Palladium-Catalysed Synthesis of α-(Trifluoromethyl)styrenes by Means of Directed C-H Bond Functionalization

Article abstract of DOI:10.1002/ejoc.201501217

We report the first introduction of 2-bromo-3,3,3-trifluoropropene (BTP) by directed C-H bond functionalization. The developed method gives straightforward access to α-(trifluoromethyl)styrene derivatives without prior prefunctionalization of the substrates. This palladium-catalysed transformation was applied to a broad range of substrates, and the corresponding trifluoromethylated products were obtained in good yields. This approach represents an alternative pathway to the classical method previously used to access such molecules.

Full text of DOI:10.1002/ejoc.201501217

DOI: 10.1002/ejoc.201501217
Full Paper
Fluorinatd Molecules
Palladium-Catalysed Synthesis of α-(Trifluoromethyl)styrenes by
Means of Directed C–H Bond Functionalization
[
a]
[a]
[a]
[a]
Qun Zhao, Tatiana Besset, Thomas Poisson, Jean-Philippe Bouillon,* and
Xavier Pannecoucke[
a]
Abstract: We report the first introduction of 2-bromo-3,3,3-tri- was applied to a broad range of substrates, and the correspond-
fluoropropene (BTP) by directed C–H bond functionalization. ing trifluoromethylated products were obtained in good yields.
The developed method gives straightforward access to α-(tri- This approach represents an alternative pathway to the classical
fluoromethyl)styrene derivatives without prior prefunctionaliza- method previously used to access such molecules.
tion of the substrates. This palladium-catalysed transformation
Introduction
sponding organometallic species (B or Zn) (Scheme 1). Regard-
ing the first approach, in 1993 Hu and coworkers reported a
Sonagashira cross-coupling reaction with BTP as a coupling
During the last 10 years, organofluorine chemistry has under-
gone a tremendous expansion. Due to the high impact of
fluorinated molecules in the discovery and development of new
pharmaceuticals and agrochemicals, the demand for fluorinated
[
6]
partner. Later, Deng and coworkers demonstrated the aryl-
ation of BTP by means of a palladium-catalysed Suzuki cross-
[
7]
coupling reaction. The Yamakawa group went on to report a
nickel- and palladium-catalysed Corriu–Kumada reaction with
[
1]
molecules is rapidly increasing. This mainly results from the
remarkable properties of the fluorine atom and fluorinated
[
8]
BTP. In parallel, the formation of the corresponding organo-
zinc or organoboron species and their use in Negishi and Suzuki
[
2]
groups. The introduction of such fluorine-containing moieties
into molecules strongly affects their biological and physical
properties. Particular attention has been paid to the trifluoro-
[
9]
cross-coupling reactions were reported by Jiang and Xu. How-
ever, to the best of our knowledge, no report dealing with di-
rect C–H bond functionalization with BTP has been reported.
Hence, as part of our ongoing research program devoted to
[
3]
methyl group. This group can easily replace a methyl group,
for example, to avoid in vivo hydrolysis, although its steric de-
mand is closer to that of an isopropyl group than a methyl
group. Hence, a wide range of elegant and straightforward
methods to introduce this key motif into molecules have been
reported. Among these recent advances, direct C–H bond func-
tionalization has appeared as an atom-economical pathway for
the introduction of fluorinated moieties, and particularly for the
[
10]
the direct introduction of fluorinated building blocks, in this
paper, we report the use of BTP for the direct introduction of
the α-(trifluoromethyl)vinyl motif into aromatic rings. This atom-
[
4]
introduction of the CF group. However, although this latter
3
approach has been widely explored, the direct introduction of
small building blocks bearing a CF moiety has been less stud-
3
ied. Part of the portfolio of trifluoromethylated building blocks,
2-bromo-3,3,3-trifluoropropene (BTP) has appeared as an excel-
lent and readily available reagent. This reagent is not classified
as an ozone-depleting agent, and it has turned out to be an
interesting and inexpensive candidate for use as a fire suppress-
[
5]
ant. This building block has been already used in classical
cross-coupling reactions to access α-(trifluoromethyl)vinyl deriv-
atives, either directly or through conversion into the corre-
[
a] Normandie Université, COBRA, UMR 6014 et FR 3038,
Université de Rouen, INSA Rouen, CNRS
1
rue Tesnière, 76821 Mont Saint-Aignan Cedex, France
E-mail: jean-philippe.bouillon@univ-rouen.fr
http://www.lab-cobra.fr/
http://www.univ-rouen.fr/
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/ejoc.201501217.
Scheme 1. State-of-the art and proposed approach. DG = directing group.
76 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2016, 76–82

Full Paper
economical approach should give a rapid and straightforward
access to α-(trifluoromethyl)styrene derivatives.
Results and Discussion
At the outset of the project, we chose N-pivaloylaniline (1a) as a
model substrate to determine the reaction conditions (Table 1).
Table 1. Optimization of the reaction conditions.[a]
Entry
[Pd]
Additive
Solvent
T [°C]
Yield [%][b]
1
2
3
4
5
6
7
8
9
PdCl
PdCl
PdCl
PdCl
PdCl
PdCl
Pd(TFA)
Pd(OAc)
PdBr
PdBr
PdBr
2
AgOTf
AgOTf
AgOTf
AgOTf
DMF
toluene
THF
90
90
90
90
90
90
90
90
90
90
70
13
0
18
38
0
2
2
2
2
2
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
2
Ag O
Cu(OAc)
AgOTf
AgOTf
AgOTf
AgOTf
AgOTf
2
0
2
19
18
40
61
2
2
2
2
[c]
1
1
0
[c,d]
[e]
1
99 (74)
[
(
a] 1a (0.2 mmol), BTP (1 mmol), [Pd] (0.02 mmol), additive (0.2 mmol), solvent
2 mL). [b] Yields were determined by 19F NMR spectroscopic analysis using
α,α,α-trifluoroacetophenone as an internal standard. [c] 1.5 equiv. of AgOTf
was used. [d] 15 mol-% of [Pd] was used, and the reaction time was extended
to 24 h. [e] Isolated yield.
An initial attempt was carried out using PdCl as the catalyst
2
in the presence of AgOTf in DMF at 90 °C. Pleasingly, the desired
α-(trifluoromethyl)styryl derivative (i.e., 2a) was obtained in
1
3 % yield (Table 1, Entry 1). A screening of solvents showed
Scheme 2. Scope of the reaction. [a] Isolated yields. [b] Yields were deter-
mined by F NMR spectroscopic analysis using α,α,α-trifluoroacetophenone
as an internal standard. [c] Reaction was carried out on a 4.18 mmol scale.
1
9
that toluene was inefficient (Table 1, Entry 2), whereas THF gave
a slight enhancement of the yield with 18 % (Table 1, Entry 3).
By switching from THF to 1,4-dioxane, the yield increased to
[
d] Reaction was carried out on a 4.26 mmol scale. [e] Reaction was carried
out on a 3.95 mmol scale.
38 % (Table 1, Entry 4). A survey of additives revealed that
AgOTf was crucial to ensure a decent conversion into the de-
sired product (i.e., 2a), since no reaction occurred when Ag O
First para-substituted anilides bearing an electron-donating
2
or Cu(OAc) was used (Table 1, Entries 5 and 6). Finally, several group were studied. para-Methyl-, -ethyl-, and -tert-butyl-substi-
2
palladium catalysts were evaluated: Pd(TFA) , Pd(OAc) , and tuted anilides were readily converted into the corresponding
2
2
PdBr (Table 1, Entries 7–9), of which PdBr was the most effi- trifluoromethylated products (i.e., 2b–2d) in good yields. The
2
2
cient (40 %) (Table 1, Entry 9). An increase in the amount of reaction was readily carried out on a larger scale, which demon-
AgOTf from 1.0 to 1.5 equiv. provided the desired product (i.e., strates the versatility of the process. Indeed, 2b and 2d were
2
a) in 61 % yield (Table 1, Entry 10). To our delight, a decrease obtained in similar yields, 70 and 57 %, respectively, when the
in the temperature to 70 °C, along with the use of 15 mol-% reactions were carried out on a ca. 4 mmol scale. The electron-
PdBr , gave the α-(trifluoromethyl)styrene 2a in almost quanti- donating methoxy group was tolerated, and the resulting α-
2
tative yield, as determined by 19F NMR spectroscopy, and 74 % (trifluoromethyl)styrene derivative (i.e., 2e) was isolated in 61 %
isolated yield (Table 1, Entry 11). Note, that under our optimized yield. Interestingly, anilides bearing a halogen atom in the para
conditions, other nitrogen-based directing groups were ineffi- position reacted under our reaction conditions to give trifluoro-
[
11]
cient at promoting the reaction.
methylated products 2f and 2g in moderate yields. Note that
Having established the optimized reaction conditions, we no alteration of the halogen atom was observed, since no trace
next sought to investigate the scope of the reaction with other of product 2a (which would result from a dehalogenation proc-
substrates (Scheme 2).
ess) was detected in the crude reaction mixture. An ester moi-
Eur. J. Org. Chem. 2016, 76–82
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77
© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
ety was compatible with this transformation, which demon-
strates the functional-group tolerance of our method. The reac-
tion was then tested with meta-substituted anilides 1i–1m as
substrates. Alkyl-substituted anilides gave the desired products
(
i.e., 2i and 2j) in fairly decent yields (78 and 61 %, respectively).
Halogen-substituted anilides 1k and 1l gave the corresponding
trifluorovinyl compounds (i.e., 2k and 2l) in moderate yields,
still with no alteration of the C–halogen bond, thus opening
the possibility of postfunctionalization. In addition, the ester-
substituted anilide 1m gave 2m in 61 % isolated yield. The pres-
ence of an ortho substituent did not hamper the reaction, and
2
n was isolated in 72 % yield, and in 71 % yield on a gram
Scheme 4. Synthetically useful transformations of the products. [a] Reaction
was carried out on a 3 mmol scale. [b] Reaction was carried out on a 1 mmol
scale.
scale. Disubstituted anilides 1o–1p reacted smoothly to give
trifluoromethylated adducts 2o–2p in moderate to good yields.
[
12]
Based on a previous paper,
dox-neutral mechanism to explain the reaction outcome
Scheme 3). First, the Pd catalyst reacts with N-pivaloyl-
we propose the following re-
methyl)styryl derivatives in moderate to good yields. The pro-
ducts were subsequently modified to demonstrate the versatil-
ity of these trifluoromethylated building blocks.
(
aniline 1 to form the corresponding palladacycle (i.e., I). This
species then coordinates to BTP (intermediate II), and carbo-
palladation of the alkene takes place. The resulting organo-
palladium species (i.e., III) undergoes β-halide elimination
to deliver the product
alyst.
the success of the process, we speculate that it could assist
with the β-halide elimination. However, we cannot rule out a
plausible Pd /Pd catalytic cycle, since no clear evidence about
the reaction mechanism was obtained.
Experimental Section
2
and regenerates the cat-
[
12,13]
General Methods: All reactions were carried out using oven-dried
glassware and magnetic stirring under argon, unless otherwise
stated. Reaction temperatures are reported as the temperatures of
the bath surrounding the vessel. NMR spectra were recorded with
As we know that the presence of AgOTf is crucial for
II
IV
1
13
a Bruker DXP 300 instrument; H NMR spectra at 300.1 MHz,
C
19
NMR spectra at 75.5 MHz, F NMR spectra at 282.4 MHz. Chemical
shifts (δ) are quoted in parts per million (ppm), and spectra were
calibrated using the residual solvent peak for CDCl (δ = 7.26 ppm;
3
H
δ = 77.0 ppm) or using external CFCl (δ = 0.0 ppm). The following
C
3
F
abbreviations have been used: δ (chemical shift), J (coupling con-
stant), br. (broad), s (singlet), d (doublet), dd (doublet of doublets),
t (triplet), q (quartet), m (multiplet). High-resolution mass spectra
(HRMS) were recorded with a Waters LCT Premier instrument. Infra-
red spectra were recorded with a Perkin–Elmer Paragon 100 (ATR)
FTIR spectrometer; the wave numbers (ν˜) of recorded IR signals are
–
1
quoted in cm . Melting points were recorded with a Kofler appara-
tus. Analytical thin-layer chromatography was carried out on pre-
®
coated silica gel 60 Alugram Xtra SIL G/UV2 sheets with a layer
54
thickness of 200 μm. Spots on the plates were visualized with short-
wave UV light (λ = 254 nm), and/or staining with phosphomolybdic
acid or KMnO solution followed by heating. Flash chromatography
4
was carried out on Merck silica gel (40–63 mesh) either by the
standard technique, or by using a Biotage Isolera One flash purifica-
tion system (gradient of solvents). Reverse-phase chromatography
was carried out with a puriFlash 215 instrument using a puriFlash
C18HP 15 μm 55G Flash column. AgOTf was purchased from ABCR,
Scheme 3. Proposed mechanism.
®
®
Finally, we investigated the versatility of our products
(
Scheme 4). The directing group was readily cleaved under and PdBr from Alfa Aesar, and both were stored in a glove box.
2
acidic conditions to give the desired aniline derivatives (i.e., 3a Dry 1,4-dioxane (sealed bottle) was purchased from Acros Organics,
and 3b) in 69 and 70 % yields, respectively. Selective reduction and 2-bromo-3,3,3-trifluoropropene (BTP) from Fluorochem, and
both were used as received.
of the double bond was achieved using Pd/C as a catalyst under
hydrogen to provide anilide 4 in 85 % yield.
General Procedure for the Synthesis of Pivalamides 1: Pivaloyl
chloride (1.4 mL, 11 mmol, 1.1 equiv.) was slowly added to a solu-
tion of the aniline derivative (1.2 g, 10 mmol, 1.0 equiv.) and Et N
3
Conclusions
(1.5 mL, 11 mmol, 1.1 equiv.) in dry THF (30 mL) at 0 °C. The reaction
mixture was then allowed to warm to room temperature, and
stirred for an additional 3 h. The formed triethylammonium chloride
was removed by filtration, and the solvents were removed under
We describe in this paper the first direct introduction of the
α-(trifluoromethyl)vinyl motif by means of directed C–H bond
functionalization. This method was applied to a broad range of vacuum. The residue was purified by chromatography on silica gel.
[
14a]
[14b]
anilide derivatives to give the corresponding α-(trifluoro- All the spectral data of the pivalamides (1a, 1b, 1f),
1d,
(1e,
Eur. J. Org. Chem. 2016, 76–82
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78 © 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
h),[14c] 1g,[14d] 1i,[14e] (1k, 1l, 1m, 1p),[14f] 1n,[14g] and 1o[14h] are
122.5, 39.7, 27.5, 20.7 ppm. HRMS (ESI ): calcd. for C H F NO [M
15 19 3
+
1
+
in agreement with literature data.
+ H] 286.1419; found 286.1421 (+0.7 ppm).
N-(4-Ethylphenyl)pivalamide (1c): Purification by silica gel column
chromatography (height 100 mm, width 80 mm; eluent: petroleum
N-[4-Ethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pivalamide
(2c): Purification by silica gel column chromatography (Biotage sys-
ether/EtOAc, from 80:20 to 66:34) gave 1c (0.89 g, 86 %) as a white tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
solid, on a 5.0 mmol scale. R (petroleum ether/Et O, 66:34) = 0.75;
Et O, from 85:15 to 75:25) gave 2c (39 mg, 66 %) as a white solid.
f
2
2
m.p. 117–118 °C. IR: ν˜ = 3325, 2955, 1651, 1599, 1514, 1407, 833, R (petroleum ether/Et O, 75:25) = 0.37; m.p. 49–50 °C. IR: ν = 3272,
f
2
˜
–
1
1
–1 1
7
7
1
12 cm . H NMR (300.1 MHz, CDCl ): δ = 7.43 (d, J = 8.4 Hz, 2 H),
2982, 1646, 1514, 1166, 1153, 1126, 1069, 960, 825, 648 cm . H
3
.28 (br. s, 1 H), 7.14 (d, J = 8.4 Hz, 2 H), 2.61 (q, J = 7.5 Hz, 2 H),
.31 (s, 9 H), 1.21 (t, J = 7.5 Hz, 3 H) ppm. C NMR (75.5 MHz,
NMR (300.1 MHz, CDCl ): δ = 8.05 (d, J = 8.4 Hz, 1 H), 7.40 (br. s, 1
3
1
3
H), 7.23 (dd, J = 8.4, J = 1.8 Hz, 1 H), 7.01 (d, J = 1.8 Hz, 1 H), 6.24
(d, J = 1.2 Hz, 1 H), 5.67 (d, J = 1.2 Hz, 1 H), 2.62 (q, J = 7.5 Hz, 2
CDCl ): δ = 176.4, 140.2, 135.6, 128.2, 120.1, 39.5, 28.3, 27.6,
3
+
+
19
1
5.7 ppm. HRMS (ESI ): calcd. for C H NO [M + H] 206.1545;
H), 1.25 (s, 9 H), 1.22 (t, J = 7.5 Hz, 3 H) ppm. F NMR (282.4 MHz,
1
3 20
13
found 206.1544 (+0.5 ppm).
CDCl ): δ = –67.6 (s) ppm. C NMR (75.5 MHz, CDCl ): δ = 176.4,
3
3
1
5
1
40.2, 136.4 (q, JC,F = 31.6 Hz), 133.5, 129.4, 129.3, 124.7 (q, JC,F
=
N-(3-Ethylphenyl)pivalamide (1j): Purification by silica gel column
chromatography (height 100 mm, width 80 mm; eluent: petroleum
ether/EtOAc, from 80:20 to 66:34) gave 1j (1.21 g, 89 %) as a white
.1 Hz), 124.6, 122.7 (q, J = 274.1 Hz), 122.6, 39.7, 28.1, 27.5,
C,F
+
+
5.5 ppm. HRMS (ESI ): calcd. for C H F NONa [M + Na] 322.1395;
16 20 3
found 322.1389 (–1.9 ppm).
solid, on a 6.6 mmol scale. R (petroleum ether/EtOAc, 66:34) = 0.78;
f
m.p. 121–122 °C. IR: ν˜ = 3310, 2968, 1652, 1590, 1539, 1428, 794,
N-[4-(tert-Butyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pival-
amide (2d): Purification by silica gel column chromatography (Biot-
age system 25 g; height 80 mm, width 30 mm; eluent: petroleum
–1 1
6
97 cm . H NMR (300.1 MHz, CDCl ): δ = 7.46 (s, 1 H), 7.38–7.28
3
(
7
m, 2 H), 7.24–7.17 (m, 1 H), 6.95 (d, J = 6.6 Hz, 1 H), 2.64 (q, J =
.5 Hz, 2 H), 1.33 (s, 9 H), 1.24 (t, J = 7.5 Hz, 3 H) ppm. 13C NMR
ether/Et O, from 90:10 to 80:20) gave 2d (41 mg, 62 %) as a beige
2
(
3
75.5 MHz, CDCl ): δ = 176.5, 145.3, 138.0, 128.8, 123.7, 119.5, 117.2,
3
solid; the reaction was also run on a 4.26 mmol scale to give 2d
(800 mg. 57 %). R (petroleum ether/Et O, 75:25) = 0.40; m.p. 76–
+
9.6, 28.9, 27.6, 15.5 ppm. HRMS (ESI ): calcd. for C H NO [M +
1
3 20
f
2
+
H] 206.1545; found 206.1541 (–1.9 ppm).
7
1
8
7 °C. IR: ν˜ = 3278, 2967, 1645, 1514, 1395, 1368, 1344, 1267, 1176,
–
1 1
128, 1071, 956, 820, 639 cm . H NMR (300.1 MHz, CDCl ): δ =
Typical Procedure for the Palladium-Catalysed Synthesis of α-
3
.08 (d, J = 8.7 Hz, 1 H), 7.42 (dd, J = 8.7, J = 2.1 Hz, 1 H), 7.41 (br.
(
Trifluoromethyl)styrenes: A dried tube was loaded with PdBr2
s, 1 H), 7.18 (d, J = 2.1 Hz, 1 H), 6.25 (d, J = 1.2 Hz, 1 H), 5.68 (d, J =
(8.0 mg, 0.03 mmol, 0.15 equiv.), AgOTf (77.1 mg, 0.3 mmol,
1
9
1
.2 Hz, 1 H), 1.30 (s, 9 H), 1.25 (s, 9 H) ppm. F NMR (282.4 MHz,
1.5 equiv.), and pivalamide 1 (0.2 mmol, 1.0 equiv.) under Ar. Then
1,4-dioxane (2 mL) and 2-bromo-3,3,3-trifluoropropene (0.1 mL,
1.0 mmol, 5.0 equiv.) were added. The tube was sealed, and the
13
CDCl ): δ = –67.6 (s) ppm. C NMR (75.5 MHz, CDCl ): δ = 176.4,
3
3
47.1, 136.6 (q, JC,F = 31.5 Hz), 133.3, 127.0, 126.9, 124.7 (q, JC,F
1 =
5
.1 Hz), 124.1, 122.8 (q, J = 274.3 Hz), 122.1, 39.8, 34.3, 31.2,
suspension was stirred at 70 °C for 24 h. The reaction mixture was
diluted with diethyl ether (10 mL), and filtered through a plug of
C,F
+
+
27.5 ppm. HRMS (ESI ): calcd. for C H F NO [M + H] 328.1888;
18 25 3
®
found 328.1873 (–4.6 ppm).
Celite . The solvents were removed under vacuum, and the residue
was purified by a flash chromatography with a Biotage Isolera One
flash purification system.
N-[4-Methoxy-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pival-
amide (2e): Purification by silica gel column chromatography (Biot-
age system 25 g; height 80 mm, width 30 mm; eluent: petroleum
N-[2-(3,3,3-Trifluoroprop-1-en-2-yl)phenyl]pivalamide (2a): Puri-
fication by silica gel column chromatography (Biotage system 25 g;
ether/Et
2
O, from 92:8 to 85:15) gave 2e (37 mg, 61 %) as a beige
(petroleum ether/Et
O, 75:25) = 0.17; m.p. 60–61 °C. IR: ν˜ =
3309, 2840, 1646, 1614, 1501, 1220, 1174, 1118, 1066, 1041, 803 cm
height 80 mm, width 30 mm; eluent: petroleum ether/Et O, from solid. R
2
f
2
–
9
0:10 to 80:20) gave 2a (40 mg, 74 %) as a beige solid. R (petroleum
f
1
1
ether/Et O, 75:25) = 0.39; m.p. 66–67 °C. IR: ν˜ = 3328, 2963, 1694,
. H NMR (300.1 MHz, CDCl
651, 1510, 1174, 1163, 1119, 770, 749 cm . H NMR (300.1 MHz, s, 1 H), 6.94 (dd, J = 9.0, J = 3.0 Hz, 1 H), 6.75 (d, J = 3.0 Hz, 1 H),
CDCl ): δ = 8.23 (d, J = 8.1 Hz, 1 H), 7.48 (br. s, 1 H), 7.43–7.37 (m,
6.21 (d, J = 1.2 Hz, 1 H), 5.67 (d, J = 1.2 Hz, 1 H), 3.79 (s, 3 H), 1.25
3
): δ = 7.93 (d, J = 9.0 Hz, 1 H), 7.26 (br.
2
–
1 1
1
3
(s, 9 H) ppm. 19F NMR (282.4 MHz, CDCl
): δ = –67.5 (s) ppm.
13
C
1
H), 7.21–7.11 (m, 2 H), 6.27 (s, 1 H), 5.69 (s, 1 H), 1.26 (s, 9 H) ppm.
3
1
9
13
F NMR (282.4 MHz, CDCl ): δ = –67.7 (s) ppm. C NMR (75.5 MHz,
NMR (75.5 MHz, CDCl ): δ = 176.6, 156.2, 136.0 (q, JC,F = 31.7 Hz),
3
3
CDCl ): δ = 176.5, 136.7 (q, J = 31.5 Hz), 136.0, 130.1, 130.0, 125.0
128.9, 127.0, 125.0, 124.7 (q, JC,F = 5.2 Hz), 122.7 (q, JC,F = 274.0 Hz),
3
C,F
+
(
2
q, JC,F = 5.4 Hz), 124.2, 124.0, 122.7 (q, J = 274.0 Hz), 122.3, 40.0,
115.7, 115.0, 55.5, 39.6, 27.5 ppm. HRMS (ESI ): calcd. for
C,F
+
+
+
7.5 ppm. HRMS (ESI ): calcd. for C H F NO [M + H] 272.1262;
C
15
H
19
F
3
NO
2
[M + H] 302.1368; found 302.1370 (+0.7 ppm).
1
4 17 3
found 272.1258 (–1.5 ppm).
N-[4-Chloro-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pivalamide
(2f): Purification by silica gel column chromatography (Biotage sys-
tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
N-[4-Methyl-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pivalamide
2b): Purification by silica gel column chromatography (Biotage sys-
(
tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
Et O, from 90:10 to 80:20) gave 2f (28 mg, 46 %) as a white solid.
2
Et O, from 90:10 to 80:20) gave 2b (40 mg, 70 %) as a beige solid;
the reaction was also run on a 4.18 mmol scale to give 2b (850 mg, 2963, 1651, 1497, 1169, 1165, 1123, 897, 818, 802, 641 cm .
R (petroleum ether/Et O, 75:25) = 0.44; m.p. 67–68 °C. IR: ν˜ = 3321,
2
f
2
–1 1
H
7
0 %). R (petroleum ether/Et O, 75:25) = 0.42; m.p. 46–47 °C. IR: ν˜ =
NMR (300.1 MHz, CDCl ): δ = 8.19 (d, J = 9.0 Hz, 1 H), 7.43 (br. s, 1
f
2
3
–
3
325, 2962, 1652, 1505, 1154, 1124, 1119, 1071, 819, 806, 749 cm
H), 7.37 (dd, J = 9.0, J = 1.8 Hz, 1 H), 7.19 (d, J = 1.8 Hz, 1 H), 6.30
1
1
19
.
H NMR (300.1 MHz, CDCl ): δ = 8.03 (d, J = 8.4 Hz, 1 H), 7.38 (br.
(s, 1 H), 5.71 (s, 1 H), 1.25 (s, 9 H) ppm. F NMR (282.4 MHz, CDCl3):
3
s, 1 H), 7.20 (dd, J = 8.1, J = 1.2 Hz, 1 H), 7.00 (br. s, 1 H), 6.23 (d,
J = 1.2 Hz, 1 H), 5.65 (d, J = 1.2 Hz, 1 H), 2.32 (s, 3 H), 1.25 (s, 9 H)
δ = –67.5 (s) ppm. 13C NMR (75.5 MHz, CDCl ): δ = 176.5, 135.2 (q,
3
JC,F = 32.0 Hz), 134.7, 130.1, 129.9, 129.1, 125.7 (q, JC,F = 5.1 Hz),
ppm. 19F NMR (282.4 MHz, CDCl ): δ = –67.6 (s) ppm. C NMR
13
125.6, 123.4, 122.4 (q, J = 274.1 Hz), 39.9, 27.4 ppm. HRMS (ESI ):
+
3
C,F
calcd. for C14H1535ClF NONa [M + Na] 328.0692; found 328.0683
+
(75.5 MHz, CDCl ): δ = 176.5, 136.3 (q, JC,F = 31.6 Hz), 133.9, 133.3,
3
3
1
30.6, 130.5, 124.7 (q, JC,F = 5.1 Hz), 124.6, 122.7 (q, JC,F = 274.1 Hz),
(–2.7 ppm).
Eur. J. Org. Chem. 2016, 76–82
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Full Paper
N-[4-Bromo-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pivalamide
2g): Purification by silica gel column chromatography (Biotage sys-
tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
R (petroleum ether/Et O, 75:25) = 0.37; m.p. 187–188 °C. IR: ν˜ =
f
2
(
3315, 2969, 1659, 1496, 1342, 1220, 1166, 1149, 1126, 1087, 966,
–
1 1
795, 781, 726, 664 cm . H NMR (300.1 MHz, CDCl ): δ = 7.48 (d,
3
Et O, from 95:5 to 85:15) gave 2g (21 mg, 30 %) as a yellow solid.
J = 7.8 Hz, 1 H), 7.29–7.18 (m, 2 H), 7.04 (br. s, 1 H), 6.04 (s, 1 H),
2
19
R (petroleum ether/Et O, 75:25) = 0.44; m.p. 78–79 °C. IR: ν˜ = 3305,
5.69 (s, 1 H), 1.28 (s, 9 H) ppm. F NMR (282.4 MHz, CDCl ): δ =
f
2
3
2
6
7
5
–
962, 1717, 1652, 1494, 1256, 1164, 1121, 1067, 883, 816, 799,
–66.7 (s) ppm. 13C NMR (75.5 MHz, CDCl ): δ = 177.0, 135.6 (q, J
=
=
3
C,F
–1 1
38 cm . H NMR (300.1 MHz, CDCl ): δ = 8.16 (d, J = 8.7 Hz, 1 H),
31.6 Hz), 134.9, 133.5, 133.2, 130.5, 129.1, 128.2, 124.0 (q, J
3
C,F
+
.51 (d, J = 8.7 Hz, 1 H), 7.43 (br. s, 1 H), 7.33 (s, 1 H), 6.30 (s, 1 H),
5.1 Hz), 122.8 (q, J = 273.5 Hz), 39.2, 27.4 ppm. HRMS (ESI ): calcd.
C,F
1
9
35
+
.71 (s, 1 H), 1.25 (s, 9 H) ppm. F NMR (282.4 MHz, CDCl ): δ = for C H
ClF NONa [M + Na] 328.0692; found 328.0699
3
3
14 15
67.5 (s) ppm. 13C NMR (75.5 MHz, CDCl ): δ = 176.5, 135.2, 135.1
(+2.1 ppm).
N-[5-Bromo-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pivalamide
2l): Purification by silica gel column chromatography (Biotage sys-
3
(
1
q, JC,F = 32.0 Hz), 133.0, 132.7, 125.9 (q, JC,F = 5.1 Hz), 125.8, 123.6,
+
22.4 (q, J = 274.1 Hz), 116.6, 39.9, 27.4 ppm. HRMS (ESI ): calcd.
C,F
(
7
9
+
for C H
BrF NONa [M + Na] 372.0187; found 372.0179
3
14
15
tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
Et O, from 95:5 to 85:15) gave 2l (32 mg, 46 %) as a white solid. Rf
2
(–2.2 ppm).
Ethyl
4-Pivalamido-3-(3,3,3-trifluoroprop-1-en-2-yl)benzoate (petroleum ether/Et O, 75:25) = 0.56; m.p. 114–115 °C. IR: ν˜ = 3319,
2
–1 1
(2h): Purification by silica gel column chromatography (Biotage sys- 2969, 1652, 1479, 1342, 1187, 1163, 1127, 1084, 817, 609 cm . H
tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
NMR (300.1 MHz, CDCl ): δ = 8.55 (d, J = 1.8 Hz, 1 H), 7.47 (br. s, 1
3
Et O, from 95:5 to 85:15) gave 2h (29 mg, 42 %) as a beige solid. R
H), 7.27 (dd, J = 8.4, J = 1.8 Hz, 1 H), 7.05 (d, J = 8.4 Hz, 1 H), 6.30
2
f
1
9
(
petroleum ether/Et O, 75:25) = 0.25; m.p. 45–46 °C. IR: ν˜ = 3447, (d, J = 1.2 Hz, 1 H), 5.70 (d, J = 1.2 Hz, 1 H), 1.25 (s, 9 H) ppm.
F
2
13
2
1
8
975, 1717, 1585, 1512, 1480, 1285, 1264, 1170, 1123, 1107, 1069,
NMR (282.4 MHz, CDCl ): δ = –67.7 (s) ppm. C NMR (75.5 MHz,
3
–1 1
022, 768, 637 cm . H NMR (300.1 MHz, CDCl ): δ = 8.47 (d, J =
CDCl ): δ = 176.5, 137.2, 135.5 (q, J = 31.9 Hz), 131.1, 127.0, 125.7
3
3
C,F
.7 Hz, 1 H), 8.07 (dd, J = 8.7, J = 1.8 Hz, 1 H), 7.88 (d, J = 1.8 Hz, 1
(q, JC,F = 5.2 Hz), 124.7, 124.1, 122.5, 122.4 (q, J = 274.1 Hz), 40.0,
C,F
+
79
+
H), 7.65 (br. s, 1 H), 6.36 (d, J = 1.2 Hz, 1 H), 5.74 (d, J = 1.2 Hz, 1
H), 4.37 (q, J = 7.2 Hz, 2 H), 1.39 (t, J = 7.2 Hz, 3 H), 1.27 (s, 9 H)
27.4 ppm. HRMS (ESI ): calcd. for C H
BrF NONa [M + Na]
15 3
14
372.0187; found 372.0196 (+2.4 ppm).
Ethyl 3-Pivalamido-4-(3,3,3-trifluoroprop-1-en-2-yl)benzoate
2m): Purification by silica gel column chromatography (Biotage
ppm. 19F NMR (282.4 MHz, CDCl ): δ = –67.6 (s) ppm. C NMR
13
3
(
75.5 MHz, CDCl ): δ = 176.5, 165.6, 140.1, 135.6 (q, JC,F = 32.1 Hz),
3
(
1
2
31.7, 131.6, 126.0 (q, JC,F = 5.1 Hz), 125.5, 123.0, 122.4 (q, JC,F =
system 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
+
74.3 Hz), 120.4, 61.1, 40.2, 27.4, 14.3 ppm. HRMS (ESI ): calcd. for
Et O, from 95:5 to 85:15) gave 2m (42 mg, 61 %) as a beige solid.
2
+
C H F NO Na [M + Na] 366.1293; found 366.1290 (–0.8 ppm).
17
20
3
3
R (petroleum ether/Et O, 75:25) = 0.19; m.p. 60–61 °C. IR: ν˜ = 3272,
f
2
N-[5-Methyl-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pivalamide
2969, 1717, 1653, 1485, 1287, 1256, 1227, 1191, 1171, 1111, 1064,
–
1 1
(2i): Purification by silica gel column chromatography (Biotage sys- 1024, 903, 774, 742, 628 cm . H NMR (300.1 MHz, CDCl ): δ = 8.76
3
tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
(d, J = 1.5 Hz, 1 H), 7.76 (dd, J = 8.4, J = 1.5 Hz, 1 H), 7.43 (br. s, 1
Et O, from 80:20 to 70:30) gave 2i (44 mg, 78 %) as a beige solid.
H), 7.21 (d, J = 8.4 Hz, 1 H), 6.23 (d, J = 1.2 Hz, 1 H), 5.64 (d, J =
1.2 Hz, 1 H), 4.31 (q, J = 7.2 Hz, 2 H), 1.32 (t, J = 7.2 Hz, 3 H), 1.20
2
R (petroleum ether/Et O, 75:25) = 0.50; m.p. 93–94 °C. IR: ν˜ = 3305,
f
2
–
1
1
19
13
2
968, 1646, 1514, 1480, 1344, 1186, 1159, 1125, 816, 612 cm . H (s, 9 H) ppm. F NMR (282.4 MHz, CDCl ): δ = –67.4 (s) ppm.
C
=
3
NMR (300.1 MHz, CDCl ): δ = 8.08 (s, 1 H), 7.45 (br. s, 1 H), 7.08 (d,
NMR (75.5 MHz, CDCl ): δ = 176.6, 165.8, 136.2, 135.6 (q, J
3
3
C
,
F
J = 7.8 Hz, 1 H), 6.95 (d, J = 7.8 Hz, 1 H), 6.24 (d, J = 1.2 Hz, 1 H), 32.0 Hz), 132.3, 130.2, 128.6, 125.3 (q, JC,F = 5.1 Hz), 125.2, 123.3,
1
9
+
5
(
.65 (d, J = 1.2 Hz, 1 H), 2.37 (s, 3 H), 1.26 (s, 9 H) ppm. F NMR
122.4 (q, JC,F = 274.4 Hz), 61.3, 39.9, 27.4, 14.3 ppm. HRMS (ESI ):
1
3
+
282.4 MHz, CDCl ): δ = –67.7 (s) ppm. C NMR (75.5 MHz, CDCl3):
calcd. for C H F NO Na [M + Na] 366.1293; found 366.1302
3
17 20
3
3
δ = 176.5, 140.3, 136.2 (q, JC,F = 31.6 Hz), 135.7, 129.9, 124.9 (q,
JC,F = 5.1 Hz), 124.8, 122.73 (q, JC,F = 274.1 Hz), 122.66, 121.4, 39.9,
(+2.5 ppm).
N-[3-(3,3,3-Trifluoroprop-1-en-2-yl)-1,1′-biphenyl-2-yl]pival-
amide (2n): Purification by silica gel column chromatography (Biot-
age system 25 g; height 80 mm, width 30 mm; eluent: petroleum
+
+
2
7.5, 21.5 ppm. HRMS (ESI ): calcd. for C H F NO [M + H]
15 19 3
2
86.1419; found 286.1412 (–2.4 ppm).
N-[5-Ethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pivalamide
ether/Et O, from 90:10 to 75:25) gave 2n (50 mg, 72 %) as a yellow
2
(2j): Purification by silica gel column chromatography (Biotage sys- solid; the reaction was also run on a 3.95 mmol scale to give 2n
tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/ (970 mg, 71 %). R (petroleum ether/Et O, 75:25) = 0.17; m.p. 160–
f
2
Et O, from 80:20 to 70:30) gave 2j (37 mg, 61 %) as a white solid. 161 °C. IR: ν˜ = 3314, 2974, 1651, 1497, 1455, 1219, 1167, 1122, 964,
2
–
1 1
R (petroleum ether/Et O, 75:25) = 0.43; m.p. 79–80 °C. IR: ν˜ = 3326,
757, 738, 699 cm . H NMR (300.1 MHz, CDCl ): δ = 7.32–7.18 (m,
f
2
3
2
6
7
1
7
968, 1652, 1494, 1346, 1189, 1167, 1116, 1075, 965, 831,
8 H), 6.82 (br. s, 1 H), 6.04 (d, J = 1.2 Hz, 1 H), 5.75 (d, J = 1.2 Hz, 1
–1
1
19
27 cm . H NMR (300.1 MHz, CDCl ): δ = 8.12 (d, J = 1.5 Hz, 1 H),
.47 (br. s, 1 H), 7.11 (d, J = 7.8 Hz, 1 H), 6.97 (dd, J = 7.8, J = 1.5 Hz,
H), 6.25 (d, J = 1.2 Hz, 1 H), 5.66 (d, J = 1.2 Hz, 1 H), 2.66 (q, J = JC,F = 31.3 Hz), 133.7, 133.0, 131.1, 130.0, 128.8, 128.1, 127.5, 127.4,
.5 Hz, 2 H), 1.26 (s, 9 H), 1.25 (t, J = 7.5 Hz, 3 H) ppm. F NMR 123.7 (q, J = 5.1 Hz), 123.1 (q, JC,F = 273.6 Hz), 38.8, 27.2 ppm.
H), 1.02 (s, 9 H) ppm. F NMR (282.4 MHz, CDCl ): δ = –66.9 (s)
3
3
ppm. 13C NMR (75.5 MHz, CDCl ): δ = 177.2, 141.6, 139.0, 136.1 (q,
3
19
C,F
+
1
3
+
(
282.4 MHz, CDCl ): δ = –67.7 (s) ppm. C NMR (75.5 MHz, CDCl3):
HRMS (ESI ): calcd. for C H F NONa [M + Na] 370.1395; found
3
20 20 3
δ = 176.5, 146.6, 136.2 (q, JC,F = 31.5 Hz), 135.8, 129.9, 129.8, 124.9
370.1389 (1.6 ppm).
(
2
3
q, JC,F = 5.1 Hz), 123.6, 122.7 (q, J = 274.1 Hz), 121.5, 39.9, 28.9,
7.5, 15.3 ppm. HRMS (ESI ): calcd. for C H F NONa [M + Na]
16 20 3
22.1395; found 322.1397 (+0.6 ppm).
C,F
N-[4,5-Dimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pival-
amide (2o): Purification by silica gel column chromatography (Biot-
age system 25 g; height 80 mm, width 30 mm; eluent: petroleum
+
+
N-[5-Chloro-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pivalamide
ether/Et O, from 90:10 to 80:20) gave 2o (38 mg, 63 %) as a yellow
2
(
2k): Purification by silica gel column chromatography (Biotage sys- solid. R (petroleum ether/Et O, 75:25) = 0.37; m.p. 82–83 °C. IR: ν˜ =
f
2
tem 25 g; height 80 mm, width 30 mm; eluent: petroleum ether/
Et O, from 90:10 to 80:20) gave 2k (25 mg, 41 %) as a white solid.
3272, 2963, 1651, 1495, 1455, 1175, 1119, 1103, 949, 876, 675,
–
1 1
640 cm . H NMR (300.1 MHz, CDCl ): δ = 7.96 (s, 1 H), 7.36 (br. s,
2
3
Eur. J. Org. Chem. 2016, 76–82
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
1
2
H), 6.96 (s, 1 H), 6.21 (d, J = 0.9 Hz, 1 H), 5.63 (d, J = 0.9 Hz, 1 H),
vacuum, and the crude residue was purified by silica gel column
chromatography (Biotage system 25 g; height 80 mm, width
1
9
.27 (s, 3 H), 2.23 (s, 3 H), 1.25 (s, 9 H) ppm. F NMR (282.4 MHz,
1
3
CDCl ): δ = –67.6 (s) ppm. C NMR (75.5 MHz, CDCl ): δ = 176.5,
30 mm; eluent: petroleum ether/Et O, 80:20 to 75:25) to give 4
3
3
2
1
38.7, 136.2 (q, JC,F = 31.5 Hz), 133.5, 132.7, 130.8, 124.6 (q, JC,F
=
(24 mg, 85 %) as a white solid. R (petroleum ether/Et O, 75:25) =
f
2
5
.1 Hz), 123.7, 122.8 (q, JC,F = 274.1 Hz), 122.2, 39.7, 27.5, 19.8, 0.22; m.p. 110–111 °C. IR: ν˜ = 3282, 2925, 1647, 1496, 1163, 1129,
+
+
–1 1
1
9.1 ppm. HRMS (ESI ): calcd. for C H F NO [M + H] 300.1575;
1106, 1042, 986, 812 cm . H NMR (300.1 MHz, CDCl ): δ = 7.29 (d,
1
6
21
3
3
found 300.1563 (–4.0 ppm).
J = 8.1 Hz, 1 H), 7.28 (s, 1 H), 7.10 (d, J = 8.1 Hz, 1 H), 3.61–3.50 (m,
1
H), 2.34 (s, 3 H), 1.51 (d, J = 7.2 Hz, 3 H), 1.34 (s, 9 H) ppm; note
N-[4,6-Dimethyl-2-(3,3,3-trifluoroprop-1-en-2-yl)phenyl]pival-
19
that one proton (NH) is missing. F NMR (282.4 MHz, CDCl ): δ =
3
amide (2p): Purification by reverse-phase chromatography (carried
–
1
3
71.8 (d, J = 9.0 Hz) ppm. 13C NMR (75.5 MHz, CDCl ): δ = 177.3,
38.7, 135.5, 127.9, 127.7, 127.6, 127.5 (q, JC,F = 280.1 Hz), 127.4,
9.4, 37.7 (q, J = 27.1 Hz), 27.6, 20.9, 13.7 (q, J = 3.0 Hz) ppm.
®
3
out on a puriFlash C18HP 15 μm 55G flash column; eluent: H O/
2
CH CN) gave 2p (18 mg, 30 %) as a white solid. R (petroleum ether/
3
f
C,F
C,F
Et O, 75:25) = 0.23; m.p. 152–153 °C. IR: ν˜ = 3332, 2961, 1651, 1506,
2
+
+
HRMS (ESI ) calcd. for C H F NO [M + H] 288.1575; found
–
1
1
15 21 3
1
355, 1237, 1162, 1152, 1116, 966, 861, 667 cm . H NMR
288.1573 (–0.7 ppm).
(
5
(
300.1 MHz, CDCl ): δ = 7.09 (s, 1 H), 6.91 (br. s, 2 H), 6.01 (s, 1 H),
3
19
.57 (s, 1 H), 2.31 (s, 3 H), 2.19 (s, 3 H), 1.26 (s, 9 H) ppm. F NMR
1
3
282.4 MHz, CDCl ): δ = –67.4 (s) ppm. C NMR (75.5 MHz, CDCl3): Acknowledgments
3
δ = 177.0, 136.9, 136.8, 136.4 (q, JC,F = 31.2 Hz), 132.2, 132.1, 131.2,
This work was partially supported by INSA Rouen, Rouen Uni-
versity, the Centre National de la Recherche Scientifique (CNRS),
the European Fund for Research Development (EFRD), Labex
SynOrg (ANR-11-LABX-0029), and the Région Haute-Normandie
1
2
3
28.6, 123.1 (q, JC,F = 5.3 Hz), 123.0 (q, J = 273.5 Hz), 39.1, 27.6,
C,F
+
+
0.9, 18.2 ppm. HRMS (ESI ): calcd. for C H F NO [M + H]
1
6 21 3
00.1575; found 300.1570 (–1.7 ppm).
General Procedure for the Removal of the Directing Group:
Compound 2b or 2d (1.0 mmol) was dissolved in a mixture of 1,4-
(
(
Crunch Network). Q. Z. thanks the China Scholarship Council
CSC) for a doctoral fellowship.
dioxane (5 mL) and HCl (12
M; 5 mL), and the reaction mixture
was heated at reflux overnight. The mixture was cooled to room
temperature, then Na CO (satd. aq.) was added until the pH had
Keywords: Synthetic methods · Fluorine · C-H activation ·
Palladium · Homogeneous catalysis
2
3
reached 9–10. The mixture was extracted with ethyl acetate (3 ×
0 mL). The combined organic phases were washed with brine
20 mL) and dried with anhydrous MgSO , and then the solvents
3
(
4
[
1] a) S. Purser, P. R. Moore, S. Swallow, V. Gouverneur, Chem. Soc. Rev. 2008,
7, 320–330; b) H.-J. Böhm, D. Banner, S. Bendels, M. Kansy, B. Kuhn, K.
were evaporated under reduced pressure. The residue was purified
by silica gel column chromatography.
3
Müller, U. Obst-Sander, M. Stahl, ChemBioChem 2004, 5, 637–643; c) K.
Müller, C. Faeh, F. Diederich, Science 2007, 317, 1881–1886; d) J. Wang,
M. Sánchez-Roselló, J. L. Aceña, C. del Pozo, A. E. Sorochinsky, S. Fustero,
V. A. Soloshonok, H. Liu, Chem. Rev. 2014, 114, 2432–2506; e) E. A. Ilardi,
E. Vitaku, J. T. Njardarson, J. Chem. Educ. 2013, 90, 1403–1405; f) E. A.
Ilardi, E. Vitaku, J. T. Njardarson, J. Med. Chem. 2014, 57, 2832–2842.
4
-Methyl-2-(3,3,3-trifluoroprop-1-en-2-yl)aniline (3a): Purifica-
tion by silica gel column chromatography (Biotage system 25 g;
height 80 mm, width 30 mm; eluent: petroleum ether/Et O, from
2
9
3
2
5:5 to 85:15) gave 3a (412 mg, 69 %) as a yellow liquid on a
.0 mmol scale. R (petroleum ether/Et O, 75:25) = 0.40. IR: ν˜ = 3385,
[2] a) D. O'Hagan, Chem. Soc. Rev. 2008, 37, 308–319; b) R. D. Chambers,
Fluorine in Organic Chemistry, Blackwell, Oxford, 2004; c) K. Uneyama,
Organofluorine Chemistry, Blackwell, Oxford, 2006.
f
2
–
1
1
924, 1624, 1506, 1344, 1156, 1117, 958, 814 cm . H NMR
(
(
(
300.1 MHz, CDCl ): δ = 6.94 (d, J = 8.1 Hz, 1 H), 6.93 (s, 1 H), 6.59
3
[
3] a) H. Egami, M. Sodeoka, Angew. Chem. Int. Ed. 2014, 53, 8294–8308;
Angew. Chem. 2014, 126, 8434–8449; b) T. Liang, C. N. Neumann, T. Ritter,
Angew. Chem. Int. Ed. 2013, 52, 8214–8264; Angew. Chem. 2013, 125,
d, J = 8.1 Hz, 1 H), 6.12 (s, 1 H), 5.61 (s, 1 H), 3.55 (br. s, 2 H), 2.21
s, 3 H) ppm. 1 F NMR (282.4 MHz, CDCl ): δ = –67.2 (s) ppm.
9
13
C
3
NMR (75.5 MHz, CDCl ): δ = 142.0, 136.4 (q, J = 31.0 Hz), 130.5,
3
C,F
8
372–8423;c)G.Landelle,A.Panossian,S.Pazenok,J.-P.Vors,F.R.Leroux,Beil-
1
1
2
30.4, 127.2, 123.8 (q, JC,F = 5.3 Hz), 123.1 (q, J = 274.0 Hz), 118.9,
C,F
stein J. Org. Chem. 2013, 9, 2476–2536; d) G. Landelle, A. Panossian, F. R.
Leroux, Curr. Top. Med. Chem. 2014, 14, 941–951; e) for a special issue
on fluorine chemistry, see: Chem. Rev. 2015, 115, 563–1306.
+
+
15.9, 20.0 ppm. HRMS (ESI ): calcd. for C H F N [M + H]
1
0 11 3
02.0844; found 202.0840 (–2.0 ppm).
[
4] a) P. Chen, G. Liu, Synthesis 2013, 45, 2919–2939; b) H. Liu, Z. Gu, X.
Jiang, Adv. Synth. Catal. 2013, 355, 617–626; c) X.-F. Wu, H. Neumann, M.
Beller, Chem. Asian J. 2012, 7, 1744–1754; d) T. Besset, C. Schneider, D.
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4
-(tert-Butyl)-2-(3,3,3-trifluoroprop-1-en-2-yl)aniline (3b): Purifi-
cation by silica gel column chromatography (Biotage system 25 g;
height 80 mm, width 30 mm; eluent: petroleum ether/Et O, from
2
9
5:5 to 85:15) gave 3b (171 mg, 70 %) as a yellow liquid. R (petro-
f
leum ether/Et O, 75:25) = 0.36. IR: ν˜ = 3347, 2964, 1623, 1505, 1345,
2
–
1 1
1
162, 1124, 969, 826 cm . H NMR (300.1 MHz, CDCl ): δ = 7.24 (d,
3
1
34, 1298–1304; h) N. D. Litvinas, P. S. Fier, J. F. Hartwig, Angew. Chem.
J = 8.4 Hz, 1 H), 7.09 (s, 1 H), 6.70 (d, J = 8.4 Hz, 1 H), 6.20 (s, 1 H),
1
9
Int. Ed. 2012, 51, 536–539; Angew. Chem. 2012, 124, 551–554; i) T. Liu, X.
Shao, Y. Wu, Q. Shen, Angew. Chem. Int. Ed. 2012, 51, 540–543; Angew.
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V. I. Babushok, G. T. Linteris, D. R. Burgess Jr., P. T. Baker, Combust. Flame
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5
.69 (s, 1 H), 3.67 (br. s, 2 H), 1.29 (s, 9 H) ppm. F NMR (282.4 MHz,
1
3
CDCl ): δ = –67.3 (s) ppm. C NMR (75.5 MHz, CDCl ): δ = 141.8,
3
3
1
1
41.1, 136.7 (q, JC,F = 31.0 Hz), 126.98, 126.94, 124.0 (q, JC,F = 5.2 Hz),
23.1 (q, JC,F = 274.4 Hz), 118.7, 115.7, 33.9, 31.4 ppm. HRMS (ESI ):
[
+
+
calcd. for C H F N [M + H] 244.1313; found 244.1314 (+0.4 ppm).
13 17 3
6
82; d) D. R. Burgess Jr., V. I. Babushok, G. T. Linteris, J. A. Manion, Int. J.
N-[5-Methyl-2-(1,1,1-trifluoropropan-2-yl)phenyl]pivalamide
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Chem. Kinet. 2015, 47, 533–563.
(
[
[
[
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were added to EtOH (2 mL). The suspension was stirred at 50 °C
under hydrogen (1 atm) overnight. The mixture was cooled to room
temperature, then it was diluted with diethyl ether (10 mL), and
®
filtered through a plug of Celite . The solvents were removed under
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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[
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[
[
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Published Online: November 16, 2015
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7
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© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim