literature
suggested the direct pathway B and charged transition state to
induce the solvent ordering for the C(sp2)−OH bond-forming
reductive elimination. DFT calculations also predicted the
hydrogen bond between the hydroxo ligand and solvent
molecule to stabilize the transition state. An analysis of
molecular orbitals also suggested that the character of this
process was nucleophilic attack of hydroxide ligand at the ipso
carbon of the aryl ligand. Knowledge from this study on the
acceleration of C(sp2)−OH bond-forming reductive elimina-
tions by polar solvents may inspire establishment of a new
strategy for a challenging reaction containing the formation of
carbon−hydroxide bonds.
The rotation of the hydroxo ligand to construct the TS can
be explained as an orbital interaction (Figure 10). In the
ASSOCIATED CONTENT
■
S
* Supporting Information
Text, figures, tables, and CIF files giving details for all
experimental, computational, and crystal structure studies.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Figure 10. HOMO and LUMO of 5-CO2Me and HOMO-9 of TSwo.
ground state of 5-CO2Me, where the hydroxo ligand was
coplanar with the square plane of the palladium atom, the 2p
orbital of the oxygen atom was found in the HOMO to interact
with a d orbital of the central palladium. On the other hand, the
LUMO has the character as a π* orbital of the aromatic ring. In
the transition state TS, the hydroxo ligand was orthogonal to
the square plane of the palladium. An interaction between the
2p orbital of oxygen and the π* orbital was found in HOMO-9
of the TS. On the basis of the above observations, it is indicated
that the C(sp2)−OH bond-forming reductive elimination has
the character of a nucleophilic attack of the hydroxo ligand at
the aryl ligand. This is in agreement with the reactivity of 5, that
an aryl ligand with an electron-withdrawing group accelerates
reductive elimination (5-NO2 > 5-CO2Me, 5-CF3 ≫ 5-Me),
which is also reported for other C(sp2)−heteroatom bond-
forming reductive eliminations.2
AUTHOR INFORMATION
■
Corresponding Author
*makoto@oec.chem.chuo-u.ac.jp (M.Y.); nozaki@chembio.t.u-
tokyo.ac.jp (K.N.).
Present Address
†Department of Applied Chemistry, Faculty of Science and
Engineering, Chuo University, 1-13-27, Kasuga, Bunkyo-ku,
Tokyo 112-8551, Japan,
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the Funding Program for Next
Generation World-Leading Researchers, Green Innovation
from the JSPS and KAKENHI (No. 23105510) from MEXT
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Organometallics
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of Japan. The computations were performed by the Research
Center for Computational Science, Okazaki, Japan.
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