Nanocrystalline titania-supported palladium(0) nanoparticles for Suzuki-Miyaura cross-coupling of aryl and heteroaryl halides

Article abstract of DOI:10.1002/adsc.201100012

The Suzuki cross-coupling reaction of various aryl and heteroaryl halides with arylboronic and heteroarylboronic acids was studied using a titania-supported palladium(0) catalyst at room temperature under air. The conversion and selectivity results obtained for many substrates were excellent and similar to those provided by more active or even homogeneous catalysts. The methodology is similarly effective using 2-bromo-3,4,5-trimethoxybenzaldehyde as the coupling partner and gave products in good yield. Furthermore, it has been shown that it is useful for the synthesis of terphenyl and tetraphenyls. The catalyst is quantitatively recovered from the reaction by simple filtration and reused for a number of cycles without significant loss of activity. Inductively coupled plasma (ICP) mass-spectrometric analysis of the filtrate from the reaction mixture demonstrated that the palladium metal hardly leached into the solution within the limits of the detector (1 ppm), thus suggesting that the present Suzuki-Miyaura reaction proceeded by heterogeneous catalysis. Copyright

Full text of DOI:10.1002/adsc.201100012

FULL PAPERS
DOI: 10.1002/adsc.201100012
Nanocrystalline Titania-Supported Palladium(0) Nanoparticles for
Suzuki–Miyaura Cross-Coupling of Aryl and Heteroaryl Halides
B. Sreedhar,a,* Divya Yada,a and P. Surendra Reddya
a
Inorganic and Physical Chemistry Division, Indian Institute of Chemical Technology (Council for Scientific and Industrial
Research), Hyderabad – 500007, India
Fax : (+91)-40-2716-0921; phone: (+91)-40-2719-1715; e-mail: sreedharb@iict.res.in
Received: January 16, 2011; Revised: June 9, 2011; Published online: October 10, 2011
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adcs.201100012.
Abstract: The Suzuki cross-coupling reaction of vari- lyst is quantitatively recovered from the reaction by
ous aryl and heteroaryl halides with arylboronic and simple filtration and reused for a number of cycles
heteroarylboronic acids was studied using a titania- without significant loss of activity. Inductively cou-
supported palladium(0) catalyst at room temperature pled plasma (ICP) mass-spectrometric analysis of the
under air. The conversion and selectivity results ob- filtrate from the reaction mixture demonstrated that
tained for many substrates were excellent and similar the palladium metal hardly leached into the solution
to those provided by more active or even homogene- within the limits of the detector (1 ppm), thus sug-
ous catalysts. The methodology is similarly effective gesting that the present Suzuki–Miyaura reaction
using 2-bromo-3,4,5-trimethoxybenzaldehyde as the proceeded by heterogeneous catalysis.
coupling partner and gave products in good yield.
Furthermore, it has been shown that it is useful for Keywords: aryl halides; arylboronic acids; heteroaryl
the synthesis of terphenyl and tetraphenyls. The cata- halides; palladium; Suzuki–Miyaura coupling; titania
Introduction
gands,[10] aryloximes,[11] arylimines,[12] N-acylami-
dines,[13] and simple amines,[14] have been used in the
The biaryl moiety is an important structural motif in Suzuki cross-coupling reaction. Despite the synthetic
a great number of biologically active compounds and elegance and high turnover numbers, the non-reusa-
functional molecules,[1] which include the natural bility of the precious palladium precludes wide syn-
products[2] Biphenomycin, the pharmaceuticals[3] Val- thetic applications in the pharmaceutical industry. In
sartan, Telmisartan, Felbinac, Losartan, Imatinib, the view of the above, it is desirable to develop a ligand-
agrochemical Boscalid,[4] liquid crystals for LCD free and reusable catalytic system for the Suzuki cou-
screens,[5] chiral ligands for catalysis[6] and organic pling. Heterogeneous catalysis is particularly attrac-
functional materials. The palladium-catalyzed Suzuki– tive as it allows the production and ready separation
Miyaura cross-coupling reaction is one of the most of large quantities of products with the use of a small
useful methods for the synthesis of biaryl molecules.
amount of catalyst. In recent years, numerous hetero-
Consequently, considerable effort has been directed geneous supported palladium catalysts were success-
to the development of efficient and selective methods fully employed in Suzuki cross-coupling reactions.[15]
for the Suzuki–Miyaura cross-coupling reaction. Gen-
Metal nanoparticles are attractive for catalysis be-
erally phosphine ligands are used to complex and acti- cause of their large surface area-to-volume ratio,
vate the palladium species, and excellent results have which allows the effective utilization of expensive
been reported for the palladium-catalyzed Suzuki– metals.[16] Palladium nanoparticles, particularly with a
Miyaura cross-coupling reaction.[7,8] The use of such li- dimension of less than 10 nm, exhibit unexpectedly
gands is undesirable because of their toxicity and air- high catalytic activities toward different types of reac-
as well as moisture-sensitive nature with conversion tions, a property not revealed in bulk palladium.[17]
to, for example, phosphine oxide species. However, Unfortunately, however, aggregation of naked nano-
few phosphine-free N-based ligands, such as N- particles often prohibits tailoring of particle size.[18] To
heteroACHTUNGTRENNUNG
cyclic carbenes,[9] N,O- or N,N-bidentate li- overcome this problem, palladium nanoparticles are
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B. Sreedhar et al.
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generally dispersed on support materials, among Results and Discussion
which nano metal oxides are commonly used.[19] This
is because when the size of the support materials is Preparation of Nanocrystalline TiO2-Supported Pd(0)
decreased to the nanometer scale, the surface area of Catalyst
nanoparticles will increase dramatically. As a conse-
quence, nanoparticle supports could have higher cata- Preparation of the catalyst was carried out as outlined
lyst loading capacity than many conventional support in Scheme 2. In the first step of the synthesis, titanium
matrixes, leading to the improved catalytic activity of tetrachloride is added dropwise and under vigorous
the nanoparticle-supported catalysts. Among many stirring to a mixture of benzyl alcohol and dopamine
nanomaterials, titanium dioxide is a material with out- and the dark red reaction mixture is aged at room
standing chemical and physical properties, which are temperature for about 2 h and subsequently heated to
of interest for a wide variety of different applications 808C for 72 h. The dopamine-functionalized TiO2 is
in gas sensing,[20] catalysis,[21] photocatalysis,[22] recovered by centrifugation and subsequently washed
optics,[23] photovoltaics,[24] and pigmentation.[25] Titani- with chloroform or dichloromethane and dried at
um dioxide is a useful support because it is inexpen- 608C to furnish a pale brown powder in good yield.[27]
sive, inert, and non-toxic, as well as having an elec- 1 g of the dried dopamine-functionalized titania
tronic band structure suitable for the aforementioned powder was dissolved in water, titania with dopamine
applications. One of the major areas of current re- ligands having positively charged terminal amine
search in the field of catalysis is the synthesis of sur- groups results in particle-particle repulsion and leads
face-modified nanoparticles with appropriate surface- to a stable aqueous colloidal solution. To this solution
modifying agents and these surface-modified nanopar- Na2PdCl4 solution in water was added to the mixture
ticles can be used as noble metal supports to prepare to get 10 wt% of Pd. A dilute solution of hydrazine
heterogeneous catalysts that are more accessible to monohydrate was added drop wise to adjust the pH
the reactants as compared to conventional heteroge- to 9. The reaction mixture was stirred overnight at
neous systems.[26]
room temperature and then allowed to settle. Herein
In this article we report that nanocrystalline TiO2- hydrazine monohydrate acts as a reducing agent to
supported palladium(0) is an effective catalyst for the reduce Pd(II) into Pd(0) during the reaction. The
Suzuki–Miyaura cross-coupling of aryl and heteroaryl product Pd(0) on titania was washed several times
halides with aryl and heteroaryl boronic acids under with water, centrifuged and dried at room tempera-
aqueous conditions (Scheme 1). This catalyst also ture and the product is referred as TiO2-Pd(0).
showed outstanding reusability without loss of signifi-
cant activity.
Scheme 1.
Scheme 2. Preparation of TiO2-supported palladium catalyst.
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Nanocrystalline Titania-Supported Palladium(0) Nanoparticles for Suzuki–Miyaura Cross-Coupling
Characterization of Ti-Pd(0)
servations confirming the synthesis of dopaminefunc-
tionalized TiO2-Pd(0) catalyst (please see Supporting
The prepared catalyst was well characterized with IR, Information). The amount of palladium in the catalyst
TGA-MS, XRD, TEM, XPS and ICP-AES. was determined using inductively coupled plasma-
The FT-IR spectra of pure dopamine, surface-func- atomic emission spectroscopy (ICP-AES) technique
tionalized TiO2 nanoparticles, and TiO2-Pd(0) are and it was found to be 0.16 mmolgÀ1. The XRD peaks
given in the Supporting Information. From the FT-IR of TiO2-Pd(0) clearly show the anatase form of
[27]
spectrum of surface-functionalized TiO2 nanoparticles TiO2 and the appearance of peak at 39.868 confirms
the peak at 3383 cmÀ1 has been assigned to the sur- the presence of palladium in metallic state (Figure 1).
face-adsorbed water and the peak at 1623 cmÀ1 is due Furthermore, the catalyst was characterized by trans-
À1
À
to the N H bending. The peak at 1489 cm is due to mission electron microscopy (TEM). From the TEM
À
C H bending of aromatic groups, whereas peaks at images of both the fresh and used catalysts, it is seen
1259 cmÀ1 and 1156 cmÀ1 are due to C O stretching that the average size of TiO2 nanoparticles is in the
À
À
and aliphatic C H bending, respectively. The pres- range of 10–15 nm in diameter and palladium nano-
ence of these peaks in the TiO2-Pd(0) catalyst clearly particles of about 2–3 nm and are uniformly dispersed
suggests that the functionalizing agent is intact in the on TiO2 nanoparticles (the size distributions for both
final catalyst. Furthermore, the presence of dopamine TiO2 and Pd nanoparticles are shown in Supporting
in TiO2-Pd(0) catalyst was confirmed by TGA-MS Information). Although we followed the same proce-
analysis. When the TiO2-Pd(0) catalyst was subjected dure as Niederberger et al.,[27] the size of TiO2 parti-
to TGA-MS, an evolved gas fragment 44 a.m.u was cles is larger. possibly due to the difference in the
observed which can be attributed due to the fragment aging times. This clearly confirms that there is no
CH2 CH2 NH2, a side chain present in dopamine, change in the morphology even after five cycles
and this also is consistent with the XPS and FT-IR ob- [Figure 2 (b)]. X-ray photoelectron spectroscopic
(XPS) investigation of TiO2-Pd nanoparticles of used
À
À
À
and fresh catalysts was carried out. XPS survey scans
of both fresh and used catalyst showed characteristic
peaks of Ti 2p, O 1s and Pd 3d along with C 1s peak
(please see Supporting Information). High resolution
narrow scans for Pd 3d level show peaks at 335.08 eV
and 340.41 eV and 334.92 eV and 340.26 eV for Pd
3d5/2 and Pd 3d3/2, respectively, which clearly indicates
that the palladium is in the zero oxidation state
(Figure 3) even after five catalytic cycles. Two peaks
were observed for O 1s at 529.79 eV and 531.94 eV
for the fresh and 529.60 eV and 531.69 eV for the
used catalyst. The peak at 529 eV is attributed to the
oxygen bonding in TiO2 whereas the 531.6 eV peak is
Figure 1. XRD spectrum of TiO2-Pd(0) nanoparticles.
due to OH present in dopamine. This observation
Figure 2. TEM images of TiO2-Pd(0) nanoparticles before (a) and after (b) catalysis as observed at 120 kV.
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Table 1. Optimization of reaction conditions for Suzuki–
Miyaura cross-coupling.[a]
Figure 3. High resolution XPS scan of Pd 3d in (a) fresh and
(b) used catalyst – TiO2-Pd(0) nanoparticles.
also suggests that TiO2 is functionalized with dopa-
mine in the present catalytic system. Furthermore, the
BET surface area of TiO2-Pd(0) is found to be
142 m2gÀ1(please see Supporting Information).
Suzuki–Miyaura Cross-Coupling using Ti-Pd(0)
[a]
Reaction conditions: 4-bromotoluene (1 mmol), phenyl-
boronic acid (1.2 mmol), catalyst (0.8 mol%), base
(1.5 equiv.), solvent (2 mL), room temperature.
Yield after column chromatography.
Reaction conducted at 808C.
In an endeavor to identify the best catalytic system
for Suzuki coupling, various bases in combination
with different solvents were investigated using 4-bro-
motoluene and phenylboronic acid as the model sub-
strates and the results are presented in Table 1. The
solvent has a pronounced effect in these reactions out
of which ethanol/water (1:1) has been proven to the
[b]
[c]
best solvent. Ethanol, methanol and methanol/water are presented in Table 2. Notably, even electron-defi-
(1:1) gave the product in moderate yield, whereas 2- cient arylboronic acids, which are known to be usually
propanol, n-butanol and water gave the product in reluctant to give Suzuki–Miyaura products very likely
low yield. However, water with TBAB (1.2 equiv.) at because they are less nucleophilic than their electron-
808C proved to be equally good as ethanol/water neutral analogues and consequently tend to transme-
(1:1) and gave the product 4-methylbiphenyl in good talate more slowly, gave the desired derivatives in ex-
yield within 2 h (Table 1, entries 1–9). Among the var- cellent yields (Table 2). Arylboronic acids bearing
ious bases screened in ethanol/water (1:1), the rela- ortho substituents can also be used to prepare hin-
tively weak and less expensive K2CO3 gave the best dered cross-coupling products in high yield (Table 2,
result. Reactions with other bases such as Na2CO3, entries 3 and 5). Furthermore, heteroaryl boronic
K3PO4 and Cs2CO3 generate the desired product in acids such as pyridine-2-boronic acid and thiophene-
good yields (Table 1, entries 10, 11and 14), whereas, t- 2-boronic acid underwent the reaction smoothly to
BuOK and NaOH gave the product in low yield give the desired product in good yield under the opti-
(Table 1, entries 12 and 13).
mized reaction conditions (Table 2, entries 16 and 17).
Moreover, the potassium organofluoroborate also
We are gratified to observe that the best conditions
developed for phenylboronic acid and 4-bromoto- reacted smoothly to give the desired product in excel-
luene were found to be broadly applicable for a varie- lent yield by using TiO2-Pd(0) as the catalyst
ty of neutral, electron-rich, and electron-poor arylbor- (Scheme 3).
onic acids and heteroarylboronic acids proving the
However, unfortunately, this catalyst was ineffec-
scope and generality of TiO2-Pd-prompted Suzuki– tive for the reaction of alkylboronic acid (cyclohexyl-
Miyaura reaction to afford the corresponding biaryls boronic acid) with 4-bromotoluene even under harsh
in high to excellent yields and our preparative results reaction conditions (Scheme 4).
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Nanocrystalline Titania-Supported Palladium(0) Nanoparticles for Suzuki–Miyaura Cross-Coupling
Table 2. TiO2-Pd(0) catalyzed Suzuki–Miyaura cross coupling of 4-bromotoluene with different arylboronic
acids.[a]
[a]
Reaction conditions: 4-bromotoluene (1 mmol), arylboronic acid (1.2 mmol), TiO2-Pd(0) catalyst
(0.8 mol%), K2CO3 (1.5 mmol), and ethanol/water mixture
Yield after column chromatography.
ACHTUNGTNER(NUNG 1:1) (2 mL), room temperature.
[b]
Scheme 4.
Scheme 3. Suzuki–Miyaura cross-coupling of bromotoluene
with potassium trifluoroborates.
Unsubstituted as well as 4-methyl-, 4-methoxy-sub-
stituted bromobenzenes underwent smooth reaction
with good yields when compared to 2-methyl- and 2-
The optimized conditions could also be extended to methoxybromobenzenes (Table 3, entries 1–6). Fur-
the Suzuki–Miyaura coupling reaction of both b-styr- thermore, the reaction was extended to other aryl hal-
ylboronic acid and b-styryl trifluroborates with 4-bro- ides having electron withdrawing groups to generate
motoluene to form the Suzuki–Miyaura coupling biaryl products in good to excellent yields (Table 3,
product with 95% and 90% yields, respectively entries 7–11). It is interesting to note that coupling of
(Scheme 5.
3,5-dibromobenzaldehyde with phenylboronic acid
Encouraged by these results, we next investigated gave 3-phenyl-5-bromobenzaldehyde in 73% along
the scope of the reaction with respect to the aryl with 10% diphenyl product and when we used
halide substrate. We tested a variety of substituted 2 equivalents of phenylboronic acid the reaction un-
aryl bromides under the optimized reaction condi- derwent smoothly to afford terphenyl in 83% yield
tions with phenylboronic acid as cross-coupling coun- (Table 3, entry 11). As terphenyls are known to pos-
terpart. Various aryl bromides, including the deacti- sess biological activities with potential therapeutic
vated aryl bromides, were readily converted to the value,[28] we have tested the TiO2-Pd(0) catalyst for
corresponding coupled products in excellent yields as the preparation of o-, m-, and p-terphenyls under
shown in Table 3.
standard reaction conditions (Table 4). To our delight
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its use for the preparation of hindered biaryls from 2-
bromomesitylene and different phenylboronic acids.
As can be seen from Table 6, arylboronic acids with
electron-donating groups such as methoxy, hydroxy,
tert-butyl, 3,4-dimethoxy and 3,4-methylenedioxy
groups (Table 6, entries 1–6) underwent smooth reac-
tion with excellent yields compared to those with
electron-withdrawing group (Table 6, entry 7) present
in the phenylboronic acid ring.
To explore the scope and limitations of the coupling
reaction fully, the coupling of a number of substituted
arylboronic acids with 2-bromo-3,4,5-trimethoxyben-
zaldehyde was studied as the resulting products are
present in number of bioactive compounds
(Figure 4)[29] and the results are summarized in
Table 7. Arylboronic acids with substituents at the
Scheme 5. Reaction
(1 mmol), arylboronic acid (1.2 mmol), TiO2-Pd(0) catalyst
(0.8 mol%), K2CO3 (1.5 mmol) and ethanol/water mixture-
ACHTUNGTRENNUNG(1:1) (2 mL), room temperature. Yield after column chro-
conditions:
(i)
4-bromotoluene
[a]
matography.
1,3- and 1,4-dibromobenzenes undergo cross-coupling para and meta positions were well tolerated and gave
with o-methylphenylboronic acid smoothly to give the the products in yields comparable to their unsubstitut-
desired products in good yields (Table 4, entries 1 and ed phenylboronic acid (Table 7, entries 1–6). In addi-
2). Further as shown in Table 4, the coupling of 1,2-di- tion, electronic effects associated with the substituent
bromobenzene and 1,3,5-tribromobenzenes with p- did not manifest themselves in either the yields of
methylphenylboronic acid also gave terphenyl and product obtained or the conditions required to ach-
tetraphenyl, respectively (Table 4, entries 3 and 4).
ieve the coupling. However, coupling efficiency was
Under the same reaction conditions, a number of significantly altered when strong electron-withdrawing
bromonaphthalenes and 9-bromophenanthroline were substituents are present on the aromatic ring (Table 7,
also found to be reactive with p-tert-butylphenylbor- entries 7–9) and this effect is not observed with the
onic acid and gave the products in good yield dichloro and difluoro substitutions (Table 7, entries 10
(Table 5).
and 11). Furthermore, b-styrylboronic acid underwent
Given the remarkably high levels of catalytic activi- the cross-coupling reaction smoothly and gave the de-
ty displayed with TiO2-Pd(0) catalyst, we investigated sired product in good yield (Table 7, entry 12).
Table 3. Nano-TiO2-Pd(0) catalyzed Suzuki–Miyaura cross coupling of different bromoarenes with
phenylboronic acid.[a]
[a]
Reaction conditions: aryl halide (1 mmol), phenylboronic acid (1.2 mmol), TiO2-Pd(0) catalyst
(0.8 mol%), K2CO3 (1.5 mmol), and ethanol/water mixture
Yield after column chromatography.
ACHTUNGTNER(NUNG 1:1) (2 mL), room temperature.
[b]
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Nanocrystalline Titania-Supported Palladium(0) Nanoparticles for Suzuki–Miyaura Cross-Coupling
Table 4. Synthesis of different o-, m-, p-terphenyls and tetraphenyls.[a]
[a]
Reaction conditions: aryl halide (1 mmol), arylboronic acid (2.5 mmol), TiO2-Pd(0)
catalyst (0.8 mol%), K2CO3 (3 mmol), and ethanol/water mixtureACTHNUTRGNE(UNG 1:1) (3 mL), room
temperature.
Yield after column chromatography.
[b]
[c]
Reaction conditions: aryl halide (1 mmol), arylboronic acid (3.5 mmol), TiO2-Pd(0)
catalyst (1.2 mol%), K2CO3 (4.5 mmol) and ethanol/water mixture(1:1) (5 mL), room
temperature.
AHCTUNGTRENNUNG
However, this catalyst was ineffective for the reac- tool for the modification of such compounds is the
tion of alkyl halide (2-phenylethyl bromide) with phe- Suzuki–Miyaura coupling,[31] which has been applied
nylboronic acid under the optimized reaction condi- for the preparation of arylpyridines,[32] bipyridines,[33]
tions.
arylpyrimidines,[34] and the synthesis of nucleosides.[35]
Owing to the stability of the carbon-chlorine bond, Unfortunately, nitrogen-containing heterocycles are
aryl chlorides are challenging substrates for various difficult substrates for Suzuki–Miyaura cross-coupling
coupling reactions. Encouraged with these results we reactions.[36] In this regard, we next wanted to demon-
chose to investigate heterogeneous TiO2-Pd(0) cata- strate the generality of the optimized reaction condi-
lyst to activate aryl chlorides for Suzuki–Miyaura tions for Suzuki–Miyaura reactions of heteroaryl
cross coupling. Unfortunately the catalytic system was chlorides with arylboronic acids using nano TiO2-
less effective for the aryl chlorides. However, best re- Pd(0) as the catalyst.
sults were obtained by increasing the temperature to
The coupling of both electron-rich and electron-
1008C and changing the solvent from H2O/EtOH to poor arylboronic acids proceeded smoothly with 2-
H2O/DMA and K2CO3 as the base. Under the above chloropyridine and a quantitative yield of 2-phenyl-
conditions, the TiO2-Pd(0) possessed good catalytic pyridines were obtained in the presence of TiO2-
activity for aryl chlorides.
Pd(0) at 1008C (Table 9, entries 1 and 2). 2-Chloro-6-
Unsubstituted as well as 4-methyl-, 4-methoxy- methoxypyridine also underwent the desired reaction
ACHTUNGTRENNUNG
(Table 8, entries 5–9).
hours, affording 82–95% yields of the corresponding
According to a recent MDL Drug Data Report, products. Amexol reacted even faster to give the de-
pyridines are the most common heterocycles in phar- sired products in excellent yields (Table 9, entries 4–
maceutically active compounds.[30] A useful synthetic 7). It was also found that this method could be readily
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Table 5. Nano-TiO2-Pd(0)-catalyzed Suzuki–Miyaura cross-
coupling of different bromonaphthlenes with p-tert-butyl-
phenylboronic acid.[a]
Figure 4.
[a]
Reaction conditions: aryl halide (1 mmol), 4-tert-butyl-
lysts occurred on the solid surface or was catalyzed by
Pd species in the liquid phase. To address this issue,
we conducted two separate experiments with 4-bro-
motoluene and phenylboronic acid. In the first experi-
ment, the reaction was terminated after 1 h, and the
phenylboronic acid (1.2 mmol), TiO2-Pd(0) catalyst
(0.8 mol%), K2CO3 (1.5 mmol) and ethanol/water
mixtureACHTUNGTRENNUNG
[b]
applicable to 2-chlorothiazole to afford the corre- conversion of 4-bromotoluene was found to be 34%.
sponding product in good yield (Table 9, entry 8). At this juncture, the catalyst was separated from the
The heterogeneity of the catalyst was also evaluat- reaction mixture and the reaction was continued with
ed to study whether the reaction using solid Pd cata- the filtrate for an additional 5 h. In the second experi-
Table 6. Synthesis of hindered biaryls using Nano-TiO2-Pd(0)-catalyzed Suzuki–
Miyaura cross-coupling.[a]
[a]
Reaction conditions: 2-bromomesitylene (1 mmol), arylboronic acid
(1.2 mmol), TiO2-Pd(0) catalyst (0.8 mol%), K2CO3 (1.5 mmol), and ethanol/
water mixtureCAHTUNGTRENNNUG
[b]
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Nanocrystalline Titania-Supported Palladium(0) Nanoparticles for Suzuki–Miyaura Cross-Coupling
Table 7. Nano-TiO2-Pd(0)-catalyzed Suzuki–Miyaura coupling of 2-bromo-3,4,5-trimethxy ben-
zaldehyde with different arylboronic acids.[a,b]
[a]
Reaction conditions: 2-bromo-3,4,5-trimethoxybenzaldehyde (1 mmol), arylboronic acid
(1.2 mmol), TiO2-Pd(0) catalyst (0.8 mol%), K2CO3 (1.5 mmol), and ethanol/water mixture-
ACHTUNGTRENNUNG(1:1) (2 mL), room temperature.
Yield after column chromatography.
[b]
Table 8. Nano-TiO2-Pd(0)-catalyzed Suzuki–Miyaura cross-coupling of chloroarenes with
phenylboronic acid.[a]
[a]
Reaction conditions: aryl chloride (1 mmol), arylboronic acid (1.2 mmol), TiO2-Pd(0)
catalyst (1.5 mol%), K2CO3 (1.5 mmol), and DMA/water mixture
ACHTUNGTRENNUNG
under air.
Yield after column chromatography.
[b]
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Table 9. Nano-TiO2-Pd(0)-catalyzed Suzuki–Miyaura cross-coupling of different heteroaryl
halides with arylboronic acids.[a]
[a]
Reaction conditions: heteroaryl chloride (1 mmol), arylboronic acid (1.2 mmol), TiO2-
Pd(0) catalyst (1.5 mol%), K2CO3 (1.5 mmol), and DMA/water mixture
1008C, under air.
Yield after column chromatography.
ACHTUNGTRENUN(NG 2:1) (3 mL),
[b]
ment, the reaction was terminated after 2 h at 65% 7% yield depending on the substrate, which can also
conversion, and the catalyst was removed. The reac- be attributed to the marginal increase in the size of
tion was continued with the filtrate for an additional the Pd nanoparticles as is seen from the histogram of
5 h. In both the cases, the conversion remained size distribution (Figure 2 in Supporting Information).
almost unchanged. Inductively coupled plasma (ICP)
mass-spectrometric analysis of the filtrate from the re-
action mixture demonstrated that the palladium metal Conclusions
hardly leached into the solution within the limits of
the detector (1 ppm), thus suggesting that the present In summary, we have developed a simple, general cat-
Suzuki–Miyaura reaction proceeded heterogeneously alytic system for the Suzuki–Miyaura cross-coupling
with palladium bound to the support throughout the reaction with a broad substrate scope with an ability
reaction.
to make truly hindered biaryls, synthesis of terphenyls
To check the reusability of the catalyst, as can be and the ability to operate at room temperature. Nota-
seen from Table 10, the reaction was performed with bly, the reaction is performed at room temperature
different aryl halides with phenylboronic acid under with the use of a ligand-free heterogeneous palladium
the optimized reaction conditions. After completion catalyst. This methodology is similarly suitable for the
of the reaction the catalyst was separated from the re- coupling of 2-bromo- and 3,4,5 trimethoxybenzalde-
action mixture by simple filtration and reused for five hydes with different arylboronic acids and gave prod-
times showing partial loss in activity, i.e., between 4– ucts in good yield. This catalytic system is also effec-
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Nanocrystalline Titania-Supported Palladium(0) Nanoparticles for Suzuki–Miyaura Cross-Coupling
Table 10. Suzuki–Miyaura cross-coupling of different aryl halides with phenylboronic acid over
five cycles.[a]
[a]
Reaction conditions: aryl bromide (1 mmol), arylboronic acid (1.2 mmol), TiO2-Pd(0) catalyst
(0.8 mol%), K2CO3 (1.5 mmol), and ethanol/water mixtureACTHNUTRGENUG(N 1:1) (2 mL), room temperature,
4 h.
[b]
[c]
Reaction conducted at 808C.
Reaction conditions: aryl chloride (1 mmol), arylboronic acid (1.2 mmol), TiO2-Pd(0) catalyst
(1.5 mol%), K2CO3 (1.5 mmol) and DMA/water mixture (2:1) (3 mL), 1008C, under air.
Yield after column chromatography.
[d]
were recorded on Varian 400 MHz or Bruker-Avance
tive for Suzuki cross-couplings of both aryl and heter-
oaryl chlorides and heteroarylboronic acids, thus pro-
viding the desired products in generally good yields.
The catalyst is quantitatively recovered from the reac-
tion by simple filtration and reused for a number of
cycles without significant loss of its catalytic activity.
The simple procedure for catalyst preparation, easy
recovery, and reusability of the catalyst is expected to
contribute to its utilization for the development of
benign chemical processes and products.
300 MHz spectrometers. Chemical shifts (d) are reported in
ppm, using TMS (d=0) as an internal standard in CDCl3.
ESI mass spectra were recorded on a Finnigan LCQ Advan-
tagemax spectrometer. EI mass spectra were recorded on a
GC-MS QP2010 Plus (Shimadzu). The morphology, size and
shape distribution of the Pd nanoparticles were recorded
using a TECNAI FE12 TEM instrument operating at
120 kV. In each image more than 150 particles were ana-
lyzed using SIS imaging software to create the size distribu-
tion histogram. The diffraction patterns were recorded at se-
lected area to determine the crystal structure and phases of
crystals at 660 mm camera length. X-ray diffraction meas-
urements of the Pd nanoparticles were recorded using a
Rikagu diffractometer (Cu radiation, l=0.1546 nm) running
at 40 kV and 40 mA (Tokyo, Japan). X-ray photoelectron
spectroscopy (XPS) measurements were obtained on a
KRATOS-AXIS 165 instrument equipped with dual alumi-
num-magnesium anodes using Mg Ka radiation (hn=
1253.6 eV) operated at 5 kV and 15 mA with pass energy
80 eV and an increment of 0.1 eV. The samples were de-
gassed out for several hours in the XPS chamber to mini-
mize air contamination to sample surfaces. In order to over-
come the charging problem, a charge neutralizer of 2 eV
was applied and the binding energy of C 1s core level (BE=
284.6 eV) of adventitious hydrocarbon was used as a stan-
dard. The XPS spectra were fitted using a non-linear square
method with the convolution of Lorentzian and Gaussian
Experimental Section
General Remarks
All chemicals were purchased from Sigma–Aldrich and S.D
Fine Chemicals, Pvt. Ltd. India and used as received.
ACME silica gel (100–200 mesh) was used for column chro-
matography and thin-layer chromatography was performed
on Merck-precoated silica gel 60-F254 plates. All the other
chemicals and solvents were obtained from commercial
sources and purified using standard methods. The IR spectra
of all compounds were recorded on a Perkin–Elmer, Spec-
trum GX FTIR spectrometer. The IR values are reported in
reciprocal centimeters (cmÀ1). The 1H, 13C NMR spectra
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asc.wiley-vch.de
2833

B. Sreedhar et al.
FULL PAPERS
functions after a polynomial background was subtracted
from the raw spectra. The amounts of Pd in the sample and
filtrate are determined with an IRIS Intrepid II XDL induc-
tively coupled plasma, atomic emission spectroscopy
(ICPAES) instrument.
acetate and chromatographed on silica gel using hexane/
ethyl acetate as an eluent to afford the pure product.
Acknowledgements
Preparation of the Dopamine-Functionalized TiO2
Nanoparticles
P.S.R. thanks the Council of Scientific and Industrial Re-
search, New Delhi for the award of a Senior Research Fel-
lowship
In a typical synthesis, 1.89 g (10 mmol) of 3-hydroxytyra-
mine hydrochloride was dispersed in 200 mL of benzyl alco-
hol in a glovebox. The vial was sealed and taken out of the
box. 15 mL (137 mmol) of TiCl4 were slowly added to the
benzyl alcohol-ligand mixture under vigorous stirring at
room temperature. The vial was sealed, and with continuous
stirring heated to 808C for 72 h. The resulting pale brown
suspension was centrifuged and the precipitate thoroughly
washed twice with chloroform. After each washing step, the
solvent was removed by centrifugation. The collected mate-
rial was left to dry in air at room temperature and subse-
quently at 608C, yielding the dopamine-functionalized TiO2
nanoparticles.
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Experimental Procedure for Suzuki–Miyaura
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