Invisible Chelating Effect Exhibited between Carbodicarbene and Phosphine through π-π Interaction and Implication in the Cross-Coupling Reaction

Article abstract of DOI:10.1021/acs.organomet.7b00692

Palladium complexes supported with the mixed ligands carbodicarbene (CDC) and different phosphine ligands (PPh₃, PTol₃, and PCy₃) were prepared, and their molecular structures were characterized. Examination of the structures of 2-PPh₃ and 2-PTol₃ with cis configuration discloses the existence of an unexpected π-π interaction between one phenyl group of the phosphine and the benzimidazole ring of a CDC. The palladium complex 2-PPh₃ is an active Suzuki-Miyaura catalyst with a wide scope of substrates containing various functional groups and steric demands. In contrast to electron-withdrawing aryl bromide, the yield of product for electron-rich substrates was improved by adding a catalytic amount of DMSO under aerobic conditions. The solution NMR and structural analysis has revealed that the intramolecular π-π interaction between CDC and phosphine ligands has a positive influence on the activity of the reaction, which is further supported by quantum chemical calculations.

Full text of DOI:10.1021/acs.organomet.7b00692

Article
pubs.acs.org/Organometallics
Cite This: Organometallics XXXX, XXX, XXX-XXX
Invisible Chelating Effect Exhibited between Carbodicarbene and
Phosphine through π−π Interaction and Implication in the Cross-
Coupling Reaction
Wei-Chih Shih,† Yun-Ting Chiang,†,‡ Qing Wang,§ Ming-Chun Wu,† Glenn P. A. Yap,∥ Lili Zhao,*,§
and Tiow-Gan Ong*,†,‡
§Institute of Advanced Synthesis, School of Chemistry and Molecular Engineering, Jiangsu National Synergetic Innovation Center for
Advanced Materials, Nanjing Tech University, Nanjing 211816, People’s Republic of China
†Institute of Chemistry, Academia Sinica, Nangang, Taipei, Taiwan, Republic of China
‡The Department of Applied Chemistry, National Chiao Tung University, Hsin-chu, Taiwan, Republic of China
∥The Department of Chemistry and Biochemistry, University of Delaware, Newark, Delaware 19716, United States
S
* Supporting Information
ABSTRACT: Palladium complexes supported with the mixed
ligands carbodicarbene (CDC) and different phosphine
ligands (PPh3, PTol3, and PCy3) were prepared, and their
molecular structures were characterized. Examination of the
structures of 2-PPh3 and 2-PTol3 with cis configuration
discloses the existence of an unexpected π−π interaction
between one phenyl group of the phosphine and the
benzimidazole ring of a CDC. The palladium complex 2-
PPh3 is an active Suzuki−Miyaura catalyst with a wide scope of substrates containing various functional groups and steric
demands. In contrast to electron-withdrawing aryl bromide, the yield of product for electron-rich substrates was improved by
adding a catalytic amount of DMSO under aerobic conditions. The solution NMR and structural analysis has revealed that the
intramolecular π−π interaction between CDC and phosphine ligands has a positive influence on the activity of the reaction,
which is further supported by quantum chemical calculations.
ligands may improve the stability of an active species and
prolong the life span or increase the turnover number of the
catalyst in the reaction. An olefin metathesis catalyst based on
the Grubbs second-generation ruthenium complexes bearing a
mixed NHC and phosphine framework is living proof of
employing a mixed ligand strategy to improve thermal and
functional robustness as well as activity of the catalysts.5 Other
related prominent examples that have relied on a mixed ligand
concept can also be witnessed in the recent development of a
Pd-mediated C−C and C−N catalytic cross-coupling reaction,
the so-called PEPPSI-NHC catalyst (pyridine, enhanced,
precatalyst, preparation, stabilization, and initiation).6
Previously, our group has focused efforts on developing
synthetic methods of expanding the structural diversity of CDC
scaffolds.7 Despite the ever-increasing utility of strongly σ
donating ligands, a CDC, with two lone pairs of electrons, has
no spare orbital (or LUMO with sufficient low energy) for
possible π back-bonding from low-oxidation-state metal
centers.2 Definitely, a low affinity of the CDC for an
electron-rich metal complex would have detrimental con-
sequences toward engineering a more robust and resilient
INTRODUCTION
■
The remarkable discovery of N-heterocyclic carbenes (NHCs)
as neutral σ-donating ligand platforms prompted a massive
breakthrough in homogeneous transition-metal catalysis.1 In
addition to the broadly explored NHCs, recent efforts toward
discovering a stable unique carbon species has also yielded
carbodicarbenes (CDCs) or carbones,2 featuring a dicoordi-
nated central carbon(0) atom bearing two electron lone pairs.
Because of these two electron lone pairs, CDCs show a far
stronger σ-donor strength in comparison to NHC ligands. For
instance, our group recently isolated a highly electron deficient
dicationic boron complex supported by a CDC framework,3 a
demonstrative case where similar stabilization could not be
achieved by normal NHC ligands. In addition, our group and
those of Meek and Stephan have independently established
CDCs as useful ligands for many catalytic transformations.4
Nonetheless, it is clear that much remains to be done in order
to understand the topological properties of CDCs and their
potential in catalysis.
Although a monoligand framework has been always
dominated the realm of transition-metal catalysis, mixed ligand
systems have occasionally appeared as a complementary
strategy to facilitate the efficiency of the reaction. The
synergistic effect invoked by cooperative effects between two
Received: September 10, 2017
© XXXX American Chemical Society
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Scheme 1. Synthesis of Mixed Ligand Pd(II) Complexes
Figure 1. Molecular structures of Pd complexes 2-PPh3 (left), 2-PTol3 (center), and 2-PCy3 (right) with thermal ellipsoids drawn at the 30%
probability level. There are two unique asymmetric structures in 2-Tol3, but only one of the units is used for the representative drawing. All hydrogen
atoms are omitted for clarity. Selected bond lengths (Å) and angles (deg): 2-PPh3, Pd−Cl(1) 2.3679(6), Pd−Cl(2) 2.3733(6), Pd−C(1) 2.063(2),
Pd−P(1) 2.2503(6), C(1)−C(2) 1.383(3), C(1)−C(11) 1.409(3), C(2)−C(1)−C(11) 115.63(19), P(1)−Pd−C(1) 96.35(6); 2-Tol3, Pd(1)−P(1)
2.261(1), Pd(1)−Cl(1) 2.383(1), Pd(1)−Cl(2) 2.367(2), Pd(1)−C(1) 2.049(4), C(1)−C(2) 1.374(7), C(1)−C(11) 1.412(8), C(11)−C(1)−
C(2) 117.7(4), Pd(1)−C(1)−C(2) 126.3(4), Pd(1)−C(1)−C(11) 114.0(4), C(1)−C(2)−N(1) 128.5(5), C(1)−C(2)−N(2) 125.4(5), N(1)−
C(2)−N(2) 106.1(4), C(1)−C(11)−N(3) 125.5(5), C(1)−C(11)−N(4) 127.5(5), N(3)−C(11)−N(4) 106.7(4); 2-PCy3, Pd(1)−P(1) 2.3385(7),
Pd(1)−Cl(1) 2.3245(7), Pd(1)−Cl(2) 2.3107(8), Pd(1)−C(1) 2.111(2), C(1)−C(2) 1.343(3), C(1)−C(11) 1.415(4), C(11)−C(1)−C(2)
123.6(2), Pd(1)−C(1)−C(2) 124.1(2), Pd(1)−C(1)−C(11) 112.3(2), C(1)−C(2)−N(1) 127.6(2), C(1)−C(2)−N(2) 128.2(2), N(1)−C(2)−
N(2) 104.1(2), C(1)−C(11)−N(3) 126.7(2), C(1)−C(11)−N(4) 125.7(2), N(3)−C(11)−N(4) 107.3(2).
ligated catalytic species in molecular reactions. To facilitate the
use of carbodicarbene in reactions, we envisaged a metal
complex possessing mixed ligands of CDC and phosphine with
dual functional tasks. Through a strong σ-dative bonding, a
CDC scaffold would facilitate the reactivity of a high-oxidation-
state metal in the catalytic cycle. At the same time, the PPh3
ligand with a LUMO orbital for π back-bonding would
modulate the reaction, as the metal complex cycled back into
a lower oxidation mode. In line with our strategy, we have
elected the palladium-mediated Suzuki−Miyaura cross-coupling
reaction as our model of study to examine the efficacy and to
obtain mechanistic insight. During the course of our study, we
serendipitously discovered an unexpected intramolecular π−π
interaction between a CDC and phosphine ligands within the
palladium complex. Such a unique interaction accounts for an
invisible and bridging linkage between these two ligands,
enforcing cisoid conformation in the complex and exerting a
certain degree of positive influence on the coupling activity,
which is unprecedented so far. Herein we wish to present our
comprehensive studies on the synthesis and structural
characterization of a series of [(CDC)(PR3)PdCl2] complexes,
which act as precatalysts in the carbon−carbon cross-coupling
reaction. We also show how these two ligands are working in a
dynamic manner and identify the chemical principles that
govern how carbodicarbene-based complex systems promoted
the sterically hindered coupling process.
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1
Figure 2. Variable-temperature H NMR spectra of 2-PPh3 complexes in the range of δ 6−9 ppm and in the temperature range between 210 and
330 K.
PTol3 as a cis square-planar complex (Figure 1, center), and
most structural parameters are relatively comparable to those of
2-PPh3, warranting no further comment.
RESULTS AND DISCUSSION
■
Synthesis and Structure Characterization. Expanding
upon our recent success in diversifying the library of CDCs, we
set out to prepare a number of CDC palladium complexes with
several different phosphine ligands. In order to take advantage
of its NMR simplicity in characterization, we chose the
unsymmetrical scaffold 1 as the CDC ligand target in our
investigative efforts (Scheme 1). The preparation of the CDC 1
can be achieved in a good yield via the SN2 reaction of an N-
heterocyclic olefin adduct with thioether developed recently by
our group.7 We succeeded in preparing the palladium
complexes 2-PPh3 and 2-PTol3 by the reactions of CDC 1
with the corresponding PdCl2(PAr3)2 complexes8 in THF
solution at ambient temperature. The blue crude solid product
can be further purified and isolated in satisfactory yield (∼80%)
π−π Interaction between PPh3 and Carbodicarbene
Ligands. Of particular interest, both 2-PPh3 and 2-PTol3 have
adopted an unexpected cis arrangement, considering that most
known mixed ligand [(NHC)(PR3)PdX2] complexes embrace a
trans configuration to minimize unnecessary high-energy steric
hindrance within the coordination environment.10 Close
examination of the structures of 2-PPh3 and 2-PTol3 disclosed
that an unexpected π−π interaction existed between one of the
phenyl groups of the phosphine and the benzimidazole ring of
the CDC with estimated centroid−centroid distances of 3.25
and 3.30 Å, respectively. Small dihedral angles of 4.62° (2-
PPh3) and 5.93° (2-PTol3) between least-squares planes
confirmed the presence of parallel intramolecular π−π stacking,
which indeed is more like a face to face or sandwich pattern.11
Such an unexpected intramolecular stacking π interaction has
perhaps promoted 2-PPh3 and 2-PTol3 to adopt a cis
geometry. Few studies of the influence of π stacking on olefin
metathesis reactions have been reported on NHC-based
Grubbs ruthenium catalysts, and these have concerned
intramolecular noncovalent interactions between NHC and
the benzylidene moiety.12 To the best of our knowledge, no
report so far has mentioned or identified structures with
intramolecular π−π stacking between an NHC and phosphine
within a coordination complex. In this context, the intraligand
π−π stacking may serve as an invisible bridging linkage for a
chelating effect, which would exert a certain degree of influence
on the catalytic reaction.
1
with a THF treatment to wash off excess phosphine. The H
NMR of 2-PPh3 is notably distinct from that of its original
CDC ligand 1 with two new methyl signals at δ 4.51 and 2.18
ppm and four other notable isopropyl doublets at δ 2.14, 1.53,
1.17, and 1.11 ppm. These NMR patterns clearly reflect an
unsymmetrical environment in the palladium coordination
sphere.
Crystals of 2-PPh3 suitable for an X-ray diffraction
experiment were grown from a concentrated CH2Cl2 solution
layered with hexane at laboratory temperature. This compound
crystallized in the triclinic space group P1. The molecular
̅
structure of 2-PPh3 (see Figure 1, left) unambiguously adopts
an imperfect square-planar palladium geometry with two
chlorides arranged in a cis manner. The C(1)−Pd−P(1)
angle is 96.35(6)°, larger than the ideal 90° to avoid
unfavorable steric interactions with the CDC ligand. The
Pd−carbone bond distance is about 2.063(2) Å, which is
slightly shorter than that for the (CDC)Pd(η3-allyl)Cl complex
(2.10 Å) previously reported by our group,2d indicating a
robust σ-dative Pd←C bond. As expected, the trans influence of
PPh3 and carbodicarbene leads to a lengthening effect on the
Pd−Cl bond distances (2.3732(5) and 2.3679(6) Å,
respectively).9 Alternatively, we also established compound 2-
To gain more insight into the role of intramolecular π−π
stacking, we synthesized the CDC palladium complex 2-PCy3
bearing a phosphine ligand containing no aryl moiety. In the
absence of a collaborative π−π connection, the structure of 2-
PCy3 embraces a trans conformation to avoid unfavorable steric
interactions arising from the close proximity between ligands
(the cone angle of PCy3 is 170°).13 Interestingly, the trans
effect invoked by PCy3 led to an elongated Pd−CDC bond
C
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distance, while the Pd−Cl bond lengths have been shortened to
2.324 and 2.311 Å in comparison to 2-PPh3 and 2-PTol3.
Certainly the structural evidence indicating the π−π
interaction between CDC and phosphine in 2-PPh3 and 2-
PTol3 could be due to the crystal packing or alignment of the
molecular units in the solid state. We were curious if a specific
nonbonding intramolecular interaction is still effective in a
more environmentally dynamic solution. Thus, we have
employed proton NMR to probe this possibility in solution
(Figure 2). In principle, the cis isomer has lower symmetry in
comparison to the trans isomer. This geometric phenomenon
has been exemplified by the case of cis-2-PPh3, with two
chemically distinct NMR signals arising from the methyl
pendant arms of CDC (δ 4.51 and 2.18 ppm) at ambient
temperature, while trans-2-PCy3 possesses only a single methyl
peak at δ 3.71 ppm. We postulated that increasing the solution
temperature of 2-PPh3 might break the π−π interaction that
holds the CDC and phosphine ligand together in a cis
configuration, and isomerization might occur in the solution
state with detection of the trans analogue. Increasing the
solution temperature to 60 °C did not seem to affect the
geometry of 2-PPh3, as it showed no change in chemical shift
or peak pattern distribution for the methyl and isopropyl
groups. When the proton NMR of 2-PPh3 was monitored at a
colder temperature of −63 °C, we unexpectedly observed two
new triplet peaks located at 8.25 and 8.40 ppm accompanied by
multiple broad upfield peaks ranging from 6.50 to 6.80 ppm.
Because of a slow rotation of the phosphine ligand around the
Pd−P bond at low temperature, we attributed these two triplet
signals at 8.25 and 8.40 ppm to m-C−H moieties residing at
two aryl groups of PPh3 that are far away from the CDC ring.
On the other hand, multiple broad peaks at 6.50−6.80 ppm are
thought to be related to the other aryl group of the phosphine
close to the CDC ring for more effective π−π interaction,
triggering an unorthodox upfield shift in aromatic signals
resulting from the shielding effect of the CDC ring. An upfield
chemical shift for acceptor nuclei resulting from the ring
current effect between both aromatic rings has been reported
previously.14 Unambiguous peak identification of the PPh3
derived from characteristic upfield-shifted signals (π−π
interaction) and two triplet signals (non-π−π interaction)
was further ascertained by results from 1H−1H−COSY (see the
Supporting Information for further details). In short, we
confidently believe that the intramolecular π−π interaction
does exist within the molecules of 2-PPh3 complexes in the
solution state, which is important in enforcing the cis
configuration of 2-PPh3. This is supported by quantum
chemical calculations at the RI-BP86+(D3BJ)/def2-SVP level
of theory (see the Supporting Information for computational
details). As shown in Figure 3a, the optimized structure of cis-2-
PPh3 is in excellent agreement with the experimental structure.
The calculated distance of the intramolecular π−π interaction
of 3.215 Å was in line with experimental value of 3.25 Å, which
accounted for the stability of the cis isomer by 9.9 kcal/mol
relative to the trans form (see the Supporting Information for
the optimized geometry of the trans isomer).
Figure 3. Optimized structures of (a) PPh3[CDC]PdIICl2 and (b)
PPh3[CDC]Pd0 6 at the RI-BP86+(D3BJ)/def2-SVP level of theory.
Key bond distances and bond angles are given in angstroms and
degrees, respectively. Trivial hydrogen atoms have been omitted for
clarity. Color code: Pd, dark green; P, orange; N, blue; C, gray; H,
white.
bonding at the central carbon of the carbone. Obviously, such a
subtle electronic topology of the carbodicarbene would have a
dramatic influence on the catalytic reaction; thus, under-
standing the catalytic behavior is essential to stimulate novel
and exciting applications akin to those for NHCs and CAACs.
To this end, we have selected the traditional Suzuki−Miyaura
carbon−carbon cross-coupling reaction for this purpose.
To examine the viability of the C−C cross-coupling reaction
(Table 1), we attempted the reaction using 4′-bromoaceto-
phenone (3a) and phenylboronic acid (4a) at 130 °C in
toluene with 3.5 mol % of 2-PPh3 in the presence of K3PO4
(2.8 equiv). To our delight, the expected cross-coupling
product (5aa) was obtained in 62% yield (entry 1). The
efficacy of the reaction could be further improved to higher
yields of 83% and 90% by changing the base to Cs2CO3 and
CsOAc (entries 2 and 3). Changing the reaction solvent to
DME with a slightly lower reaction temperature (100 °C)
allowed for the yield to be maintained in a range of ∼90%
(entries 7 and 8) using the cesium base. Increasing the reaction
temperature to 160 °C in DMF solution had a dampening
effect on the yield of the reaction (23%, entry 5), presumably
due to the instability of the catalyst at higher temperatures.
Other solvents such as THF, dioxane, and DMSO were also
examined and found to be less suitable in this catalytic reaction.
Palladium complexes such as 2-PTol3 and 2-PCy3 (entries 11−
14) appear to be less effective than 2-PPh3, despite several
attempts to optimize the reactions under various conditions. In
spite of the slightly higher yield of reaction using CsOAc, the
Cs2CO3 reagent was selected as the choice of base in
subsequent reaction scope investigations, because it is chemi-
cally benign to substrates bearing sensitive functional groups.
With the optimization conditions in hand (entry 1, Table 2),
we examined the reaction scope with various boronic acids (4y,
black) with 4′-bromoacetophenone (3a, blue) (entries 1−7).
Excellent yields were observed for methyl substituents at
different positions of the arylboronic acid (4b−d, entry 2).
Arylboronic acids bearing sterically bulky tert-butyl and vinyl
functional groups afforded the corresponding cross-coupling
products 5ae (92%) and 5af (67%) in surprisingly good yields.
Catalytic Reaction in Carbon−Carbon Cross-Coupling
Process. Several decades have witnessed a large number of
NHC-promoted metal-mediated homogeneous catalyses. Re-
grettably, research activities focused on carbodicarbene-led
metallic catalysis are still lacking. In comparison to the well-
established NHCs and CAACs, carbodicarbene or carbone
features powerful σ donation but no vacant orbital for π back-
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Mechanistic Considerations. There is lack of detail and
systematic mechanistic investigation concerning the role of
carbodicarbene in promoting C−C cross-coupling reactions.
Therefore, a systematic mechanistic probe would be advanta-
geous for the future development of carbodicarbene in catalysis.
In this study, we want to illuminate and understand the CDC-
supported carbon−carbon cross coupling reaction on (a) the
discrepancy of this reaction with electronically different
substrates and (b) the high reactivity for sterically demanding
substrates assisted by intermolecular π−π interactions within
the metal complexes.
Table 1. Optimization Process
c
b
entry
2-x
base
solvent
T (°C)
yield (%)
1
2
3
4
5
6
7
8
K3PO4
toluene
toluene
toluene
THF
130
130
130
100
160
120
100
100
80
62
83
90
28
23
NR.
93
86
82
17
Cs2CO3
CsOAc
CsOAc
CsOAc
CsOAc
CsOAc
Cs2CO3
Cs2CO3
Cs2CO3
2-PPh3
DMF
dioxane
DME
During the course of catalytic cross-coupling studies, we
noticed a low efficiency of the reaction upon using electron-rich
aryl bromides (Scheme 2-1, entry 1) under N2. Nonetheless,
the yield of this reaction could be increased dramatically to 65%
(1.3 equiv of boronic ester) and 80% (1.5 equiv of boronic
ester) under aerobic conditions and with the addition of
DMSO. These results are at odds with the experimental
outcomes (Scheme 2-2) generated by 3a, as witnessed in its
reaction yield of 64% under N2 and 60% in air in 1 h reaction
time. At this juncture, we performed intermolecular competi-
tion experiments by using equimolar amounts of 3a and 3i
under the standard conditions in the same reaction flask
(Scheme 2-3). The reaction was complete within 2.5 h to afford
71% of 5aa and 8% of 5ia, suggesting that the stability of Pd(0)
prior to the oxidative addition step is a plausible cause for such
a divergent reactivity for dissimilar electronic substrates.
These discrepancies in catalytic outcomes between electron-
withdrawing and -donating substituents has raised a critical
question as to whether the CDC-supported catalyst is a true
homogeneous catalyst or, as discussed previously, that some of
the palladium-mediated cross-coupling reaction is heteroge-
neous.16 We performed a mercury test, a well-known catalyst
poison for heterogeneous reactions, in order to address the
nature of the reaction.17 The carbon−carbon cross-coupling
experiment with 2-PPh3 under similar catalytic conditions was
stirred with a large excess amount of Hg (∼0.175 g, 50 equiv)
(Scheme 2-4). A partial inhibition by Hg(0) was observed, as
the catalytic efficiency has been diminished to 56% from its
original yield of 88%. Furthermore, we also found that
increasing the amount of Hg(0) to 150 equiv did not
completely suppress the catalysis, which managed successfully
to maintain a catalytic activity in the range of 44% conversion.
The results of the mercury test illustrated that the residual
catalytic activity may arise from continued generation of the
remaining active homogeneous catalysts. At the same time, we
also attributed the reduced catalytic activity to instability of a
Pd(0) species, which would slowly decompose to palladium
particles prior to the occurrence of facile oxidative addition,
particularly electron-rich aryl bromide. We reasoned that the
Pd(0) species possesses a comparatively weaker affinity for
carbodicarbene ligand, which lacked a lower-lying π* orbital to
facilitate possible back-bonding that might occur from an
electron-rich Pd(0) center. In the case of 3i, the oxidative
addition step of electron-rich aryl bromide is not sufficiently
fast enough, leading to decomposition of the active species and
hence to lower conversion under an N2 atmosphere. Consistent
with our hypothesis for the rapid decomposition of Pd(0) with
electron-rich substrates, we note that adding DMSO and
carrying out the reactions in the presence of oxygen would in
fact improve the yield of the reaction. We attribute this to
DMSO facilitating the reoxidation of Pd(0) to Pd(II) under
DME
d
9
EtOH
DMSO
d
10
100
11
12
2-PTol3
2-PCy3
CsOAc
DME
DME
100
100
37
d
Cs2CO3
43, 76
13
14
CsOAc
DME
DME
100
100
26
d
Cs2CO3
69
a
Unless specified otherwise, reactions were carried out with aryl
bromide 3a (1 mmol), arylboronic acid 4a (1.3 mmol), base (2.67
mmol), and Pd catalyst 2-X (3.5 mol %) in a selected solvent under N2
b
for 2.5 h. Determined by 1H NMR spectroscopy using 1,3,5-
c
trimethoxybenzene as an internal standard. 2.67 equiv of base (except
for Cs2CO3) was used. 2.5 equiv was added when Cs2CO3 was used as
d
base. In air.
Electron-deficient substrates bearing CN (4g) and NO2 (4h)
groups were also examined and found to have high conversions
(entries 5 and 6). An arylboronic acid bearing an electron-
donating methoxy moiety (4i) was also a suitable coupling
reagent for electron-withdrawing aryl bromide (3a) and neutral
aryl bromide (3b). Subsequently, we examined the viability of
the Suzuki−Miyaura cross coupling reaction of phenylboronic
acid (4a) with various aryl bromide derivatives (Table 2, entries
9−14).
Encouraged by these results, we tested the effect of
substitutions on the aryl bromide and found that both
electron-donating and-withdrawing substituents did not affect
the efficiency (3b−h). It is worth noting that a catalytic amount
of DMSO additive in methylphenyl bromide in air is required
to guarantee high yields for the formation of 5ba−da (entry 9;
vide infra for subsequent explanation). To our surprise, this
method is also capable of streamlining products 5ia (Table 2,
entry 14) and 5ja (entry 17) possessing the hydroxyl moiety in
satisfactory yield. Finally, we also successfully performed a cross
experiment to permute two different electronic environments
for aryl bromide and boronic acid (entries 15 and 16),
demonstrating the flexibility of this reaction procedure.
To further demonstrate the capability of the catalyst, we have
tested several more challenging substrates, as illustrated in
Table 3. High efficiency in cross coupling for the sterically
crowded mesityl and 9-phenanthrene boronic ester with aryl
bromide 3a can be achieved to afford 5ak,al, respectively.
Similarly, representative sterically challenging coupling prod-
ucts such as 5ka,kp,qp,mb were also obtained in good yield by
switching to relatively bulky aryl bromide derivatives. Finally,
this method is also appropriate for constructing π-extended
compounds useful for possible photomaterial applications,
exemplified by the formation of 5op,tg,rs.15
E
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a
Table 2. Scope of Cross-Coupling Reaction
a
Reactions were carried out with aryl bromide (0.5 mmol), arylboronic acid (0.65 mmol), Cs2CO3 (1.25 mmol), and Pd catalyst 2-PPh3 (3.5 mol %)
b
c
d
in DME at 100 °C under N2 for 2.5 h. Isolated yield. DMSO 12.8 mol % was added. In air.
a b
,
Table 3. Scope of Sterically Challenging Substrates
a
Reactions were carried out with aryl bromide (0.5 mmol), arylboronic acid (0.65 mmol), Cs2CO3 (1.25 mmol), Pd catalyst 2-PPh3 (3.5 mol %),
b
c
and DMSO (5 mg) in DME at 100 °C under N2 for 2.5 h. Isolated yield. Reaction without DMSO.
F
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ab
,
Scheme 2. Selected Reactions for Mechanistic Study
a
Reactions were carried out with aryl bromide (0.5 mmol), arylboronic acid (0.65 mmol), Cs2CO3 (1.25 mmol), and 2-PPh3 (3.5 mol %) in DME at
b
100 °C except for those with additional notation. The above yields were determined by 1H NMR spectroscopy using 1,3,5-trimethoxybenzene as an
internal standard. Isolated yield.
c
aerobic conditions and thus minimizing the competitive
formation of inactive palladium particles.18
far in any cross-coupling reaction studies employing a mixed
ligand system. Interestingly, Peris and co-workers have
demonstrated how homogeneous catalysts with polyaromatic
functionalities of the NHC possess properties that clearly differ
from those of analogues without π−π interactions.20 The
results in Table 1 showed clearly that trans-2-PCy3 was a less
effective catalyst than its counterparts 2-PPh3 and 2-Tol3,
clearly hinting that the intramolecular π−π interaction plays a
secondary role in the catalytic reaction. At this point, we could
not rule out the possibility that sterics also played some role in
that respect. We believe that this unique π−π interaction
between ligands may function as an invisible and weak bridging
linkage between these two ligands, enforcing cisoid con-
formation in the complex. Moreover, we speculated that the
geometric structure invoked by π−π interaction should exert a
certain degree of positive influence on (i) the coupling activity,
especially with sterically demanding substrates, and (ii) their
persistent stability in the catalytic turnover. First, the role of
π−π interactions is supported by the fact that 2-PPh3 is capable
of delivering the sterically hindered and polyaromatic coupling
product in excellent yield. To understand the phenomena, we
conducted another intermolecular competition reaction
between 3q and 3k with arylboronic ester 4p (Scheme 4-2)
under our standard conditions, which provided almost equal
yields of both aryl bromides, as demonstrated previously in
Table 3. To our surprise, the more sterically crowded 3q (66%)
has reacted preferentially in comparison to 3k (33%). This
observation provides a possible clue that intramolecular π−π
interactions reinforced the cis configuration of the metal
complex to create a larger space to fit the incoming substrate
with large steric functional substituents. At the same time, the
π−π interaction force between ligands has also aided a more
Taking together all of these outcomes and the available
literature, we propose in Scheme 3 that two catalytic cycles are
involved in the carbodicarbene palladium complex catalysis for
the carbon−carbon cross-coupling reaction. In a cross-coupling
cycle, 2-PPh3 is transformed into the active dicoordinated
palladium(0) species 6 by reduction, which should undergo
oxidative addition more easily with an aryl bromide bearing an
electron-withdrawing group to afford palladium(II) complex 7.
Transmetalation of arylboronic ester occurred to generate 8
followed by a reductive elimination process, affording 5, the
cross-coupling product. In the catalyst regeneration cycle, the
active species 6 could also be in equilibrium with the
palladium(0) species 9 assisted by DMSO as a resting state
and serving as a catalyst reservoir (step E). Complex 9 reacted
with O2 to yield the peroxo complex 10, eventually leading to
hydroxy complexes 11 in the presence of a trace amount of
H2O. An NHC palladium peroxo complex like 10 has been
isolated and fully characterized.19 An excess of the arylboronic
acid was added to complex 11, reducing it back to Pd(0) 6.
Such a proposed notion is consistent with the single individual
experiment demonstrated in Scheme 4-1, where 2-PPh3 could
promote homocoupling of arylboronic acid 3i to furnish 5ii
under aerobic conditions.
The second intriguing aspect of this catalytic reaction is that
the CDC-supported cross-coupling reaction is capable of
promoting reactions with sterically hindered substrates. In
light of the solid structural and solution NMR evidence, we
were curious if the intramolecular π−π interaction between
CDC and phosphine ligands within the palladium complex
played any critical role in catalysis, which is undocumented so
G
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a
Scheme 3. Proposed Mechanism
a
Legend: (A) oxidative addition; (B) transmetalation; (C) reductive elimination; (D) irreversible formation of palladium black; (E) DMSO
coordination; (F) oxidation; (G) H2O reaction; (H) transmetalation via boronic ester; (I) reductive elimination.
Scheme 4. Selected Experiments
rapid reductive elimination process through a more rigid cis
configuration. This beneficial effect resulting from π−π
interactions was further verified, as no cross-coupling reaction
was observed from a blank reaction of 3k and 4p mediated by
mol. Subsequently, the oxidative addition step proceeded
through a transition state (TS-A) with a free energy barrier of
11.3 kcal/mol to generate the intermediate PPh3[CDC]-
PdII(Ar)Br 7, which is relatively more stable (40 kcal/mol) in
comparison to its starting material of 3a + 6. The energy barrier
for the transmetalation step 7 → 8 via the transition state TS-B
was observed to be abnormally high, 40.4 kcal/mol with respect
to the former intermediate 7. However, it is well known that
the ideal gas-phase model intrinsically overestimates the
entropic contributions, especially in the presence of multiple
components in the reaction. For example, a reaction containing
m to n components has an additional free energy correction of
21
the CDC-free complex (PPh3)2PdCl2·
To gain insight into the reaction mechanism, we conducted a
detailed computational mechanistic study for the cross-coupling
reaction of aryl bromide 3a and phenylboronic acid 4a
mediated by the active species PPh3[CDC]Pd0 6 (see Figure
4). In the initial stage, aryl bromide 3a approached the
coordinatively unsaturated complex 6, generating the weakly
bonded intermediate im-A that was exothermic by 15.1 kcal/
H
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Figure 4. Calculated energy profile at the RI-BP86+(D3BJ)/def2-SVP level for the cross-coupling reaction of aryl bromide and boronic acid
mediated by 2-PPh3. Key bond distances and bond angles are given in angstroms and degrees, respectively. Trivial hydrogen atoms have been
omitted for clarity. Color code: Pd, dark green; P, orange; N, blue; C, gray; H, white.
(m − n) × 4.3 kcal/mol.22 Alternatively, a scaling factor of 0.5
to the entropic contributions should be applied as a rough
estimation on the basis of the experimental observations.23 On
the basis of overestimated entropy penalty, the barrier for the
transmetalation step should be reduced to ca. 31 kcal/mol.
Clearly, even the corrected value in the transmetalation step is
still slightly higher for the proposed mechanism to be
energetically feasible under ambient conditions. However, the
value agrees well with the reaction performed at high
temperature (>100 °C). In the final step of the reaction
pathway, the reductive elimination process proceeds smoothly
to regenerate the active species 6 with a free energy barrier of
9.1 kcal/mol, which is the smallest activation energy in the
whole calculated reaction pathway. These computational
findings clearly support the notion that the cis conformation
enforced by the π−π interaction within the complex
encouraged the facile reductive elimination process for sterically
demanding substrates. The overall reaction from 3a + 4a
leading to 5a is moderately exothermic by 21.1 kca/mol, which
provides a driving force for this reaction. Our calculations
provide firm support to the hypothesis that the strong
intramolecular π−π stacking interactions (i.e., the red dashed
lines), with average distances between 3.2 and 3.7 Å, play a very
important role in stabilizing the transition states and
intermediates during the whole catalysis.
159.9°. The Pd−C(1) bond length of 2.074 Å is marginally
longer than that in 2-PPh3 (2.063 Å), while the Pd−P bond
length of 2.223 Å is slightly shorter than 2.25 Å, showing that
the bonding contribution of phosphine ligand is much more
significant than that of the CDC for palladium in a low
oxidation state. In addition, we also saw no evidence of π−π
interaction, as the phenyl group in PPh3 was no longer parallel
with the benzimidazole ring of CDC ligand. Nonetheless, the
weak agostic interaction (Pd- - -H(1) (2.526 Å) and Pd- - -H(2)
(2.082 Å)) from the Me and iPr ligands in CDC played an
essential role in stabilizing the Pd(0) intermediate as well as
holding the weakly coordinated CDC from being completely
dissociated away from the metal center. Again, this computa-
tional finding is consistent with the notion that the low
reactivity of electron-rich aryl bromide under an N2 atmosphere
is due to the instability of complex 6, as discussed earlier in our
first part of mechanistic studies.
CONCLUSION
■
In summary, we have successfully prepared and characterized
palladium complexes containing carbodicarbene mixed with
different phosphine ligands. The corresponding palladium
complexes have also been effectively demonstrated to be active
catalysts in Suzuki−Miyaura C−C cross-coupling reactions,
particularly for sterically demanding substrates. The solution
NMR and structural analysis revealed an unexpected intra-
molecular π−π interaction between the CDC and phosphine
ligands within the palladium complexes, which served as an
invisible bridging linkage to enforce a cis conformation of the
complex. The computational studies supported that the π−π
At the equilibrium step of E in the catalyst regeneration
cycle, we were curious whether the π−π stacking persisted in
Pd(0) complex 6 with a linear geometry. As illustrated in Figure
3b by the theoretical calculations, the calculated structure of 6
is bent slightly from linearity with a P−Pd−C(1) angle of
I
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Article
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The implications for catalysis and the extension to a wide
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ASSOCIATED CONTENT
* Supporting Information
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Cartesian coordinates of the calculated structures (XYZ)
Experimental details and characterization data of 1, 2-
PPh3, 2-PTol3, and 2-PCy3, including their catalytic
reactions in C−C cross-coupling reactions, and computa-
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Accession Codes
CCDC 1573441−1573443 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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AUTHOR INFORMATION
Corresponding Authors
*E-mail for L.Z.: ias_llzhao@njtech.edu.cn.
*E-mail for T.-G.O.: tgong@gate.sinica.edu.tw.
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■
ORCID
Tiow-Gan Ong: 0000-0001-9817-6300
Notes
The authors declare no competing financial interest.
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ACKNOWLEDGMENTS
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This work was financially supported by the Ministry of Science
& Technology of Taiwan (MOST-104-2628-M-001-005-MY4
grant) and an Academia Sinica Career Development Award
(104-CDA-M08). The theoretical work was supported by
Nanjing Tech University (Grant No. 39837123), and a SICAM
Fellowship from Jiangsu National Synergetic Innovation Center
for Advanced Materials, Natural Science Foundation of Jiangsu
Province for Youth (Grant No. BK20170964), and National
Natural Science Foundation of China (Grant No. 21703099).
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