Palladium-catalyzed C-C bond formation from β-chloroacroleins in aqueous media

Article abstract of DOI:10.1055/s-2001-12775

The Suzuki coupling of several β-chloroacroleins with arylboronic acids was successfully performed with good yields under mild conditions (3 h at 45°C) in aqueous media without any organic co-solvent.

Full text of DOI:10.1055/s-2001-12775

PAPER
755
Palladium-Catalyzed C-C Bond Formation from -Chloroacroleins in
Aqueous Media
P
alladium-Cat
t
alyze
d
é
C-
C
Bond
p
Formation
f
r
h
omb-Chlor
o
a
acroleins in
n
A
queous
M
i
e
dia e Hesse, Gilbert Kirsch*
Laboratoire de Chimie Organique, Groupe de Synthèse Organique et Hétérocyclique, Faculté des Sciences, Ile du Saulcy, 57045 Metz Ce-
dex, France
E-mail: kirsch@sciences.univ-metz.fr
Received 30 January 2001; revised 2 February 2001
Dedicated to Prof. Emeritus D. Cagniant on the occasion of her 80th birthday
rabutylammonium bromide in water, without organic co-
Abstract: The Suzuki coupling of several -chloroacroleins with
solvent, considerably enhances the rate of the Suzuki cou-
pling of aryl bromides with aryl and vinyl boronic acids.
arylboronic acids was successfully performed with good yields un-
der mild conditions (3 h at 45°C) in aqueous media without any or-
ganic co-solvent.
However, to our knowledge, few publications report
Key words: aqueous media, boronic acids -chloroacroleins, pal- cross-coupling under those conditions. Recently, 5-aryl
ladium catalysis, Suzuki coupling
furfurals and aryl thiophene-2-carboxaldehydes were syn-
thesized via palladium-catalyzed C-C bond formation in
aqueous media at room temperature.9 We were greatly in-
In 1981, Suzuki1 described the palladium-catalyzed cross-
coupling reaction between phenylboronic acids and aryl
halides. This reaction constitutes a powerful and general
methodology for the formation of C-C bonds. The avail-
ability of the reagents and the mild experimental condi-
tions all contribute to the versatility of this reaction.2 This
method of C-C bond formation offers several advantages:
boronic acids are largely unaffected by the presence of
water and tolerate a broad range of functional groups.
Moreover, the inorganic byproduct is non-toxic and can
be easily removed from the reaction mixture, thereby
making the Suzuki reaction suitable not only for laborato-
ry scale but also for industrial processes.
terested in this mild procedure and, as a part of our syn-
thetic project, focussed on the synthesis of new tetracyclic
systems, we examined the behaviour of a series of -chlo-
roacroleins. Those compounds were coupled with a wide
variety of boronic acids in the presence of 2 mol% of pal-
ladium(II) acetate, tetrabutylammonium bromide and po-
tassium carbonate in water (Scheme 2). No organic
solvents in addition to water were used. All reactions were
almost complete after 3 h at 45°C.
Using water as solvent is safe and inexpensive. Therefore,
methods for carrying out organic reactions in aqueous me-
dia are of heightened interest. During the past ten years,
palladium-catalyzed cross-coupling reactions have been
imported into aqueous media, but most of the time water
was only used as co-solvent.3–6 Jeffery7 has shown that
palladium-catalyzed cross-coupling reactions can be per-
formed in water alone, without any organic solvent, under
mild conditions, and in the presence of a tetraalkylammo-
nium salt (Scheme 1). In 1997, Badone8 found that tet-
Scheme 2
Although aryl chlorides are less reactive due to the higher
energy required for the oxidative insertion of the palladi-
um catalyst into the C-Cl bond,10 Suzuki coupling of vinyl
chlorides is almost easier. Moreover, the presence of an
electron-withdrawing group leads to an increase of the re-
action rate allowing the use of derivatives such as 3-chlo-
roenones.11 Thus, -chloroacroleins are highly activated
substrates and constitute good partners for coupling. They
were prepared with good to excellent yields by a Vilsmei-
er-Haack-Arnold12 reaction on the corresponding ketones.
This kind of compounds, widely used for the synthesis of
heterocyclic systems,13 also gives good yields in coupling
with boronic acids under mild conditions (Table).
Ph
5% [Pd(OAc)2, 2PPh3]
PhI
+
CO2Me
CO2Me
K2CO3 or Na2CO3
QX, H2O
4
4
4
4
Easy access to -chloroacroleins and boronic acids may
give this methodology a very broad application.
Scheme 1
Pd(OAc)2 was purchased from Aldrich and Bu4NBr from Lancaster.
-Chloroacroleins12 and boronic acids14 were prepared according to
literature procedures. Melting points were determined on a Kofler
bench and are uncorrected. 1H and 13C NMR spectra were recorded
Synthesis 2001, No. 5, 12 04 2001. Article Identifier:
1437-210X,E;2001,0,05,0755,0758,ftx,en;Z01501SS.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0039-7881

756
S. Hesse, G. Kirsch
PAPER
Table Coupling of Aryl Boronic Acids and -Chloroacroleins in Water in the Presence of Bu4NBr
Entry
1a-1c
-Chloroacrolein
Boronic acid
Product
Yield (%)a
Cl
R
66 (R = H)
65 (R = CH3)
75 (R = OCH3)
CHO
R
B(OH)2
CHO
2
3
69
62
Cl
S
CHO
B(OH)2
S
CHO
OCH3
CHO
CHO
B(OH)2
OCH3
S
S
Cl
4
5
65
86
87
OCH3
Cl
CHO
OCH3
CHO
B(OH)2
S
S
OCH3
O
O
B(OH)2
CHO
OCH3
CHO
CHO
Cl
6
OCH3
Cl
S
B(OH)2
OCH3
CHO
S
7a,7b
50 (R = H)
51 (R = OCH3)
OCH3
R
R
H
CHO
H
B(OH)2
CHO
Cl
OCH3
8
59
OCH3
Cl
CHO
B(OH)2
OCH3
CHO
a Isolated yield by column chromatography.
on a AC Bruker 250 MHz spectrometer in CDCl3. Infrared spectra
were measured on a Perkin-Elmer 881 spectrometer. Mass spectra
were obtained on a Hewlett-Packard 5971 A GCMS instrument
with an ionization voltage of 70 eV.
Representative Procedure
-Chloroacrolein (2.59 mmol, 1 equiv), boronic acid (2.83 mmol,
1.1 equiv), tetrabutylammonium bromide (2.60 mmol, 1 equiv), pal-
ladium acetate (0.053 mmol, 2 mol%) and potassium carbonate
(6.45 mmol, 2.5 equiv) were added to a 10 mL round-bottom flask.
Synthesis 2001, No. 5, 755–758 ISSN 0039-7881 © Thieme Stuttgart · New York

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Palladium-Catalyzed C-C Bond Formation from -Chloroacroleins in Aqueous Media
757
Deionized H2O (5 mL) was added, and the reaction was stirred vig-
orously for 3 h at 45°C. The reaction mixture became dark and non-
homogenous. Then the mixture was diluted with 15 mL H2O, and
the product was extracted with EtOAc (3 30 mL). The organic
products were separated, and the free floating material as well as the
syrupy layer was collected. The organic products were stirred over
charcoal for 30 min followed by drying over sodium sulfate. Then
the organic products were filtered and concentrated.
GC-MS: m/z (%): 240 (100), 211 (38), 178 (60), 165 (30), 128 (28).
7-(o-Anisyl)-4,5-dihydrobenzo[b]thiophene-6-carboxaldehyde (3)
Yellow solid, purified by column chromatography on silica gel us-
ing CH2Cl2-C6H12 (3:2) as eluent, mp 126°C.
IR (KBr) cm-1: 1640 (CO)
1H NMR (250 MHz, CDCl3): = 2.81 (m, 2H), 2.90 (m, 2H), 3.76
(s, 3H, CH3O), 6.97 (d, 1H, J = 4.81 Hz), 6.96–7.06 (m, 2H), 7.25
(dd, 1H, J = 7.14 and 1.68 Hz), 7.36 (d, 1H, J = 4.92 Hz), 7.43 (ddd,
1H, J = 7.91, 7.69 and 1.59 Hz), 9.47 (s, CHO).
13C NMR (62.9 MHz, CDCl3): = 20.75 (CH2), 23.42 (CH2), 55.61
(CH3O), 111.15 (CH), 120.40 (CH), 124.31 (C), 127.70 (CH),
128.76 (CH), 130.07 (C), 130.52 (CH), 131.25 (CH), 138.09 (C),
141.32 (C), 146.70 (C), 157.09 (C), 192.22 (CHO).
1-Phenyl-3,4-dihydronaphtalene-2-carboxaldehyde (1a)
Yellow solid, purified by column chromatography on silica gel us-
ing CH2Cl2-C6H12 (1:1) as eluent, mp 84°C.
IR (KBr): = 1660 (CO) cm-1.
1H NMR (250 MHz, CDCl3): = 2.69 (m, 2H), 2.89 (m, 2H), 6.86
(d, 1H, J = 7.87 Hz), 7.13 (m, 1H), 7.27–7.34 (m, 4H), 7.45–7.48
(m, 3H), 9.58 (s, CHO).
GC-MS: m/z (%): 270 (22), 239 (100), 208 (15).
13C NMR (62.9 MHz, CDCl3): = 20.29 (CH2), 27.62 (CH2),
126.60 (CH), 127.80 (CH), 128.27 (CH), 128.43 (CH), 130.00
(CH), 130.17 (CH), 130.46 (CH), 134.39 (C), 135.10 (C), 135.28
(C), 138.62 (C), 154.37 (C), 193.34 (CHO).
4-(o-Anisyl)-6,7-dihydrobenzo[b]thiophene-5-carboxaldehyde (4)
Yellow solid, purified by column chromatography on silica gel us-
ing CH2Cl2-C6H12 (3:2) as eluent, mp 81°C.
IR (KBr): = 1685 (CO) cm-1.
1H NMR (250 MHz, CDCl3): = 2.85 (m, 2H), 3.01 (m, 2H), 3.74
(s, 3H, CH3O), 6.52 (d, 1H, J = 5.19Hz), 6.97–7.05 (m, 3H), 7.17
(dd, 1H, J = 7.37 and 1.70 Hz), 7.56 (ddd, 1H, J = 7.88, 7.71 and
1.73 Hz), 9.49 (s, CHO).
GC-MS: m/z (%): 234 (100), 205 (54), 128 (30).
1-(o-Tolyl)-3,4-dihydronaphtalene-2-carboxaldehyde (1b)
Yellow solid, purified by column chromatography on silica gel us-
ing CH2Cl2-C6H12 (3:2) as eluent, mp 54°C.
13C NMR (62.9 MHz, CDCl3): = 21.07 (CH2), 22.83 (CH2), 55.53
(CH3O), 110.98 (CH), 120.35 (CH), 122.06 (CH), 124.37 (C),
126.11 (CH), 130.05 (CH), 130.34 (C), 131.32 (CH), 136.65 (C),
142.35 (C), 147.92 (C), 157.09 (C), 192.84 (CHO).
IR (KBr): = 1660 (CO) cm-1.
1H NMR (250 MHz, CDCl3): = 2.08 (s, 3H, CH3), 2.62 (m, 1H),
2.79 (m, 1H), 2.94 (m, 2H), 6.74 (d, 1H, J = 7.58 Hz), 7.11–7.18 (m,
3H), 7.24–7.36 (m, 4H), 9.48 (s, CHO).
13C NMR (62.9 MHz, CDCl3): = 19.62 (CH3), 19.84 (CH2), 27.57
(CH2), 125.72 (CH), 126.80 (CH), 127.48 (CH), 127.89 (CH),
128.49 (CH), 129.16 (CH), 130.24 (CH), 130.49 (CH), 134.30 (C),
134.39 (C), 134.80 (C), 136.77 (C), 138.43 (C), 154.25 (C), 193.12
(CHO).
GC-MS: m/z (%): 270 (20), 239 (100).
5-(o-Anisyl)-2,3-dihydro-1-benzoxepine-4-carboxaldehyde (5)
Yellow solid, purified by column chromatography on silica gel us-
ing CH2Cl2-C6H12 (1:1) as eluent, mp 77°C.
1H NMR (250 MHz, CDCl3): = 2.74 (m, CH2), 3.67 (s, CH3O),
4.58 (m, CH2), 6.84 (dd, 1H, J = 7.83 and 1.57 Hz), 6.95–7.03 (m,
3H), 7.10–7.15 (m, 2H), 7.31 (ddd, 1H, J = 7.68, 7.57 and 1.57 Hz),
7.41 (ddd, 1H, J = 7.92, 7.54 and 1.76 Hz), 9.56 (s, CHO).
13C NMR (62.9 MHz, CDCl3): = 25.20 (3-CH2), 55.65 (CH3O),
79.46 (2-CH2O), 111.28 (CH), 120.39 (CH), 122.41 (CH), 123.34
(CH), 126.02 (C), 130.41 (CH), 130.54 (CH), 130.63 (CH), 132.78
(CH), 133.83 (C), 137.42 (C), 153.97 (C), 157.06 (C), 157.61(C),
192.02 (CHO).
GC-MS: m/z (%): 248 (30), 233 (100).
1-(o-Anisyl)-3,4-dihydronaphtalene-2-carboxaldehyde (1c)
Yellow solid, purified by column chromatography on silica gel us-
ing CH2Cl2 as eluent, mp 82°C.
IR (KBr): = 1660 (CO) cm-1.
1H NMR (250 MHz, CDCl3): = 2.69 (m, 2H), 2.93 (m, 2H), 3.71
(s, 3H, CH3O), 6.81 (d, 1H, J = 7.76 Hz), 7.01 (d, 1H, J = 8.16 Hz),
7.06 (d, 1H, J = 7.72 Hz), 7.10–7.17 (m, 2H), 7.26 (m, 2H), 7.44
(ddd, 1H, J = 8.06, 7.69 and 1.81 Hz), 9.53 (s, CHO).
GC-MS: m/z (%): 280 (10), 249 (100).
13C NMR (62.9 MHz, CDCl3): = 20.07 (CH2), 27.56 (CH2), 55.60
(CH3O), 110.97 (CH), 120.45 (CH), 124.10 (C), 126.56 (CH),
127.38 (CH), 127.76 (CH), 129.90 (CH), 130.04 (CH), 131.91
(CH), 134.61 (C), 134.86 (C), 138.42 (C), 152.05 (C), 157.51 (C),
193.50 (CHO).
4-(o-Anisyl)-thiochromen-3-carboxaldehyde (6)
Yellow solid, purified by column chromatography on silica gel us-
ing CH2Cl2 as eluent, mp 112°C.
1H NMR (250 MHz, CDCl3): = 3.71 (s, CH3O), 3.76 (s, CH2S),
6.85 (dd, 1H, J = 7.90 and 1.24 Hz), 6.98–7.07 (m, 3H), 7.11 (dd,
1H, J = 7.38 and 1.92 Hz), 7.21 (ddd, 1H, J = 7.46, 7.62 and 1.57
Hz), 7.38–7.48 (m, 2H), 9.43 (s, CHO).
GC-MS: m/z (%): 264 (15), 233 (100), 202 (21).
1-(2-Thienyl)-3,4-dihydronaphtalene-2-carboxaldehyde (2)
Yellow solid, purified by column chromatography on silica gel us-
ing CH2Cl2-C6H12 (1:1) as eluent, mp 82°C.
IR (KBr): = 1655 (CO) cm-1.
13C NMR (62.9 MHz, CDCl3): = 22.07 (CH2S), 55.61 (CH3O),
111.07 (CH), 120.53 (CH), 124.17 (C), 125.44 (CH), 127.70 (CH),
128.78 (C), 129.58 (CH), 130.06 (CH), 130.49 (CH), 132.03 (CH),
134.44 (C), 136.32 (C), 151.42 (C), 157.50 (C), 191.48 (CHO).
1H NMR (250 MHz, CDCl3): = 2.69 (m, 2H), 2.90 (m, 2H), 7.10–
7.14 (m, 2H), 7.16–7.35 (m, 4H), 7.52 (dd, 1H, J = 4.88 and 1.07
Hz), 9.79 (s, CHO).
GC-MS: m/z (%): 282 (34), 251 (100).
3-(o-Anisyl)-3-phenyl-propenal (7a)
Orange solid, purified by column chromatography on silica gel us-
ing CH2Cl2 as eluent, mp 87°C.
13C NMR (62.9 MHz, CDCl3): = 20.74 (CH2), 27.39 (CH2),
126.74 (CH), 127.02 (CH), 127.75 (CH), 128.13 (CH), 130.40
(CH), 130.60 (CH), 130.70 (CH), 134.98 (C), 135.36 (C), 136.91
(C), 138.35 (C), 146.69 (C), 192.87 (CHO).
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S. Hesse, G. Kirsch
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1H NMR (250 MHz, CDCl3): = 3.69 (s, 3H, CH3O), 6.65 (d, 1H,
J = 8.05 Hz), 7.02–7.08 (m, 2H), 7.19 (dd, 1H, J = 5.75 and 1.70
Hz), 7.36 (s, 5H), 7.45 (m, 1H), 9.45 (d, CHO, J = 8.05 Hz)
13C NMR (62.9 MHz, CDCl3): = 55.62 (CH3O), 111.30 (CH),
120.49 (CH), 125.43 (C), 127.39 (CH), 128.52 (CH), 130.13 (CH),
130.61 (CH), 131.92 (CH), 139.20 (C), 157.26 (C), 158.71 (C),
193.69 (CHO).
158.35 (C, B), 160.01 (C, A), 161.46 (C, B), 193.72 (CHO, B),
193.88 (CHO, A).
GC-MS: m/z (%): 268 (14), 237 (100).
2-(o-Anisyl)-cyclohexen-1-carboxaldehyde (8)
Orange oil, purified by column chromatography on silica gel using
C6H12-EtOAc (8:2) as eluent.
GC-MS: m/z (%): 237 (10), 207 (100).
1H NMR (250 MHz, CDCl3): = 1.77 (m, 5H), 2.34 (m, 3H), 3.79
(s, 3H, CH3O), 6.90–6.98 (m, 2H), 7.06 (dd, 1H, J = 7.32 and 1.78
Hz), 7.32 (ddd, 1H, J = 8.20, 7.51 and 1.82 Hz), 9.39 (s, CHO).
3-(o-Anisyl)-3-(p-anisyl)-propenal (7b)
Orange solid, purified by column chromatography on silica gel us-
ing CH2Cl2 as eluent, mp 80°C.
13C NMR (62.9 MHz, CDCl3): = 21.52 (CH2), 21.93 (CH2), 22.28
(CH2), 32.95 (CH2), 55.38 (CH3O), 110.77 (CH), 120.18 (CH),
128.28 (C), 129.27 (CH), 130.11 (CH), 135.54 (C), 156.23 (C),
157.18 (C), 193.57 (CHO).
The two isomers could not be separated neither by column chroma-
tography on silica gel nor by gas chromatography, but they can be
distinguished by NMR.
GC-MS: m/z (%): 216 (5), 185 (100).
H3CO
H3CO
H
CHO
H
References
CHO
(1) Miyaura, N.; Suzuki, A.; Yanagi, T. Synth. Commun. 1981,
11, 513.
OCH3
OCH3
(2) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
(3) Jeffery, T. J. Chem. Soc., Chem. Commun. 1984, 19, 1287.
(4) Casalnuovo, A. L.; Calabrese, J. C. J. Am. Chem. Soc. 1990,
112, 4324.
A (18%)
B (82%)
(5) Bumagin, N. A.; More, P. G.; Beletskaya, I. P. J.
Organomet. Chem. 1989, 371, 397.
Figure
(6) Genêt, J. P.; Blart, E.; Savignac, M. Synlett 1992, 715.
(7) Jeffery, T. Tetrahedron Lett. 1994, 35, 3051.
(8) Badone, D.; Baroni, M.; Cardamone, R.; Ielmini, A.; Guzzi,
U. J. Org. Chem. 1997, 62, 7170.
(9) Bussolari, J. C.; Rehborn, D. C. Org. Lett. 1999, 1, 965.
(10) Fitton, P.; Rick, E. A. J. Organomet. Chem. 1971, 28, 287.
(11) Satoh, N.; Ishiyama, T.; Miyaura, N.; Suzuki, A. Bull. Chem.
Soc. Jpn. 1987, 60, 3471.
(12) Arnold, Z.; Zemlicka, J. Collect. Czech. Chem. Commun.
1959, 24, 2385.
(13) (a) Marson, C. M.; Giles, P. R. Synthesis using Vilsmeier
Reagents CRC Press, Boca Raton, Ann Arbor: London,
1994. (b) Sekhar, B. C. Heterocycles 2000, 53, 941.
(14) Thompson, W. J.; Gaudino, J. J. Org. Chem. 1984, 49, 5237.
1H NMR (250 MHz, CDCl3): = 3.69 (s, CH3O, A), 3.71 (s, CH3O,
B), 3.83 (s, CH3O, B), 3.86 (s, CH3O, A), 6.49 (d, 1H, J = 7.97 Hz,
A), 6.62 (d, 1H, J = 7.98 Hz, B), 6.86 (d, 2H, J = 9.02 Hz, B), 6.92–
7.23 (m, 3H B + 6H A), 7.31–7.35 (m, 2H B + 2H A), 7.44 (m, 1H,
B), 9.38 (d, CHO, J = 8.16 Hz, B), 9.65 (d, CHO, J = 8.15 Hz, A).
13C NMR (62.9 MHz, CDCl3): = 55.30 (CH3O, A), 55.33 (CH3O,
B), 55.61 (CH3O, A), 55.64 (CH3O, B), 111.21 (CH, B), 111.71
(CH, A), 113.45 (CH, A),113.99 (CH, B), 120.44 (CH, B), 120.47
(CH, A), 125.52 (CH, B), 129.11 (CH, B), 129.90 (CH, A), 130.43
(CH, B), 130.55 (C, B), 130.93 (CH, A), 131.27 (C, B), 131.44 (CH,
A), 131.75 (CH, A), 131.78 (CH, B), 157.21 (C, B), 157.59 (C, A),
Synthesis 2001, No. 5, 755–758 ISSN 0039-7881 © Thieme Stuttgart · New York