A mesoporous organosilica grafted Pd catalyst (MOG-Pd) for efficient base free and phosphine free synthesis of tertiary butyl esters via tertiary-butoxycarbonylation of boronic acid derivatives without using carbon monoxide

Article abstract of DOI:10.1039/c4gc02443e

A mesoporous organosilica grafted palladium(ii) catalyst was synthesized and characterized using various spectroscopic techniques. Its catalytic activity was evaluated for the synthesis of tertiary butyl esters via tert-butoxycarbonylation of boronic acid

Full text of DOI:10.1039/c4gc02443e

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Mesoporous Organosilica Grafted Pd Catalyst (MOG-Pd) For Efficient
Base Free and Phosphine Free Synthesis of Tertiary Butyl Esters via
tertiary-Butoxycarbonylation of Boronic Acid Derivatives Without Using
Carbon Monoxide
Kajari Ghosha, Rostam Ali Mollaa, Md. Asif Iqubalb, S. M. Islama*
aDepartment of Chemistry, University of Kalyani, Kalyani, Nadia, 741235, W.B., India.
bDepartment of Chemistry, IIT Roorkee, Roorkee 247667, Uttarakhand, India
Abstract
A mesoporous organosilica grafted palladium(II) catalyst was synthesized and characterized
using various spectroscopic techniques. Its catalytic activity was evaluated for the synthesis
of tertiary butyl esters via tert-butoxycarbonylation of boronic acid derivatives. The tertiary
butyl esters were obtained directly from boronic acid pinacol esters and di-tert-butyl
dicarbonate. The reaction was optimized by varying the bases, temperature and solvents. The
catalyst was very stable and can be facilely recovered and reused six times without significant
decrease in its activity and selectivity.
Keywords: Mesoporous organosilica, Palladium(II) complex, tertiary butyl esters, non CO
process, phosphine free.
** Author to whom correspondence should be addressed.
Dr. Sk. Manirul Islam
Department of Chemistry, University of Kalyani, Kalyani, Nadia, 741235, W.B., India.
Phone: + 91- 33-2582-8750, Fax: 91-33-2582-8282, E-mail: manir65@rediffmail.com
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Introduction
Esters are some of the most important compounds in organic synthesis and are used in
production of bulk and fine chemicals, natural and pharmacological compounds.1 Derivatives
of aryl (heteroaryl) esters are important source of carboxylic acids.2 Esterification reactions
are also widely employed as a means of installing protecting groups.3 Therefore, a
tremendous number of approaches for ester synthesis have been developed. tert-butyl group
is a very important protecting group for acids, alcohols, phenols and peptide synthesis,4
because of their stability toward strong basic conditions like organolithium and
organomagnesium compounds, its relative resistance to nucleophilic attack and its ready
removal by acidolysis. tert-Butyl groups are one of the underused protecting groups, since
they are sensitive toward strong acids and harsh formation conditions.5 However, the high
utility of tertiary esters, especially as protecting groups for the free carboxylic acid, calls for
the continuous development towards their synthesis.6 Although numerous protocols are
reported in the literature, the formation of tertiary esters under mild conditions remains a
persistent challenge.
Carbonylation chemistry has been the focus of extensive research in laboratory-scale
organic syntheses, including industrial processes.7 Because of the continuous progress in this
area, its versatility and increasing elaboration as a synthetic tool has led to broader
applications in the synthesis of a wide variety of simple carbonyl compounds to more
complex organic molecules. Despite the fact that Pd-catalyzed carbonylative reactions are
among the most studied, only a limited amount of work has been published regarding the
formation of tertiary esters.8 The obvious drawback in such reactions is the high sterical bulk
of the incoming alcohol impeding its coordination to the metal centre.9 The use of toxic
gaseous carbon monoxide, phosphine and homogeneous Pd catalyst also stands as hindrances
from the viewpoint of economical and sustainable chemistry.
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The above mentioned methods suffer from some major disadvantages; the difficulty
in handling toxic, gaseous carbon monoxide, including its storage and transport, represents
real problems. All these disadvantages reduce the overall utility of traditional carbonylation
method. Many efforts to develop the method without the use of carbon monoxide are
continuously in progress and many interesting reports have appeared in past few years. In all
cases, the key to success is in knowing how a carbonyl group can be transferred by using
substitutes for carbon monoxide.10
On the other hand, arylboronic acid derivatives are air and moisture stable, and are
compatible with a broad range of common functional groups.11 Since Suzuki first reported the
palladium(0)-catalyzed crosscoupling reaction of aryl boronate derivatives,12 the exciting
breakthroughs have been achieved as an important C−C bond forming reaction extensively
used in the synthesis of natural products and pharmaceutical compounds. Organoboron
reagents are stable and easily obtained structure. So it is a powerful substrate as an alternative
to the conventional organometallic building blocks. For these reasons, they have been widely
applied in chemical syntheses.13 In contrast, the relevant palladium(II)-catalyzed
alkoxycarbonylation of organoboron compounds has remained far less explored. There exist
only few reports on the methoxycarbonylation of vinyl and arylboron reagents.14 Similarly,
di-t-butyl dicarbonate or Boc2 is inexpensive and widely known as a useful stable raw
material for the protection of amines and amine derivatives. It is also an efficient tert-
butoxycarbonylating agent for phenols and thiols and used in tert-butoxycarbonylation of
alcohols, amides, lactams and carbamates.15 But except Y. Wu et al, none before has reported
the use of Boc2 in alkoxycarbonylation reaction for the synthesis of tert-butyl esters from
boronic acid or boronic acid pinacol esters as an alternative method of tert-
butyloxycarbonylation reaction without carbon monoxide.16 In this protocol tert-butyl esters
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are prepared directly from boronic acids or boronic acid pinacol esters and di-t-butyl
dicarbonate.
In all the above mentioned procedures for tert-butoxycarbonylation reactions, the Pd
catalysts used are homogeneous in nature. So the catalysts are not easily separable from
reaction mixtures and they are non-recyclable. Our group reported quite a few heterogeneous
and recyclable catalysts for carbonylation reaction7d-h and now we have focussed on tertiary
butoxycarbonylation in a green pathway.
In this regard, ordered mesoporous silica materials have opened many new
possibilities for applications in the field of heterogeneous catalysis, adsorption, and
separation due to their large, well-defined pore sizes and high surface areas.17 Organically
functionalized mesoporous materials have attracted great attention in recent times due to their
huge potential applications in gas storage, sensing, light-harvesting, catalysis, drug-delivery
and so on.18 Surface functionalization with catalytic homogeneous systems especially metal
complexes has been widely applied in order to generate active sites onto these mesoporous
silica material surfaces. The immobilization of catalytically active metal complexes onto the
surfaces offer advantages of combination of high catalytic activity, selectivity and stability
with easier separation of the catalysts from the reaction media thus making it a reusable and
efficient system.20 In this context, the amine group containing organic moiety, 3-
aminopropyltriethoxysilane (3-APTES), has been first anchored on the surface of
mesoporous silica via Si-O-Si bonds, taking advantage of the surface silanol groups. Then
Schiff-base condensation between the amine group and aldehyde group of furfural lead to the
formation of the coordinating ligand in the mesoporous matrix which then binds covalently
with palladium(II) ions
Herein we report the synthesis and characterization of a newly synthesized
mesoporous silica grafted Pd(II) catalyst and its catalytic applications towards tertiary
4

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butoxycarbonylation reaction in a green pathway under carbon monoxide free, base free and
phosphine free conditions.
Experimental
Materials and Instruments
Analytical-grade reagents and freshly distilled solvents were used throughout the
experiment. The reagents were supplied by Sigma-Aldrich chemicals Company, USA and
Merck Co. The chemical analysis was done by the usual procedure. The purities of solvents
and substrates were checked by gas chromatography. Liquid substrates were predistilled and
dried with appropriate molecular sieves. Distillation and purification of the solvents and
substrates were done by standard procedures.20
1H NMR and C spectra were recorded on a Bruker DPX-400 NMR spectrometer in
13
pure deuterated solvents with TMS as internal standard at 400MHz and 100MHz
respectively. FTIR spectra of the samples were recorded on a Perkin-Elmer FTIR 783
spectrophotometer using KBr pellets. Nitrogen adsorption/desorption isotherms were
obtained by using a Belsorp-HP instrument (Bel Japan Inc.) at 77 K. Prior to gas adsorption
measurements, all samples were degassed for 4 h at 423 K. A Mettler Toledo TGA/SDTA
851 instrument was used for the thermogravimetric (TGA) analysis. Powder X-ray diffraction
patterns of the pure functionalized materials were recorded on a Bruker D-8 Advance
diffractometer operated at 40 kV voltage and 40 mA current using a Cu tube ( λ = 0.15406
nm) as the radiation source. TEM analysis was carried outby using a JEOL 2010 TEM
operated at 200 kV. The metal content in the catalyst was determined using a Varian AA240
atomic absorption spectrophotometer (AAS).
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Synthesis of catalyst
Preparation of mesoporous silica (A)
In a typical synthesis, 2.96 g of cetyltrimethylammonium bromide (CTAB) (8.14 mmol) and
1.5 g of Brij-35 (C12H25(OC2H4)23OH, a polyether and aliphatic hydrocarbon chain
surfactant) were dissolved in an acidic aqueous solution of tartaric acid (TA, 0.78 g in 60.00
g H2O) under vigorous stirring at room temperature for 0.5 h. Then 3.50 g of
tetraethylorthosilane (TEOS; 16.8 mmol) was added to the mixture under continuous stirring
for 1 h. Tetramethylammonium hydroxide (TMAOH, 25% aqueous solution) was thereby
added dropwise and the pH was maintained at approximately 11.0. The resulting mixture was
aged overnight under stirring at room temperature and then heated at 353 K for 72 h without
stirring. The solid product was then recovered by filtration, washed several times with water,
and dried under vacuum in a lypholyzer. The resulting powder was calcined in the flow of air
at 723 K for 8 h to remove all the organic surfactants.
Preparation of Amine Functionalized Mesoporous Silica (B):
Modification of the mesoporous silica material with 3-APTES has been done by stirring 0.1 g
of the obtained silica material in previous step with 0.18 g of 3-APTES in dry ethanol at room
temperature for 12 h under N2 atmosphere.21 The white solid aminopropylfunctionalized
silica thus obtained was filtered, washed repeatedly with ethyl acetate and acetone, and
finally dried in air.
Preparation of functionalized mesoporous silica ligand (C) and its Pd(II) complex (D)
The 3-APTES-functionalized silica was refluxed with the furfural dissolved in
methanol (20 ml) for 24 h at 333 K. The obtained silica ligand (2 g) in methanol (20 mL) was
reacted with 5 mL methanolic solution of Pd(OAc)2 under constant stirring and then refluxed
for 24 h. The colour of the complex changes from brown to deep brown. The polymer-
6

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anchored metal complex obtained in this process was filtered and washed successively with
acetic acid, methanol and finally dried under vacuum (Scheme 1).
O
O
O
Si
NH2
OH
OH
OH
EtO
EtO
EtO
Si(CH2)3NH2
+
(A)
3-APTES
(B)
H
C
O
O
s
i
d
front view
e
v
i
e
w
Pd(OAc)2
MeOH
(C)
(D)
H
C
O
O
O
Si
N
Pd
O
AcO
OAc
Scheme 1 Synthesis of functionalized mesoporous silica grafted Pd(II) complex
General procedure for tert-butoxycarbonylation catalysed by MOG-Pd(II)
A dried round bottomed flask equipped with a magnetic stir bar was charged with 25
mg MOG-Pd(II) catalyst (6.44 x 10-3 mmol), 10 mol % DABCO, aryl(hetero) boronic acid
pinacol esters (1 mmol) and di-tert-butyl dicarbonate (1.8 mmol). Anhydrous dioxane (2.0
mL) was added to the reaction flask and the mixture was charged with argon gas three times.
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The reaction mixture was then stirred at 80℃ under argon gas 12h. The reaction progress was
monitored by TLC. After completion of the reaction, the reaction mixture was washed with
brine solution (3 × 5 mL) and extracted with ethyl acetate (3 × 5 mL). It was then dried over
Na2SO4 and then evaporated in vacuum. The residue was purified by column chromatography
on silica gel with petroleum ether-ethyl acetate as the eluent to afford the corresponding
tertiary butyl esters. The products were characterized by 1H NMR and 13C NMR.
Results and Discussion
Characterization of the catalyst
The attachment of metal onto the mesoporous support was confirmed by comparison
of the FT-IR spectra (Fig. 1) of the support before and after loading with Pd, both in the mid-
IR (4,000–400 cm-1) region. FTIR spectra of both MOG (Fig. 1a) and MOG-Pd (Fig.2a)
materials reveal bands at around 1087 cm-1 which is due to Si-O-Si linkages of the silica
network. From Fig. 1a, it is evident that the peak at 1645 cm-1 is for C=N. For the Pd
anchored mesoporous material the C=N stretching frequency is shifted to lower wavelength
at 1628 cm-1 indicating the C=N bond is coordinated to Pd through the lone pair of electrons
of nitrogen.22
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Fig. 1. FT-IR spectra of mesoporous silica (a) and grafted Pd(II) catalyst (b).
The electronic spectra (Fig. 2) of the polymer-supported metal complex were recorded
in diffuse reflectance spectrum mode as MgCO3/BaSO4 disks. The present MOG material and
MOG-Pd(II) complex shows a showed bands at 250-260 and 310-360 nm due to π →π* and
LMCT transitions. A broad band appears in the region 575-750 nm in MOG-Pd(II) complex
due to d-d transitions.23
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1.6
1.2
0.8
0.4
0.0
MOG-Pd
MOG
300
400
500
600
700
800
Wavelength(nm)
Fig. 2. DRS-UV vis spectra of MOG-Pd(II) complex
Thermal stability of complex was investigated using TGA over a temperature range of
0
0-700 C. TGA curve of mesoporous silica grafted Pd(II) complex is shown in Fig. 3. The
initial sharp weight loss up to 150 °C may be due to the pore occupancy by solvent molecules
and moistures. A maximum weight loss has been observed from 300 °C to 700 °C and this
could be attributed to the loss of the organic fragments from MOG-Pd.24
Fig. 3. TGA curve mesoporous organosilica grafted Pd(II) catalys
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The mesoporous organosilica grafted Pd(II) catalyst was also characterized by HR-
TEM analysis (Fig. 4). The presence of 2D-hexagonal mesophase and hexagonal arrangement
of the pore channels are clearly observed and are shown in Fig. 4. Low electron density spots
(pores) are present throughout the specimen and they are arranged in a honeycomb-like
hexagonal array. FFT pattern shown in the inset of Fig. 4(B) further confirmed the hexagonal
arrangement of the pores. This result suggests that the ordered arrangement of the porous
framework of MOG-Pd remains unperturbed after palladium loading on MOG.24 Further,
atomic absorption spectroscopy (AAS) analysis revealed loading of 2.74 wt% Pd in MOG-
Pd. The EDX image of MOG-Pd complex (Fig. 4c) confirms the presence of the respective
atoms: C, N, O, Si and Pd. The TEM image of the reused catalyst is provided in Fig. S2
(supporting information).
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Fig. 4. HR-TEM (a-b) and EDX (c) images of mesoporous organosilica grafted Pd(II)
catalyst
The powder X-ray diffraction patterns for the MOG and MOG-Pd complex are shown
in Fig. 5. Fig. 5(a) is highly ordered, showing three strong diffraction peaks for the 100, 110,
and 200 planes of the 2D-hexagonal mesophase.25 MOG exhibits a single intense peak with
maxima at a 2θ value of 2.28, indicating presence of mesophase in the sample. After loading
with Pd, intensity of the peak was reduced and it shifted towards high angle, having a 2θ
value of 2.42. The d spacing for MOG and MOG-Pd are 3.70 nm and 3.58 nm respectively
indicating the retaintion of mesophase both before and after loading with Pd. The XRD
pattern of the reused catalyst (Fig S1, supporting information) is almost similar to the fresh
MOG-Pd(II) catalyst
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5000
4000
3000
2000
1000
d= 3.70
MOG
(a)
d= 3.58
(b)
MOG-Pd
2
4
6
8
10
2 theta (degree)
Fig. 5. XRD curve of MOG and MOG-Pd(II) catalyst
The N2 adsorption-desorption isotherms at 77 K of the MOG-Pd material reveals typical type
IV isotherms which suggests the presence of a mesoporous network (Fig. 6). The BET
surface area and pore width for the amine functionalized mesoporous silica material are 881
m2g-1 and 3.2 nm respectively, whereas the corresponding values for sample MOG-Pd have
decreased to 156 m2g-1 and 2.6 nm respectively. This decreased in pore width surely due to
the Pd loading at the inner pores of mesoporous silica. A considerable decrease in the BET
surface area suggests that Pd-centers have been anchored on the surfaces.26
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Fig. 6. N2 adsorption-desorption of MOG-Pd(II) catalyst
Catalytic activity
As we have seen and reported several supported27 palladium catalyst that exhibit high
catalytic activity in the field of carbonylation reactions using carbon monoxide, we decided to
investigate the catalytic activity of the MOG-Pd catalyst to preparare tertiary butyl esters via
carbonylation reaction without using carbon monoxide.
The reaction between 3 pyridineboronic acid pinacol ester (A) and di tertiary butyl di
carbonate (B) in argon atmosphere was chosen as the model reaction (Scheme 2). The effect
of base, solvent, temperature and reaction atmosphere was monitored for the reaction.
DABCO (1,4-diazabicyclo[2.2.2]octane) was used as a green, efficient and inexpensive
reagent to activate and stabilize the palladium complex instead of phosphine which is
expensive, air-sensitive and is not easily separable from products.28
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O
O
O
O
O
MOG-Pd
O
B
+
DABCO, dioxane
800C, 12h
O
O
O
N
N
(B)
(A)
(C)
Scheme 2: Model reaction for tertiary butoxycarbonylation reaction
As bases play a very important role in a chemical reaction, so the first thing we
studied after choosing the model reaction was the effect of bases. In most cases, the addition
of a base increases the product yield.29 The influence of various bases was studied for this
butoxycarbonylation reaction. Na2CO3 gave a very good amount of tert-butoxy carbonylative
product. Even K2CO3 and K3PO4 gave moderate amount of yield. KOAc and CsF were not
very effective as bases and tBuOK did not furnish any carbonylative product. The most
interesting point that was noted for this carbonylation reaction was that the reaction
proceeded best in the absence of a base. This could be due to the oxidative addition of the Pd
catalyst into di-tbutyl dicarbonate leading to the formation of an equivalent of tertiary
butoxide, which may be serving as the base for the whole process.30 The decreased yields
with external bases added (especially strong bases) could be due to the fact that di-tertiary-
butyl dicarbonate decomposes at high temperatures and in presence of strong base.31 When
no base was used in the reaction 96% carbonylative product was obtained.
Table 1: Effect of bases on MOG-Pd catalyzed tertiary butoxy carbonylation reaction
Yield of
isolated product
(%)
Entry
1
Base
Na2CO3
87
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2
3
K2CO3
KOAc
K3PO4
CsF
70
45
4
73
5
45
6.
7.
t-BuOK
No base
trace
96
Reaction conditions: 1mmol A, 1.8 mmol B, 25mg (6.44 x 10-3 mmol) MOG-Pd(II)
catalyst, 10 mol % DABCO, 2 ml dioxane, 80 0C, 12 h, 2.2 mmol base.
The next important parameter that was optimized for the reaction was the effect of solvent.
Solvents were found to have significant effects on the tertiary butoxycarbonylation reaction.
Solvents like dioxane, DMF, toluene and DME were screened (Table 2). It was observed that
the reaction proceeded well with moderately polar aprotic solvent and thus dioxane provided
the best outcome (96%) at 80 0C (Table 2, entry 1).
Table 2: Effect of solvent on MOG-Pd catalyzed tertiary butoxy carbonylation reaction
Entry
1.
Solvent
dioxane
Yield of isolated
product (%)
96
2.
3.
4.
DMF
toluene
DME
4
66
62
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Reaction conditions: 1 mmol A, 1.8 mmol B, 25 mg (6.44 x 10-3 mmol) MOG-Pd(II)
catalyst, 10 mol % DABCO, 2 ml solvent, 80 0C, 12 h.
The reaction temperature was also varied to obtain the best yield of the tert
butoxycarbonylative product. The reaction was conducted with a wide range of temperature
0
varying from 60 C to 120 C. It was observed that the temperature of 80 C served as the
0
0
best reaction temperature giving an isolated product yield of 96%. Raising the temperature
0
above 80 C and upto 100 C did not affect the product yield much. Above 100 C, the
0
0
desired ester yield started to decrease. This may be probably due to the decomposition of the
0
di tertiary butyl dicarbonate.32 Thus 80 C was chosen as the optimized reaction temperature
(Fig. 7).
100
95
90
85
80
75
70
60
70
80
90
100
110
120
Temperature (0C)
Fig. 7. Effect of temperature on MOG-Pd catalyzed tertiary butoxy carbonylation reaction
After optimizing the reaction temperature, another important parameter that was taken into
account was reaction time. The best result was obtained when the reaction was carried out for
12 hrs (Fig S3, supporting information).
The amount of catalyst was also varied for tertiary butoxycarbonylation reaction. It was
found that maximum yield was obtained when 25mg (6.44 x 10-3 mmol) of the MOG-Pd
catalyst was used in the reaction (Fig S4, supporting information).
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The reaction was also performed under oxygen atmosphere, but the product yield (80%) was
less than that obtained by using argon atmosphere (96%).
After optimizing various reaction parameters, a range of pyridine boronic acid pinacol
esters were explored to extend the reaction scope. Both electron donating and withdrawing
pyridine boronic acid pinacol esters were converted to their corresponding products in good
to excellent yields (Table 3, entries 1-15). A wide range of functional groups like nitrile,
ether, ester, alkyl, vinyl, amino and naphthyl were found to be compatible with the present
reaction conditions. The position of boronic acid pinacol esters of pyridine showed a
prominent change in the yield of the tertiary butyl ester products (Table 3, entry 1-3). Tert-
butyl isonicotinate furnished a low yield of the desired product (Table 3, entry 3) while tert-
butyl nicotinate gave excellent yield of the product (Table 3, entry 2) and ter-butyl picolinate
also gave a moderate yield of the desired product (Table 3, entry 1). For the nitrile substituted
pinacol esters a moderate yield of the ester product was obtained (Table 3, entries 4 and 5).
tert-butyl 5-ethoxynicotinate and tert-butyl 6-(benzyloxy)nicotinate gave excellent yields of
the respective ester products (Table 3, entries 6 and 7). The other functional groups like
esters, vinyl, amino and naphthyl produced moderate yields. The position of these functional
groups did not have any pronounced effect on the product yield (Table 3, entries 8-15).
Table 3- MOG-Pd(II) Catalyzed tert-Butyloxycarbonylation Reactions of Various Pyridine
Boronic Acid Pinacol Esters with Di-tert-butyl Dicarbonatea
O
O
O
O
MOG-Pd
Ar
B
+
Ar
O
DABCO, dioxane
800C, 12h
O
O
O
O
(B)
(A1)
(C1)
Entry
Ar
Product
Isolated Yield (%)
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O
N
N
72
1
O
O
O
96
48
52
57
2
3
4
5
N
N
O
O
N
N
O
NC
NC
O
N
N
O
O
NC
N
NC
N
O
O
O
91
6
O
N
N
O
98
7
O
O
N
O
N
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O
O
O
52
8
N
O
N
O
O
O
O
O
O
O
O
62
62
54
9
N
N
N
N
O
O
10
N
O
O
11
N
N
N
O
O
N
58
12
N
O
O
60
13
N
N
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O
O
70
14
N
N
O
O
55
15
N
N
aReaction conditions: 1mmol A1, 1.8 mmol B, 25mg (6.44 x 10-3 mmol) MOG-Pd(II)
0
catalyst, 10 mol % DABCO, 2 ml dioxane, 80 C, 12 h. The products were characterized by
1H NMR and 13C NMR.
We also investigated a variety of substituted phenyl boronic acid pinacol esters after
the successful product yield of the tert-butyl esters from pyridine boronic acid pinacol esters.
The substituted phenyl boronic acid pinacol esters furnished good to excellent yields of the
respective tertiary butyl ester products. The results are summarized in Table 4. Both electron
rich and electron deficient systems proved reactive towards the catalytic system, and the
desired tert-butyl ester products were obtained in yields ranging from 66% to 89% (Table 4,
entries 1-9). 4-biphenyl and 2-naphthyl boronic acid pinacol esters furnished excellent yields
of the corresponding esters (Table 4, entries 10 and 12) while 1-naphthyl and 2-thiophenyl
boronic acid pinacol esters gave quite good yields of the respective products (Table 4, entries
11 and 13).
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Table 4-MOG-Pd(II) Catalyzed tert-Butyloxycarbonylation Reactions of Various Boronic
Acid Pinacol Esters with Di-tert-butyl Dicarbonatea
O
O
O
O
O
MOG-Pd
O
B
+
DABCO, dioxane
800C, 12h
O
O
(B)
O
(A2)
(C2)
R
R
Entry
R
Product
Isolated Yield (%)
O
1
2-Me
4-OMe
3,4-di-OMe
2-F
O
84
O
O
2
3
4
5
89
86
72
79
MeO
MeO
O
O
MeO
O
O
F
O
O
4-F
F
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O
O
6
7
8
9
2-Cl
4-Cl
66
76
81
81
Cl
O
O
Cl
O
O
4-CF3
F3C
O
O
4-CN
NC
O
O
10
4-biphenyl
93
O
O
11
12
1-napthyl
2-napthyl
70
90
O
O
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O
13
2-thiophenyl
62
O
S
aReaction conditions: 1mmol A2, 1.8 mmol B, 25mg (6.44 x 10-3 mmol) MOG-Pd(II)
0
catalyst, 10 mol % DABCO, 2 ml solvent, 80 C, 12 h. The products were characterized by
1H and 13C NMR.
Although the exact reaction sequence was not determined, based on former mechanistic
studies of palladium-catalyzed reactions,16, 28, 33 a probable reaction pathway is given in
Scheme 3.
O
O
R1
R1
R1
silica
Pd(0)
R2
O
O
O
O
O
C
O
Pd(II)
R1O
OR1
O
OR1
Pd
R2
R2X
O
R1=tBu
R2 = Ar
R1
O
OX
X= B(OH)2,
Boronate ester
Scheme 3: Proposed reaction mechanism for tertiary butyl ester synthesis
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Test for heterogeneity
The leaching of palladium from polymer anchored palladium(II) complex was
confirmed by carrying out analysis of the used catalyst (EDX, IR) as well as the product
mixtures (AAS, UV-vis). Analysis of the used catalyst did not show appreciable loss in the
palladium content as compared to the fresh catalyst. IR spectrum of the recycled catalyst was
quite similar to that of fresh sample indicating the heterogeneous nature of this complex.
Analysis of the product mixtures showed that if any palladium was present it was below the
detection limit. The UV-vis spectroscopy was also used to determine the stability of this
catalyst. The UV-vis spectra of the reaction solution, at the first run, did not show any
absorption peaks characteristic of palladium metal, which indicates that the leaching of metal
did not take place during the course of the reaction. The metal content of the recycled catalyst
was determined with the help of AAS and it was found that palladium content of the recycled
catalyst remained almost unaltered. These observations strongly suggest that the present
catalyst is truly heterogeneous in nature.
Heterogeneity test for the tertiary butoxycarbonylation of 3 pyridineboronic acid
0
pinacol ester and di tert- butyl di carbonate in argon atmosphere was carried out at 80 C
using MOG-Pd catalyst. Then after 6 h, the MOG-Pd complex catalyst was filtered off and
was allowed to react further. We found that no further reaction occurred after this hot
filtration procedure; hence, this experimental finding suggests there is no palladium leaching
from the MOG-Pd complex during the progress of a reaction. In addition, to reconfirm this
observation, AAS analysis of the reaction mixture was carried out after 6 and 12 h, which
revealed a below detectable level (below 0.01 ppm) of palladium in solution.
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To ascertain if the reactions are truly heterogeneous we have also performed the
three-phase test34 for tert-butoxy carbonylation reaction. The three-phase test, developed by
Rebek et al35, is used to detect the presence of catalytically active homogeneous metal species
in the reaction medium. In this test, one of the substrates is anchored to a solid support and
can only react if a soluble catalytic Pd source is present. In our present study, 4-CHO
substituted
pyridine
boronic
acid
pinacol
ester
was
funtionalized
to
aminopropylfunctionalized silica and used in the three-phase test. The reaction mixture of 25
mg MOG-Pd(II) catalyst, 10 mol % DABCO, 3-pyridine boronic acid pinacol ester (1 mmol),
di-tert-butyl dicarbonate (1.8 mmol), anhydrous dioxane (2.0 mL) was added to the reaction
0
flask and the mixture was stirred at 80 C under argon gas 12h. Resulting mixture was then
cooled to room temperature, extracted with ethyl acetate. The combined organic layer was
washed with water and brine solution. Then the combined organic layer was dried over
1
anhydrous Na2SO4 and evaporated to dryness. The extracted product was analyzed by H
NMR which showed the compound was 3-pyridine tertiary butyl ester. The obtained residue
was refluxed with 2M HCl and the solution was extracted with diethyl ether. The obtained 4-
CHO pyridine boronic acid pinacol ester product confirms that it did not take part in the
tertiarybutoxy carbonylation reaction. If any Pd leached to the solution, then anchored 4-
CHO pyridine boronic acid pinacol ester would take part in the tertiarybutoxy carbonylation
reaction. But this did not occur with MOG-Pd(II) catalyst here. Thus, this three-phase test
provides further evidence that the reaction is truly heterogeneous in nature and there is no
leaching of palladium during the course of reaction.
Recycling of catalyst
The catalyst remains insoluble in the present reaction conditions and hence can be
easily separated by simple filtration followed by washing. The catalyst was washed with ethyl
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0
acetate and acetone and dried at 100 C. tert-butoxycarbonylation reaction was carried out
with the recycled catalyst under the optimized reaction conditions. The catalyst was recycled
in order to test its activity as well as stability. After each run, AAS of the catalyst was
performed and it was found that palladium content remained almost unchanged. The obtained
results are presented in Fig. 8. As seen from Fig. 8, the catalyst did not show any appreciable
change in its activity which indicates that the catalyst is stable and can be regenerated for
repeated use.
Fig. 8. Recycling efficiency of the MOG-Pd complex for the tertiary butoxy carbonylation
reaction.
Conclusions
A mesoporous silica grafted palladium complex was prepared and characterized. The
complex was an active and reusable catalyst for the tert butoxycarbonylation reaction of
boronic acid derivatives with di-tert-butyl dicarbonate under base, CO and phosphine free
conditions. The catalyst is stable and recyclable under the used reaction conditions. This
heterogeneous catalyst shows no significant loss of activity in recycling experiments. The
active sites do not leach out from the support and thus can be reused without appreciable loss
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of activity, indicating effective anchoring. The reusability of this catalyst is high without
significant decrease in its initial activity.
Acknowledgements
SMI acknowledges Department of Science and Technology (DST), Council of Scientific and
Industrial Research (CSIR) and University Grants Commission (UGC), New Delhi, India for
funding. RAM acknowledges UGC, New Delhi, India for his Maulana Azad National
Fellowship. We also acknowledge DST and UGC for providing funds to University of
Kalyani under FIST, PURSE and SAP programmes.
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