An I2O5-promoted decarboxylative trifluoromethylation of cinnamic acids

Article abstract of DOI:10.1016/j.tetlet.2014.11.076

An I₂O₅-promoted decarboxylative trifluoromethylation of a series of cinnamic acids and their derivatives by using sodium trifluoromethanesulfinate in aqueous media was demonstrated. This strategy provides a safe and convenient access to various trifluoromethylated (E)-alkenes in a very high selectivity.

Full text of DOI:10.1016/j.tetlet.2014.11.076

Tetrahedron Letters 56 (2015) 233–235
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
An I2O5-promoted decarboxylative trifluoromethylation of cinnamic
acids
b
b,
Xiao-Jie Shang a, , Zejiang Li , Zhong-Quan Liu
⇑
⇑
a College of Resources and Environment, Gansu Agricultural University, Lanzhou, Gansu 730070, PR China
b State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
An I2O5-promoted decarboxylative trifluoromethylation of a series of cinnamic acids and their derivatives
by using sodium trifluoromethanesulfinate in aqueous media was demonstrated. This strategy provides a
safe and convenient access to various trifluoromethylated (E)-alkenes in a very high selectivity.
Ó 2014 Elsevier Ltd. All rights reserved.
Received 11 October 2014
Revised 13 November 2014
Accepted 16 November 2014
Available online 21 November 2014
Keywords:
Decarboxylation
Free-radical
Trifluoromethylation
Sodium trifluoromethanesulfinate
Cinnamic acid
Numerous highly valuable pharmaceuticals, agrochemicals, and
materials contain the trifluoromethyl (CF3) group, which provides
a driving force for exploring more efficient strategies for incorpora-
tion of CF3 into organic molecules.1 Among them, free-radical-ini-
tiated trifluoromethylation has drawn much attention and
considerable developments have been made in the past decades.2,3
The Langlois reagent, sodium trifluoromethanesulfinate, first syn-
thesized by Langlois et al., is one of the most commonly used tri-
fluoromethyl sources in atom transfer trifluoromethylation
processes.4 For example, a series of efficient trifluoromethylation
of heterocycles using NaSO2CF3 via direct CAH bond functionaliza-
tion was achieved by Baran and co-workers in 2011.5 Later, several
other groups such as Sanford,6 Maiti,7 Qing,8 and ours9 successively
reported free-radical trifluoromethylation using Langlois reagent.
However, most of the systems require large excess of potentially
explosive peroxides and/or transition metal salts. Very recently,
we have developed a series of safe and transition-metal free strat-
egies for radical trifluoromethylation.10 In these novel systems, a
low-cost and stable inorganic compound, iodine pentoxide (I2O5,
IP) was used as the single electron oxidant, which oxidizes sodium
trifluoromethanesulfinate to the corresponding trifluoromethyl
radical resulting in a variety of CACF3 bond formations.
In 2012, we successfully realized a very efficient decarboxyla-
tive CAC bond construction through coupling reaction of various
a
, b-unsaturated carboxylic acids with a wide range of molecules
containing sp3CAH bond such as alcohols, alkanes, ethers, and
amines.11 Subsequently, a copper-catalyzed decarboxylative triflu-
oromethylation and iron-catalyzed difluoromethylation of cin-
namic acids using NaSO2CF3 and zinc difluoromethanesulfinate,
respectively via a free-radical addition/elimination process was
Previous work:
O
20 mol% CuF2.2H2O
COOH
CF3
+
O
Ar
Ar
H2O/dioxane, 80 o
C
I
CF3
10 mol% CuSO4.5H2O
TBHP (5 equiv)
CF3
CF3
COOH
COOH
NaSO2CF3
+
+
Ar
Ar
Ar
Ar
DCM/H2O, 50 o
C
FeCl3 (1 equiv)
K2S2O8 (4 equiv)
NaSO2CF3
MeCN/H2O, 50 o
C
This work:
COOH
I2O5 (3 equiv)
⇑
CF3
Corresponding authors. Tel.: +86 931 8911636; fax: +86 931 8915557 (X.-J.S.);
CF3
NaSO2
+
Ar
CH2Cl2/H2O, 60 o
C
Ar
tel.: +86 931 8912280; fax: +86 931 8915557 (Z.-Q.L.).
E-mail addresses: shangxiaojie@yahoo.cn (X.-J. Shang), liuzhq@lzu.edu.cn
(Z.-Q. Liu).
Scheme 1. Decarboxylative trifluoromethylation of cinnamic acid.
http://dx.doi.org/10.1016/j.tetlet.2014.11.076
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

234
X.-J. Shang et al. / Tetrahedron Letters 56 (2015) 233–235
Table 1
Optimization of the typical reaction conditionsa
MeO
CF3
MeO
COOH
I2O5
+
NaSO2CF3
OMe
OMe
Entry
NaSO2CF3 (equiv)
I2O5 (equiv)
Solvent (V/V, mL)
T (°C)b
Yieldc (%)
1
2
3
4
5
6
7
8
2
3
5
3
3
3
3
3
3
3
3
1
5
3
3
3
DCM/H2O(2.5/1)
DCM/H2O(2.5/1)
DCM/H2O(2.5/1)
DCM/H2O(2.5/1)
DCM/H2O(2.5/1)
DCM/H2O(2.5/1)
DCM/H2O(2.5/1)
CH3CN/H2O(2.5/1)
60
60
60
60
60
25
90
60
20
80
76
Trace
72
Trace
56
Trace
a
b
c
Reaction conditions: (E)-3-(2,5-dimethoxyphenyl)acrylic acid (1 equiv, 0.2 mmol), sealed tube, 22 h.
Measured temperature of the oil bath.
Relative yield based on the conversion of the starting material.
developed by us.9 Inspired by these previous studies, we began to
In order to test our hypothesis of the free radical trifluorome-
thylation of ,b-unsaturated carboxylic acids by using NaSO2CF3
reason whether a decarboxylative trifluoromethylation of
a,b-
a
unsaturated carboxylic acids by using NaSO2CF3 and I2O5 through
free radical addition–elimination process could be realized. If it
does work, it would be attractive to organic synthetic chemistry
because this method would hold the advantages of metal-free,
low-cost, and safe over the previous protocols (Scheme 1).12
and I2O5, a series of experiments were carried out to optimize
the typical reaction conditions. It can be seen from Table 1 that
the amount of NaSO2CF3 and I2O5, solvent as well as temperature
are very important to this transformation. Finally, the desired
product was obtained in 80% yield under the following conditions:
1 equiv of cinnamic acid, 3 equiv of NaSO2CF3, 3 equiv of I2O5,
CH2Cl2/H2O (2.5/1, 3.5 mL), 60 °C (Measured temperature of the
oil bath), in a sealed tube, and 22 h.
Table 2
a
Trifluoromethylation of cinnamic acids by using NaSO2CF3 and I2O5
We next investigate the substrate scope with the modified con-
ditions in hand. As depicted in Table 2, various electron-rich aryl
COOH
CF3
I2O5 (3 equiv)
+
NaSO2CF3
COOH
FG
FG
CH2Cl2/H2O, 60 o
C
substituted
a,b-unsaturated carboxylic acids gave the desired
1
2
CF3-substituted (E)-styrenes in high yields and selectivities. The
substrates with para-, meta-, and ortho-substituent on the aromatic
core led to the corresponding products in 75–90% yields, and the
ratio of E/Z range from 13/1 to 49/1 (entries 1–8). However, no
desired product was observed by using cinnamic acids with elec-
tron-withdrawing groups such as NO2 and CN substituted on the
Entry
1
Substrate
Product
E/Zb
Yieldc (%)
CF3
32/1
32/1
32/1
13/1
49/1
19/1
19/1
80
O
MeO
2a
COOH
CF3
aryl (entry 9). Although only electron-rich aryl-substituted
a,b-
2
3
4
5
6
7
90
75
83
85
82
85
unsaturated carboxylic acids are effective substrates in this system,
it is believed to be attractive to organic synthetic chemistry with
the features of easy operation and no requirement of transition-
metal salts.
The mechanistic studies through combination of electron-spin
resonance (ESR) with spin trapping technology are designed to
gain insight into the details of this process. Since free radical inter-
mediates would be involved in this system, a radical spin trap
2b
COOH
COOH
CF3
CF3
EtO
EtO
2c
MeO
MeO
2d
CF3
COOH
OMe
OMe
2e
O
O
COOH
MeO
MeO
CF3
2f
COOH
CF3
O
O
O
O
2g
MeO
COOH
OMe
COOH
MeO
CF3
8
9
19/1
—
80
—
OMe
2h
O2N
—
a
Reaction conditions: cinnamic acid (1 equiv, 0.2 mmol), NaSO2CF3 (3 equiv,
0.6 mmol), I2O5 (3 equiv, 0.6 mmol), CH2Cl2/H2O (2.5/1, 3.5 mL), 60 °C (Measured
temperature of the oil bath), sealed tube, 22 h.
b
Ratio of the E/Z isomers determined by 19F NMR spectroscopy.
Relative yield of the E/Z isomers based on the conversion of the starting
c
material (see also the Supporting information).
Figure 1. ESR spectra of radical intermediate trifluoromethyl tert-butyl nitroxide.

X.-J. Shang et al. / Tetrahedron Letters 56 (2015) 233–235
235
O
MNP
spin trapping
N
A
CF3
I2O5
I2
CF3SO2Na
CF3
SET[O]
COOH
addition
elimination
Ar
COOH
CF3
CF3
Ar
Ar
-e, -CO2, -H+
B
Scheme 2. Possible mechanism.
Macé, Y.; Magnier, E. Eur. J. Org. Chem. 2012, 2479; (r) Liang, T.; Neumann, C. N.;
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reagent 2-methyl-2-nitrosopropane (MNP) was added into the
reaction. As a result, a sextet signal was recorded by ESR with
g = 2.0060 and a = 12.25 G, which should be the radical adduct tri-
fluoromethyl tert-butyl nitroxide (Fig. 1).10,13 It indicates that the
trifluoromethyl radical would be formed in this system.
A free-radical addition/elimination mechanism for this process
was proposed in Scheme 2. Single-electron oxidation of Langlois
reagent by IP would generate the trifluoromethyl radical, which
adds to acrylic acid leading to radical B. Single-electron-transfer
(SET) followed by elimination of CO2 and deprotonation would give
the final product.
In conclusion, we have developed an I2O5-promoted decarboxy-
lative trifluoromethylation of cinnamic acids and its derivatives by
using Langlois reagent in aqueous media. A series of trifluorome-
thylated (E)-styrenes could be prepared through this method.
Mechanistic investigations suggest it might undergo a free-radical
addition/elimination process.
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Acknowledgment
This project is supported by the National Science Foundation of
China (No. 21272096, 21472080).
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Supplementary data
Supplementary data (experimental procedures and spectral
data) associated with this article can be found, in the online ver-
sion, at http://dx.doi.org/10.1016/j.tetlet.2014.11.076.
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