Microwave-promoted cross-coupling of acid chlorides with arylboronic acids: a convenient method for preparing aromatic ketones

Article abstract of DOI:10.1016/j.tet.2006.09.055

Simple catalytic systems for cross-coupling reactions of acyl chlorides with arylboronic acids under microwave conditions were tested. Microwave irradiation facilitated the reaction course. Mild reaction conditions afford the symmetrical and unsymmetrical aryl ketones in reasonable to high yields within a short time. A wide range of substrates bearing an electron-donating or an electron-withdrawing substituent on aryl ring of acid chloride as well as on boronic acid were examined and high yields of ketones were produced.

Full text of DOI:10.1016/j.tet.2006.09.055

Tetrahedron 62 (2006) 11675–11678
Microwave-promoted cross-coupling of acid chlorides
with arylboronic acids: a convenient method for
preparing aromatic ketones
*
ˇ
´
Viera Pol ꢀa ꢁc kov ꢀa , Stefan Toma and Iveta Augustınov ꢀa
Faculty of Natural Sciences, Comenius University, Bratislava, SK-842 15 Bratislava, Slovakia
Received 27 June 2006; revised 4 September 2006; accepted 15 September 2006
Available online 19 October 2006
Abstract—Simple catalytic systems for cross-coupling reactions of acyl chlorides with arylboronic acids under microwave conditions were
tested. Microwave irradiation facilitated the reaction course. Mild reaction conditions afford the symmetrical and unsymmetrical aryl ketones
in reasonable to high yields within a short time. A wide range of substrates bearing an electron-donating or an electron-withdrawing substit-
uent on aryl ring of acid chloride as well as on boronic acid were examined and high yields of ketones were produced.
Ó 2006 Elsevier Ltd. All rights reserved.
1
. Introduction
aryl iodides and aryl bromides, and especially microwave
irradiation,
chlorides.
1
6–18
which also promotes the reaction of aryl
Aromatic ketones are important building blocks for a large
number of natural products and are most frequently prepared
by a Friedel–Crafts type reaction. Suzuki cross-coupling
reaction is a very attractive method for the formation of car-
bon–carbon single bonds between boronic acids and alkenyl
or arylhalides, which is demonstrated in several review arti-
1
The main goal of our work was to examine if Suzuki–
Miyaura coupling of arylboronic acids with acyl chlorides
can be promoted by microwave irradiation. The second aim
was also to find out if this reaction can be used also for the
preparation of unusually substituted aryl ketones.
2
3
–5
cles devoted to this field of chemistry. The cross-coupling
reaction between arylboronic acids, carbon monoxide
(1 atm), and aryl iodides in the presence of palladium cata-
lyst and base also provided biaryl ketones in high yields.
6
2. Results and discussion
7
At the beginning of our work we decided to examine the
effect of the catalytic system (Pd source and base) on the
course of Suzuki cross-coupling of phenylboronic acid with
4-nitrobenzoyl chloride (Scheme 1, Table 1). While our work
was in progress an interesting paper appeared, describing a
very rapid reaction of arylboronic acids with different acyl
On the other hand in the recent review are just three
papers,
8
–10
describing Pd-catalyzed reaction of different
acyl chlorides with boronic acids. To get good yields of the
product it is necessary to heat the reaction mixture for sev-
eral hours up to 100 C, or to prolong the reaction time up
to several days. This was also the case when aliphatic acid
chlorides as well as unsaturated acyl chlorides were used as
Coupling of substituted benzoyl chlorides
with phenylboronic acid proceeded at room temperature in
a short time in the case when equivalent amount of copper(I)
thiophene-2-carboxylate was used as a co-catalyst. Several
non-traditional methods have been developed for the Suzuki–
Miyaura synthesis of unsymmetrical biaryls such as high
ꢀ
1
9
chlorides by grinding reactants with PdCl
We decided to test this catalytic system in toluene under
MWI too. Catalytic systems PdCl and Na CO (entry 1)
and Na CO .
2
2 3
1
1,12
the substrates.
2
2
3
and Pd(OAc)
MWI.
and K
CO
(entry 2) was not effective under
2
2
3
1
3
O
O
5
mol % [Pd]
14,15
intensity ultrasound,
which accelerates the reactions of
B(OH)2
+
3 eq. Base
Cl
Toluene
MWI 10 min
O N
NO2
2
Keywords: Palladium; Cross-coupling reaction; Boronic acid; Acyl chlo-
rides; Ketones; Microwave irradiation.
1
2
3
*
Corresponding author. E-mail: polackova@fns.uniba.sk
Scheme 1.
0
040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.09.055

11676
V. Pol aꢀ cꢁ kov aꢀ et al. / Tetrahedron 62 (2006) 11675–11678
Table 1. Effect of catalyst systems on the Suzuki–Miyaura coupling of
phenylboronic acid with 4-nitrobenzoyl chloride in toluene, under MWI,
reaction time 10 min
results are very dependent on the quality of potassium phos-
phate, which is in accord with Ref. 11.
Entry
[Pd]
Base
Na CO
Yield 3 (%)
Our next aim was to test the applicability of the catalytic sys-
tem Pd(PPh ) and Cs CO for Suzuki coupling of different
arylboronic acids with various acid chlorides. Results are
summarized in Table 2.
3
4
2
3
1
2
3
4
5
6
PdCl
Pd(OAc)
Pd[PPh
PdCl
PdCl
PdCl
2
2
3
n.d.
n.d.
93 (13)a
91 (79)
2
K
Cs
2
CO
CO
3
a
3
]
4
2
3
2
2
2
(PPh
(PPh
(PPh
3
)
3
)
3
)
2
2
2
K
K
K
3
PO
PO
PO
4
4
4
$1.5H
$1H
2
O
a
3
3
2
O
35 (25)
8
The present methodology is important because it provided
the ketones in high yields within a short reaction time
a
On oil bath for 10 min.
(10 min). The reactions of acid chlorides bearing electron-
withdrawing (entries 2, 3) and electron-donating (entries 8,
9) groups proceed in good to high yields. Heteroaromatic
acid chloride such as 2-furyl (entries 19, 20) afforded the
corresponding ketones in 72 and 74% isolated yields. Alkyl-
and alkenyl-acid chlorides (entries 14, 21) gave no desired
product. The reactions with arylboronic acids bearing elec-
tron-donating groups (entries 5–7, 10–12) gave reasonable
On the other hand Pd(PPh ) and Cs CO (entry 3) was
3
4
2
3
found to be the best catalyst system because the cross-
coupling product 3 was isolated in 93% yield. Control exper-
iment, without microwave irradiation gave only 13% yield
of product 3. We decided to test also PdCl (PPh ) and
2
3 2
K PO as catalyst system (entries 4–6), and we found that
3
4
3 4
Table 2. Effect of the substituent on acid chlorides and of arylboronic acids on the microwave-promoted Suzuki-type coupling catalyzed by Pd(PPh ) in toluene
with Cs
2
CO
3
as the base, rt, 10 min
Entry
Arylboronic acid
Acid chloride
Ketone
Product
Yield (%)
O
O
B(OH)2
B(OH)2
Cl
21
1
2
4
68
O
O
Cl
2
93
0
3
NO2
CF3
CF3
O N
2
O
O
O
O
B(OH)2
Cl
2
2
2
3
4
5
5
90
18
F3C
O
B(OH)2
Cl
O
2
F3C
B(OH)2
Cl
2
60
3
4
5
6
H C
3
H C
NO2
O N
3
2
O
O
B(OH)2
Cl
2
6
7
8
9
7
8
57
49
73
60
80
74
H C
3
F3C
F3C
CH3
O
O
B(OH)2
Cl
O
21
CH O
3
OCH3
O
B(OH)2
Cl
2
2
1
1
8
CH O
OCH3
CH3
3
O
O
B(OH)2
B(OH)2
Cl
9
H C
3
O
O
O
O
Cl
Cl
21
22
1
1
0
1
9
H C
3
CH3
CH3
B(OH)2
10
CH3
(
continued)

V. Pol aꢀ cꢁ kov aꢀ et al. / Tetrahedron 62 (2006) 11675–11678
11677
Table 2. (continued)
Entry
Arylboronic acid
Acid chloride
Ketone
Product
Yield (%)
O
O
CH3
CH3
B(OH)2
CH3
Cl
22
1
1
1
2
3
4
11
61
41
0
O
O
B(OH)2
Cl
22
11
12
O
B(OH)2
B(OH)2
O
Cl
O
O
O
Cl
25
77
1
5
6
13
13
O
Cl
B(OH)2
2
2
5
2
1
74
O
O
O
O
B(OH)2
B(OH)2
Cl
Cl
1
1
7
8
14
15
80
26
50
H C
3
O
O
O
S
B(OH)2
S
S
2
7
8
19
16
74
Cl
O
B(OH)2
S
2
2
2
0
1
17
18
72
0
Cl
O
H C
3
O
B(OH)2
Cl
to high yield of the cross-coupling products. A sterically
hindered 2-methylphenylboronic acid (entry 12) gave 61%
yield of the product 11. On the other hand, the reaction of
benzoyl chloride with arylboronic acid bearing electron-
4. Experimental
4.1. General
withdrawing CF -group (entry 4) gave only 18% yield of
3
All microwave experiments were carried out in the Initiator-
Biotage reactor (power setting 260 W, 10 min at 98 C). The
ꢀ
reactions were performed in an argon atmosphere. All the
4
-(trifluoromethyl)benzophenone 5, but this product 5 was
obtained in 90% yield when phenylboronic acid with 4-(tri-
fluoromethyl)benzoyl chloride was used (entry 3).
1
products were analyzed by H NMR and GC–MS and
compared with the authentic samples of the products. The
1
H NMR spectra were measured at 300 MHz on a Varian
Gemini spectrometer in CDCl with tetramethylsilane as
3. Conclusion
3
an internal standard. GC–MS measurements were performed
on a gas chromatograph Trace GC 2000 Series Thermoquest
CE Instruments with a flame ionization detector and a
Voyager GC–MS Thermoquest Finnigan in SCAN-mode.
Mass spectral data were obtained by cyclic scanning from
15 to 350 mass units with a cyclic time of 0.2 s. Transfer
In summary we found that microwave irradiation had posi-
tive effect on the Suzuki reaction of acid chlorides with aryl-
boronic acids. Catalytic system (Pd(PPh ) and Cs CO )
under microwave irradiation gave ketones in good to high
yields in moist toluene (water content in toluene was not
controlled). The present methodology is important because
it provides a new convenient method for the synthesis of
diaryl ketones.
3
4
2
3
ꢀ
line temperature was 200 C. Quadrupole conditions were
as follows: electron energy 70 eV, emission current
ꢀ
150 mA, and ion source temperature 150 C. Each GC

11678
V. Pol aꢀ cꢁ kov aꢀ et al. / Tetrahedron 62 (2006) 11675–11678
peak was inspected for constancy of MS pattern in order to
detect possible overlapping compounds and to measure their
retention time. Melting points were determined on a Kofler
hot stage.
References and notes
1. Friedel–Crafts and Related Reactions; Olah, G. A., Ed.;
Interscience: New York, NY, 1964; Vol. 3.
2
. Miyaura, N.; Yanagi, T.; Suzuki, A. Synth. Commun. 1981, 11,
513–519.
4
.2. Reactions under thermal heating
3
. Suzuki, A. Pure Appl. Chem. 1991, 63, 419–422.
Base Cs CO (1.5 mmol, 0.488 g) and Pd(PPh3)4
2
4. Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457–2483.
5. Miyaura, N. Advances in Metal–organic Chemistry;
Liebeskind, L. S., Ed.; Jai: London, 1999; Vol. 6, pp 187–243.
6. Ishiyama, T.; Kizaki, H.; Miyaura, N.; Suzuki, A. Tetrahedron
Lett. 1993, 34, 7595–7598.
7. Kotha, S.; Lahiri, K.; Kashinath, D. Tetrahedron 2002, 58,
9633–9695.
8. Cho, C. S.; Itotani, K.; Uemura, S. J. Organomet. Chem. 1993,
443, 253–259.
9. Bumagin, N. A.; Korolev, D. N. Tetrahedron Lett. 1999, 40,
3057–3060.
10. Haddach, M.; McCarthy, J. R. Tetrahedron Lett. 1999, 40,
3109–3112.
11. Urawa, Y.; Ogura, K. Tetrahedron Lett. 2003, 44, 271–273.
12. Urawa, Y.; Nishiura, K.; Souda, S.; Ogura, K. Synthesis 2003,
3
(
5 mol %, 0.029 g) catalyst were added to the solution of
phenylboronic acid (0.5 mmol, 0.061 g) and 4-nitrobenzoyl
chloride (1 mmol 0.186 g) in 7 mL solvent of toluene. The
ꢀ
reaction mixture was heated on the oil bath at 98 C for
0 min. The solution was washed with sodium bicarbonate,
1
water, and brine, and dried over anhydrous sodium sulfate.
After evaporation of the solvent, product 3 was separated
by column chromatography (silica gel, 1:9 ethyl acetate–
hexanes) and identified by spectroscopic analyses. Com-
ꢀ
1
pound 3: 13%; Mp 137–138 C; H NMR (300 MHz,
CDCl ): d 7.52 (2H, t, J¼8.0 Hz), 7.64 (1H, d, J¼7.6 Hz),
3
7
.81 (2H, d, J¼7.9 Hz), 7.94 (2H, d, J¼8.4 Hz), 8.35 (2H,
1
d, J¼8.4 Hz). H NMR spectroscopy and melting point
2
0
were compared with the authentic samples of the product.
.3. Reactions under microwave irradiation
Base Cs CO (1.5 mmol, 0.488 g) and Pd(PPh ) (5 mol %,
2
882–2885.
13. Nishihara, Y.; Inoue, Y.; Fujisawa, M.; Takagi, K. Synlett 2005,
309–2312.
4
2
14. Pol ꢀa ꢁc kov ꢀa , V.; Hu ˇt ka, M.; Toma, S. Ultrason. Sonochem. 2005,
ˇ
2
3
3 4
0
.029 g) catalyst were added to the solution of phenylboro-
nic acid (0.5 mmol, 0.061 g) and 4-nitrobenzoyl chloride
1 mmol, 0.186 g) in 7 mL solvent of toluene. The reaction
12, 99–102.
15. Cravotto, G.; Beggiato, M.; Penoni, A.; Palmisano, G.; Tollari,
S.; Leveque, J. M.; Bonrath, W. Tetrahedron Lett. 2005, 46,
2267–2271.
16. Bedford, R. B.; Butts, C. P.; Hurst, T. E.; LindstrTm, P. Adv.
Synth. Catal. 2004, 346, 1627–1630.
17. Kappe, C. O. Angew. Chem., Int. Ed. 2004, 43, 6250–6284.
18. Leadbeater, N. E.; Marco, M. J. Org. Chem. 2003, 68, 888–892.
19. Bandgar, B. P.; Patil, A. V. Tetrahedron Lett. 2005, 46, 7627–
7630.
(
mixture was microwave-irradiated for 10 min. The solution
was washed with sodium bicarbonate, water, and brine, and
dried over anhydrous sodium sulfate. After evaporation of
the solvent, product 3 was separated by column chromato-
graphy (silica gel, 1:9 ethyl acetate–hexanes) and identified
by spectroscopic analyses. Compound 3: 93%; Mp 137–
ꢀ
38 C; H NMR (300 MHz, CDCl ): d 7.52 (2H, t,
3
1
1
J¼8.0 Hz), 7.64 (1H, d, J¼7.6 Hz), 7.81 (2H, d, J¼7.9 Hz),
20. Suzuki, H.; Murashima, T. J. Chem. Soc., Perkin Trans. 1 1994,
903–908.
21. Hwang, J. P.; Prakash, G. K. S.; Olah, G. A. Tetrahedron 2000,
56, 7199–7203.
1
7
spectroscopy and melting point were compared with the
.94 (2H, d, J¼8.4 Hz), 8.35 (2H, d, J¼8.4 Hz). H NMR
2
0
authentic samples of the product.
2
2. Wang, D.; Zhang, Zh. Org. Lett. 2003, 24, 4645–4648.
The same procedure was used for preparation of product
4–18. All products were found to be identical ( H NMR
data) with the data described in literature.
23. Findeis, M. A.; Kaiser, E. T. J. Org. Chem. 1989, 54, 3478–
3482.
24. Leigh, W. J.; Arnold, D. R.; Humphreys, R. W. R.; Wong, Ch. P.
Can. J. Chem. 1980, 58, 2537–2549.
1
2
0–28
2
5. Asao, N.; Aikawa, H.; Yamamato, Y. J. Am. Chem. Soc. 2004,
126, 7458–7459.
Acknowledgements
2
6. Utley, J. H. P.; Rozenberg, G. G. Tetrahedron 2002, 58, 5251–
5265.
Our thanks are due to Dr. B. Horvath and his staff for NMR
measurements. This work was carried out under auspices of
COST D32/0010 action and financial support of the Ministry
of Education of Slovak Republic (VTP 1012/2003) is greatly
acknowledged.
27. Goossen, L. J.; Ghosh, K. Eur. J. Org. Chem. 2002, 19, 3254–
3267.
28. Jeon, K. O.; Jun, J. H.; Yn, J. S.; Lee, Ch. K. J. Heterocycl.
Chem. 2003, 40, 763–772.