Tripod immobilization of triphenylphosphane on a silica-gel surface to enable selective mono-ligation to palladium: Application to suzuki-miyaura cross-coupling reactions with chloroarenes

Article abstract of DOI:10.1002/chem.201304081

A silica-supported triphenylphosphane (Silica-3p-TPP) with a Ph ₃P-type core, immobilized on a silica surface, was synthesized and characterized by nitrogen-absorption measurements and solid-state NMR spectroscopy. The tripodal immobilization constrains the mobility of the phosphane molecule and causes the lone pair on the phosphorus atom to face in the direction perpendicular to the support, resulting in the selective formation of a 1:1 metal-phosphane species that is free from unfavorable steric repulsions caused by the silica surface. Heterogeneous Pd catalysts created in this manner enabled room-temperature Suzuki-Miyaura cross-coupling reactions with unactivated chloroarenes, despite the moderate electronic and steric nature of the Ph₃P-based ligands. These catalysts also showed potential in reactions with more challenging substrates under mild conditions. Tripodally immobilized and well-dispersed phosphanes on the silica surface were crucial for high catalytic activity. Copyright

Full text of DOI:10.1002/chem.201304081

DOI: 10.1002/chem.201304081
Full Paper
&
Heterogeneous Catalysis
Tripod Immobilization of Triphenylphosphane on a Silica-Gel
Surface to Enable Selective Mono-Ligation to Palladium:
Application to Suzuki–Miyaura Cross-Coupling Reactions with
Chloroarenes
Tomohiro Iwai, Ryotaro Tanaka, Tomoya Harada, and Masaya Sawamura*[a]
Abstract: A silica-supported triphenylphosphane (Silica-3p-
TPP) with a Ph3P-type core, immobilized on a silica surface,
was synthesized and characterized by nitrogen-absorption
measurements and solid-state NMR spectroscopy. The tripo-
dal immobilization constrains the mobility of the phosphane
molecule and causes the lone pair on the phosphorus atom
to face in the direction perpendicular to the support, result-
ing in the selective formation of a 1:1 metal–phosphane spe-
cies that is free from unfavorable steric repulsions caused by
the silica surface. Heterogeneous Pd catalysts created in this
manner enabled room-temperature Suzuki–Miyaura cross-
coupling reactions with unactivated chloroarenes, despite
the moderate electronic and steric nature of the Ph3P-based
ligands. These catalysts also showed potential in reactions
with more challenging substrates under mild conditions. Tri-
podally immobilized and well-dispersed phosphanes on the
silica surface were crucial for high catalytic activity.
Introduction
cause of the high degree of coordinative unsaturation of the
metal center.[6–9]
Triphenylphosphane (Ph3P, TPP) is the most commonly used
tertiary phosphane ligand in transition-metal catalysis.[1,2]
Owing to an intrinsic stability in air and the ease of structural
modification, various derivatives of Ph3P with different steric
and electronic natures have been developed for modulating
and improving catalytic performance. These phosphanes are
categorized as triarylphosphanes.
Recently, a series of studies by Tsuji and co-workers showed
that effective catalysts for the cross-coupling of chloroarenes
can be produced by using Ph3P-based ligands that have a high
steric demand in the periphery of the ligand, where direct
ligand–substrate steric interaction does not occur.[10–12] These
studies not only confirmed the importance of the 1:1 Pd0–P
species, but also afforded two important new concepts regard-
ing ligand design for Pd catalysts. Firstly, strong electron-do-
nating ligand effects are not always required. Secondly, ligand
steric effects do not have to occur in the proximity of the
metal center. Despite this conceptual advance and the advant-
age of using an air-stable Ph3P core, the synthetic effort re-
quired to introduce large substituents in a dendritic manner
makes this strategy challenging.
In contrast, trialkylphosphanes are more electron rich than
triarylphosphanes, thus, trialkylphosphanes can be used to in-
crease the electron density at the metal center of transition-
metal catalysts, regardless of their sensitivity toward air oxida-
tion.[3] For example, a sterically demanding trialkylphosphane
ligand, such as tBu3P or Cy3P (Cy=cyclohexyl), can be used for
Pd-catalyzed cross-coupling reactions with challenging electro-
philic coupling partners, such as unactivated or sterically de-
manding chloroarenes.[4,5] The electron-donating ligand assists
oxidative addition of the CÀCl bond to a Pd0–P species. The
steric demand of the ligand is believed to be important for the
formation of this 1:1 Pd0–P species, which is highly active be-
Immobilization on a solid surface, for site isolation, could be
an efficient strategy for making Ph3P an effective ligand for Pd-
catalyzed cross-coupling reactions. Linking the Ph3P core,
which has C3v symmetry, to the solid surface in a tripodal
manner[13–15] by using linkers that possess minimal flexibility is
possibly the most effective way to achieve immobilization. If
the solid surface is assumed to be virtually flat, the cone-
shaped Ph3P core would stand upright on the surface, turning
its P-atom lone pair upwards, resulting in effective site isola-
tion and preventing steric interactions between the solid sur-
face and the catalytic center. This assumption is based on the
knowledge that Silica-SMAP,[16,17] silica-supported trialkylphos-
phane (see Scheme 2 for the chemical structure), featuring
a compact cage structure with a bridgehead P atom and
a cage-to-surface direct linkage through a disiloxane bond, ex-
[a] Dr. T. Iwai, R. Tanaka, T. Harada, Prof. Dr. M. Sawamura
Department of Chemistry, Faculty of Science
Hokkaido University
Sapporo 060-0810 (Japan)
Fax: (+81)11-706-3749
E-mail: sawamura@sci.hokudai.ac.jp
Homepage: http://wwwchem.sci.hokudai.ac.jp/~orgmet/index.php
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201304081.
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Figure 1. Silica-supported triarylphosphanes.
hibited excellent ligand performance in Pd-catalyzed cross-cou-
pling reactions with challenging chloroarenes.[17e]
Scheme 1. Preparation of Silica-3p-TPP.
We have prepared a tripod phosphane, Silica-3p-TPP, with
dimethylsilylene linkers, and bipod and monopod reference
compounds, Silica-2p-TPP, Silica-1p-TPP, and Silica-1p-EtTPP
(Figure 1). The tripod phosphane produced effective catalysts
for Pd-catalyzed room-temperature Suzuki–Miyaura coupling
reactions with relatively challenging chloroarenes. The 31P NMR
studies indicated that tripod immobilization of the Ph3P-based
ligand resulted in selective formation of a 1:1 metal–phos-
phane species. This indicates that strong electron-donating
ability and steric demand of a ligand would not be essential to
provide coordinatively unsaturated and catalytically active spe-
cies by the aid of immobilization.
phane Silica-3p-TPP(SiOH) (1.62 g; “SiOH” indicates that surface
silanols are unmodified). Combustion elemental analysis on
carbon showed that the loading of the TPP moiety (equivalent
to P atom loading, [P]) on the silica gel was 0.20 mmolgÀ1, as-
suming that all of the iPrO groups were removed.[20] The re-
maining surface silanols were Me3Si endcapped upon treat-
ment of Silica-3p-TPP(SiOH) (1.62 g) with excess TMS-imidazole
(5.0 mL; TMS=trimethylsilyl), at 608C for 12 h, to afford Silica-
3p-TPP (1.62 g). The combustion elemental analysis on carbon
and 29Si cross-polarization magic-angle spinning (CP/MAS) NMR
analysis indicated that the approximate TMS/TPP ratio for
Silica-3p-TPP was 2:1. The loading level of TPP on the silica-gel
surface could be controlled in the range of 0.06–0.20 mmolgÀ1
by varying the initial amount of 3p-TPP relative to silica gel.[21]
Results and Discussion
Preparation of a silica-supported tripod phosphane
The preparation of a silica-supported tripod phosphane, Silica-
3p-TPP,[18] containing a disiloxane linkage at the para position
of each aromatic ring of the Ph3P core is shown in Scheme 1.
The conversion of bromobenzene derivative 1a, containing
a (iPrO)Me2Si substituent at the para position, into the corre-
sponding Grignard reagent, followed by treatment with PCl3,
afforded soluble sila-functionalized Ph3P species 3p-TPP in
80% yield. The (iPrO)Me2Si groups survived the conditions for
generating the Grignard reagent and the subsequent reaction
with PCl3. Furthermore, 3p-TPP could be purified by silica-gel
chromatography without decomposition or reaction with the
silica gel.
Surface area and coverage
Nitrogen-adsorption measurements of Silica-3p-TPP ([P]=
0.20 mmolgÀ1) showed that the surface modification of the
CARiACT Q10 silica gel with the tripod phosphane and the
TMS groups resulted in a reasonable reduction of structural pa-
rameters, such as surface area (284 versus 271 m2 gÀ1), pore di-
ameter (17.8 versus 15.6 nm), and pore volume (1.32 versus
1.03 mLgÀ1).[17b] On the basis of the surface area value and the
TPP loading, the surface P-atom density for Silica-3p-TPP was
calculated to be 0.44 nmÀ2. The adsorption–desorption iso-
therm showed a hysteresis curve that is typical for silica gel
with mesopores (see Figure S1 in the Supporting Information).
Species 3p-TPP (183 mg, 0.30 mmol) was then grafted onto
the silica-gel surface (1.50 g, CARiACT Q-10, 75–150 mm) in
benzene (15 mL) heated at reflux, in the presence of imidazole
(1.5 mmol).[19] After gentle stirring for 12 h, during which time
3p-TPP was completely consumed, colorless solids were col-
lected by filtration, washed with MeOH, CH2Cl2, and Et2O, and
dried under vacuum to afford silica-supported tripod phos-
Solid-state NMR spectra of silica-supported tripod phos-
phane
The silica-supported tripod phosphane was characterized by
solid-state NMR spectroscopy.[22] The 31P, 29Si, and 13C CP/MAS
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spectra of Silica-3p-TPP(SiOH) ([P]=0.20 mmolgÀ1) and 3p-TPP/
SiO2, which was prepared by mixing 3p-TPP with unmodified
silica gel as a control experiment, are shown in Figures 2–4.
The supported phosphane, Silica-3p-TPP(SiOH), was used
before Me3Si endcapping for these NMR measurements to pre-
vent peak overlap between the Me2Si group of the linker and
the Me3Si group of the endcap in the 29Si and 13C NMR spectra
(Figure 3b and 4b).
The 31P CP/MAS spectrum of Silica-3p-TPP(SiOH) displayed
a resonance at d=À5 ppm (Figure 2b), which was assigned to
the P atom of free phosphane, based on the comparison of
this signal with the 31P NMR signal (d=À5.1 ppm) for soluble
3p-TPP in CDCl3 and the 31P CP/MAS NMR signal (d=À6 ppm)
for nonimmobilized 3p-TPP/SiO2 (Figure 2a). This similarity in
the 31P chemical-shift values indicates that the cone angle of
Silica-3p-TPP(SiOH) is virtually the same as that of the nonim-
mobilized ligand 3p-TPP.
Notably, the 31P CP/MAS spectrum of Silica-3p-TPP(SiOH)
also indicated that formation of a phosphane oxide did not
occur. Silica-3p-TPP(SiOH) and Silica-3p-TPP are bench-stable
and easy-to-handle materials. Interestingly, the air stability of
the supported Ph3P-based phosphanes was dependent on the
number of linkages. In contrast to the tripod phosphanes, the
corresponding bipod and monopod phosphanes, Silica-2p-TPP
and Silica-1p-TPP, respectively, were susceptible to air oxidation
even after isolation, the latter being much less stable (see Fig-
ures S10–S12 in the Supporting Information). The reason for
the difference in stability seems to be related to the remark-
able air stability of the SMAP-type caged trialkylphosphanes,
though details remain to be investigated. This air stability
might arise from the geometrical constraint of the C-P-C
angles, limiting the geometrical change that can occur in the
pathway toward the transition state for the oxidation.[23] Ph-
SMAP is stable even without a solid support.[16,17b]
Figure 3b shows the 29Si CP/MAS spectrum of Silica-3p-TPP-
(SiOH). The peak at d=3 ppm, assigned to the Si atom para to
the P atom, is significantly shifted compared with that of the
3p-TPP/SiO2 mixture (d=9 ppm, Figure 3a). Importantly, the
peak at d=3 ppm in the spectrum of Silica-3p-TPP(SiOH) does
not accompany a detectable peak in the lower field region
(Figure 3b).[24] These results, combined with the difference in
air stability between Silica-3p-TPP(SiOH) and Silica-2p-TPP-
(SiOH), indicate that almost all of the (iPrO)Me2Si groups were
used for disiloxane bond formation, leading to successful
tripod immobilization of the TPP core to the silica surface. If
the third immobilization of 3p-TPP was unsuccessful, the re-
sulting (bipod) phosphane should show a lower-field 29Si signal
for the intact SiÀOÀC moiety and be susceptible to air oxida-
tion.
It should be noted that the 13C CP/MAS spectrum of Silica-
3p-TPP(SiOH) shows two weak signals at d=27 and 67 ppm
(Figure 4b, see also Figure 4a for comparison). These signals
can be assigned to iPrO groups that are chemically bonded to
the silica gel support.[25]
Figure 2. 31P CP/MAS NMR spectra of a) 3p-TPP/SiO2 and b) Silica-3p-TPP-
(SiOH).
Figure 3. 29Si CP/MAS NMR spectra of a) 3p-TPP/SiO2 and b) Silica-3p-TPP(SiOH).
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Figure 4. 13C CP/MAS NMR spectra of a) 3p-TPP/SiO2 and b) Silica-3p-TPP(SiOH). Isopropoxy groups derived from 3p-TPP ( ).
*
Coordination with a PdII complex
The coordination properties of the silica-supported tripod triar-
ylphosphanes were investigated, in the reaction with [PdCl2-
(PhCN)2], by solid-state NMR spectroscopy. Specifically, the re-
action of Silica-3p-TPP ([P]=0.20 mmolgÀ1) was conducted
with an excess amount of [PdCl2(PhCN)2] (2:1 Pd/P), in benzene
at room temperature. After filtration, washing, and drying, the
31P CP/MAS NMR spectrum of the resulting brown solid
showed a single peak at d=33 ppm, indicating that mono-P-li-
gated Pd complex [PdCl2(PhCN)(Silica-3p-TPP)] was formed se-
lectively (Figure 5a), and that all P species participated in coor-
dination to the Pd complex. Importantly, the mono-P-ligated
Pd complex was formed selectively, even in the presence of
excess P species (1:3 Pd/P), as indicated by the 31P CP/MAS
spectrum (Figure 5b); free phosphane was observed at d=
À5 ppm.
In contrast, the reaction of [PdCl2(PhCN)2] with excess mo-
nopod-type silica-supported phosphane Silica-1p-TPP[17f,26] (1:3
Pd/P based on [P]) afforded two 31P signals at low field (d=30
and 22 ppm), along with a signal for free phosphane (d=
À4 ppm, Figure 5c). The corresponding homogeneous reaction
between [PdCl2(PhCN)2] and 1p-TPP (1:1 or 1:2 Pd/P) in CDCl3
formed a mixture of mono-P-ligated complex [PdCl2(PhCN)(1p-
TPP)] (d=33.3 ppm) and di-P-ligated complex [PdCl2(1p-TPP)2]
(d=23.7 ppm, see Figure S15 in the Supporting Information).
Thus, the two signals afforded by the reaction with the mo-
nopod phosphane (Figure 5c) were assigned to [PdCl2-
(PhCN)(Silica-1p-TPP)] (d=30 ppm) and [PdCl2(Silica-1p-TPP)2]
(d=22 ppm). These results indicate that the mobility of the P
center of monopod phosphane Silica-1p-TPP is significant and
that monopodal immobilization was not an effective method
for inhibiting bidentate P-atom coordination on the silica-gel
surface. This difference in selectivity is additional proof of the
tripod immobilization of 3p-TPP.
Pd-catalyzed Suzuki–Miyaura cross-coupling of chloroar-
enes: ligand effects
Figure 5. 31P CP/MAS spectra after the reaction of [PdCl2(PhCN)2] with
Despite recent progress in Pd-catalyzed cross-coupling reac-
tions, only a limited number of catalyst systems are capable of
a) Silica-3p-TPP (2:1 Pd/P); b) Silica-3p-TPP (1:3 Pd/P); and c) Silica-1p-TPP
(1:3 Pd/P). Spinning side bands ( ).
*
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promoting Suzuki–Miyaura coupling reactions with unactivated
chloroarenes at room temperature with a reasonable catalyst
loading.[27,28] Thus, the silica-supported tripod phosphane was
examined for catalytic activity in the room-temperature Pd-cat-
alyzed Suzuki–Miyaura coupling reaction between p-chloroani-
sole (2a) and phenylboronic acid (3a) (Scheme 2). To elucidate
the effect of surface-immobilization modes, not only silica-sup-
ported cage-type trialkyl- and triarylphosphanes (Silica-SMAP
and Silica-TRIP[29,30]), but also bipodal- or monopodal-immobi-
lized Ph3P-based ligands were examined. The coupling reaction
between 2a (0.5 mmol) and 3a (0.75 mmol) was conducted at
258C for 16 h, in the presence of KF (1.5 mmol) as a base,
[PdCl2(PhCN)2] (1 mol% Pd), and a phosphane ligand (2 mol%
P, 1:2 Pd/P). Yields of 4-methoxy-1,1’-biphenyl (4a), determined
would be efficient ligands for the Suzuki–Miyaura coupling of
chloroarenes. In fact, Silica-3p-TPP afforded 4a in 97% yield
(100% conversion, 92% isolated product) at room temperature
(Scheme 2).
The effect of the number of linkages was then investigated.
As shown in Scheme 2, silica-supported Ph3P-based bipod
phosphane Silica-2p-TPP gave 4a in 49% yield. The monopo-
dal-immobilized Ph3P-based ligand, Silica-1p-TPP, which has
a direct disiloxane linkage between the aromatic ring of the
TPP core and the silica surface, was far less effective (12%
yield). Furthermore, another silica-supported phosphane, Silica-
1p-EtTPP, which has a longer and more flexible linker chain,
was also much less effective (11% yield) than the tripod phos-
phane. Homogeneous reactions employing the soluble sila-
functionalized Ph3P-type ligand, 3p-TPP, as well as the parent
Ph3P ligand, did not induce coupling activity under the room-
temperature conditions. Phosphane-free [PdCl2(PhCN)2] did not
promote any reaction.
1
by H NMR spectroscopy, are summarized in Scheme 2.
Silica-SMAP ([P]=0.07 mmolgÀ1) afforded 4a in 53% yield
under the conditions in Scheme 2, in accordance with the pre-
vious report.[17e] Surprisingly, the reaction with triptycene-type
ligand Silica-TRIP ([P]=0.07 mmolgÀ1) was more efficient than
that with Silica-SMAP, resulting in complete conversion of 2a
(99% yield), irrespective of the moderate electron-donating
power of the triarylphosphane. These results lead to the hy-
pothesis that a strong electron-donating effect is not essential
for surface-presented mono-P-ligated Pd complexes to display
activity toward ArÀCl oxidative addition.
These ligand effects can be summarized as follows: Firstly,
immobilization on the solid surface is crucial for the Ph3P-
based ligands to be effective in the coupling reaction. Second-
ly, tripod immobilization (Silica-3p-TPP) is as efficient as cage-
to-surface direct linking (Silica-TRIP), and is more efficient than
bipod (Silica-2p-TPP) or conventional flexible monopod immo-
bilization (Silica-1p-TPP, Silica-1pEtTPP). These results suggest
that non-cage monopod disiloxane immobilization, which is
a conventional method for obtaining a solid-support ligand for
heterogeneous catalysis, is insufficient for suppressing mobility
of the P center and for site isolation. This assumption is strong-
ly supported by results from the NMR analysis of Pd–P coordi-
nation (Figure 5); Silica-3p-TPP formed a mono-P-ligated Pd
species exclusively, but Silica-1p-TPP gave a mixture involving
di-P-ligated species as a result of bidentate P-atom coordina-
tion with two neighboring TPP moieties.
With this hypothesis in mind, we envisaged that silica-sup-
ported Ph3P-based phosphanes ([P]=0.19–0.20 mmolgÀ1)
Effect of P-atom density
Next, we investigated the effect of surface P-atom density on
the efficiency of the Pd-catalyzed Suzuki–Miyaura coupling re-
action between 2a and 3a (Figure 6, 1 mol% Pd, 1:2 Pd/P).
Time–yield profiles for this reaction, in the presence of tripod
phosphanes with different P-atom densities, are shown in
Figure 6. The tripod phosphane with the highest P-atom densi-
ty ([P]=0.29 mmolgÀ1), prepared using excess 3p-TPP[21] pos-
sessed markedly lower catalytic activity compared with the
other tripod phosphanes ([P]=0.06, 0.11, and 0.20 mmolgÀ1).
The latter three surfaces exhibited only a slight reduction in ac-
tivity on increasing the degree of phosphane modification.
This suggests that the Silica-3p-TPP surface, with the highest
P-atom density, caused over-modification of this surface.[31] In
contrast, the much smaller impact of the P-atom density
among the other three surfaces indicates that effective catalyst
site isolation was nearly equal in this range.
Scheme 2. Ligand effects in the Pd-catalyzed Suzuki–Miyaura cross-coupling
reaction between 2a and 3a. Conditions: 2a (0.5 mmol), 3a (0.75 mmol),
Figure 6 also shows time–yield profiles for the reaction be-
tween 2a and 3a in the presence of silica surfaces modified
with monopod phosphane molecules (Silica-1p-TPP) at two dif-
ferent P-atom densities. The profiles indicate that the low cata-
[PdCl2(PhCN)2] (0.005 mmol, 1 mol% Pd), ligand ([P]=0.19–0.20 mmolgÀ1
,
0.01 mmol, 2 mol% P), KF (1.5 mmol), THF (1 mL), 258C, 16 h. Yields of 4a
1
were determined by H NMR spectroscopy. Silica-SMAP, [P]=0.07 mmolgÀ1
;
Silica-TRIP, [P]=0.07 mmolgÀ1
.
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3a by using K3PO4 as a base, at 608C (entry 9). The coupling
reaction between 3-chloropyridine (2k) and 3,5-dimethylphen-
ylboronic acid (3b) afforded the corresponding heterocyclic
compound (4k) in 82% yield (entry 10). Notably, these condi-
tions allowed the use of an aryl triflate (5) as an electrophile
for the coupling with 3a to afford 4l in 97% yield (entry 11).
Arylboronic acids with electron-withdrawing functionality,
such as acetyl (3c), cyano (3d), or trifluoromethyl (3e) groups
were also employed successfully as nucleophilic coupling part-
ners for room-temperature cross-coupling reactions (Table 1,
entries 12–14). Ortho-substituted arylboronic acids, such as o-
tolylboronic acid (3 f) and 1-naphthylboronic acid (3g), were
also suitable substrates for coupling with p-chloroanisole (2a)
to produce the corresponding sterically congested biaryls (4p,
K3PO4, 608C, 82%; 4q, KF, 258C, 93%; entries 15 and 16). The
sterically more congested, tri-ortho-substituted biaryl 4r could
be obtained through the coupling of 2,6-dimethyl-chloroben-
zene (2j) with o-tolylboronic acid (3 f) in 80% yield (entry 17).
Figure 6. Effects of P-atom density (time–yield profiles) for heterogeneous
Pd-catalyzed coupling between 2a and 3a. Conditions: 2a (0.5 mmol), 3a
(0.75 mmol), [PdCl2(PhCN)2] (0.005 mmol, 1 mol% Pd), ligands ([P]=0.06–
0.29 mmolgÀ1, 0.01 mmol, 2 mol% P), KF (1.5 mmol), dibenzyl (0.5 mmol as
an internal standard for GC analysis), THF (1 mL), 258C. Yields of 4a were de-
~
&
*
termined by GC analysis. For Silica-3p-TPP [P]=0.06 ( ), 0.11 ( ), 0.20 ( ),
À1
À1
~
&
^
0.29 ( ) mmolg . For Silica-1p-TPP [P]=0.10 ( ), 0.19 ( ) mmolg
.
Catalyst recovery and reuse
In the heterogeneous Silica-3p-TPP/Pd system, the catalyst
could easily be separated from the products by filtration
through Celite. After the reaction of p-chloroanisole (2a) and
phenylboronic acid (3a), under the conditions in Scheme 2, in-
ductively coupled plasma–atomic emission spectroscopy (ICP–
AES) indicated that Pd leaching was below the detection limit
(0.02% of the loaded Pd). A hot-filtration test of the Silica-3p-
TPP/Pd catalyst indicated that no meaningful reaction occurred
in the solution phase.
lytic efficiency of the Silica-1p-TPP/Pd system used for the
ligand evaluation (Scheme 2, [P]=0.19 mmolgÀ1) could be im-
proved significantly by decreasing the P-atom density to [P]=
0.10 mmolgÀ1. This improvement seems to be due to a disper-
sion effect, meaning that better site isolation of the catalytic
center was achieved by increasing the dispersion level for the
monopod-type supported phosphane. Nevertheless, further
improvement of catalytic activity based on the dispersion
effect was unsuccessful.
To test catalyst reusability, the reaction of p-chlorotoluene
(2b, 0.5 mmol) with 3a (0.75 mmol), in THF at 408C, was con-
ducted in the presence of a heterogeneous catalyst system
prepared from [{PdCl(h3-cinnamyl)}2] (1 mol% Pd) and Silica-3p-
TPP ([P]=0.11 mmolgÀ1, 2 mol% P) (Scheme 3).[32] The reaction
reached completion after 2 h (99% yield of 4b) and the solids
containing the catalyst and inorganic salts were collected on
a cotton filter. The inorganic salts were removed by washing
with H2O, and solvent displacement was performed with THF
followed by Et2O. After drying under vacuum, the residue was
applied to the next catalytic reaction. The Pd catalyst in the
second run showed higher activity than that in the first run,
the reaction reaching completion within 1 h. The third and
fourth runs also proceeded smoothly to give 4b in 99 and
95% yields, respectively. The Silica-3p-TPP/Pd catalyst main-
tained most of its activity even in the fifth run, however, the
yield was reduced to 74%.
These results demonstrate that tripodal immobilization is
a novel and effective method for catalyst site isolation. The ef-
fective site isolation is due to the highly constrained mobility
of the P center, with upward directionality of the lone pair of
the P atom.
Substrate scope of Suzuki–Miyaura coupling reactions in the
presence of Silica-3p-TPP
The scope of the heterogeneous Pd-catalyzed Suzuki–Miyaura
coupling reaction with Silica-3p-TPP ([P]=0.11 mmolgÀ1) is
summarized in Table 1 (1 mol% Pd unless otherwise noted).
Electronically unbiased chloroarene p-chlorotoluene (2b) react-
ed with phenylboronic acid (3a) at 258C to afford 4b in 91%
yield (entry 1). Even p-chloro-N,N-dimethylaniline (2c), which is
strongly deactivated by an electron-donating substituent, re-
acted with 3a at 258C, however, this transformation demand-
ed a slightly higher catalyst loading (2 mol% Pd) to achieve
a satisfactory yield (entry 2). Chloroarenes with electron-with-
drawing groups, such as formyl (2d), acetyl (2e), methoxycar-
bonyl (2 f), nitro (2g), and cyano groups (2h) at the para posi-
tion, smoothly reacted with 3a to form the corresponding
biaryls 4d–h in good to high yields (entries 3–7).
Conclusion
A new type of silica-supported phosphane (Silica-3p-TPP),
which features a Ph3P-type core tripodally immobilized on
a silica surface, was developed. The synthesis of this material is
straightforward and the effort and cost of its preparation is
comparable to that of most sophisticated homogeneous phos-
phane ligands. The structure and coordination behavior of
a Pd complex of this immobilized phosphane was character-
o-Chlorotoluene (2i) yielded ortho-substituted biphenyl 4i in
80% yield (Table 1, entry 8). More sterically hindered 2,6-dime-
thylchlorobenzene (2j) underwent the coupling reaction with
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Table 1. Silica-3p-TPP/Pd-catalyzed Suzuki–Miyaura cross-coupling reaction between chloroarenes 2 and arylboronic acids 3.[a]
Entry
Chloroarene
Arylboronic
acid 3
Base
T
[8C]
Product
Yield
[%][b]
2
4
1
2
2b
2c
3a
KF
KF
25
25
4b
4c
91[c]
85[d]
3a
3a
3
4
5
2d
2e
2 f
KF
KF
KF
25
25
25
4d
4e
4 f
81
97
94
3a
3a
6
7
2g
2h
3a
3a
KF
KF
25
25
4g
4h
87
88
8
9
2i
2j
3a
3a
KF
25
60
4i
4j
80[c]
85[c]
K3PO4
10
2k
5
3b
K3PO4
60
4k
82
11
12
3a
K3PO4
KF
60
25
4l
97
96
2b
3c
4m
13
14
2b
2a
3d
3e
KF
KF
25
25
4n
4o
87
88
15
16
2a
2a
3 f
K3PO4
KF
60
25
4p
4q
82
93
3g
17
2j
3 f
K3PO4
60
4r
80[c]
[a] Conditions: Chloroarenes (2, 0.5 mmol), arylboronic acid (3, 0.75 mmol), [PdCl2(PhCN)2] (0.005 mmol, 1 mol% Pd), Silica-3p-TPP ([P]=0.11 mmolgÀ1
,
0.01 mmol, 2 mol% P), base (1.5 mmol), THF (1 mL), 258C, 16 h. [b] Yield of isolated product. [c] Homocoupling products of 3 that could not be separated
from 4 were also present. The amount of byproduct was estimated by 1H NMR spectroscopy and GC analysis (biphenyl: entry 1, 2%; entry 8, 2%; entry 9,
2%. 2,2’-dimethylbiphenyl: entry 17, 4%). [d] [PdCl2(PhCN)2] (0.01 mmol, 2 mol% Pd), Silica-3p-TPP ([P]=0.11 mmolgÀ1, 0.02 mmol, 4 mol% P).
ized by 13C, 29Si, and 31P CP/MAS NMR spectroscopy as well as
nitrogen-absorption measurements. The NMR analysis indicat-
ed efficient site isolation of each phosphane center, allowing
independent coordination to the metal center to form mono-
P-ligated Pd complexes (1:1 Pd/P). In contrast, NMR analysis of
the corresponding monopod phosphane (Silica-1p-TPP)
showed that the P center of the monopod phosphane is signif-
icantly mobile and that monopodal immobilization is not effec-
Scheme 3. Reuse of Silica-3p-TPP/Pd in the Suzuki–Miyaura cross-coupling
reaction between 2b and 3a.
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tive at inhibiting bidentate P-atom coordination on the silica-
gel surface.
ACT-C (JST). T.I. is grateful for the Grants-in-Aid for Young Sci-
entists (B and Start-up) from JSPS and for the Regional R&D
Proposal-Based Program from the Northern Advancement
Center for Science & Technology of Hokkaido, Japan. Mr. Naka-
gawa (NMR Laboratory, Graduate School of Engineering, Hok-
kaido University) is acknowledged for solid-state NMR spectros-
copy measurements.
Catalyst systems composed of Pd and the silica-supported
tripod phosphane enabled room-temperature Suzuki–Miyaura
coupling reactions with unactivated chloroarenes, despite the
moderate electronic and steric natures of the Ph3P-based
ligand. A comparison of various Ph3P-based ligands, with differ-
ent modes of linkage to the silica surface, in Pd-catalyzed
cross-coupling reactions, indicated that immobilization of triar-
ylphosphane molecules to the surface is crucial and that tripo-
dal linking is as efficient as immobilization of the cage-shaped
ligand Silica-TRIP.
Keywords: chloroarenes
·
cross-coupling
·
palladium
·
phosphanes · silica-supported catalysts
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Under argon, Mg turnings (510 mg, 21 mmol, 10 equivalents) in
THF (10 mL) were activated by treatment with 1,2-dibromoethane
(10 mL). A solution of (4-bromophenyl)(isopropoxy)dimethylsilane
(1a, 2.00 g, 7.3 mmol) in THF (10 mL) was added to the flask over
10 min, while maintaining the temperature below 258C with
a water bath. The mixture was stirred for 1 h. PCl3 (183 mL,
2.1 mmol) was then added to the solution at 08C over 5 min, fol-
lowed by stirring at room temperature for 10 h. After quenching
with aq. NH4Cl, the mixture was extracted with Et2O. The organic
layer was washed with water, dried over MgSO4, filtered, and con-
centrated. The residue was purified by silica-gel chromatography
(30:1 hexanes/ethyl acetate) to give 3p-TPP as a white solid
(1.02 g, 80% yield).
In a glovebox, 3p-TPP (183 mg, 0.30 mmol), anhydrous CARiACT Q-
10 silica gel (1.50 g), imidazole (102 mg, 1.5 mmol), and anhydrous
degassed benzene (15 mL) were placed in a 50 mL glass tube con-
taining a magnetic stirring bar. The tube was screw-capped and
the suspension was heated at reflux for 12 h. The resulting solids
were collected by filtration through a cotton plug, washed succes-
sively with MeOH, CH2Cl2, and Et2O, and dried under vacuum at
1208C for 6 h. The obtained functionalized silica gel, Silica-3p-TPP-
(SiOH), (1.62 g, [P]=0.20 mmolgÀ1 determined by combustion ele-
mental analysis on carbon), was treated with N-trimethylsilylimid-
azole (5.0 mL, excess) at 608C for 12 h. The solids were collected
by filtration through a cotton plug, washed successively with
MeOH, CH2Cl2, and Et2O, and dried under vacuum at 1208C for 6 h
to provide 1.62 g of Silica-3p-TPP.
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Acknowledgements
This work was supported by Grants-in-Aid for Scientific Re-
search on Innovative Areas “Reaction Integration” (MEXT), and
Chem. Eur. J. 2014, 20, 1057 – 1065
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[31] Inhomogeneity of surface modification is obvious in the 29Si CP/MAS
spectrum of Silica-3p-TPP(SiOH), which displayed an unidentified signal
at d=0 ppm in addition to the expected peak at d=3 ppm (see Fig-
ure S6 in the Supporting Information). One possibility for the origin of
the higher field signal is the presence of a silica-supported dimeric spe-
cies with a disiloxane linkage between the two aromatic rings of the
TPP core (ArMe2SiOSiMe2Ar).
[18] Silica-3p-TPP is an abbreviation for TPP (triphenylphosphane) deriva-
tives supported on silica gel through three linkages at the para posi-
tions of the phenyl rings.
[19] Without imidazole as an additive, immobilization of 3p-TPP on silica gel
barely occurred, leaving 94% of 3p-TPP unreacted.
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azole support that showed high activity for the Suzuki–Miyaura cou-
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[20] The actual TPP loading must be somewhat lower than [P] determined
by combustion elemental analysis on carbon because some iPrO
groups were confirmed to remain in the obtained material (see, Fig-
ure 4b). Regardless of this apparent overestimation, this value will be
used for the TPP loading for convenience.
Received: October 18, 2013
Published online on December 20, 2013
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