Silver(I)-catalyzed denitrative trifluoromethylation of β-nitrostyrenes with CF3SO2Na

Article abstract of DOI:10.1016/j.tetlet.2016.09.016

A novel and convenient approach to the synthesis of substituted β-trifluoromethyl styrenes via a silver(I)-catalyzed denitrative trifluoromethylation with CF₃SO₂Na under relatively mild conditions has been developed. This protocol delivered excellent stereoselectivity and showed wide substrate tolerance.

Full text of DOI:10.1016/j.tetlet.2016.09.016

Accepted Manuscript
Silver(I)-Catalyzed Denitrative Trifluoromethylation of β-Nitrostyrenes with
CF3SO2Na
Ping Huang, Yaming Li, Xinmei Fu, Rong Zhang, Kun Jin, Wenxin Wang,
Chunying Duan
PII:
S0040-4039(16)31165-0
DOI:
http://dx.doi.org/10.1016/j.tetlet.2016.09.016
TETL 48086
Reference:
Tetrahedron Letters
To appear in:
Received Date:
Accepted Date:
2 September 2016
6 September 2016
Please cite this article as: Huang, P., Li, Y., Fu, X., Zhang, R., Jin, K., Wang, W., Duan, C., Silver(I)-Catalyzed
Denitrative Trifluoromethylation of β-Nitrostyrenes with CF3SO2Na, Tetrahedron Letters (2016), doi: http://
dx.doi.org/10.1016/j.tetlet.2016.09.016
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Tetrahedron Letters
Silver(I)-Catalyzed Denitrative Trifluoromethylation of β-Nitrostyrenes with
CF3SO2Na
Ping Huanga, Yaming Lia*, Xinmei Fua, Rong Zhanga, Kun Jina, Wenxin Wanga and Chunying Duana*
a State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, Liaoning, P.R. China
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
A novel and convenient approach to the synthesis of substituted β-trifluoromethyl styrenes via a
silver(I)-catalyzed denitrative trifluoromethylation with CF3SO2Na under relatively mild
conditions has been developed. This protocol delivered excellent stereoselectivity and showed
wide substrate tolerance.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
Trifluoromethylation
Denitrative coupling reaction
Stereoselectivity
Ag(I)-catalyzed
1. Introduction
nitration.10 Yao11 reported a series of approaches that β-
nitrostyrenes reacted with carbon-centre radicals to construct new
C-C bonds accompanied by releasing of the NO2 radical.
Recently, denitrative reaction of β-nitrostyrenes has attracted
The introduction of fluorinated moieties into the organic
molecules often results in dramatic changes in the physical,
chemical, pharmacological and biological properties of these
compounds.1 Especially, the incorporation of CF3 groups into
aromatics generally enhances their chemical and metabolic
stability, lipophilicity and binding selectivity.2 Therefore, many
chemists have been focusing their attention on the discovery and
development of the new trifluoromethylation reaction recently.3
Scheme 1. Formation of Cvinyl-R moieties (R= CF3, PO3Et2, SO2Ar).
In the past decade, various synthetic strategies for
trifluoromethylations of arenes have been developed.4
Particularly, protocols concerning the construction of Cvinyl-CF3
bonds have been gotten so much attention. As shown in Scheme
1, there are two routes which are mainly used to synthesize
trifluoromethylating olefins. One route is decarboxylative
trifluoromethylation, which often requires prefunctionalized
alkenes as substrates and suffers from expensive Togni`s
reagents.5 The process developed by Hu[5a] mainly relies on
utilizing a costly and electrophilic trifluoromethyl reagent
(Scheme 1a). To overcome these limitations, our group5e reported
a
kind of mild copper/silver-mediated decarboxylative
trifluoromethylation of α,β-unsaturated carboxylic acids with
cheap CF3SO2Na (Scheme 1a). Another route is direct C-H
trifluoromethylation of alkenes.6 However, it requires either
costly catalysts or trifluoromethyl reagents.
Nitro olefins are regarded as the significant and valuable
reagents in the synthesis of complex target compounds for their
easy availability.7 The Henry reaction, condensing aldehydes
with nitroalkanes, is one of the general methods to access
conjugated nitro olefins.8 Other useful methods for synthesizing
nitro olefins are nitration of alkenes9 and decarboxylative

2
Tetrahedron Letters
much attention as a useful method for the construction of Cvinyl
-
trifluoromethylation of β-nitrostyrenes with CF3SO2Na (Table 2).
R moieties. Pan12a and Yadav12c discovered the formation of
Cvinyl-P and Cvinyl-S bonds by denitrative reaction respectively
(Scheme 1b). In addition, Yi12b reported a Fe(III)-catalyzed
trifluoromethylation of β-nitrostyrenes using Togni reagent as
CF3 source (Scheme 1b). Herein, we report the silver(I)-catalyzed
denitrative trifluoromethylation of β-nitrostyrenes with
electrophilic trifluoromethyl radical derived from inexpensive
Langlois reagent CF3SO2Na.
The denitrative trifluoromethylation reactions of β-nitrostyrenes
with electron-donating groups at o-, m- or p-position, such as
Me-, t-Bu-, AcO-, and MeO-, afforded corresponding
trifluoromethyl styrenes in moderate to good yields (Table 2, 1b-
1g). Moreover, dimethoxyl substituted β-nitrostyrene gave
desired product in good yield (Table 2, 1h). It is pleased to find
that the trifluoromethylation of o-, p-bromo and p-chloro
substituted β-nitrostyrenes worked relatively well (Table 2, 1i, 1j,
1k). Interestingly, the dichloro substituted β-nitrostyrenes also
gave the trifluoromethylated product in moderate yield (Table 2,
1l). p-Phenyl substituted β-nitrostyrenes only gave the target
product in 48% yield owing to its big conjugate system (Table 2,
1m). Similarly, β-nitrovinyl-naphthalene was also a poor
substrate only obtaining 38% yield of trifluoromethylated
product (Table 2, 1n). The substrates with electron-withdrawing
groups gave trifluoromethylated products in poor yields because
of their lower electron density (Table 2, 1o, 1p). Notably, the
reactions were found to be highly stereoselective, and only the E-
isomer of the desired product was observed in each process
through J value of 1H-NMR(see datas in Experimental
Section).
2. Results and discussion
Initially, denitrative trifluoromethylation of β-nitrostyrene (1)
with CF3SO2Na was selected as a model reaction (Table 1).
When this reaction was carried out with 1.0 equivalent AgNO3 as
catalyst, di-t-butyl peroxide (DTBP) as oxidant, tetra-(n-butyl)
ammonium iodide (TBAI) as PTC at 70°C for 24 h, β-
trifluoromethylstyrene (1a) was obtained only in 22% yield
(entry 1). Fortunately, addition of acids could improve the yield
of the target product (1a) (entries 2-5). Among those screened
acids, TsOH is the best one. Moreover, testing different catalysts
showed that AgNO3 is superior to the other silver salts, such as
Ag2O, AgOAc and Ag2CO3 (entries 5-7). When the amount of
AgNO3 catalyst was decreased to 15 mol%, the yield of 1a was
increased to 83% (entries 8-9). Maybe excess AgNO3 catalyst led
to the generation of trifluoromethyl radical fastly, so that other
side reaction took place rather than the slow denitrative
trifluoromethylation of β-nitrostyrene. Without AgNO3 catalyst,
the yield of 1a was only 23% (entry 10). Screening various
oxidants, such as di-t-butyl peroxide (DTBP), t-butyl
hydroperoxide (TBHP), Bz2O2, H2O2, K2S2O8, we found that
DTBP showed the best result (entries 9, 11-14). Finally, without
addition of TBAI caused a lower yield (entry15). Notably, no
detectable amount of Z-isomers of target products was found in
these reactions.
Table 2. Silver(I)-catalyzed denitrative trifluoromethylation of β-
nitrostyrenes with CF3SO2Naa
Table 1. Optimization of reaction conditions
Entry
1
Catalysis
AgNO3(100)
Addictiv
TBAI
Yieldb
22
oxidant
DTBP
Acid
-
AgNO3(100)
AgNO3(100)
AgNO3(100)
Ag2O(100)
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
DTBP
TBHP
H2O2
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
TBAI
-
TFA
28
34
2
AlCl3
TsOH
TsOH
TsOH
TsOH
TsOH
TsOH
TsOH
TsOH
TsOH
TsOH
TsOH
TsOH
3
65
4
42
5
a
Reaction conditions: 1(0.4 mmol), CF3SO2Na (3.0 equiv), AgNO3 (15
AgOAc(100
61
6
mol%), TBAI (0.2 equiv), DTBP (5.0 equiv), DMSO/ CH2Cl2= 0.8/2 mL,
)
TsOH (1.0 equiv), 70 oC, 24 h. b Isolated yields.
Ag2CO3(100
50
7
)
AgNO3 (56)
53
8
AgNO3 (15)
-
83
To gain mechanistic insights into the current denitrative
trifluoromethylation, a set of comparative experiments were
designed (Scheme 2). We chose 1,1-diphenyl-ethylene (2 equiv)
as a radical scavenger to capture the trifluoromethyl radical. The
reaction of CF3SO2Na with 1,1-diphenyl-ethylene was tested
under the standard conditions. The desired trifluoromethyl 1,1-
diphenyl-ethylene product 4a was detected by GC-MS, and the
yield of 4a was determined by 19F-NMR (Eq.(1) of Scheme 2).
Notably, when 1,1-diphenyl-ethylene was added to take the
competition reaction with β-nitrostyrene and CF3SO2Na, the
trifluoromethylated product (1a) was not detected. However, the
trifluoromethyl 1,1-diphenyl-ethylenen 4a was obtained in 20 %
in 19F-NMR yield (Eq.(2) of Scheme 2). The controlled
experiments showed that the reaction proceeded through a radical
process.
9
23
10
11
12
13
14
15
AgNO3 (15)
AgNO3(15)
AgNO3(15)
AgNO3(15)
AgNO3(15)
70
trace
trace
trace
60
Bz2O2
K2S2O8
DTBP
a Reaction conditions: 1 (0.1 mmol), 2 (3.0 equiv), additive (0.2 equiv),
oxidant (5.0 equiv), DMSO/ CH2Cl2= 0.4/1 mL, acid (1.0 equiv), 70 °C, 24
h. b Yields were determined by GC analysis, using n-dodecane as internal
standard.
With the optimized conditions in hand, we next investigated the
substrate
scope
of
silver(I)-catalyzed
denitrative

Based on the experimental results and earlier studies12, 14, a
plausible silver(I)-catalyzed denitrative trifluoromethylation
mechanism was proposed as follows (Scheme 3). Initially,
silver(I) was oxidized to silver(II) by DTBP due to its strong
References and notes
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–
oxidation. In the presence of silver(II) ions, CF3SO2 was
oxidized to CF3SO2, which subsequently released one molecule
of SO2 to generate a trifluoromethyl radical. The addition of the
in situ generated trifluoromethyl radical to the double bond of 1
led to the formation of intermediate 5 which subsequently
underwent the elimination of NO2 radical to give the desired
product 1a.
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Scheme 3 Proposed mechanism for β-nitrostyrenes trifloromethylation
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3. Conclusions
In summary, we have developed an efficient protocol for the
construction of Cvinyl-CF3 bonds through a silver(I)-catalyzed
denitrative trifluoromethylation of β-nitrostyrenes with
CF3SO2Na. This method tolerates a variety of functional groups
and provides a useful and practical strategy for stereospecific
synthesis of CF3-substituted E-alkenes with operational
simplicity under relatively mild conditions. Since both β-
nitrostyrenes and CF3SO2Na are easily available, this denitrative
trifluoromethylation method will have great advantages for
academic and industrial application.
9.
Acknowledgments
This work was supported by the National Natural Science
Foundation of China (NSFC) (Project No 21176039 and
20923006)
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Supplementary Material
Supplementary data (experimental section and copies of 1 H , 13C,
19F NMR, MS spectral data) associated with this article can be
found,
in
the
online
version,
at
http://dx.doi.org/xx.xxxx/j.tetlet.2016.xx.xxx.
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4
Tetrahedron Letters
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Highlights
►A novel silver(I)-
catalyzed denitrative trifluoromethylation was developed.
►The cheap and economical trifluoromethyl reagent was used.
► The protocol to synthesize β-
trifluoromethyl styrenes delivered stereoselectivity.
► The approach was under mild conditions and showed wide
substrate tolerance.

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Silver(I)-Catalyzed Denitrative Trifluoromethylation of
β-Nitrostyrenes with CF3SO2Na
Leave this area blank for abstract info.
Ping Huang, Yaming Li*, Xinmei Fu,
Rong Zhang, Kun Jin, Wenxin Wang and Chunying Duan*
State Key Laboratory of Fine Chemicals, School of Chemical Engineering,
Dalian University of Technology Dalian 116024, Liaoning, P.R. China