Rhodium(III)-catalyzed β-arylation and- alkenylation of α-trifluoromethylacrylic acid

Article abstract of DOI:10.1246/cl.190024

The β-arylation and - alkenylation of trifluoromethylacrylic acid with arylboronic acids and alkenes proceed smoothly under rhodium(III) catalysis. The procedures provide useful synthetic routes from readily available building brocks to β-aryl-α-trifluoromethylpropanoic acid and 5, 5, 5-trifluoro-1, 3-butadiene derivatives. Some of the obtained butadienes exhibit strong fluorescence in the solid state.

Full text of DOI:10.1246/cl.190024

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Rhodium(III)-Catalyzed -Arylation and -Alkenylation of -TrifluoromethylacrylicAcid
Risa Yoshimoto, Yoshinosuke Usuki, and Tetsuya Satoh*
Advance Publication on the web February 5, 2019
doi:10.1246/cl.190024
© 2019 The Chemical Society of Japan
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1
b
a
Rhodium(III)-Catalyzed -Arylation and -Alkenylation of -Trifluoromethylacrylic Acid
Risa Yoshimoto, Yoshinosuke Usuki, and Tetsuya Satoh*
Department of Chemistry, Graduate School of Science, Osaka City University, 3-3-138 Sugimoto, Sumiyoshi-ku, Osaka 558-8585
E-mail: satoh@sci.osaka-cu.ac.jp
C–H bond cleavage11 and decarboxylation12,13 to produce
5,5,5-trifluoro-1,3-butadiene derivatives. These new findings
are described herein.
The
b-arylation
and
-alkenylation
of
trifluoromethylacrylic acid with arylboronic acids and alkenes
proceed smoothly under rhodium(III) catalysis. The
procedures provide useful synthetic routes from readily
available
building
brocks
to
b-aryl-a-
trifluoromethylpropanoic acid and 5,5,5-trifluoro-1,3-
butadiene derivatives. Some of obtained butadienes exhibit
strong fluorescence in the solid state. Keywords: rhodium
catalyst; arylation, alkenylation, organofluorine compound
CF3
CO2H
ArB(OH)2
CF3
CO2H
R
CF3
Ar
R
cat. [Cp*RhCl2]2
Ag salt
cat. [Cp*RhCl2]2
Ag salt
–CO2
Scheme 1.
In an initial attempt, phenylboronic acid (1a) (1 mmol)
Organofluorine compounds are of importance in
pharmaceutical, agrochemical, and polymer industries as well
as in material sciences.1 Trifluoromethyl group is the most
fundamental fluorine-containing unit, which can be seen in a
wide range of fine chemicals. The introduction of
trifluoromethyl group into organic molecules2 can influence
the electron distribution and lipophilicity of parent molecules
to enhance biological and physical properties.3 Among such
was treated with a-trifluoromethylacrylic acid (2) (0.5 mmol)
in the presence of [Cp*Rh(MeCN)3][SbF6]2 (0.02 mmol, 4
mol% Rh), Ag2O (1 mmol), and PivOH (0.5 mmol) under
o
argon in t-AmOH (3 mL) at 50 C for 20 h. After subsequent
methyl-esterification using methyl iodide (2.5 mmol) and
K2CO3 (1.5 mmol) in DMF at rt, methyl 2-benzyl-3,3,3-
trifluoropropanate (3a) was formed as a 1,4-conjugate
addition product in 72% yield (entry 1 in Table S1). Under
optimal conditions using [Cp*RhCl2]2 (0.01 mmol), AgSbF6
(0.1 mmol), and Ag2O (1 mmol), 3a was produced in 95%
yield (entry 15 in Table S1).14 The volatility of ester 3a made
the posttreatment difficult. Fortunately, the corresponding
acid, 2-benzyl-3,3,3-trifluoropropanoic acid (3a’), could be
obtained in 93% isolated yield by avoidance of the methyl-
esterification procedure (Table 1). It was confirmed that the
present reaction can be readily scaled up. Thus, 3a was
obtained in 75% isolated yield (813 mg) from 1a (10 mmol)
and 2 (5 mmol) (entry 16 in Table S1).
trifluoromethyl-substituted
molecules,
b-aryl-a-
trifluoromethylpropanoic acids have attracted attention
because of their biological activities and utilities as important
synthetic intermediates in fine chemicals producing
processes.4 For preparing the class of compounds,
nucleophilic and electrophilic trifluoromethylation reactions
of a-activated carbonyl compounds have been developed. For
example, Hu and co-workers reported copper-mediated
nucleophilic trifluoromethylation of a-diazo esters with
TMSCF3.5 As an electrophilic reagent, Poisson, Besset, and
co-workers used Togni’s reagent in their NHC carbene-
catalyzed trifluoromethylation of a-chloroaldehydes.6 In these
precedents, however, reactive substrates and/or reagents have
to be employed for preparing desired b-aryl-a-
trifluoromethylpropanoic acids efficiently. An alternative is to
utilize stable, readily available building blocks containing a
trifluoromethyl group.7 We focused attention on commercially
available a-trifluoromethylacrylic acid. The catalytic coupling
of this substrate can provide straightforward synthetic routes
to trifluoromethyl-containing compounds. In the context of
our continuous studies of rhodium(III)-catalyzed coupling
reactions,8 we found that a-trifluoromethylacrylic acid
undergoes b-arylation upon treatment with arylboronic acids
under rhodium(III) catalysis to produce b-aryl-a-
trifluoromethylpropanoic acids9 (Scheme 1). This type of 1,4-
conjugate addition of arylboron reagents toward a,b-
unsaturated carboxylic acids and related compounds has been
conducted mainly under palladium(II)-, rhodium(I)-, or
ruthenium(II) catalysis.10 In contrast, the rhodium(III)-
catalyzed version has been less explored. In addition, the
rhodium(III)-catalyzed oxidative coupling of this building
block with alkenes was also examined. Fortunately, we
succeeded in finding that the b-alkenylation proceeds through
Under the optimized conditions (entry 15 in Table S1),
we next examined the reactions of variously substituted
phenylboronic acids
1 with 2. (Table 1). Electron-
withdrawing (-Cl (2b), -Br (2c), -CO2Et (2d), and -CN (2e))
and -donating groups (-Me (2f) and -OMe (2g)) were tolerated
to
give
the
corresponding
b-phenyl-a-
trifluoromethylpropanoic acids 3b’-g’ in 51-92% yields. In
cases using 4-biphenyl- (2h) and 2-naphthylboronic acids (2i),
products 3’ were found to be sparingly soluble in common
organic solvents. Therefore, they were treated with MeI and
K2CO3 to make posttreatment easy. Thus, methyl esters 3h
and 3i were obtained in 73 and 50% isolated yields,
respectively.

2
methacrylic acid (4). Therefore, the carboxylate moiety can
readily coordinate to the rhodium center to form B’, which
may show resistance to undergoing b-hydrogen elimination.15
Finally, hydrolysis of B or B’ appears to take place to
selectively produce 3 and to regenerate an active Cp*-
rhodium(III) species. It is also possible that the hydrolysis
step proceeds more smoothly in the presence of acidic 2,
compared to that in the case with 4.
Table 1. Reaction of Arylboronic Acids 1 with a-
Trifluoromethylacrylic Acid (2)a
[Cp*RhCl2]2 / AgSbF6
CF3
CF3
CO2H
Ag2O
Ar
Ar B(OH)2
+
CO2H
t-AmOH
1
2
3
product yield (%)
CF3
Ar B(OH)2
Cl
Br
CF3
CF3
CF3
Ar
Cp*RhIIIX2
1
CO2H
3
CO2H
3a’ 93%
CO2H
CO2H
3c’ 88%
XB(OH)2
3b’ 84%
EtO2C
NC
Ar
X
CF3
CF3
CO2H
Cp*Rh
HX
CO2H
3d’ 92%
A
3e’ 51%
Ar
Cp*Rh
Ar
Me
MeO
CF3
CO2H
CF3
CF3
CO2H
CF3
CO2H
CF3
O
or
Cp*Rh
CO2H
O
X
2
3f’ 84%
3g’ 75%
B
B’
CF3
CF3
Scheme 3.
CO2Me
3h 73%b
CO2Me
3i 50%b
Next, the alkenylation of a-trifluoromethylacrylic acid
(2) was examined. Previously, we reported that methacrylic
acid (4) undergoes b-alkenylation upon treatment with
alkenes such as styrene in the presence of Cp*-rhodium(III)
catalyst and cupper salt oxidant (Scheme 4).13 Under similar
conditions, 2 reacted with styrene (6a) accompanied by
decarboxylation16 to produce ((1E,3E)-5,5,5-trifluoropenta-
1,3-dien-1-yl)benzene (7a) selectively, albeit with a low yield
(entry 1 in Table S2). In contrast to the case with 4, by-
products possessing a carboxylic group could not be detected.
The yield of 7a was enhanced to 46% by using AgOAc as
oxidant in NMP (Table 2, entry 11 in Table S2). In most cases,
small amounts (<5%) of geometric isomer(s) were detected. It
should be noted that trifluoromethyl-capped phenylbutadiene
derivatives are of interest for their physical properties and
their reactivity.17 4-Methyl (6b) and -chlorostyrenes (6c) also
coupled with 2 under similar conditions to give 7b and 7c in
moderate yields. The reactions of 4-vinyl-1,1'-biphenyl (6d)
and 2-vinylnaphthalene (6e) could be conducted in a similar
manner to yield 7d and 7e. Butyl (6f) and Octyl acrylates (6g)
also underwent decarboxylative coupling with 2 to produce
the corresponding (2E,4E)-6,6,6-trifluorohexa-2,4-dienoates
7f and 7g. In the cases using acrylates, the use of twice
amount of rhodium catalyst gave better results.
a Reaction conditions: 1 (1 mmol), 2 (0.5 mmol), [Cp*RhCl2]2 (0.01 mmol), AgSbF6
(0.1 mmol), Ag2O (1 mmol), in t-AmOH (3 mL) under Ar at 50 oC for 20 h, unless
otherwise noted. b Isolated as a methyl ester after treatment with MeI (2.5 mmol),
K2CO3 (1.5 mmol) and DMF (2 mL) at rt for 2 h.
In contrast to trifluoromethylacrylic acid 2, methacrylic
acid (4) underwent Mizoroki-Heck type reaction upon
treatment with 1a under the present conditions (Scheme 2).
After the methyl-esterification, methyl (E)-2-methyl-3-
phenylacrylate (5) was formed selectively, albeit with a low
yield. Unexpectedly, no 1,4-conjugate addition product was
detected at all.
Me
+
CO2H
B(OH)2
1a (1 mmol)
4 (0.5 mmol)
[Cp*Rh(MeCN) ][SbF6]2 (0.02 mmol) 2) MeI (2.5 mmol)
1)
3
Me
CO2Me
Ag2O (1 mmol)
K2CO3 (1.5 mmol)
t-AmOH (3 mL)
120 oC, 5 h
DMF (2 mL)
rt, 3 h
5, 35%
Scheme 2.
A plausible mechanism for the 1,4-conjugate addition of
Me
Me
CO2H
CO2H
arylboronic acid 1 to a-trifluoromethylacrylic acid (2) is
shown in Scheme 3. First, a Cp*-rhodium(III) species
undergoes transmetalation with 1 to form an arylrhodium
intermediate A. Then, A may undergo the insertion of 2 into
its Ar–Rh bond to form a rhodium enolate intermediate B.
Only a C-bonded tautomer is depicted in the scheme for
clarity. The carboxylic group in B seems to be more acidic for
the electron-withdrawing effect of its CF3 group compared to
that in the corresponding intermediate in the reaction of
previous work
cat. [Cp*RhCl2]2
CF3
oxidant
CF3
CO2H
this work
Scheme 4.

3
produce trifluoromethyl-capped butadienes. Some of the latter
products exhibit intense fluorescence in the solid state.
This work was partly supported by JSPS KAKENHI
Grant Numbers 18H04267 (in Precisely Designed Catalysts
with Customized Scaffolding) and 18K19083 (Grant-in-Aid
for Challenging Research (Exploratory)), Nagase Science
Technology Foundation, and Yamada Science Foundation to
T.S. and JSPS KAKENHI Grant Number JP18H04627 (in
Frontier Research on Chemical Communications) to Y.U. We
also thank Prof. Dr. N. Tohnai (Osaka University) for
fluorescence quantum efficiency measurements and helpful
discussions.
Table 2. Reaction of a-Trifluoromethylacrylic Acid (2)
with Alkenes 6a
[Cp*RhCl2]2
CF3
CO2H
AgOAc
CF3
+
R
R
NMP
6
2
7
product yield (%)
CF3
CF3
CF3
Me
Cl
7a 46%
7b 40%
7c 41%
Supporting Information is available electronically on J-
STAGE.
CF3
CF3
References and Notes
7d 34%
7e 40%
1
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CF3
CF3
(n-Bu)O2C
7f 40%b
(n-C8H17)O2C
7g 39%b
a Reaction conditions: 6 (2 mmol), 2 (0.5 mmol), [Cp*RhCl2]2 (0.005 mmol),
AgOAc (1 mmol) in NMP (2.5 mL) under Ar at 120 oC for 6 h, unless otherwise
noted. b [Cp*RhCl2]2 (0.01 mmol) was used.
2
For representative reviews, see: a) X. Liu, C. Xu, M. Wang, Q. Liu,
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Finally, we conducted preliminary investigations on the
properties of prepared trifluoromethyl-capped butadienes.
Compounds 7d and 7e showed strong fluorescence in the
solid state at 383 and 395 nm (excited at 310 nm) (Figure 1).
The quantum efficiency of the solid-state fluorescence was
determined to be absolute values of 0.30 and 0.29,
respectively.
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9
Prakash, Olah, and co-workers reported an example for the b-
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form mixtures of regioisomers: G. K. S. Prakash, F. Paknia, H.
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10
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Wavelength / nm
Figure 1. Normalized photoluminescence spectra (excited at
310 nm) of 7d (dotted line) and 7e (solid line) in solid state.
11
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In summary, we have demonstrated that the b-arylation
of readily available a-trifluoromethylacrylic acid can be
achieved upon treatment with arylboronic acids in the
presence of a rhodium(III) catalyst and a silver salt additive.
Obtained b-aryl-a-trifluoromethylpropanoic acids are of
interest because of their biological activities and utilities as
important synthetic intermediates in fine chemicals producing
processes. Moreover, it has been found that a-
trifluoromethylacrylic acid also undergoes b-alkenylation
under similar conditions accompanied by decarboxylation to

4
12
For representative reviews, see: a) Y. Wei, P. Hu, M. Zhang, W. Su,
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13
14
S. Mochida, K. Hirano, T. Satoh, M. Miura, J. Org. Chem. 2011,
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In most cases, small amounts (~10%) of biphenyl were also formed
as a by-product. One of possible roles of Ag2O seems to be as a
reoxidant for a RhI species generated during the dimerization of 1a.
Under rhodium(I) catalysis, there are several precedents involving
15
an arylation/b-fluoride elimination sequence: a) T. Miura, Y. Ito, M.
Murakami, Chem. Lett. 2008, 37, 1006-1007. b) Y. Huang, T.
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16147-16151.
16
17
However, the detailed mechanism of the decarboxylation step is
not clear at the present stage.
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2011, 115, 5660-5664. b) F. B. Sayyed, C. H. Suresh, S. R. Gadre,
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