A fast and convenient heck reaction in water under microwave irradiation

Article abstract of DOI:10.1055/s-2007-965936

A fast and convenient base-free Heck reaction of acrylic acid and allyl alcohol with hypervalent iodonium salts was achieved under microwave irradiation in water, providing a simple method for synthesis of trans-cinnamic acids and trans-cinnamyl alcohols in good yields in short time. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2007-965936

PAPER
853
A Fast and Convenient Heck Reaction in Water under Microwave Irradiation
A
F
ast and Convenient
i
H
eck
n
a
b
Received 19 October 2006; revised 30 December 2006
seconds in a microwave oven, even at comparable reac-
tion temperatures. Recently, more interest has been fo-
cused on microwave-irradiated procedures that use water
as a medium for organic synthesis due to their efficient
and environmentally benign conditions.6 We have report-
ed a rapid Suzuki reaction using hypervalent iodine com-
pounds under microwave irradiation in water.7 In this
paper, we wish to report a rapid and convenient base-free
Heck reaction using iodonium salts for the synthesis of
trans-cinnamic acids and relative compounds under mi-
crowave irradiation in water. To the best of our knowl-
edge, this is the first report of the rapid synthesis of trans-
cinnamic acids using iodonium salts under microwave ir-
radiation.
Abstract: A fast and convenient base-free Heck reaction of acrylic
acid and allyl alcohol with hypervalent iodonium salts was achieved
under microwave irradiation in water, providing a simple method
for synthesis of trans-cinnamic acids and trans-cinnamyl alcohols
in good yields in short time.
Key words: Heck reaction, hypervalent iodonium salts, microwave
irradiation, trans-cinnamic acids
The formation of a C–C bond by palladium-catalyzed
coupling of aryl or vinyl halides with alkenes, known as
the Heck reaction, has become a powerful tool in organic
chemistry.1 Considerable effort has been devoted to im-
proving the efficiency of this reaction, and, recently, there
has been increased interesting in the use of hypervalent io-
dine compounds as alternatives to replace aryl halides or
triflates in the Heck reaction. Hypervalent iodine com-
pounds, especially iodonium salts,2 can react with a series
of nucleophilic reagents under mild conditions due to the
excellent leaving group ability of the phenyliodanyl
group, which provides a useful route for the synthesis of
various alkenes.3 There have been a number of reports on
the use of iodonium salts in the Heck reaction in recent
years;4 an interesting paper from Bumagin and et al. re-
ports a mild Heck reaction with water as the medium
(Scheme 1).4a However, the time and temperature of the
reaction varied greatly, and the yields varied from 50% to
97%. Therefore, the development of a simple, fast, and
environmentally more benign Heck reaction is still a
much sought-after process.
Initially we mixed acrylic acid (1a, 1 equiv) and diphe-
nyliodonium chloride (2a, 1 equiv) with sodium carbonate
(2 equiv) and a catalytic amount of palladium(II) chloride
(1.0 mol%) in water. We found that under a microwave-
assisted condition (200 W), only after 20 seconds that the
reaction was complete, affording trans-cinnamic acid (3a)
in 85% yield. The same reaction was repeated in the ab-
sence of sodium carbonate, it was also found to occur eas-
ily and gave the same product 3a due to the facile
oxidative addition of hypervalent iodine compounds with
the palladium(0) species.8 This result prompted us to fur-
ther investigate the reaction and we found that when two
equivalents of acrylic acid were used, trans-cinnamic acid
(3a) was obtained in 95% yield. Under the optimized con-
ditions, the Heck reaction of acrylic acid (1a) with a series
of iodonium salts 2a–f for synthesis of trans-cinnamic ac-
ids was investigated (Scheme 2), the results are shown in
Table 1.
Pd(OAc)2, Na2CO3
H2C CHCO2H + Ar2I+X–
ArHC CHCO2H
From Table 1, it is notable that with the exception of iodo-
nium salts 2c and 2d which contain electron-withdrawing
substituents in the phenyl ring and hence require longer
reaction times (entries 3 and 4), all aryliodonium salts 2
reacted with acrylic acid (1a) rapidly under microwave ir-
radiation; the reaction was complete in 20 seconds. It is
also notable that the products 3 were generally obtained in
>85% yield, and some reactions were almost quantitative.
When allyl alcohol (1b) was used in place of acrylic acid
(1a), the reaction also gave excellent results in a short
time (entries 7 and 8). Alkenyliodonium salt 2g and alky-
nyliodonium salt 2h were also active, like aryliodonium
salts, in the reaction and provided the corresponding prod-
ucts 3i and 3j in good yields in 20 seconds.
50–97%
Scheme 1
Microwave-assisted organic synthesis is a new and rapid-
ly expanding area of synthetic organic chemistry.5 This
technique is based on the empirical observation that some
organic reactions proceed much faster and with higher
yields under microwave irradiation compared to conven-
tional heating. In many cases reactions that normally re-
quire many hours at reflux temperature under classical
conditions can be completed with several minutes or ever
SYNTHESIS 2007, No. 6, pp 0853–0856
x
x
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x
x
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0
0
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Advanced online publication: 13.02.2007
DOI: 10.1055/s-2007-965936; Art ID: P12306SS
© Georg Thieme Verlag Stuttgart · New York
The classical method for the synthesis of cinnamic acids
is the Knoevenagel condensation of malonic acid with

854
M. Zhu et al.
PAPER
Ar1
In summery, a rapid and convenient method for C–C bond
formation is afforded by microwave-promoted, base-free
Heck reaction using hypervalent iodonium salts in neat
water. The reactions are simple to perform, rapid and af-
ford trans-cinnamic acids 3 in excellent yields.
PdCl2, H2O
microwave
H2C CHR + Ar1Ar2I+X–
R
1
2
3
Scheme 2
carbonyl compounds, which is an important route for the
formation of substituted a,b-unsaturated acids.9 This in-
volves heating aromatic aldehydes and malonic acid in the
presence of an excess of a basic solvent, such as pyridine
and piperidine, to facilitate the easy decarboxylation of
the initially generated a,b-unsaturated malonic acids to
give cinnamic acids. However, this method is tedious,
time consuming, and requires a large number of solvents.
Mps were determined on a digital mp apparatus and were not cor-
rected. IR spectra were recorded on a FT-170 SX instrument, H
1
NMR spectra were measured on a Bruker AM-400 FT-NMR spec-
trometer, and MS were determined on HP5989A mass spectrome-
ter. Iodonium salts were prepared according to literature
procedures.10–13 Acrylic acid and allyl alcohol are commercially
available.
Table 1 Heck Reaction of Acrylic Acid and Allyl Alcohol with Iodonium Salts
Entry
1
Alkene
Iodonium salt
Product
Time (s)
20
Yielda (%)
95
H2C=CHCO2H
Ph2I+Cl–
Ph
1a
2a
CO2H
3a
4-MeC6H4
2
3
4
5
6
H2C=CHCO2H
1a
(4-MeC6H4)2I+BF4
20
40
60
20
20
94
86
80
90
86
–
2b
CO2H
CO2H
CO2H
CO2H
3b
4-BrC6H4
H2C=CHCO2H
1a
(4-BrC6H4)2I+Br–
2c
3c
H2C=CHCO2H
1a
(3-O2NC6H4)2I+Br–
2d
3-NO2C6H4
3d
H2C=CHCO2H
1a
(4-MeOC6H4)PhI+Br–
2e
4-MeOC6H4
3e
H2C=CHCO2H
(2-thienyl)PhI+OTs–
1a
2f
S
CO2H
3f
Ph
7
8
9
H2C=CHCH2OH
1b
Ph2I+Cl–
20
20
20
92
84
78
2a
CH2OH
3g
H2C=CHCH2OH
1b
(4-MeOC6H4)PhI+Br–
2e
4-MeOC6H4
CH2OH
3h
Ph
–
H2C=CHCO2H
[(E)-PhCH=CH]PhI+BF4
1a
2g
CO2H
3i
10
H2C=CHCO2H
(PhC≡C)PhI+BF4
2h
20
82
–
Ph
1a
CO2H
3j
a Isolated yields.
Synthesis 2007, No. 6, 853–856 © Thieme Stuttgart · New York

PAPER
A Fast and Convenient Heck Reaction
855
trans-Cinnamic Acid (3a); Typical Procedure
MS (EI, 75 eV): m/z (%) = 134 (M+, 60.1), 92 (100).
Acrylic acid (1a, (36.0 mg, 0.50 mmol, 2.0 equiv), diphenyliodoni-
um chloride (2a, 79.1 mg, 0.25 mmol, 1.0 equiv), PdCl2 (0.5 mg, 1.1
mmol%), and H2O (5 mL) were added to a glass tube placed in bea-
ker and irradiated for 20 s in a domestic microwave oven at 30% full
power (650 W). The mixture was cooled to r.t. and extracted with
EtOAc (3 × 10 mL) and the combined organic layers were dried (an-
hyd MgSO4) and evaporated in vacuo. The crude product was sep-
arated by flash chromatography (EtOAc–petroleum ether, 1:1) to
give 3a; yield: 95%; mp 132–134 °C (Lit.14 132–135 °C).
IR (KBr): 3027, 1686, 1631 cm–1.
1H NMR (CDCl3): d = 6.47 (d, J = 16.0 Hz, 1 H), 7.40–7.42 (m, 3
H), 7.50–7.60 (m, 2 H), 7.81 (d, J = 16.0 Hz, 1 H).
trans-4-Methoxycinnamyl Alcohol (3h)
Mp 144–146 °C (Lit.19 145–148 °C).
IR (KBr): 3310, 3025, 1096, 1070 cm–1.
1H NMR (CDCl3): d = 3.20 (s, 1 H), 3.79 (s, 3 H), 4.26 (d, J = 5.6
Hz, 2 H), 6.25 (dt, J = 15.6, 5.6 Hz, 1 H), 6.56 (d, J = 15.6 Hz, 1 H),
6.81–6.92 (m, 2 H), 7.30–7.37 (m, 2 H).
MS (EI, 75 eV): m/z (%) = 164 (M+, 100).
(E,E)-5-Phenylpenta-2,4-dienoic Acid (3i)
Mp 162–164 °C (Lit.20 163–164 °C).
IR (KBr): 3367, 3043, 1682, 1631 cm–1.
MS (EI, 75 eV): m/z (%) = 148 (M+, 100).
1H NMR (CDCl3): d = 5.90 (d, J = 15.1 Hz, 1 H), 6.70–6.80 (m, 2
H), 7.10–7.30 (m, 3 H), 7.40 (d, J = 7.9 Hz, 2 H), 7.49 (d, J = 15.0,
1 H).
trans-4-Methylcinnamic Acid (3b)
Mp 197–199 °C (Lit.15 200–201 °C).
MS (EI, 75 eV): m/z (%) = 174 (M+, 100).
IR (KBr): 3029, 1682, 1623 cm–1.
1H NMR (CDCl3): d = 2.34 (s, 3 H), 6.40 (d, J = 15.9 Hz, 1 H),
7.18–7.22 (m, 2 H), 7.44–7.48 (m, 2 H), 7.62 (d, J = 15.9 Hz, 1 H).
MS (EI, 75 eV): m/z (%) = 162 (M+, 100).
(E)-5-Phenylpent-2-en-4-ynoic Acid (3j)
Mp 128–130 °C (Lit.21 129–132 °C).
IR (KBr): 3370, 3042, 1666, 1610, 1410 cm–1.
1H NMR (CDCl3): d = 6.34 (d, J = 15.9 Hz, 1 H), 7.11(d, J = 15.9
trans-4-Bromocinnamic Acid (3c)
Mp 258–260 °C (Lit.16 262–264 °C).
Hz, 1 H), 7.33–7.43 (m, 3 H), 7.50–7.55 (m, 2 H).
MS (EI, 75 eV): m/z (%) = 172 (M+, 100).
IR (KBr): 3073, 1695, 1629 cm–1.
1H NMR (CDCl3): d = 6.59 (d, J = 15.9 Hz, 1 H), 7.59 (d, J = 16.0
Hz, 1 H), 7.61–7.64 (m, 2 H), 7.66–7.68 (m, 2 H).
MS (EI, 75 eV): m/z (%) = 226 (M+, 100).
Acknowledgment
Financial support from the Zhejiang Province Education Founda-
tion of China (Project 20060417) is greatly appreciated.
trans-3-Nitrocinnamic Acid (3d)
Mp 194–196 °C (Lit.17 197 °C).
IR (KBr): 3092, 1699, 1634, 1525, 1361 cm–1.
1H NMR (CDCl3): d = 6.55 (d, J = 15.9 Hz, 1 H), 7.72–8.15 (m, 3
H), 7.75 (d, J = 15.9 Hz, 1 H), 8.51–8.53 (m, 1 H).
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Synthesis 2007, No. 6, 853–856 © Thieme Stuttgart · New York