Air-stable and highly active dendritic phosphine oxide-stabilized palladium nanoparticles: Preparation, characterization and applications in the carbon-carbon bond formation and hydrogenation reactions

Article abstract of DOI:10.1002/adsc.200700441

Dendrimer-stabilized palladium nanoparticles were formed in the reduction of palldium bis-(acetylacetonate) [Pd(acac)₂] in the presence of phosphine dendrimer ligands using hydrogen in tetrahydrofuran. The resulting Pd nanoparticles were characterized by TEM, ³¹P NMR and ³¹P MAS NMR. The results indicated that the dendritic phosphine ligandswere oxidized to phosphine oxides. These dendrimer-stabilized Pd nanoparticles were demonstrated to be efficient catalysts for Suzuki and Stille coupling reactionsand hydrogenations. The dendritic wedges served as a stabilizer for keeping the nanoparticlesfrom aggregating, and asa vehicle for facilitating the separation and/or the recycling of the Pd catalyst. In the case of the Suzuki coupling reaction, these Pd nanoparticles exhibited high catalytic efficiency (TON up to 65,000) and air stability as compared with the commonly used homogeneous catalyst tetrakis(triphenylphosphine)palladium [Pd-(PPh ₃)₄]. In addition, the results obtained from the bulky dendritic substrate suggest that the Pd nanoparticles might act asres ervoir of catalytically active species, and that the reaction is actually catalyzed by the soluble Pd(0) and/or Pd(II) species leached from the nanoparticle surface.

Full text of DOI:10.1002/adsc.200700441

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DOI: 10.1002/adsc.200700441
Air-Stable and Highly Active Dendritic Phosphine Oxide-
Stabilized Palladium Nanoparticles: Preparation,
Characterization and Applications in the Carbon-Carbon Bond
Formation and Hydrogenation Reactions
Lei Wu,a Zhi-Wei Li,a Feng Zhang,a Yan-Mei He,a and Qing-Hua Fana,*
a
Beijing National Laboratory for Molecular Sciences, Center for Chemical Biology, Institute of Chemistry, Chinese
Academy of Sciences, Beijing 100080, Peopleꢀs Republic of China
Fax : +(86)-10-6255-4449; e-mail: fanqh@iccas.ac.cn
Received: September 4, 2007; Revised: February 4, 2008; Published online: March 20, 2008
Supporting information for thisarticle isavailable on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Dendrimer-stabilized palladium nanoparti- action, these Pd nanoparticles exhibited high catalyt-
cleswere formed in the reduction of palldium bi-s
(acetylacetonate) [Pd(acac)2] in the presence of compared with the commonly used homogeneous
phosphine dendrimer ligands using hydrogen in tet- catalyst tetrakis(triphenylphosphine)palladium [Pd-
ic efficiency (TON up to 65,000) and air stability as
A
ACHTREUNG
rahydrofuran. The resulting Pd nanoparticles were
ACHTRE(UNG PPh3)4]. In addition, the results obtained from the
characterized by TEM, 31P NMR and 31P MAS bulky dendritic substrate suggest that the Pd nano-
NMR. The results indicated that the dendritic phos- particlesmight act asreservoir of catalytically active
phine ligandswere oxidized to phopshine oxide.s
species, and that the reaction is actually catalyzed by
These dendrimer-stabilized Pd nanoparticles were the soluble Pd(0) and/or Pd(II) species leached from
demonstrated to be efficient catalysts for Suzuki and the nanoparticle surface.
Stille coupling reactionsand hydrogenation.s The
dendritic wedges served as a stabilizer for keeping
the nanoparticlesfrom aggregating, and asa vehicle
Keywords: hydrogenation; palladium nanoparticles;
for facilitating the separation and/or the recycling of phosphine dendrimer; Stille coupling reaction;
the Pd catalyst. In the case of the Suzuki coupling re- Suzuki coupling reaction
Introduction
It has been demonstrated that the size, shape, and sur-
face propertiesof metal nanoparticlescan be con-
trolled by the nature of protective stabilizers.
Dendrimersare well-defined, highly branched,
three-dimensional macromolecules, and behave as
Colloidal metal particlesand metal clutsershave at-
tracted much interest because of their unique proper-
tiesand potential applicability to microelectronic,s
[1]
chemical sensing,[2] data storage,[3] and catalysts.[4] molecular boxes.[9] The formation of metal nanoparti-
Due to their large surface-to-volume ratio and dense- clestsabilized by dendrimerswasoriginally demon-
ly populated unsaturated surface coordination sites, strated by the groups of Crooks, Tomalia and
nanosized transition metal particles have proven to Esumi.[10] The nanoparticlescould be encapuslated
exhibit much higher catalytic efficiency ascompared
inside dendrimers, or located at the dendrimer periph-
with the corresponding bulk materials.[4] However, ery. Dendrimer-stabilized metal nanoparticles in catal-
such metal nanoparticles are prone to formation of ysis are one of their main applications. For example,
bulk materials of identical composition, and necessari- polyamidoamines (PAMAMs)-encapsulated metal
ly require stabilization to prevent aggregation and particleshave been demonstrated to be effective cata-
À
precipitation, which would sacrifice most of their de- lysts for olefin hydrogenations and C C coupling re-
sirable advantages. Recently, a number of methods actions, and the dendrimers acted as both templates
hasbeen developed to control the formation of metal
and porousnanoreactors. [11] In addition, different den-
nanoparticles by using surfactants,[5] organic li- drimer terminal groupscan be selected to provide de-
gands,[6,7] polymers[8] and dendrimers[4b] astsabilizer.s
sirable solubility in organic, aqueous, or fluorous
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Air-Stable and Highly Active Dendritic Phosphine Oxide-Stabilized Palladium Nanoparticles
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medium, which enable us to facilitate easy separation the dendritic phosphine oxide-stabilized metal nano-
and reuse of the nanoparticles.
particles.[15] These Pd nanoparticles were found to be
Alternatively, dendronswith coordinating groupsat
air-stable and could be easily recycled via solvent pre-
the focal point can be used as capping ligands for the cipitation. Herein, we describe the details of our re-
preparation and stabilization of metal nanoparticles. search.
In contrast to the small molecule ligand-stabilized
nanoparticles, limited dendritic ligands can be bound
to metallic coresdue to the sterically demanding den-
dritic structure. Therefore a substantial fraction of
Results and Discussion
their surface is unpassivated and available to partici- Synthesis of Dendritic Phosphine Ligands
pate in catalytic reactions. These properties have the
potential to promote the activity of the nanoparticle FrØchet-type polyaryl ether dendronsrequired for the
catalysts. However, successful examples of such metal synthesis of Pd nanoparticle-cored dendrimers were
nanoparticlesreported in catalyissare rather limit-
prepared by the reported convergent method.[16]
ed.[12,13] Recently, Fox et al. reported the first example Then, the three different generation phosphine li-
of thiol dendrimer-stabilized Pd nanoparticles using a gands GnDenP (n=1–3) were synthesized by reaction
third-generation FrØchet-type dendrimer with a disul- of the corresponding dendritic bromides with KPPh2
fide group at the core.[12] These nanoparticles exhibit- according to the reported procedure with some modi-
ed very high catalytic activitiesin Heck and Suzuki
[17]
fications(Scheme 1).
Upon completion of the reac-
coupling reactions. However, no activity was observed tion, the dendritic phosphine ligands could be easily
for hydrogenation reactionsdue to the hydrogenolysis
of the carbon-sulfur bonds.
isolated via solvent precipitation, and further purified
by flash column chromatography. Their molecular
More recently, in the hope of combining the desira- structures and purities were confirmed by 1H and
[4b]
ble propertiesof both dendrimer
and phosphine 31P NMR aswell aselemental analysis.
ligand[7,14] into palladium nanoparticles, we reported
the synthesis and application of a new type of phos-
phine dendrimer-stabilized Pd nanoparticles.[13] We Preparation and Characterization of Dendrimer-
expected that the dendritic ligandscould serve multi-
ple functions, that is, as a stabilizer for keeping the
nanoparticlesfrom aggregating; asa ligand for adjust-
ing the catalytic activity; and asa vehicle for facilitat-
ing the catalyst recycling. The preliminary results
Stabilized Palladium Nanoparticles
According to the published method,[18] palladium
nanoparticleswere prepared by the reduction of Pd-
AHCTRE(UNG acac)2 with hydrogen in THF in the presence of the
have demonstrated that these Pd catalysts were highly dendritic phosphine ligand GnDenP (Scheme 2). Dif-
effective for Suzuki coupling reactionsand hydroge- ferent from the commonly used Brustꢀs two-phase
nations. To our astonishment, our further study indi- method, no phase-transfer agent was needed, which
cated that the dendritic phosphine ligands were oxi- affirmatively contaminate the metal nanoparticles.[19]
dized during the formation of Pd nanoparticles, giving Firstly, the Pd(II) complex was formed in situ by reac-
Scheme 1. Synthesis of dendritic phosphine ligands.
Scheme 2. Preparation of dendritic phosphine ligand-stabilized Pd nanoparticles.
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Table 1. 31P NMR data of dendritic phosphine, Pd com-
plexes, and Pd nanoparticles.
tion of PdACHTREUNG(acac)2 with ligand GnDenP (n=1–3) in
THF at room temperature under a nitrogen atmos-
phere. Then, the obtained complex wasreduced by
hydrogen (25 atm) at 608C in THF overnight, gener-
ating a black solution. Notably, the ligand/Pd mole
ratio was found to influence the stability of the result-
ing nanoparticles in solution significantly. For exam-
ple, in the case of a ligand/Pd ratio of 2, we did not
observe any precipitation or formation of insoluble
materialsfor esveral monthsin air. However, when
the ligand/Pd ratio decreased to 1, Pd black was
formed already after one week. Upon evaporation of
the solvent, a black solid was isolated and could be
redissolved in low polar organic solvents, such as
THF, toluene, chloroform, and dichloromethane. On
the other hand, all these Pd nanoparticles were in-
soluble in methanol, ethanol, and diethyl ether. This
difference in solubility would provide a possibility for
catalyst recycling by a solvent precipitation method.
Ligand or complex 31P NMR (ppm) 31P MAS NMR (ppm)
G1DenP
G2DenP
G3DenP
G1DenP-Pd
G2DenP-Pd
G3DenP-Pd
G3DenP-Pd(II)[a]
G3DenP-Pd(0)[b]
G3DenP oxide
À10.30
À10.32
À10.32
28.64
28.64
28.70
30.07
21.45, 22.54
29.00
À10.9
28.1
20.4
[a]
Complex G3DenP-Pd(II) wasprepared in situ by mixing
of Pd(acac)2 with G3DenP (2 equiv.) in THF.
Complex G3DenP-Pd(0) wasprepared in situ by mixing
of Pd(dba)2 and G3DenP (2 equiv.) in THF.
AHCTREUNG
[b]
AHCTREUNG
In addition, we attempted to purify these Pd nanopar- drimer-stabilized Pd nanoparticles suggested that
ticles by sonication in ethanol for several times. Un- there wasno exitsence of any type of Pd complexe.s
fortunately, some of the excess phosphine ligands Furthermore, we also characterized the Pd(0) com-
could not be removed due to their very similar solu- plex and the Pd nanoparticlescontaining the third-
bility with that of the nanoparticles. The Pd contents generation dendrimer ligand in solid state by using
in the first- to the third-generation nanosized catalysts 31P MAS NMR. Although the NMR linesbroadened
were determined by ICP-XRF asfollow:s G1DenP- obviously, the peak shifts were very close to those ob-
Pd, 6.46%; G2DenP-Pd, 5.96%; and G3DenP-Pd, tained in the solution state.
5.15%. We also estimated the Pd content in the cata-
Considering the very similar chemical shifts for the
lyst G3DenP-Pd by using an elemental analysis Pd nanoparticles and the corresponding phosphine
method. A very similar result was obtained as com- oxide (28.70 ppm vs. 29.00 ppm), we determined the
pared to that obtained from ICP-XRF (5.14% vs. 31P NMR of the mixture of G3DenP, G3DenP oxide
5.15% Pd).
and G3DenP-Pd. Surprisingly, only two peaks with
shifts of d=28.36 and À10.17 ppm were observed, in-
The formation of Pd nanoparticleswasconfirmed
by TEM (Figure 1). The diameter and size distribu- dicating that the phosphine ligands might be oxidized
tion of these nanosized catalysts G1DenP-Pd, upon nanoparticle formation. The reproducibility of
G2DenP-Pd and G3DenP-Pd were found to be thisexperiment, however, wasascertained even under
5.0 nmÆ0.4 nm, 4.6 nmÆ0.5 nm and 3.2 nmÆ0.5 nm, strict exclusion of oxygen.[21] Although the oxidization
respectively. Thus, the mean diameter decreased with mechanism is not clear at the present stage, the trace
the increase of the generation of the dendritic ligands, amount of water in the reaction system was consid-
and a similar trend was observed in other reported ered as the source of oxygen in the phosphine oxida-
dendrimer-stabilized metal nanoparticles.[20]
tion reaction.[22] During our study, a similar oxidiza-
We tried to further characterize these Pd nanoparti- tion of phosphine ligand in the preparation of Rh
clesby using 31P NMR spectroscopy, and the data are nanoparticlesin the presence of hydrogen wasreport-
summarized in Table 1. Based on the high stability of ed by Kläui et al.[15b]
the nanoparticles solution as described above, it
seems reasonable to assume that the dendritic phos-
phine ligandshave coordinated to the usrface of the
Suzuki Coupling Reaction
Pd nanoparticles. Interestingly, the 31P NMR spectra
showed no signal at ca. À10 ppm for the excess non- The catalytic activitiesof GnDenP-Pd catalysts were
coordinated ligands. Instead, a strong signal at ca. first examined in the Suzuki coupling reactions. This
28.7 ppm wasobserved for all the three Pd nanoparti-
choice was based on the fact that such a reaction pro-
cles. For comparison, we also determined the vides a powerful tool for the synthesis of biaryls,
31P NMR spectra of the G3DenP-Pd(II) and G3DenP- which are found in many natural and synthetic prod-
Pd(0) complexes. These data are also collected in ucts.[23,24] Furthermore, the coupling reactionsare gen-
Table 1. The comparison of the peak shifts for the Pd erally carried out at high temperature and in the pres-
complexes[ G3DenP-Pd(II): 30.07 ppm; G3DenP- ence of a base, which requires a catalyst with high sta-
Pd(0): 21.45, 22.54 ppm] and d=28.7 ppm for the den- bility.
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Figure 1. TEM imagesof GnDenP-Pd nanoparticles.
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Table 2. Effect of bases and solvents on the coupling reac-
tions.[a]
Entry
Base
Solvent
Yield [%][b]
1
2
NaOAc
NaOAc
Toluene
Toluene/H2O
<10
45
AHCTRE(GNU 4:1, v/v)
3
4
5
6
7
K3PO4·7H2O
Et3N
K3PO4 (anhydrous)
K3PO4·7H2O
K2CO3
Toluene
Dioxane
Dioxane
Dioxane
Dioxane/H2O
AHCTREUNG
94
<10
94
97
52
Figure 2. Plot of conversion versus reaction time for the cou-
pling reaction of 5-bromo-1,2,3-trimethoxylbenzene with
phenylboronic acid under air.
8
K3PO4·7H2O
97
AHCTREUNG
alyzed by G3DenP-Pd nanoparticlesand G3DenP-
Pd(0) complex were examined in dioxane/water (4:1,
v/v) under identical reaction conditionsin air
(Figure 2). We chose the coupling of 5-bromo-1,2,3-
trimethoxylbenzene with phenylboronic acid asmodel
9
K3PO4·7H2O
K3PO4·7H2O
K3PO4·7H2O
THF
DMF
Dioxane
91
92
98
10
11[c]
[a]
1.25 mmol bromobenzene, 1.87 mmol benzylboronic acid,
2.50 mmol base, 0.06 mol% G2DenP-Pd, 10 mL solvent,
reflux, 20 h.
Isolated yield based on bromobenzene.
Under N2 atmosphere.
1
reaction, and used H NMR to monitor the progress
[b]
[c]
of the coupling reaction. At the beginning of the reac-
tion, the G3DenP-Pd(0) complex could catalyze the
reaction efficiently although the rate waslower than
that of the Pd nanoparticles. However, the reaction
suddenly stopped at about 30% conversion after 4 h.
Palladium black wasobserved in the reaction mixture,
Firstly, the coupling reaction of bromobenzene with indicating decomposition of the Pd(0) complex. In
phenylboronic acid in the presence of G2DenP-Pd contrast, almost quantitative conversion to coupling
wasstudied to optimize the reaction conditions. A va- product wasachieved for the Pd nanoparticle catalyst
riety of bases and solvents were screened and the ex- approximately after 15 h. It wasnoted that no Pd pre-
perimental results are summarized in Table 2. It was cipitate was observed under such rigorous conditions
found that the reaction yield was quite sensitive to during the whole reaction. Therefore, these dendritic
the base used. When triethylamine, sodium acetate, phosphine oxide-stabilized Pd nanoparticles have
potassium carbonate or potassium phosphate was proven to be air stable, and their catalytic activity was
used as the base, the reaction was carried out with virtually independent of the presence of air.
low to high reaction yields (entries 1–8). Potassium
phosphate was found to be the best base for this reac- the coupling reactionsbetween a range of aryl halides
tion. Furthermore, the reaction wasalso influenced by (I and Br) and different arylboronic acidswere car-
On the basis of the optimized reaction conditions,
the solvent. Among the solvents investigated, dioxane ried out under an air atmosphere. As shown in
was found to be the best choice of solvent for this re- Table 3, no obviousdifference in catalytic activity was
action. We also noticed that a small amount of water observed when aryl iodides or aryl bromides were
could slightly improve the formation of the coupling used in the reactions (entries 1–3). In contrast, when
products(entries5, 6, 8 and 11). The catalytic reac-
tion proceeded smoothly in the solvent mixture of di- catalyst, aryl bromides reacted only at elevated tem-
oxane/H2O (4:1, v/v) in a homogeneousmanner
perature (1538C in DMF).[11g] Aryl bromideswith
PAMAM-encapsulated Pd nanoparticles were used as
(entry 8). Notably, the reaction carried out in air also electron-withdrawing substituents were found to give
gave a comparable result to that in nitrogen under excellent to quantitative yields(entries4–10). Reac-
otherwise identical conditions (entries 6 and 11). This tionsbetween phenylboronic acid and a variety of
result indicated that the Pd nanoparticle catalyst was electron-rich substrates like 3-methoxy-, 4-methyl-, 2-
highly stable and insensitive to oxygen.
methyl-, and 4-amino-substituted aryl bromides, also
To gain more insight into the air stability of these proceeded smoothly, giving the coupling products in
dendrimer-stabilized nanoparticles, the time conver- good to excellent yields(entries11–16). In addition,
sion courses of a representative coupling reaction cat- variousarylboronic acidswith electron-donating or
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[a]
Table 3. The coupling reactionsof aryl iodidesand bromideswith variousarylboronic acids.
Entry
Aryl halide
Arylboronic acid
Coupling product
Yield [%][b]
1
2
3
4
99
98
97
quant.
5
6
99
99
7
8
99
97
9
99
10
11
99
98
12
95
13
14
15
98
96
94
16
96
<
17
18
quant.
98
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Table 3. (Continued)
Entry
Aryl halide
Arylboronic acid
Coupling product
Yield [%][b]
92
19
20
21
90
88
86
22
[a]
1.25 mmol aryl halide, 1.87 mmol arylboronic acid, 2.50 mmolK3PO4·7H2O, 0.06 mol% G2DenP-Pd, 10 mL dioxane,
reflux, 20 h.
Isolated yield based on aryl halide.
[b]
electron-withdrawing substituents were used in this rather difficult coupling reaction between 2-chloro-
reaction (entries16–22). It was found that the yields pyridine and 3-pyridineboronic acid failed (entry 9).
decreased slightly for the electron-deficient arylbor- To our knowledge, these were the best results so far
onic acids. Notably, the sterically hindered ortho-sub- obtained for the preformed polymer- and/or dendri-
stituted aryl bromides also gave good to excellent mer-stabilized Pd nanoparticles.
yields(entries8, 10, 14, 18, 20 and 22).
In order to further demonstrate the high efficacy of
these Pd nanoparticles, the coupling reaction of bro- Catalyst Recycling in Suzuki Coupling Reactions
mobenzene with phenylboronic acid wasuesd to
assess the minimum amount of catalysts. When we de- Having established the efficacy of the GnDenP-Pd
creased the catalyst (G2DenP-Pd) loading from 0.06 nanoparticlesin the Suzuki coupling reaction,s we
mol% to 0.003 mol%, the reaction wasfound to pro-
then investigated their recyclability (Table 6). Al-
ceed smoothly and gave 89% yield upon a prolonged though, as homogeneous catalysts, the soluble poly-
reaction time. Notably, the third-generation catalyst mer- and dendrimer-stabilized noble metal nanoparti-
G3DenP-Pd was preserved under an air atmosphere cles showed unique catalytic characteristics, they still
for three months, and found to be very active under suffered from difficulties in separation and reuse. For
rather low catalyst loading (0.001 mol%, 65% yield in the recycling experiment, the coupling reaction of 4-
96 h). Thus, the average TON reached 65,000, to our hydroxyphenyl iodide with phenylboronic acid in the
knowledge this is the highest TON obtained so far for presence of 0.2 mol% G3DenP-Pd was chosen as stan-
the preformed Pd nanoparticles.[11g,24,25] In contrast, dard reaction. Upon the completion of the reaction,
with the most commonly used catalyst PdACHTRE(UNG PPh3)4, the the catalyst was quantitatively precipitated by adding
reaction provided a much lower yield (15%) even a large amount of methanol, and reused for at least
under 0.5 mol% catalyst loading, and palladium black eight times without any loss in activity in the first four
wasobserved from the beginning of the reaction.
runs( >95% yield) and with reduced yieldsfrom the
To further demonstrate the general effectiveness of 5th run. High yieldscould be alos achieved at pro-
these nanoparticle catalysts, we extended the sub- longed reaction times. The leaching of palladium was
strates to aryl or heteroaryl chlorides, which are con- measured by ICP-XRF at the 2nd and 3rd cycles, and
siderably more challenging and readily accessible sub- found to be no more than 0.84% (8.1 ppm) and
strates.[26] As illustrated in Table 4, several deactivated 0.37% (3.6 ppm), respectively.
or sterically hindered ortho-substituted aryl chlorides
were employed in the G3DenP-Pd catalyzed coupling
reaction with boronic acids. Good yields were The Role of Pd Nanoparticles in Suzuki Coupling
ACHTREUNGachieved with 2 mol% catalyst in all cases (Table 4). Reaction
To our delight, the coupling reactionsof pyridine-de-
rived aryl bromides, even pyridine-derived aryl chlor- Although variousmetal nanoparticleshave been ap-
ideswith phenylboronic acid or aryl chloride with 3-
pyridineboronic acid, also proceeded smoothly with in catalytic cyclesremained to be elucidated.
good yields(Table 5, entrie1s–8). However, the rather difficult task to distinguish homogeneous,
plied in catalysis, the nature of the true metal species
[27]
It isa
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[a]
Table 4. The coupling reactionsof aryl chlorideswith arylboronic acids.
Entry
Aryl chloride
Arylboronic acid
Coupling product
Yield [%][b]
1
2
94
90
3
4
88
83
5
81
6
7
80
88
8
86
84
9
[a]
0.75 mmol aryl chlorides, 1.13 mmol arylboronic acid, 1.50 mmolK3PO4·7H2O, 2 mol% G3DenP-Pd, 10 mL dioxane,
reflux, 48 h.
Isolated yield based on aryl halide.
[b]
single metal-complex catalysts from soluble nanoclus- the Pd nanoparticlesin the Suzuki reaction by per-
ter or colloid catalysts in the study of nanocluster cat- forming two typesof experimentsasfollows.
alysis.[28] Recently, El-Sayed et al. systematically stud-
Firstly, we designed and synthesized a bulky AB3-
ied the effects of size and shape of PVP- and dendri- type dendritic aryl bromide substrate for the Suzuki
mer-stabilized Pd nanoparticles on the catalytic coupling reaction. It seems reasonable to assume that
Suzuki reaction.[29] The reaction waspropoesd to
if the catalytic reaction occurred on the surface of the
occur on the surface of the nanoparticles based on Pd nanoparticlesinside the ꢂdendritic boxꢀ formed by
the fact that the phenylboronic acid bound to the sur- the dendritic ligands, the efficiency of the coupling re-
face before reacting with iodobenzene. On the other action wasgreatly affected by the size of the dendritic
hand, there isincreaisng experimental evidence that
substrate. The third-generation nanoparticle G3DenP-
demonstrated the soluble metal species to be the true Pd and the homogeneouscomplex Pd ACHTERU(GN PPh3)4 were
catalyst.[30] For example, Rothenberg et al. reported a used as the catalysts, respectively. Both reactions be-
simple experiment based on exclusion of Pd nanopar- tween dendritic bromobenzene and 4-acetylphenyl-
ticles to identify the true catalytic species in cluster- boronic acid in the presence of 0.3 mol% catalyst pro-
catalyzed Heck cross-couplings.[30e,f] They used a spe- ceeded smoothly under
a nitrogen atmosphere
cial reactor in which two compartmentswere separat-
ed by a nanoporousmembrane that only allowed the
passage of Pd atom and ions. It was found that Pd washigher than that obtained with Pd
(Scheme 3). Notably, the dendritic coupling product
wasobtained in 96% yield with G3DenP-Pd, which
A
À
nanoparticleswere not the true catalystsin C
pling reactions, and the catalysis was carried out by happen inside the dendritic box completely at least.
C cou- result indicated that the catalytic reaction should not
either Pd(0) atomsor Pd(II) ionsthat leached into
In addition, we determined the average diameter of
the solution. Here, we attempt to elucidate the role of the third-generation Pd nanoparticlesafter the ninth
catalytic cycle. Asshown in Figure 3, the recycled pal-
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[a]
Table 5. The coupling reactionsof heteroaryl halideswith arylboronic acids.
Entry
1
Aryl halide
Arylboronic acid
Product
Yield [%][b]
89
2
92
3
4
85
82
5
84
6
7
90
90
8
86
-
9
-
[a]
0.75 mmol aryl chlorides(or heteroaryl halides), 1.13 mmol arylboronic acid, 1.50 mmolK 3PO4·7H2O, 2 mol% G3DenP-
Pd, 10 mL dioxane, reflux, 48 h.
Isolated yield based on aryl halide.
[b]
Table 6. Recovery and recycling of G3DenP-Pd (0.2 mol%).[a]
Cycle
Run 1
98
Run 2
95
Run 3
96
Run 4
97
Run 5
79
Run 6
94
Run 7
95
Run 8
94
Run 9
75
Yield [%][b]
[a]
Reaction time: runs1–5, 20 h; runs6–9, 48 h.
[b]
Isolated yield. Purity was confirmed by 1H NMR.
ladium nanoparticles displayed an irregular shape functionalized molecules.[31] Recent developmentsin
with a size distribution of 10 (Æ1) nm, indicating the cross-coupling methodology allow the Stille reaction
occurrence of aggregation during the reactions. This to be performed under very mild conditions,[32] and
result further indicated that the soluble Pd(0) and/or palladium complexesbearing bulky phopshane li-
Pd(II) species leached from the nanoparticles cata- gands, such as PCAHTRE(UNG t-Bu)3 or proazaphosphatranes, were
lyzed the coupling reaction, and fell back to the nano- found to be excellent catalysts for this reaction at
particle surface during and/or at the end of reaction. room temperature.[33,34] However, these methods often
involved the use of highly air-sensitive catalysts and/
or Cu(I) salt as co-catalyst. Since our Pd nanoparticle
Stille Coupling Reaction
catalysts exhibited high activity and air stability in the
Suzuki coupling reactions, we thus further employed
The Stille reaction has established itself as one of the the most active G3DenP-Pd catalyst in the Stille cou-
two most general selective palladium-catalyzed cross- pling reaction.
coupling reactions along with the Suzuki cross-cou-
pling described above. Its tolerance towards most zoate with tributyl
functional groupsmakesthe Stille coupling reaction 1.5 mol% G3DenP-Pd in air waschosen asmodel re-
particularly effective for transformations of highly action. Asfluoride additiveshave been reported asef-
At the outset, the coupling of methyl 4-bromoben-
AHCTREUNG
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FULL PAPERS
Scheme 3. Suzuki coupling of dendritic bromobenzene with 4-acetylphenylboronic acid.
Figure 3. TEM image of G3DenP-Pd nanoparticlesafter the ninth catalytic run.
[35]
fective activatorsfor thiscoupling reaction,
CsF action proceeded smoothly, providing excellent yield
was selected as the base. To achieve the optimized re- (entry 4). Notably, a small amount of water improved
action conditions, several types of organic solvents the formation of the coupling product greatly, and the
and different reaction temperature were tested. As mixture of DMF and water (10:1, v/v) wasfound to
shown in Table 7, the reactions were found to be be the best choice of solvent for this reaction(en-
rather sluggish at room temperature even upon the tries4–9).
addition of CuI ascocatalyts (entries1–3). When re-
action temperature increased to 408C and a solvent coupling reactionsbetween a broad psectrum of aryl
mixture of DMF and water wasused, the coupling re- bromidesand tributylphenyltin or 2-(tributyltsannyl)-
Under the optimized reaction conditions, the Stille
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Table 7. Optimization of catalytic system in the Stille coupling of methyl 4-bromobenzoate with tributylACHTREUNG
Entry
Solvent
Additive
Temperature [oC]
Time [h]
1
2
3
4
5
6
7
8
9
DMF
DMF
DMF-H2O (10:1, v/v)
DMF-H2O (10:1, v/v)
DMF
-
25
25
25
40
40
40
40
40
40
20
20
20
5
5
5
5
5
5
<20
<20
<20
98
20
26
65
<5
16
CuI
-
-
-
-
-
-
-
THF
THF-H2O (10:1, v/v)
Toluene
Toluene-H2O (10:1, v/v)
[a]
0.47 mmol 4-bromobenzoate, 0.52 mmol tributyl
Isolated yield.
ACHTRE(UNG phenyl)stannane, 1.5 mol% G3DenP-Pd, 1.02 mmol CsF, 20 mL solvent.
[b]
thiophene were carried out under an air atmos- sions and high selectivities for all substrates studied
phere.[36] Asshown in Table 8, all aryl bromidesbear-
were achieved. For example, the hydrogenation of
ing electron-withdrawing or electron-donating sub- a,b-unsaturated cyclohexanone using 0.5 mol%
stituents were found to furnish the biaryl products in G2DenP-Pd under 15 atm hydrogen at 608C for 8 h
good to excellent yields(entries1–6). It wasnoted
afforded cyclohexanone in excellent yield (entry 4). It
that the sterically hindered ortho-substituted aryl bro- wasnoted that the hydrogenation of iminesunder rel-
mides, 2-bromo-m-xylene and 2-bromo-p-xylene, un- atively low temperaturesproceeded ms oothly (en-
derwent the Stille reaction smoothly, giving high tries 7 and 8). Most interestingly, unlike the common-
yields(entries5 and 6). We also noticed that reactions
ly used heterogeneous catalyst Pd/C, the Pd nanopar-
with heteroatom-containing substrates proceeded ticlescould not cleave the benzyl substituent on the N
smoothly, giving good to high yields (entries 7–10). atom. Quinoline and pyridine derivativescould alos
Notably, under these mild reaction conditions, the be hydrogenated to 1,2,3,4-tetrahydroquinoline and
cross-coupling of 4-bromophenyl 4’-chlorobenzoate piperidine derivative quantitatively by using 2 mol%
with tributylphenyltin only afforded the correspond- G3DenP-Pd ascatalyts and 25 mol% acetic acid as
ing biaryl compound without affecting the chloride additive, respectively (entries 9 and 10). Notably, in
group in 87% yield (entry 11).
all cases, hydrogenation reactions were carried out
To further extend this catalytic system to the most under homogeneousmanner. Unlike the reported
challenging yet readily accessible aryl chloride sub- thiol dendrimer-stabilized Pd nanoparticles,[12] no pal-
strates, the high reaction temperature (1108C) was ladium aggregation wasobesrved. After the reaction
tested. To our delight, the cross-coupling of both the wascompleted, the catalyts wasquantitatively pre-
activated and unactivated aryl chlorideswith tributyl-
cipitated upon addition of a large amount of metha-
phenyltin proceeded smoothly in the presence of 1.5 nol. The recycled Pd catalyst, which could be redis-
mol% G3DenP-Pd under an air atmosphere (Table 9), solved in organic solvent, however, exhibited no cata-
furnishing the biaryl compounds in good to high lytic activity.
yields. Importantly, the heteroatom-containing sub-
strates, 2-chloropyridine and 4-chloropyridine, also
gave good reaction yields(entries5 and 6).
Tandem Reaction
Finally, based on the successful applications in Suzuki
coupling and hydrogenation reactions, we employed
Hydrogenation
the G3DenP-Pd catalyst to
(Scheme 4). Firstly, Suzuki coupling of 3-pyridinylbor-
a tandem reaction
Palladium-catalyzed hydrogenation isfrequently used
not only in laboratories but also in industry. To fur- onic acid with p-bromodiphenyl wascarried out by
ther expand the catalytic scope of the dendrimer-sta- using 0.06 mol% catalyst in dioxane under refluxing
bilized Pd nanoparticles, we then investigated the cat- temperature for 20 h. Upon the completion of the
alytic hydrogenation of a range of unsaturated com- Suzuki coupling, the reaction mixture wasthen acidi-
pounds. As shown in Table 10, quantitative conver- fied with 2 equiv. acetic acid and pressurized with 40
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Air-Stable and Highly Active Dendritic Phosphine Oxide-Stabilized Palladium Nanoparticles
FULL PAPERS
[a]
Table 8. Stille croscoupling reaction of organotin reagentswith variousaryl bromides.
Entry
1
Aryl bromide
Organotin
Coupling product
Time [h]
Yield [%][b]
98
5
5
2
3
98
96
5
5
4
96
5
6
7
12
12
8
91
89
97
8
10
86
9
8
8
78
80
10
11
8
87
[a]
0.47 mmol aryl bromides, 0.52 mmol organotin, 1.5 mol% G3DenP-Pd, 1.02 mmol CsF, 20 mL solvent, 408C.
Isolated yield.
[b]
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Lei Wu et al.
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Table 9. Stille cross-coupling reaction of tributylphenyltin with aryl chlorides.[a]
Entry
1
Aryl chloride
Organotin
Product
Time [h]
20
Yield [%][b]
95
2
20
93
3
4
5
20
20
91
88
20
20
75
78
6
[a]
0.47 mmol aryl chlorides, 0.52 mmol organotin, 1.5 mol% G3DenP-Pd, 1.02 mmol CsF, 20 mL solvent, 1108C.
Isolated yield.
[b]
Scheme 4. Tandem reaction catalyzed by G3DenP-Pd.
atm H2 without addition of new Pd catalyst. The mix- Conclusions
tureswere stirred at 60 8C for further 20 h, furnishing
3-diphenylpiperidine in 96% total yield.
In conclusion, we have successfully prepared a new
type of dendritic phosphine oxide-stabilized Pd nano-
particlesashomogeneouscatalytssfor Suzuki and
Stille coupling reactionsand hydrogenation.s It was
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[a]
Table 10. Hydrogenation of variousof unsaturated compounds.
Entry
1
Substrate
Product
H2 [atm]
5
Temperature [oC]
60
Time [h]
3
Yield [%]
> 95
2
3
5
40
60
4
6
> 95
> 95
15
4
5
6
15
5
60
60
80
8
> 95
> 95
> 95
5
30
12
7
40
15
5
> 95
8
40
40
15
15
5
5
> 95
> 95
9[b]
10[b]
40
60
20
> 95
[a]
1
0.5 mol% G2DenP-Pd was used as catalyst. Reaction yields were determined based on GC or H NMR analysis.
2 mol% G3DenP-Pd was used as catalyst, and 25 mol% acetic acid as additive.
[b]
solvents were obtained as follow: THF, dioxane and toluene
were distilled from sodium and benzophenone (traces of
thiophene in toluene was firstly removed by using concen-
demonstrated that the dendritic wedges served as a
stabilizer for keeping the nanoparticles from aggre-
gating, and asa vehicle for facilitating the separation
and/or the recycling of the Pd catalyst. Unlike the
trated H2SO4); dichloromethane wasditsilled from CaH
.
2
All moisture- and air-sensitive reactions were carried out in
a flame-dried flask under a nitrogen atmosphere. Column
chromatography wasperformed with ilsica gel 200–300
commonly used homogeneous catalyst PdACHTRE(UNG PPh3)4,
these Pd nanoparticles exhibited very high catalytic
efficiency and air stability in the Suzuki and Stille
coupling reactions. We believe that this new type of
robust Pd catalysts has the potential not only for labo-
ratory scale research but also for industrial applica-
tions.
1
mesh. All H NMR (300 MHz), 13C NMR (75 MHz) spectra
were recorded on a Bruker-DMX 300 asCDCl solution in
3
the presence of tetramethylsilane as an internal standard
and are reported in ppm (d). 31P NMR (121 MHz) spectra
were measured on a Bruker-DMX 400 and referenced to an
external sample (85% H3PO4). 31P MAS NMR spectra were
measured on a Varian INOVA 400M NMR spectrometer.
Mass spectra measurements were carried out with a Finni-
gan model Mat SSQ-710 instrument. MALDI-TOF mass
spectra were recorded on a BIFLEX instrument with a-
cyano-4-hydroxycinnamic acid (CCA) asthe matrix. Ele-
mental analysis was carried out on a Flash EA 112 instru-
ment. Transmission electron microscopy (TEM): the chloro-
form dispersion of Pd catalyst was drop-cast onto a 300
Experimental Section
General Information
Unless otherwise stated, all starting materials were obtained
from commercial suppliers and used as received. Anhydrous
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Lei Wu et al.
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mesh carbon coated copper grid, and TEM pictures were
taken on a Hitachi H600 microscope at an accelerating volt-
age of 75 kV.
1,2,3-triol (205 mg, 1 mmol) in acetone wasadded K 2CO3
(5 equiv.) and 18-crown-6 (50 mg). The mixture wastsirred
in a Schlenk flask under a nitrogen atmosphere and heated
to reflux for 48 h. After the solvent was removed under re-
duced pressure, the residue was washed with water and ex-
tracted with CH2Cl2 (20 mL”3). The AB3-type dendritic
bromobenzene wasobtained asa white os lid after purifica-
tion by chromatography on a silica gel column with CH2Cl2
General Procedure for the Preparation of Dendritic
Phosphine Ligands
A flame-dried, 25-mL, two-neck flask was charged with
KPPh2 (0.5M in THF, 5 mL) and cooled to À788C. A solu-
tion of the corresponding dendritic bromide GnCH2Br (n=
1~3, 0.5 mmol) in dried and degassed THF was added drop-
wise with vigorous stirring. After 3 h, the mixture was al-
lowed to stir at room temperature for 10 h. Most of the sol-
vent was removed under reduced pressure. Then MeOH
(30 mL) wasadded to precipitate the crude product, which
was further purified by flash chromatograph on silica gel
eluting with CH2Cl2/petroleum ether (2:1, v/v), affording the
dendritic phosphine ligands in 80–90% yields.
G1DenP: yield: 82%, white solid, mp 100–1028C;
1H NMR (300 MHz, CDCl3): d=3.30 (s, 2H), 4.80 (s, 4H),
6.25 (s, 2H), 6.35 (s, 1H), 7.27–7.38 (m, 20H); 13C NMR
(75 MHz, CDCl3): d=36.31, 69.94, 100.34, 108.40, 108.49,
127.55, 127.93, 128.38, 128.46, 128.56, 128.76, 132.89, 133.14,
137.03, 159.76; 31P NMR (121 MHz, CH2Cl2): d=À10.30.
MALDI-TOF MS: m/z=489.4 ([M+H]+).
G2DenP: yield: 85%, white solid, mp 112–1148C;
1H NMR (300 MHz, CDCl3): d=3.30 (s, 2H), 4.74 (s, 4H),
4.97 (s, 8H), 6.23 (s, 2H), 6.38 (s, 1H), 6.51–6.58 (m, 6H),
7.3–7.44 (m, 30H); 13C NMR (75 MHz, CDCl3): d=36.48,
68.01, 69.80, 70.13, 100.29, 101.55, 106.37, 108.39, 108.47,
127.59, 128.03, 128.25, 128.37, 128.46, 128.62, 128.79, 132.87,
133.11, 136.83, 139.44, 139.61,159.62, 160.15; 31P NMR
(121 MHz, CH2Cl2): d=À10.32. MALDI-TOF MS: m/z=
913.4 ([M+H]+).
1
aseluent; yield: 80%; mp 135–136 8C; H NMR (300 MHz,
CDCl3): d=4.84 (s, 4H), 4.89–4.90 (m, 8H), 4.98–5.00 (m,
12H), 6.71–6.75 (m, 8H), 7.24–7.35 (m, 45H); 13C NMR
(75 MHz, CDCl3): d=71.04, 71.25, 71.66, 75.11, 75.19,
106.96, 107.76, 112.04, 116.08, 127.43, 127.48, 127.76, 127.88,
128.10, 128.15, 128.39, 128.43, 128.49, 132.11, 133.09, 136.96,
137.04, 137.70, 137.89, 138.33, 152.81, 153.11, 153.45; MS
(ESI): m/z=1453.43 ([M+Na]+).
General Procedure for Suzuki Coupling Reaction of
Aryl Halides with Arylboronic Acids
To a 25-mL flask was added aryl halide (1.25 mmol), aryl-
boronic acid (1.87 mmol), 676 mgK3PO4·7H2O, 0.06 mol%
GnDenP-Pd (1.5 mg, n=2) and 10 mL distilled 1,4-dioxane.
The reaction mixture washeated to reflux and tsirred for
20 h under air atmosphere. After most of the dioxane was
removed under reduced pressure, CH3OH (20 mL”3) was
added to the residue to extract the product and to precipi-
tate the catalyst. The collected catalyst was washed with
5 mL distilled H2O for three times, dried under reduced
pressure, then reused directly in the next run. The coupling
product in the combined MeOH solution was obtained after
purification by chromatography on a silica gel column.
Suzuki Coupling of AB3-Type Dendritic
G3DenP: yield: 90%, white solid, mp 124–126 C;
1H NMR (300 MHz, CDCl3): d=3.32 (s, 2H), 4.77 (s, 2H),
4.93 (s, 8H), 4.99 (s, 16H), 6.27 (s, 2H), 6.39 (s, 1H), 6.51–
6.67 (m, 18H), 7.28–7.39 (m, 50H); 13C NMR (75 MHz,
CDCl3): d=36.39, 69.77, 69.98, 70.08, 100.26, 101.53, 101.61,
106.38, 108.38, 108.47, 127.54, 127.97, 128.34, 128.43, 128.56,
128.76, 132.83, 133.07, 136.77, 137.92, 138.11, 139.24, 139.40,
139.59 159.63, 160.02, 160.16; 31P NMR (121 MHz, CH2Cl2):
d=À10.32; MS (APCI): m/z=1763.0 ([M+H]+); MALDI-
TOF MS: m/z=1762.0 ([M+H]+); anal. calcd. for
C117H101O14P: C 79.75, H 5.78; found: C 79.52, H 5.86%.
Bromobenzene with 4-Acetylphenylboronic Acid
To a 25-mL flask were added AB3-type dendritic bromoben-
zene (715 mg, 0.50 mmol), 4-acetylphenylboronic acid
(123 mg, 0.75 mmol), 338 mgK3PO4·7H2O, G3DenP-Pd
(3.1 mg, 0.3 mol%) or PdACTHRE(UNG PPh3)4 (4.4 mg, 0.3 mol%) and
10 mL distilled 1,4-dioxane. The reaction mixture was
heated to reflux and stirred for 20 h under N2 atmosphere.
After most of the dioxane was removed under reduced pres-
sure, the residue was washed with water and extracted with
CH2Cl2 (20 mL”3). The coupling product wasobtained
after purification by chromatography on a silica gel column.
Yield: G3DenP-Pd ascatalyts, 96%; Pd ACHTREU(NG PPh3)4 ascatalyts,
General Procedure for the Preparation of Dendrimer-
Stabilized Palladium Nanoparticles
79%. White solid, mp 139–1408C; 1H NMR (300 MHz,
CDCl3): d=2.62 (s, 3H), 4.87 (s, 4H), 4.90 (s, 2H), 4.98–5.00
(m, 14H), 5.05 (s, 4H), 6.77 (s, 4H), 6.81 (s, 2H), 6.87 (s,
2H), 7.20–7.35 (m, 45H), 7.54 (d, J=8.37 Hz, 2H), 7.99 (d,
J=8.35 Hz, 2H); 13C NMR (75 MHz, CDCl3): d=26.68,
71.07, 71.28, 71.82, 75.22, 75.33, 107.01, 107.72, 108.02,
127.07, 127.44, 127.51, 127.68, 127.78, 127.89, 128.12, 128.17,
128.41, 128.43, 128.50, 128.98, 132.62, 136.98, 137.07, 137.90,
138.30, 152.88, 153.14, 153.20, 197.56; MS (ESI): m/z=
1491.71 ([M+Na]+).
A 25-mL, glass-lined stainless autoclave with a magnetic
stirring bar was charged with 20 mg PdACHTER(UNG acac)2 (0.066 mmol),
GnDenP (2 equiv.) and 10 mL dried, degassed THF. The
mixture wastsirred for 5 min at room temperature. Then
the autoclave was pressurized with hydrogen to 25 atm, and
stirred at 608C for 18 h. After the H2 wascarefully released,
the solvent was removed under reduced pressure. The re-
sulting black powders were further purified by sonication in
ethanol several times.
General Procedure for Stille Coupling Reactions of
Aryl Halides with Organotins
Synthesis of AB3-type Dendritic Bromobenzene
To a solution of the first-generation AB3-type dendritic bro-
mide G1CH2Br (1.96 g, 4 mmol)[35] and 5-bromobenzene-
To a 25-mL flask were added aryl halide (0.465 mmol), orga-
notin (1.1 equiv., 0.512 mmol), G3DenP-Pd (1.5 mol%), CsF
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Air-Stable and Highly Active Dendritic Phosphine Oxide-Stabilized Palladium Nanoparticles
FULL PAPERS
(155.4 mg, 1.02 mmol), and DMF/H2O (20 mL, 10:1, v/v).
The mixture was stirred for the desired time and tempera-
ture until the complete consumption of the starting material
asmonitored by TLC. Then, the reaction mixture wasex-
tracted with diethyl ether two times. The combined organic
solution was washed with water, and dried over anhydrous
Na2SO4 and evaporated into dryness. The residue was puri-
fied by flash column chromatography to afford the desired
coupling products.
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General Procedure for Hydrogenation of
Unsaturated Compounds
In a 50-mL, glass-lined, stainless steel reactor with a mag-
netic stirring bar was charged with substrates (1 mmol),
G2DenP-Pd or G3DenP-Pd (0.5 mol%), and appropriate sol-
vent (10 mL). The autoclave was closed and was pressurized
with H2 (5 to 40 atm). The mixture wastsirred under the
given pressure at 15–808C for several hours. After carefully
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moved under reduced pressure. The reaction yield was de-
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1
termined by GC or H NMR.
Tandem Reaction of Suzuki Coupling and
Hydrogenation
To a 25-mL flask were added p-bromobiphenyl (583 mg,
2.50 mmol), 3-pyridinylboronic acid (461 mg, 3.75 mmol),
K3PO4·7H2O (1.69 g), G3DenP-Pd (3.1 mg, 0.06 mol%) and
newly distilled 1,4-dioxane (10 mL). The reaction mixture
was heated to reflux and stirred for 20 h under an air atmos-
phere. After the reaction wascompleted, half of the mixture
wasremoved for the determination of the coupling product
(277 mg, 96% yield). The other half of the reaction mixture
wasacidified with CH COOH to pH 5, and pressurized with
3
40 atm H2. The mixture wasthen stirred at 60 8C overnight.
After carefully venting of hydrogen, most of the reaction
solvent was removed under reduced pressure. The residue
was washed with saturated NaHCO3 aqueousoslution, and
extracted with diethyl ether. The organic solvent was re-
moved under reduced pressure, giving the reduced product
with almost quantitative yield.
Acknowledgements
Financial support from the National Natural Science Founda-
tion of China (20325209 and 205322010), the Major State
Basic Research Development Program of China (Grant No.
2005CCA06600) and Chinese Academy of Sciences are great-
ly acknowledged.
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862
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