Palladacycle-Catalyzed Carbonylative Suzuki-Miyaura Coupling with High Turnover Number and Turnover Frequency

Article abstract of DOI:10.1021/acs.joc.5b01160

This work reports the carbonylative Suzuki-Miyaura coupling of aryl iodides catalyzed by palladacycles. More importantly, the palladacycles have been used to generate high turnover numbers (TON's) and turnover frequencies (TOF's). A range of aryl iodides can be coupled with arylboronic acids, generating TON's in the range of 10⁶ to 10⁷ and TOF's in the range of 10⁵ to 10⁶ h^-1. Comparison of the palladacycles with a conventional palladium source shows their superiority in generating high TON's and TOF's.

Full text of DOI:10.1021/acs.joc.5b01160

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Palladacycle Catalyzed Carbonylative Suzuki‒Miyaura Coupling with High
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Turnover Number and Turnover Frequency
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Prashant Gautam and Bhalchandra M. Bhanage*
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Department of Chemistry, Institute of Chemical Technology, N.P. Marg, Matunga‒400019,
Mumbai, India. Fax: +91‒22 33611020; Tel: +91‒22 33612601;
E‒mail: bm.bhanage@gmail.com, bm.bhanage@ictmumbai.edu.in
Abstract Graphic
Abstract. This work reports the carbonylative Suzuki‒Miyaura coupling of aryl iodides
catalyzed by palladacycles. More importantly, the palladacycles have been used to bring out high
turnover numbers (TON’s) and turnover frequencies (TOF’s). A range of aryl iodides can be
coupled with arylboronic acids generating TON’s in the range of 106‒107 and TOF’s in the range
of 105‒106 h−1. Comparison of the palladacycles with a conventional palladium source shows
their superiority in generating high TON’s and TOF’s.
The carbonylative Suzuki‒Miyaura coupling utilizing carbon monoxide as the C1 source
is one of the pivotal reactions for the synthesis of biaryl ketones.1 Biaryl ketones are important
structural building blocks present in a wide variety of molecules which include pharmaceutical
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drugs, natural products, and sunscreen agents. These biaryl ketones have been synthesized
through carbonylative Suzuki‒Miyaura coupling using variety of palladium catalysts and the
reaction using aryl iodides is well documented in the literature.2 The main drawbacks of these
catalytic systems include high palladium loading, poor turnover numbers (TON’s) and turnover
frequencies (TOF’s) and the need to handle air and moisture sensitive phosphine ligands.
Palladacycles have been reported exhaustively for the conventional cross‒coupling reactions
(Heck, Suzuki, Sonogashira, Buchwald‒Hartwig) and have been shown to produce extremely
high TON’s and TOF’s vis‒à‒vis conventional palladium sources.3 The fact that they are air and
moisture stable is an added advantage.
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In 2002, Schnyder et al. reported a series of palladacyclic complexes with secondary
phosphines4 and showed their role as extremely active palladium sources in a series of cross‒
coupling reactions of aryl chlorides. It was shown that the complex of a palladacycle with
secondary norbornyl phosphine 1 showed the highest catalytic activity. Almost at the same time,
Bedford and co‒workers reported a mixed tricyclohexylphosphine‒triarylphosphite complex 2 as
a highly active catalyst for the Suzuki‒Miyaura coupling of aryl chlorides and thereby
documented the highest TON’s.5
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A literature survey shows that palladacycles have been seldom reported for carbonylative cross
coupling reactions.6 To the best of our knowledge, they have never been reported as a palladium
source for the carbonylative Suzuki‒Miyaura coupling using gaseous CO under thermal
conditions. The concept of low palladium loading and subsequent generation of high TON’s and
TOF’s has also not been addressed till now. Given the catalytic superiority of these palladacyclic
complexes and considering our continued interest in the catalyst development for carbonylation
reactions7, we envisioned to test their activity for the carbonylative version. The presence of
dissolved quantities of CO, a strong π‒acidic ligand, in the reaction mixture in a carbonylative
coupling makes oxidative addition to the metal and reductive elimination difficult. Moreover,
unusually high concentration of CO as compared to the catalyst tends to poison the catalyst. In
such a case, can such high TON’s and TOF’s be generated?
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We initially examined the model reaction between iodobenzene 4a and phenylboronic
acid 5a as substrates using Bedford’s palladacycle 2 (Table 1). The effect of CO pressure showed
that the reaction could be carried out at atmospheric pressure but gave a higher yield of
benzophenone 6a at 2 bar (Table 1, entries 1 and 2).
Table 1. Optimization of reaction.
Entry
CO
pressure
(bar)
Base
Time Yielda
(h)
(%)
Effect of CO pressure
1
2
3
1
2
3
K2CO3
K2CO3
K2CO3
5
5
5
89
95
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Effect of base
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K2CO3
Na2CO3
Et3N
5
95
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K3PO4
Effect of time
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K2CO3
K2CO3
K2CO3
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79
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Reaction conditions: 4a (0.5 mmol), 5a (0.75 mmol), 2 (0.1 mol%), base (1.5 mmol), anisole (11
mL). a GC yield.
Further increase in CO pressure brings down the yield. (Table 1, entry 3). The base screening
study showed that K2CO3 brings out the highest yield of the product as compared to other
inorganic and organic bases (Table 1, entries 4‒7). Further, the reaction generated the highest
yield of product in 5 h and further increase in time did not have any effect on the yield (Table1,
entries 8‒10). Carbonylative Suzuki‒Miyaura reaction typically proceeds in non‒polar solvents
like toluene and anisole2a,2b and hence a solvent screening study was not carried out. Anisole was
used as the solvent of choice in our studies given its high boiling point. Blank experiments were
carried out without the addition of phenylboronic acid and the palladium catalyst separately. In
both the cases, no product formation took place. Having established the optimized parameters,
we focused our attention to explore the maximum TON’s and TOF’s that could be generated by
lowering the catalyst loading (Table 2).
Initial catalyst loading experiments showed that a complete conversion of iodobenzene
could be achieved up to 10−3 mol% loading of palladium at 80 °C in 5 h generating a TON of
47500 (Table 2, entries 1‒3).
Table 2. Effect of catalyst loading, time and temperature.
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2
BZe
TOF
(h−1)
Entry mol (%)
TONf
%
1
1
2
3
10−
10−
10−
10−
10−
10−
10−
10−
10−
10−
10−
98 4.90 × 102 0.98 × 102
97 4.85 × 103 9.70 × 102
95 4.75 × 104 9.50 × 103
84 4.20 × 105 8.40 × 104
91 4.55 × 105 9.10 × 104
95 4.75 × 105 9.50 × 104
93 4.65 × 106 9.30 × 105
88 4.50 × 107 9.00 × 106
54 2.70 × 108 5.40 × 107
48 2.40 × 109 4.80 × 108
10 5.00 × 109 1.00 × 109
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4
5a
6b
7b
8b
9c
10d
11d
Standard reaction conditions: 4a (0.5 mmol), 5a (0.75mmol), K2CO3 (1.5 mmol), CO (2 bar),
anisole (11 mL) at 80 °C for 5 h. a 12 h. b 120 °C. c 140 °C. d 160 °C. e GC yield (calculated as an
average of triplicate measurements). f mol product per mol Pd. BZ‒benzophenone.
At 10−4 mol% loading, 10% iodobenzene remains unreacted, nevertheless generating a TON of
4.20 × 105 (Table 2, entry 4). To ensure complete conversion, the reaction was carried out for 12
h which resulted in a 91% yield of the product with 3% iodobenzene remaining unreacted (Table
2, entry 5). However, increasing the temperature to 120 °C resulted in the complete conversion
of iodobenzene within 5 h producing a TON of 4.75 × 105 (Table 2, entry 6). By further
decreasing the Pd loading to 10−6 mol% a TON of 4.50 × 107 could be generated (Table 2, entry
8). When the Pd loading was decreased through 10−7 mol% to 10−9 mol%, a temperature increase
till 160 °C was required to maximize the product yield. TON’s till 5.00 × 109 could be generated
within 5 h thus generating a TOF of 1.00 × 109 h−1 (Table 2, entries 9‒11). However, in either of
the cases, a complete conversion of iodobenzene could not be achieved. To the best of our
knowledge, these are the highest TON’s and TOF’s reported for the carbonylative Suzuki‒
Miyaura coupling of aryl iodides.
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Having established high TON’s and TOF’s for the model reaction, we focused our
attention on the scope of substrates. The emphasis was to test briefly whether different classes of
functional groups could be tolerated, rather than to carry out an elaborate substrate study (Table
3). Aryl iodides and aryl boronic acids having electron‒releasing and ‒withdrawing groups
reacted well and were smoothly coupled to give the biaryl ketones in high yields. Aryl iodides
bearing electron‒withdrawing substituents are known to encourage the non‒carbonylative
coupling leading to the synthesis of biaryl.8
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Table 3. Scope of the palladacycle catalyzed carbonylative Suzuki‒Miyaura coupling.
Entry
1
4
5
6/Yield
6b/89
TONc
TOF (h−1)
R1 = 4‒OCH3
(4b)
R1 = 4‒NH2 (4c)
R1 = 2‒NH2 (4d)
R1 = 3‒NO2 (4e)
R1 = 4‒CN (4f)
4.45 × 107 8.90 × 106
2
3
4
R2 = H (5a)
6c/94
6d/69
6e/80
6f/88
6g/90
6h/81
6i/90
4.70 × 107 9.40 × 106
3.45 × 107 6.90 × 106
4.00 × 107 8.00 × 106
4.40 × 107 8.80 × 106
4.50 × 107 9.00 × 106
4.05 × 106 8.10 × 105
5
6
1‒naphthyl (4g) R2 = 4‒F (5b)
7a
8a
4c
4f
R2 = 4‒Cl (5c)
R2 = 3‒Me
4.50 × 106 9.00 × 105
(5d)
5d
5b
5a
5a
5a
9a
4b
4e
6j/86
6k/85
6l/71
6l/89
4.30 × 106 8.60 × 105
4.25 × 106 8.50 × 105
3.55 × 106 7.10 × 105
4.45 × 104 3.70 × 103
10a
11a
12b
13b
14b
15b
16b
2‒pyridyl (4h)
2‒pyridyl (4h)
2‒thienyl (4i)
6m/88 4.40 × 104 3.66 × 103
4a
4i
4i
3‒thienyl (5e)
6n/85
6o/80
6p/82
4.25 × 104 3.54 × 103
5e
R2 = 4‒OCH3
(5f)
4.00 × 104 3.33 × 103
4.10 × 104 3.41 × 103
4.65 × 104 3.87 × 103
17b
4i
5c
6q/93
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Reaction conditions: aryl iodide (0.5 mmol), aryl boronic acid (0.75 mmol), K2CO3 (1.5 mmol),
[Pd, 2] (10−6 mol%), CO (2 bar), anisole (11 mL) at 120 °C for 5 h. a [Pd, 2] (10−5 mol%). b [Pd,
2] (10‒3 mol%), CO (5 bar) for 12 h c mol product per mol Pd.
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However, the presence of cyano and nitro functionality at the para‒ and meta‒ position lead to
the synthesis of biaryl ketone/biaryl in 88/2% and 80/9% yields wherein TON’s of 4.40 × 107
and 4.00 × 107 were observed respectively (Table 3, entries 4 and 5). Electron‒releasing
functionalities such as methoxy and amino could also be coupled to give ketones 6b and 6c in
89% and 94% yields without any biaryl formation, thus producing TON’s of 4.45 × 107 and 4.70
× 107 respectively (Table 3, entries 1 and 2). However, the presence of a substituent in the ortho
position brings down the yield and TON as compared to its presence in the para position (Table
3, entry 3). 1‒Iodonaphthalene, a poly‒aromatic substrate could be coupled with 4‒
fluorophenylboronic acid producing 6g in 90% yield, with a TON of 4.50 × 107. Unsymmetrical
ketones 6h, 6i, 6j and 6k could be synthesized by coupling aryl iodide and aryl boronic acid,
both bearing a combination of electron‒releasing and –withdrawing groups. In such a case, the
Pd loading had to be increased to 10−5 mol% to effect complete conversion of aryl iodide as well
as tolerate the increase in bulk caused by presence of substituents on both the substrates (Table 3,
entries 7‒10). Incidentally, ketones 6g, 6i, 6j and 6k were not only synthesized with high
catalytic TON’s, but were synthesized for the first time through carbonylative Suzuki‒Miyaura
coupling. 2‒Iodopyridine could be successfully coupled to give 6l in 71% yield with a TON of
3.55 × 106 with some iodopyridine remaining unreacted (Table 3, entry 11). However, on
increasing the Pd loading to 10‒3 mol%, CO pressure to 5 bar and time to 12 h, a complete
conversion could be effected. An increased yield of 6l was obtained albeit with a fall in the
values of TON and TOF. (Table 3, entry 12). The thiophenyl heterocyclic moiety could also be
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functionalized at different positions to produce the corresponding benzoylthiophenes 6m and 6n
with a TON and TOF of the order of 104 and 103 h‒1 respectively (Table 3, entries 13 and 14).
The bithiophenyl ketone 6o and benzoylthiophenes 6p and 6q containing electron‒releasing (‒
OCH3) and ‒withdrawing (‒Cl) groups on the benzene ring could also be synthesized in good
yields. The presence of the electron‒withdrawing group on the benzene ring resulted in a higher
yield (Table 3, entries 15‒17).
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Next, we screened different palladacycles and conventionally used Pd(OAc)2 for the
reaction between iodobenzene and phenylboronic acid and carried out a comparative study for
generation of high TON’s and TOF’s (Table 4).
Table 4. Comparison of palladacycles with Pd(OAc)2.
Entry
Cat.
BZa TONc
TOF
(%) (×108) (×107)
(h−1)
1
2
3
Pd(OAc)2
9
0.4
3.1
2.7
2.6
3.0
0.9
6.2
5.4
5.2
6.0
1
2
3
1
62
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60
4
5b
Reaction conditions: 4a (0.5 mmol), 5a (0.75 mmol), K2CO3 (1.5 mmol), [Pd] (10−7 mol%), CO
a
(2 bar), anisole (11 mL) at 140 °C for 5 h. GC yield (calculated as an average of triplicate
b
measurements). Scale up: 4a (5 mmol), 5a (7.5 mmol), K2CO3 (15 mmol), [Pd] (10−7 mol%),
CO (2 bar), anisole (20 mL) at 140 °C for 5 h. c mol product per mol Pd. BZ‒Benzophenone.
We were delighted to observe that the palladacycles gave superior results. Pd(OAc)2 gave a 9%
yield of the product (Table 4, entry 1) whereas all the palladacycles used gave >50% yield (Table
4, entries 2‒4). The dinorbornyl palladacycle gave the highest yield, slightly better than
Bedford’s and RuPhos9 palladacycle 3 generating a TON of 3.10 × 108 and a TOF of 6.20 × 107
h−1. Further, we tested the activity of palladacycle 1 when the reaction was scaled up to gram
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scale (5 mmol) and the catalyst maintained its activity (Table 4, entries 2 and 5). We also tested
the scope of aryl bromides, ‒chlorides and alkylboronic acids as substrates (Scheme 1). The
carbonylative coupling of 4‒bromoanisole 4j and 4‒bromobenzonitrile 4k with phenylboronic
acid at 0.1 mol% loading of palladacycle 2 gave only 61% and 30% yield of the respective
products. Much of the aryl bromide remained unreacted and failed to undergo complete
conversion. The aryl chloride 4l and n‒butylboronic acid 5f however failed to generate any
product, thus requiring a comprehensive independent investigation.
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Scheme 1. Carbonylative coupling of aryl bromide, ‒chloride and alkylboronic acid.
The role of active species in the case of the palladayclic catalysts may be responsible for
the enhanced activity. Considering oxidative addition of the aryl iodide as the rate limiting step
and a Pd(0)/Pd(II) pathway, which is normally the case in carbonylative couplings, the catalyst
tends to “rest” in a zero‒valent state. In the case of Bedford’s palladacycle 2, deorthometallation
of I gives II which is followed by in situ reduction to give III (Scheme 2).
Scheme 2. Proposed degradation of 2.
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Coordination of π‒acidic phosphite ligand and CO will stabilize the resting state [(PCy3)Pd0]
both thermodynamically and kinetically. Moreover, the decoordination of either of them would
release [(PCy3)Pd0] into the catalytic cycle.5a,5b,6b In the case of the dinorbornyl complex 1 which
contains a secondary phosphine ligand, the mode of action and nature of the catalytically active
species is unknown. However the formation of mononuclear palladium complexes with
secondary phosphine ligands as well as phosphido‒bridged di‒ and poly‒nuclear compounds
with palladium is a possibility. Additionally, secondary phosphines react with aryl halides in the
presence of palladium catalysts to form aryl phosphines.4,10 Further, we believe the palladacyclic
catalysts are not converted to Pd nanoparticles or Pd black. Even in the reaction carried out with
0.1 mol% Pd, we did not observe any particle formation or accumulation of Pd black and the
solution remained homogeneous. Similar possibility also exists for Pd(OAc)2 precursor to give
Pd nanoparticles and similar reaction results. However we did not observe this under our reaction
conditions.
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In conclusion, we have established the first palladacycle catalyzed carbonylative Suzuki‒
Miyaura coupling of aryl iodides using gaseous CO under thermal conditions for the synthesis of
biaryl ketones. These palladacycles behave as robust catalysts and have been used to bring out
high TON’s and TOF’s. Comparison with a conventional palladium source shows their
superiority in generating the same. Relative comparison of the palladacycles shows that they
exhibit almost similar catalytic activity at concentrations as low as 10−7 mol%, with the
dinorbornyl complex exhibiting a slightly better activity.
EXPERIMENTAL SECTION
Materials and Methods. The palladacyclic complexes were commercially purchased from
Sigma‒Aldrich and were used as such. All other chemicals and solvents were purchased from
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different commercial sources and were used as received without further purification. Stock
solutions of the catalyst dissolved in anisole of various concentrations (10−1 mol% to 10−10
mol%) were prepared by taking a known amount of catalyst (1 mol%) followed by successive
dilutions of the initial catalyst solution. No special precautions were taken during preparation of
the catalyst stock solutions and the catalysts were weighed and handled in air. The progress of
the reaction was monitored by gas chromatography and thin layer chromatography. GC‒MS was
used for the mass analysis of the products. Products were purified by column chromatography on
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1
100–200 mesh silica gel. The H NMR spectra were recorded on 400 MHz spectrometers in
CDCl3 using tetramethylsilane (TMS) as an internal standard. The 13C NMR spectra were
recorded on 100 MHz spectrometers in CDCl3. Chemical shifts are reported in parts per million
(δ) relative to tetramethylsilane as an internal standard. Coupling constant (J) values are reported
in Hertz (Hz). Splitting patterns of proton are described as s (singlet), d (doublet), dd (doublet of
1
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doublets), t (triplet) and m (multiplet). The products were confirmed by GC–MS, H and C
NMR spectroscopic analysis.
General Procedure for the Carbonylative Suzuki‒Miyaura coupling.
Aryl iodide (0.5 mmol), aryl boronic acid (0.75 mmol), K2CO3 (1.5 mmol, 207 mg) in 11 mL
anisole were added to a 100 mL stainless steel autoclave. The catalyst solution was subsequently
added and the autoclave was closed and flushed with nitrogen three times. The autoclave was
then pressurized with CO at ambient temperature. The reaction mixture was stirred with a
mechanical stirrer (450 rpm) at the desired temperature for the desired time. After completion of
reaction, the autoclave was cooled to room temperature and the pressure was carefully released.
The reactor vessel was washed with ethyl acetate (3 × 5 mL) to remove traces of product and
catalyst if present. The ethyl acetate layer was washed with water (2 × 5 mL), dried over Na2SO4
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and evaporated by rotary evaporation to obtain the crude product, which was either subjected to
GC analysis or in the case of substrate study purified by column chromatography (silica gel,
100–200 mesh size), with petroleum ether–ethyl acetate as the eluent to afford a pure product.
The products were confirmed by GC‒MS, 1H and 13C NMR spectroscopic analysis.
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Scale up Procedure
Iodobenzene (5 mmol, 1.02 g), phenylboronic acid (7.5 mmol, 0.91 g), K2CO3 (15 mmol, 2.07 g)
in 20 mL anisole were added to a 100 mL stainless steel autoclave. The catalyst solution was
subsequently added and the autoclave was closed and flushed with nitrogen three times. The
autoclave was then pressurized with CO at ambient temperature. The reaction mixture was
stirred with a mechanical stirrer (450 rpm) at the desired temperature for the desired time. After
cooling to room temperature, the pressure was carefully released. The reactor vessel was washed
with ethyl acetate (3 × 20 mL) to remove traces of product and catalyst if present. The ethyl
acetate layer was washed with water (2 × 20 mL), dried over Na2SO4 and evaporated by rotary
evaporation to obtain the crude product which was subsequently subjected to GC analysis.
4‒methoxybenzophenone (6b) 94.3 mg, yield 89%;
1H NMR (400 MHz, CDCl3) δH /ppm 7.84‒7.81 (m, 2H), 7.76‒7.73 (m, 2H), 7.55‒7.53 (m, 1H),
7.48‒7.43 (m, 2H), 6.93 (m, 2H), 3.87 (s, 3H). 13C{1H}NMR (100 MHz, CDCl3) δC /ppm 195.6,
163.2, 138.2, 132.5, 131.9, 130.0, 129.7, 128.1, 113.5, 55.4. GCMS (EI, 70 eV): m/z (%): 212
(40), 135 (100), 105 (14), 77 (36).
4‒aminobenzophenone (6c) 92.5 mg, yield 94%;
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1H NMR (400 MHz, CDCl3) δH /ppm 7.71‒7.68 (m, 4H), 7.54‒7.41 (m, 3H), 6.64 (d, 2H), 4.18
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(s, 2H). C{1H}NMR (100 MHz, CDCl3) δC /ppm 195.3, 151.0, 138.8, 132.9, 131.4, 129.5,
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128.0, 127.2, 113.6. GCMS (EI, 70 eV): m/z (%): 197 (39), 120 (100), 92 (24), 65 (25).
2‒aminobenzophenone (6d) 67.9 mg, yield 69%;
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1H NMR (400 MHz, CDCl3) δH /ppm 7.64‒7.61 (m, 2H), 7.53‒7.42 (m, 4H), 7.30‒7.24 (m,
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1H), 6.73 (d, 1H), 6.61‒6.56 (m, 1H), 6.10 (s, 2H). C{1H}NMR (100 MHz, CDCl3) δC /ppm
199.0, 150.9, 140.0, 134.5, 134.2, 131.0, 129.1, 128.0, 118.0, 116.9, 115.4. GCMS (EI, 70 eV):
m/z (%): 197 (65), 196 (100), 120 (48), 92 (31), 77 (36).
3‒nitrobenzophenone (6e) 90.8 mg, yield 80%;
1H NMR (400 MHz, CDCl3) δH /ppm 8.60 (s, 1H), 8.44‒8.41 (m, 1H), 8.14‒8.11 (m, 1H), 7.78
13
(d, 2H), 7.71‒7.62 (m, 2H), 7.51 (t, 2H). C{1H}NMR (100 MHz, CDCl3) δC /ppm 194.1,
148.0, 139.0, 136.2, 135.4, 133.3, 130.0, 129.6, 128.7, 126.7, 124.7. GCMS (EI, 70 eV): m/z
(%): 227 (23), 105 (100), 150 (11), 77 (50).
4‒cyanobenzophenone (6f) 91.0 mg, yield 88%;
1H NMR (400 MHz, CDCl3) δH /ppm 7.87‒7.84 (m, 2H), 7.78‒7.75 (m, 2H), 7.65‒7.60 (m,
13
1H), 7.53‒7.47 (m, 2H). C{1H}NMR (100 MHz, CDCl3) δC /ppm 195.0, 141.1, 136.2, 133.3,
132.1, 130.2, 130.0, 128.6, 118.0, 115.6. GCMS (EI, 70 eV): m/z (%): 207 (38), 130 (27), 105
(100), 77 (47).
(4‒fluorophenyl)(1‒naphthalenyl)methanone (6g) 112.5 mg, yield 90%;
1H NMR (400 MHz, CDCl3) δH /ppm 8.04 (d, 2H), 8.00 (d, 2H), 7.93‒7.87 (m, 3H), 7.58‒7.46
(m, 4H), 7.12 (t, 2H). 13C{1H}NMR (100 MHz, CDCl3) δC /ppm 196.4, 165.8 (JC‒F = 254 Hz),
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136.0, 134.5 (2C), 133.7, 133.0 (JC‒F = 10 Hz, 2C), 131.3, 130.8, 128.4, 127.5, 127.3, 126.5,
125.5, 124.3, 115.6 (JC‒F = 21 Hz, 2C). GCMS (EI, 70 eV): m/z (%): 250 (88), 155 (77), 127
(100), 95 (61), 75 (24).
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(4‒aminophenyl)(4‒chlorophenyl)methanone (6h) 93.5 mg, yield 81%;
1H NMR (400 MHz, CDCl3) δH /ppm 7.67 (d, 2H), 7.65 (d, 2H), 7.41 (d, 2H), 6.65 (d, 2H), 4.17
13
(s, 2H). C{1H}NMR (100 MHz, CDCl3) δC /ppm 193.9, 151.0, 137.6, 137.0, 132.8, 130.9,
128.3, 126.9, 113.6. GCMS (EI, 70 eV): m/z (%): 231 (10), 120 (40), 92 (8), 65 (8).
4‒ (3‒methylbenzoyl)benzonitrile (6i) 99.5 mg, yield 90%
1H NMR (400 MHz, CDCl3) δH/ppm 7.84 (d, 2H), 7.76 (d, 2H), 7.59‒7.35 (m, 4H), 2.41 (s,
13
3H). C{1H}NMR (100 MHz, CDCl3) δC /ppm 195.2, 141.3, 138.5, 136.3, 134.1, 132.1, 130.4,
130.2, 128.4, 127.3, 118.0, 115.5, 21.3. GCMS (EI, 70 eV): m/z (%): 221 (31), 119 (100), 91
(36), 65 (18).
(4‒methoxyphenyl)(m‒tolyl)methanone (6j) 97.2 mg, yield 86%;
1H NMR (400 MHz, CDCl3) δH/ppm 7.81 (d, 2H), 7.57‒7.33 (m, 4H), 6.94 (d, 2H), 3.86 (s,
13
3H), 2.40 (s, 3H). C{1H}NMR (100 MHz, CDCl3) δC /ppm 195.9, 163.1, 138.2, 138.0, 132.7,
132.5, 130.2, 130.1, 127.9, 127.0, 113.5, 55.4, 21.3. GCMS (EI, 70 eV): m/z (%): 226 (33), 135
(100), 119 (15), 91 (17), 77 (18).
(4‒fluorophenyl)(3‒nitrophenyl)methanone (6k) 104.1 mg, yield 85%;
1H NMR (400 MHz, CDCl3) δH/ppm 8.56 (s, 1H), 8.44‒8.41 (m, 1H), 8.10‒8.08 (m, 1H), 7.85‒
7.80 (m, 2H), 7.70 (t, 1H), 7.24‒7.16 (m, 2H). 13C{1H}NMR (100 MHz, CDCl3) δC /ppm 192.6,
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165.8 (JC‒F = 255 Hz), 148.03, 138.8, 135.2, 132.7 (JC‒F = 10 Hz), 132.4, 129.7, 126.7, 124.5,
116 (JC‒F = 22 Hz). GCMS (EI, 70 eV): m/z (%): 245 (23), 123 (100), 95 (39), 75 (13).
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Phenyl(2‒pyridinyl)methanone (6l) 64.9 mg, yield 71%;
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1H NMR (400 MHz, CDCl3) δH/ppm 8.68 (d, 2H), 8.04‒7.98 (m, 3H), 7.87‒7.82 (m, 1H), 7.57‒
7.52 (m, 1H), 7.46‒7.41 (m, 3H). 13C{1H}NMR (100 MHz, CDCl3) δC /ppm 193.8, 154.9, 148.5,
137.0, 136.2, 132.9, 130.9, 128.1, 126.1, 124.6. GCMS (EI, 70 eV): m/z (%): 183 (40), 155 (77),
105 (80), 77 (100), 51 (32).
2‒benzoylthiophene (6m) 82.8 mg, yield 88%;
1H NMR (400 MHz, CDCl3) δH/ppm 7.86‒7.83 (d, 2H), 7.71‒7.70 (m, 1H), 7.71‒7.55 (m, 2H),
7.50‒7.46 (m, 2H), 7.16‒7.14 (m, 1H). 13C{1H}NMR (100 MHz, CDCl3) δC /ppm 188.2, 143.5,
138.0, 134.8, 134.2, 132.2, 129.1, 128.3, 127.9. GCMS (EI, 70 eV): m/z (%): 188 (60), 111
(100), 105 (39), 77 (40), 51 (18).
3‒benzoylthiophene (6n) 80 mg, yield 85%;
1H NMR (400 MHz, CDCl3) δH/ppm 7.91‒7.90 (m, 1H), 7.84‒7.81 (m, 2H), 7.59‒7.54 (m, 2H),
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7.49‒7.45 (t, 2H), 7.38‒7.35 (m, 1H). C{1H}NMR (100 MHz, CDCl3) δC /ppm 190.0, 141.2,
138.5, 133.9, 132.3, 129.3, 128.5, 128.3, 126.2. GCMS (EI, 70 eV): m/z (%): 188 (61), 111
(100), 105 (40), 77 (39), 51 (19).
Thiophen‒2‒yl(thiophen‒3‒yl)methanone (6o) 77.7 mg, yield 80%;
1H NMR (400 MHz, CDCl3) δH/ppm 8.07‒8.06 (m, 1H), 7.77‒7.76 (m, 1H), 7.68‒7.67 (m, 1H),
7.60‒7.59 (m, 1H), 7.39‒7.36 (m, 1H), 7.17‒7.14 (m, 1H). 13C{1H}NMR (100 MHz, CDCl3) δC
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/ppm 181.2, 143.9, 141.0, 133.6, 133.5, 132.2, 128.1, 127.9, 126.3. GCMS (EI, 70 eV): m/z (%):
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194 (46), 166 (6), 111 (100), 83 (20), 45 (4).
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(4‒methoxyphenyl)(thiophen‒2‒yl)methanone (6p) 1H NMR (400 MHz, CDCl3) δH/ppm 7.88
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(dd, J = 8.8, 1.8 Hz, 2H), 7.71 – 7.58 (m, 2H), 7.27 – 7.11 (m, 1H), 7.03 – 6.89 (m, 2H), 3.87 (s,
13
3H). C{1H}NMR (100 MHz, CDCl3) δC /ppm 186.9, 163.0, 143.7, 134.0, 133.4, 131.6, 130.6,
127.7, 113.6, 55.4. GCMS (EI, 70 eV): m/z (%): 218 (57), 187 (12), 135 (100), 111 (38), 92
(13), 77 (22).
(4‒chlorophenyl)(thiophen‒2‒yl)methanone (6q) 1H NMR (400 MHz, CDCl3) δH/ppm 7.87 –
7.76 (m, 2H), 7.72 (d, J = 5.0 Hz, 1H), 7.60 (d, J = 3.7 Hz, 1H), 7.51 – 7.39 (m, 2H), 7.15 (t, J =
4.4 Hz, 1H).13C{1H}NMR (100 MHz, CDCl3) δC /ppm 186.97, 143.20, 138.71, 136.38, 134.85,
134.62, 130.62, 128.79, 128.13. GCMS (EI, 70 eV): m/z (%): 222 (32), 187 (12), 139 (25), 111
(100), 75 (14).
AUTHOR INFORMATION
Corresponding Author
*Email: bm.bhanage@gmail.com; bm.bhanage@ictmumbai.edu.in.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGEMENT
P. G. is greatly thankful to the Council of Scientific and Industrial Research (CSIR), New Delhi,
India for providing Junior Research Fellowship (JRF).
ASSOCIATED CONTENT
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Copies of H and C NMR of the products. This material is available free of charge via the
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Internet at http://pubs.acs.org.
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REFERENCES
(1) Brunet, J. –J.; Chauvin, R. Chem. Soc. Rev. 1995, 24, 89‒95.
(2) (a) Ishiyama, T.; Kizaki, H.; Miyaura, N.; Suzuki, A. Tetrahedron Lett. 1993, 34, 7595‒7598.
(b) Ishiyama, T.; Kizaki, H.; Hayashi, T.; Suzuki, A.; Miyaura, N. J. Org. Chem. 1998, 63,
4726‒4731. (c) Mingji, D.; Liang, B.; Wang, C.; You, Z.; Xiang, J.; Dong, G.; Chen, J.; Yang,
Z. Adv. Synth. Catal. 2004, 346, 1669‒1673. (d) Zheng, S.; Xu, L.; Xia, C. Appl.
Organometal. Chem. 2007, 21, 772–776. (e) Zheng, G.; Wang, P.; Cai, M. Chin. J. Chem.
2009, 27, 1420‒1426. (f) Tambade, P. J.; Patil, Y. P.; Panda, A. G.; Bhanage, B. M. Eur. J.
Org. Chem. 2009, 3022‒3025. (g) Cai, M.; Zheng, G.; Zha, L.; Peng, J. Eur. J. Org. Chem.
2009, 1585‒1591. (h) Khedkar, M. V.; Tambade, P. J.; Qureshi, Z. S.; Bhanage, B. M. Eur. J.
Org. Chem. 2010, 6981–6986. (i) Cai, M.; Peng, J.; Hao, W.; Ding, G. Green Chem. 2011, 13,
190‒196. (j) Li, H.; Yang, M.; Qi, Y.; Xue, J. Eur. J. Org. Chem., 2011, 2662‒2667. (k)
Qureshi, Z. S.; Deshmukh, K. M.; Tambade, P. J.; Bhanage, B. M. Synthesis 2011, 2, 243‒
250. (l) Niu, J. –R.; Huo, X.; Zhang, F. –W.; Wang, H. –B.; Zhao, P.; Hu, W. –Q.
ChemCatChem 2013, 5, 349‒354. (m) Zhou, Q.; Wei, S.; Han, W. J. Org. Chem. 2014, 79,
1454‒1460. (n) Niu, J.; Liu, M.; Wang, P.; Long, Y.; Xie, M.; Li, R.; Ma, J. New J. Chem.
2014, 38, 1471‒1476.
(3) See reviews: (a) Herrmann, W. A.; Bohm, V. P. W.; Reisinger, C. ‒P. J. Organomet. Chem.
1999, 576, 23‒41. (b) Dupont, J.; Pfeffer, M.; Spencer, J. Eur. J. Inorg. Chem. 2001, 1917‒
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Page 18 of 19
1
2
3
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5
6
7
8
9
1927. (c) Catellani, M. Synlett 2003, 3, 298‒313. (d) Bedford, R. B. Chem. Commun. 2003,
1787‒1796. (e) Bedford R. B.; Cazin, C. S. J.; Holder, D. Coord. Chem. Rev. 2004, 248,
2283‒2321. (f) Farina, V. Adv. Synth. Catal. 2004, 346, 1553‒1582. (g) Beletskaya, I. P.;
Cheprakov, A. V. J. Organomet. Chem. 2004, 689, 4055‒4082. (h) Dupont, J.; Consorti, C.
S.; Spencer, J. Chem. Rev. 2005, 105, 2527‒2571. (i) Alacid, E.; Alonso, D. A.; Botella, L.;
Najera, C.; Pacheco, M. C. Chem. Record. 2006, 6, 117‒132. (j) Palladacycles: Synthesis,
Characterization and Applications; Dupont, J., Pfeffer, M., Eds.; Wiley‒VCH, 2008. (k)
Dupont, J.; Flores, F. R. Handbook of Green Chemistry; Anastas, P. T., Crabtree, R. H., Eds.;
Wiley‒VCH, 2009; Vol. 1, pp 319‒342. (l) Alonso, D. A.; Najera, C. Chem. Soc. Rev. 2010,
39, 2891‒2902. (m) Mo, D. ‒L.; Zhang, T. ‒K.; Ge, G. ‒C.; Huang, X. ‒J.; Ding, C. ‒H.; Dai,
L. ‒X.; Hou, X. ‒L. Synlett 2014, 25, 2686‒2702. (n) Bruneau, A.; Roche, M.; Alami, M.;
Messaoudi, S. ACS Catal. 2015, 5, 1386‒1396.
10
11
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13
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25
26
27
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53
54
55
56
57
58
59
60
(4) Schnyder, A.; Indolese, A. F.; Studer, M.; Blaser, H. –U. Angew. Chem. Int. Ed. 2002, 41,
3668‒3671.
(5) (a) Bedford, R. B.; Cazin, C. S. J.; Hazelwood, S. L. Angew. Chem. Int. Ed. 2002, 41, 4120‒
4122. (b) Bedford, R. B.; Hazelwood, S. L.; Limmert, M. E.; Albisson, D. A.; Draper, S. M.;
Scully, P. N.; Coles, S. J.; Hursthouse, M. B. Chem. Eur. J. 2003, 9, 3216‒3227. (c) Bedford,
R. B.; Betham, M.; Coles, S. J.; Frost, R. M.; Hursthouse, M. B. Tetrahedron 2005, 61, 9663‒
9669.
(6) (a) Grigg, R.; Zhang, L.; Collard, S.; Keep, A. Tetrahedron Lett. 2003, 44 6979‒6982. (b)
Fairlamb, I. J. S.; Grant, S.; McCormack, P.; Whittall, J. Dalton Trans. 2007, 859‒865. (c)
Begouin, A.; Queiroz, M. –J. R. P. Eur. J. Org. Chem. 2009, 2820‒2827. (d) Chen, G.; Leng,
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5
6
Y.; Yang, F.; Wang, S.; Wu, Y. Chin. J. Chem. 2013, 31, 1488‒1494. (e) Friis, S. D.;
Skrydstrup, T. Buchwald, S. L. Org. Lett. 2014, 16, 4296‒4299.
7
8
9
(7) (a) Khedkar, M. V.; Sasaki, T.; Bhanage, B. M. ACS Catal. 2013, 3, 287‒293. (b) Gadge, S.
T.; Bhanage, B. M. J. Org. Chem. 2013, 78, 6793‒6797. (c) Chavan, S. P.; Bhanage, B. M.
Tetrahedron Lett. 2014, 55, 1199‒1202. (d) Gadge, S. T.; Bhanage, B. M. Org. Biomol.
Chem. 2014, 12, 5727‒5732. (e) Gadge, S. T.; Kusumawati, E. N.; Harada, K.; Sasaki, T.;
Nishio‒Hamaned, D.; Bhanage, B. M. J. Mol. Catal. A: Chem. 2015, 400, 170‒178. (f)
Chavan, S. P.; Bhanage, B. M. Eur. J. Org. Chem. 2015, 2405–2410. (g) Gadge, S. T.;
Bhanage, B. M. RSC Adv. 2014, 4, 10367‒10389. (h) Satapathy, A.; Gadge, S. T.;
Kusumawati, E. N.; Harada, K.; Sasaki, T.; Nishio‒Hamane, D.; Bhanage, B. M. Catal. Lett.
2015, 145, 824‒833. (i) Gautam, P.; Bhanage, B. M. Catal. Sci. Tech. 2015, DOI:
10.1039/C5CY00691K.
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51
52
53
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55
56
57
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59
60
(8) Bumagin, N. A.; Ponomaryov, A. B.; Beletskaya, I. P. Tetrahedron Lett. 1985, 26, 4819‒
4822.
(9) Malhotra, R.; Dey, T. K.; Basu, S.; Hajra, S. Org. Biomol. Chem. 2015, 13, 3211‒3219.
(10) Schnyder, A.; Aemmer, T.; Indolese, A. F.; Pittelkow, U.; Studer, M. Adv. Synth. Catal.
2002, 344, 495‒498 and references therein.
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