Oxy-trifluoromethylation of alkenes and its application to the synthesis of β-trifluoromethylstyrene derivatives

Article abstract of DOI:10.1016/j.jfluchem.2014.05.009

Oxy-trifluoromethylation of di-substituted styrenes and dienes was achieved by using Cu/Togni's reagent system. Not only gem-di-substituted styrenes, but also a β-methylstyrene derivative were transformed to the corresponding oxy-trifluoromethylation prod

Full text of DOI:10.1016/j.jfluchem.2014.05.009

Accepted Manuscript
Title: Oxy-trifluoromethylation of alkenes and its application
to the synthesis of β-trifluoromethylstyrene derivatives
Author: Hiromichi Egami Ryo Shimizu Yoshihiko Usui
Mikiko Sodeoka
PII:
S0022-1139(14)00138-9
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.jfluchem.2014.05.009
FLUOR 8321
To appear in:
FLUOR
Received date:
Revised date:
Accepted date:
25-4-2014
23-5-2014
26-5-2014
Please cite this article as: H. Egami, R. Shimizu, Y. Usui, M. Sodeoka,
Oxy-trifluoromethylation of alkenes and its application to the synthesis of
rmbeta-trifluoromethylstyrene derivatives, Journal of Fluorine Chemistry (2014),
http://dx.doi.org/10.1016/j.jfluchem.2014.05.009
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*Graphical Abstract - Pictogram
Graphical abstract:
Page 1 of 21

*Graphical Abstract - Synopsis
Graphical abstract:
Trifluoromethylation of - and -methylstyrenes and dienes was achieved by using Togni’s
reagent with Cu catalyst. These reactions were successfully applied for -trifluoromethylstyrene
synthesis.
Page 2 of 21

*Highlights (for review)
Highlights:
1. Trifluoromethylation of - and -methylstyrene derivatives was achieved by using Togni’s
reagent with Cu catalyst.
2. 1,4-Oxy-trifluoromethylation of dienes was accomplished.
3. -Trifluoromethylstyrene derivatives were synthesized from styrenes.
Page 3 of 21

Oxy-trifluoromethylation of alkenes and its application to the synthesis of
-trifluoromethylstyrene derivatives
Hiromichi Egamia,b, Ryo Shimizua,c, Yoshihiko Usui a,c, and Mikiko Sodeokaa,b,c,d
*
aSynthetic Organic Chemistry Laboratory, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
bSodeoka Live Cell Chemistry Project, ERATO, Japan Science and Technology Agency, 2-1 Hirosawa,
Wako, Saitama 351-0198, Japan
cGraduate School of Science and Engineering, Saitama University, 255 Shimo-okubo, Sakura-ku, Saitama
338-8570, Japan
dRIKEN Center for Sustainable Resource Science, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan
E-mail: sodeoka@riken.jp, Fax: (+81) 48-462-4666
Abstract: Oxy-trifluoromethylation of di-substituted styrenes and dienes was achieved by using
Cu/Togni’s reagent system. Not only gem-di-substituted styrenes, but also a -methylstyrene
derivative were transformed to the corresponding oxy-trifluoromethylation products.
1,4-Addition products were obtained selectively in the reaction of mono-substituted dienes. These
reactions provide a new approach for the synthesis of -trifluoromethyl styrene derivatives.
Key words: trifluoromethyl, catalysis, Togni’s reagent, styrene, diene
1. Introduction
Introduction of a trifluoromethyl group into an organic framework often results in increased
metabolic stability, lipophilicity, and bioactivity. [1] Therefore, development of new
methodologies for construction of trifluoromethylated organic compounds is of interest not only
in organic chemistry, but also in the fields of pharmaceutical and agrochemical science. [1] Indeed,
many reports on trifluoromethylation, including Csp2-CF3 and Csp3-CF3 bond formation reactions,
have appeared. [2] Among trifluoromethylation reactions, trifluoromethylation of alkenes,
especially difunctionalization-type trifluoromethylation, is a topic of growing interest. [3] We
have studied trifluoromethylation reactions of alkene, alkyne, and heteroaromatic compounds
using Togni’s reagent [4,5] and we reported the oxy-trifluoromethylation reaction of
mono-substituted styrene type compounds catalyzed by copper ion in 2012 (Scheme 1). [5c]
Szabó independently reported the same type of trifluoromethylation [6] and Buchwald reported
an intramolecular oxy-trifluoromethylation in the same year. [7a] Buchwald also developed an
asymmetric version of his reaction in 2013. [7b]
Page 4 of 21

The pioneering work by Fuchikami on oxy-trifluoromethylation using CF3I and palladium
catalyst was reported in 1987. [8] TFA was employed by Uneyama as a trifluoromethyl source for
electrochemical reactions, [9] and Nagano reported oxy-trifluoromethylation of an alkene via
iodo-trifluoromethylation. [10] Akita and Koike accomplished oxy-trifluoromethylation with a
combination of Umemoto reagent [11] and photo-redox catalysis, [12] and Studer described a
radical reaction system using Togni’s reagent with TEMPONa in 2012. [13] Intramolecular and
intermolecular oxy-trifluoromethylation reactions using Umemoto reagent, Togni’s reagent, or
Langlois reagent have recently been the main focuses of attention. [14]
In our original paper, as well as Szabo’s paper, only limited substrates, mainly
mono-substituted styrene-type compounds, were examined as substrates for intermolecular
oxy-trifluoromethylation using Cu/Togni’s reagent system (Scheme 1). [5c,6] We also reported
two examples of reactions of dienes. [5c] Xu et al. investigated ligand effects in the
diastereoselective reaction of dienes in 2013. [15] However, the scope of substrates, such as
di-substituted alkenes and dienes, in the original systems has not been fully established. In
addition, although we originally reported a direct synthesis of -trifluoromethylstyrene
derivatives from styrenes, there were only two examples. [5c,16] In the present report, we
describe the oxy-trifluoromethylation of di-substituted styrenes and diene derivatives as well as
application of this reaction leading to the synthesis of -trifluoromethyl styrene derivatives.
Scheme 1. Oxy-trifluoromethylation of mono-substituted styrene derivatives using the
combination of copper salt and Togni’s reagent
2. Results and discussion
In order to expand the substrate scope of our trifluoromethylation reaction system, we first
focused on gem-di-substituted styrene derivative 2a. The reaction with [(MeCN)4Cu]PF6, which
was reported to be a better catalyst for mono-substituted styrene derivatives, [5c] was found to
provide
a
mixture
of
-methyl--trifluoromethyl-4-methoxystyrene
3a’
and
-trifluoroethyl-4-methoxystyrene 3a”, which would be generated via E1 reaction from 3a (eq 1).
Page 5 of 21

Therefore, we concluded that cationic copper species were not suitable for the reaction of
gem-di-substituted styrene derivatives, and CuI was chosen as a catalyst for the
oxy-trifluoromethylation to suppress the E1 reaction, because CuI has a lower Lewis acidity than
[(MeCN)4Cu]PF6. Fortunately, the reaction using CuI proceeded smoothly at 40 °C and 3a was
obtained in 93% yield (Table 1). An ortho-substituent affected the reaction rate, but 3b was
obtained in high yield. The reaction of 3c having a naphthalene ring also proceeded smoothly.
However, an electron-withdrawing group, such as bromide, retarded the reaction, and 3d was
obtained in only 11% yield. In this case, 56% of the substrate was recovered, suggesting that this
reaction system is not suitable for electron-deficient substrates. In contrast, cyclic-type substrate
2e afforded the desired oxy-trifluoromethylation product 3e in 46% yield, together with 42%
yield of 4-trifluoroethyl-1,2-dihydronaphthalene 3e’. The reaction of a -methylstyrene
derivative also proceeded, albeit with low diastereoselectivity (Scheme 2). The stereochemistry
of the product was determined after hydrolysis of 5 to give a known material. [17] It is noteworthy
that the syn/anti ratio was the same in the reactions using trans- and cis-isomers.
O2CAr
[(MeCN)4Cu]PF6
CF3
Ar'
(10 mol%)
1 (1.2 equiv.)
3a (Ar = 2-I-C6H4): 4%
(1)
CH2Cl2
23 °C, 30 min
+
+
CF3
3a': 36%
CF3
= Ar'
MeO
Ar'
Ar'
3a": 31%
2a
The yields were determined by 19F NMR analysis using trifluoromethylbenzene.
Page 6 of 21

Table 1. Oxy-trifluoromethylation of gem-di-substituted styrene derivativesa
CuI (20 mol%)
1 (1.2 equiv.)
O2CAr
CF3
R
CH2Cl2, 40 °C
R
2
3: Ar = 2-I-C6H4
O2CAr
CF3
O2CAr
CF3
O2CAr
CF3
MeO
Br
OMe
3a: 93% (2 h)
3b: 93% (10 h)
3c: 81% (12 h)
CF3
O2CAr
CF3
ArCO2
CF3
3e: 46% (10 h)
3e': 42%
3d: 11% (12 h)
aThe reactions were carried out with CuI (20 mol%) and Togni’s reagent (1.2 equiv.) in CH2Cl2 (1 mL) at
40 °C on a 0.2 mmol scale.
Ar
CuI (20 mol%)
1 (1.2 equiv.)
O
O
CH2Cl2, 40 °C
MeO
CF3
MeO
5: Ar = 2-I-C6H4
4a
4b
88% (syn:anti = 1:2.2)
CuI (20 mol%)
1 (1.2 equiv.)
5: 87% (syn:anti = 1:2.2)
CH2Cl2, 40 °C
MeO
Scheme 2. Trifluoromethylation of trans- and cis--methylstyrene derivatives
We next examined the reactions of dienes. [18] A mixture of 1,4-addition product and the
corresponding 1,2-addition product was generated when [(MeCN)4Cu]PF6 was used as a catalyst
(eq 2). To our delight, however, we found that the reaction of mono-substituted dienes exclusively
afforded 1,4-adducts when CuI was used as a catalyst (Table 2, entries 1-5). 1,4-Adduct 7a was
produced from trans-1-phenyl-1,3-butadiene 6a in 93% yield and no 1,2-addition product was
detected (entry 1). Contrary to the reaction of mono-substituted styrene derivatives, dienes
bearing an electron-withdrawing group, or an electron-donating group, provided the desired
products. Although the reaction of 6b bearing a methoxy group was faster than that of 6c bearing
a fluorine atom on the phenyl ring, the corresponding products 7b and 7c were obtained in 91%
and 87% yields, respectively (entries 2 and 3). Surprisingly, aliphatic dienes 6d and 6e were also
good substrates, affording 7d and 7e, respectively, in excellent yields (entries 4 and 5). Despite
Page 7 of 21

the sterically hindered nature of 6f, compound 7f was obtained in 83% yield (entry 6). Meanwhile,
1,2-oxy-trifluoromethylation occurred exclusively when terminally di-substituted diene was used
as a substrate, and 8g was obtained from 1,1-diphenyl-1,3-butadiene 6g in 97% yield (entry 7). It
should be noted that all compounds were obtained with excellent stereo- and regio-selectivity.
[19]
[(MeCN)4Cu]PF6
Ar
Ar
(10 mol%)
1 (1.2 equiv.)
O
O
O
O
+
(2)
Ph
CF3
CF3
CH2Cl2
Ph
Ph
2a
7a (Ar = 2-I-C6H4) 8a (Ar = 2-I-C6H4)
23 °C, 2 h
40 °C, 2 h
23%
15%
15%
45%
The yields were determined by 19F NMR analysis using trifluoromethylbenzene.
Table 2. Oxy-trifluoromethylation of dienes a
Ar
Ar
CuI (10 mol%)
R3
R3
O
O
1 (1.2 equiv.)
O
O
or
R1
CF3
CF3
CH2Cl2, 40 °C, 2 h R1
R1
R2
R2
R2
6
8: Ar = 2-I-C6H4
7: Ar = 2-I-C6H4
(R3 = H)
Entry
1
Product
Yield [%]
Ar
93
7a
O
O
CF3
Ph
Ar
2
91
7b
7c
O
O
CF3
MeO
3b
87
Ar
O
O
CF3
F
4c
5c
85
92
Ar
7d
7e
O
O
CF3
5
Ar
O
O
CF3
Ar
6
83
7f
O
O
CF3
Ph
Page 8 of 21

7d
97
Ar
8g
Ph
O
O
CF3
Ph
aThe reactions were carried out with catalyst (10 mol %) and Togni's reagent 2 (1.2 equiv) in CH2Cl2 (1 mL)
at 40 °C on a 0.2 mmol scale.
bRun for 6 h.
cRun for 1 h.
dRun with [(MeCN)4Cu]PF6 as the catalyst on a 1 mmol scale.
The reaction character was completely changed by addition of a Brønsted acid. That is, the
reaction in the presence of p-TsOH provided -trifluoromethylstyrene derivatives instead of
oxy-trifluoromethylation products. To demonstrate the utility of this reaction system, various
substrates were examined (Table 3). [20] Styrenes having oxygen functionality, such as a
methoxy group, on the aryl ring reacted smoothly. Compounds 10a, 10b and 10c were obtained in
90%, 87% and 62% yields, respectively. In addition, heteroaromatic compounds tolerated these
reaction conditions (10d, 10e). A diene derivative could be successfully transformed to
trifluoromethylated diene under the same reaction conditions (10f).
Table 3. Direct formation of -trifluoromethylstyrene derivativesa
[(MeCN)4Cu]PF6
(10 mol%)
1 (1.2 equiv.)
p-TsOH (1 equiv.)
CF3
Ar
Ar
CH2Cl2, 40 °C
9
10
CF3
CF3
CF3
O
O
MeO
10a: 90% (1 h)
TBSO
10b: 87% (2 h)
10c: 62% (2 h)
CF3
CF3
CF3
Ph
S
AcN
10d: 66% (1 h)
10f: 81% (2 h)b
10e: 73% (1 h)
aThe reactions were carried out with [(MeCN)4Cu]PF6 (10 mol %), 1 (1.2 equiv) and p-TsOH (1.0 equiv) in
CH2Cl2 (1 mL) at 40 °C on a 0.2 mmol scale.
bRun with 10 mol% of CuI instead of [(MeCN)4Cu]PF6.
In general, styrene derivatives have a nature to polymerize under acidic conditions. In fact,
-trifluoromethyl-2-hydroxystyrene 10g was not obtained in the presence of acid due to rapid
Page 9 of 21

polymerization. However, it was found that addition of Et3N allowed 10g to be obtained in 73%
yield (eq 3). The base presumably suppresses polymerization and activates the hydroxyl group to
stabilize the benzylic cation. On the other hand, p-TsOH failed to accelerate the E1 reaction of a
substrate bearing an amide moiety, such as 11h. Therefore, triflic acid (TfOH) was tried, and the
desired product 10h was isolated in 99% yield (eq 4). Although the transformation of
oxy-trifluoromethylation product 11i failed under the acidic conditions, it was found that 11i
could be converted to 10i by treatment with sodium hexamethyldisilazide (NaHMDS) (eq 5).
Thus, we consider that a -trifluoromethylstyrene derivative can be accessed if the
oxy-trifluoromethylation product is obtained.
[(MeCN)4Cu]PF6
(10 mol%)
1 (1.2 equiv.)
Et3N (2 equiv.)
CF3
(3)
(4)
CH2Cl2, 23 °C, 6 h
OH
OH
9g
10g: 73%
Ar
O
O
CF3
TfOH (1.5 equiv.)
CF3
CH2Cl2, 40 °C
AcHN
12 h
AcHN
11h (Ar = 2-I-C6H4)
10h: 99%
Ar
O
O
CF3
NaHMDS (2 equiv.)
CF3
(5)
THF, –78 °C, 1 h
t-Bu
t-Bu
11i (Ar = 2-I-C6H4)
10i: 64%
3. Conclusion
In this report, we describe oxy-trifluoromethylation of di-substituted styrene derivatives and
dienes using Cu/Togni’s reagent system, which was originally reported by our group and also at
the same time by Szabó. It is noteworthy that the reactions of both cis- and trans--methylstyrene
derivatives gave similar results. 1,4-Addition products were selectively obtained in the reaction of
mono-substituted dienes using CuI, and various compounds having not only aryl but also
aliphatic groups could be utilized as substrates. In addition, we succeeded in the synthesis of
-trifluoromethylstyrene derivatives under both acidic and basic conditions. We believe that these
reactions provide a new approach for the synthesis of trifluoromethylated building blocks. Further
studies, including detailed examination of the reaction mechanism, are ongoing in our laboratory.
4. Experimental
4.1. General
Page 10 of 21

All reactions were carried out under a nitrogen atmosphere. Togni’s reagent was prepared
according to the literature. [21] Dichloromethane (CH2Cl2) was purchased from Kanto Chemical
Co., Inc.. CuI and [(CH3CN)4Cu]PF6 were obtained from commercial sources, and used as
received. Other reagents were purified by usual methods.
1H and 19F NMR spectra were measured on a JEOL JNM-ECS-400 spectrometer at 400 and 376
13
MHz, respectively. C NMR spectra were recorded on a JEOL JNM-ECS-400 spectrometer at
100 MHz. Chemical shifts were reported downfield from TMS (= 0) or CDCl3 for 1H NMR. For
13C NMR, chemical shifts were reported in the scale relative to CDCl3. For 19F NMR, chemical
shifts were reported in the scale relative to a CFCl3 external standard (0 ppm). Infrared spectra
were measured on a Thermo Nicolet iS5, and only diagnostic absorptions are listed below.
ESI-MS was taken on Waters SYNAPT G2 MS. EI-MS was taken on a JEOL JMS-700V. Column
chromatography was performed with silica gel N-60 (40-100 m) purchased from Kanto
Chemical Co., Inc. TLC analysis was performed on Silica gel 60 F254-coated glass plates (Merck).
Visualization was accomplished by means of ultraviolet (UV) irradiation at 254 nm or by
spraying a solution of 12-molybdo(VI)phosphoric acid in ethanol as the developing agent.
4.2. Typical procedure for oxy-trifluoromethylation of substituted styrene derivatives
CuI (7.6 mg, 20 mol%) and Togni’s reagent 1 (76 mg, 1.2 equiv.) were added to a Schlenk tube
which had been flame-dried under vacuum. The tube was evacuated and backfilled with nitrogen.
CH2Cl2 (1 mL) and -methyl-4-methoxystyrene 2a (29.6 mg, 0.2 mmol) were added to the tube.
The reaction mixture was stirred for 2 h at 40 °C, then diluted with EtOAc (5 mL) and quenched
with aqueous saturated NaHCO3. The mixture was extracted with EtOAc. The organic layer was
washed with brine and dried over MgSO4. After filtration, the filtrate was concentrated under
reduced pressure and the residue was purified by column chromatography on silica gel
(hexane/EtOAc = 30/1) to give product 3a (86.0 mg, 93%) as a colorless oil.
4.2.1. 4,4,4-trifluoro-2-(4-methoxyphenyl)butan-2-yl 2-iodobenzoate (3a)
Colorless oil; 86.0 mg, 93%; 1H NMR (400 MHz, CDCl3): δ = 2.11 (s, 3H), 2.95–3.24 (m, 2H),
3.81 (s, 3H), 6.92 (d, J = 7.4 Hz, 2H), 7.16 (dd, J = 7.8, 7.8 Hz, 1H), 7.37-7.44 (m, 3H), 7.84 (d, J
= 7.8 Hz, 1H), 7.99 (d, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 25.5, 44.2 (q, J = 27.0
Hz), 55.2, 81.4 (br), 93.7, 113.9, 125.2 (q, J = 277.4 Hz), 125.7, 128.0, 130.8, 132.6, 134.9, 135.6,
141.3, 159.0, 164.8; 19F NMR (376 MHz, CDCl3): δ = –60.4 (t, J = 10.4 Hz); IR (neat): 2959,
1612, 1583, 1514, 1369, 1289, 1183 cm-1; HRMS (ESI+): Calcd. for [C18H16F3IO3+Na]+: m/z =
486.9994, Found: 487.0000.
Page 11 of 21

4.2.2. 4,4,4-trifluoro-2-(2-methoxyphenyl)butan-2-yl 2-iodobenzoate (3b)
Colorless oil; 86.8 mg, 93%; 1H NMR (400 MHz, CDCl3): δ = 2.12 (s, 3H), 3.38–3.50 (m, 2H),
3.85 (s, 3H), 6.94 (d, J = 8.3 Hz, 1H), 7.00 (ddd, J = 1.4, 7.6, 8.3 Hz, 1H), 7.17 (ddd, J = 1.4, 7.8,
7.8 Hz, 1H), 7.31 (m, 1H), 7.45 (ddd, J = 0.9, 7.8, 7.8 Hz, 1H), 7.53 (dd, J = 1.4, 7.8 Hz, 1H), 7.87
(dd, J = 1.4, 7.8 Hz, 1H), 8.00 (dd, J = 0.9, 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 25.0,
40.4 (q, J = 27.0 Hz), 55.2, 81.7 (q, J = 2.9 Hz), 93.8, 111.4, 120.7, 125.6 (q, J = 278.4 Hz), 126.5,
127.9, 129.1, 129.6, 130.7, 132.3, 136.0, 141.1, 155.5, 164.9; 19F NMR (376 MHz, CDCl3): δ =
–60.4 (t, J = 10.4 Hz); IR (neat): 2939, 1721, 1581, 1439, 1387, 1368, 1316 cm-1; HRMS (ESI+):
Calcd. for [C18H16F3IO3+Na]+: m/z = 486.9994, Found: 486.9992.
4.2.3. 4,4,4-trifluoro-2-(naphthalen-2-yl)butan-2-yl 2-iodobenzoate (3c)
Colorless oil; 78.3 mg, 81%; 1H NMR (400 MHz, CDCl3): δ = 2.25 (s, 3H), 3.09–3.21 (m, 1H),
3.29-3.41 (m, 1H), 7.18 (ddd, J = 1.8, 7.8, 7.8 Hz, 1H), 7.44–7.59 (m, 4H), 7.84–7.93 (m, 5H),
8.02 (dd, J = 0.9, 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 25.7, 44.0 (q, J = 27.0 Hz), 81.5
(q, J = 1.9 Hz), 93.9, 122.2, 123.4, 125.3 (q, J = 278.4 Hz), 126.3, 126.4, 127.5, 128.0, 128.3,
128.6, 130.9, 132.6, 133.0, 135.5, 140.3, 141.3, 164.8; 19F NMR (376 MHz, CDCl3): δ = –59.8 (t,
J = 10.4 Hz); IR (neat): 3059, 1731, 1583, 1508, 1464, 1430, 1198 cm-1; HRMS (ESI+): Calcd. for
[C21H16F3IO2+Na]+: m/z = 507.0045, Found: 507.0040.
4.2.4. 2-(3-bromophenyl)-4,4,4-trifluorobutan-2-yl 2-iodobenzoate (3d)
Colorless oil; 11.1 mg, 11%; 1H NMR (400 MHz, CDCl3): δ = 2.10 (s, 3 H), 2.96–3.21 (m, 2H),
7.18 (ddd, J = 1.8, 7.8, 7.8 Hz, 1H), 7.24–7.28 (m, 1H), 7.37 (ddd, J = 1.8, 1.8, 7.8 Hz, 1H),
7.42–7.46 (m, 2H), 7.59 (dd, J = 1.8, 1.8 Hz, 1H), 7.81 (dd, J = 1.8, 7.8 Hz, 1H), .8.00 (dd, J = 0.9,
7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 25.6, 44.0 (q, J = 27.0 Hz), 80.7, 93.8, 122.9, 123.1,
125.0 (q, J = 278.4 Hz), 127.0, 128.1, 130.2, 130.8, 131.0, 132.8, 135.3, 141.4, 145.3, 164.8: 19F
NMR (376 MHz, CDCl3): δ = –59.9 (t, J = 10.4 Hz). IR (neat): 2920, 1731, 1582, 1567, 1464,
1419, 1371, 1192 cm-1; HRMS (EI+): Calcd. for [C17H13BrF3IO2]+: m/z = 511.9096, Found:
511.9088.
4.2.5. 1-(2,2,2-trifluoroethyl)-1,2,3,4-tetrahydronaphthalen-1-yl 2-iodobenzoate (3e)
Colorless oil; 42.0 mg, 46%; 1H NMR (400 MHz, CDCl3): δ = 1.84–1.95 (m, 1H), 2.10–2.18 (m,
1H), 2.43–2.47 (m, 1H), 2.81–3.21 (m, 5H), 7.12–7.16 (m, 2H), 7.20–7.22 (m, 2H), 7.41 (dd, J =
7.8, 7.8 Hz, 1H), 7.46–7.48 (m, 1H), 7.81 (d, J = 7.8 Hz, 1H), 7.97 (d, J = 7.8 Hz, 1H); 13C NMR
(100 MHz, CDCl3): δ = 20.2, 29.1, 30.5, 44.0 (q, J = 27.0 Hz), 81.2 (br), 93.8, 125.2 (q, J = 278.4
Hz), 125.5, 126.4, 127.9, 128.0, 129.3, 130.7, 132.5, 135.7, 136.7, 137.3, 141.3, 164.5; 19F NMR
(376 MHz, CDCl3): δ = –59.3 (t, J = 10.4 Hz); IR (neat): 2940, 1730, 1582, 1490, 1463, 1429,
Page 12 of 21

1375, 1153 cm-1; HRMS (ESI+): Calcd. for [C19H16F3IO2+Na]+: m/z = 483.0045, Found:
483.0038.
4.2.6. 4-(2,2,2-trifluoroethyl)-1,2-dihydronaphthalene (3e’)
Colorless oil; 17.8 mg, 42%; 1H NMR (400 MHz, CDCl3): δ = 2.30-2.35 (m, 2H), 2.76-2.80 (m,
2H), 3.23 (dq, J = 0.9, 10.7 Hz, 2H), 6.12-1.14 (m, 1H), 7.13-7.23 (m, 4H); 13C NMR (100 MHz,
CDCl3): δ = 23.34, 28.07, 36.90 (q, J = 29.9 Hz), 122.9, 126.2 (q, J = 277.4 Hz), 126.6, 126.8,
127.4, 127.9, 132.2, 133.8, 136.4; 19F NMR (376 MHz, CDCl3): δ = –64.4 (t, J = 10.7 Hz); IR
(neat): 2939, 1489, 1353, 1255, 1127 cm-1; HRMS (EI+): Calcd. for [C12H11F3]+: m/z = 212.0812,
Found: 212.0814.
4.2.7. 3,3,3-trifluoro-1-(4-methoxyphenyl)-2-methylpropyl 2-iodobenzoate; syn/anti
mixture (1:2.2) (5)
Colorless oil; 82.1 mg, 88%; 1H NMR (400 MHz, CDCl3): syn-isomer, δ = 1.00 (d, J = 6.9 Hz ,
3H), 2.90-3.00 (m, 1H), 3.81 (s, 3H), 6.10 (d, J = 8.7 Hz, 1H), 6.89-6.92 (m, 2H), 7.12-7.15 (m,
1H), 7.36 (d, J = 8.8 Hz, 2H), 7.38-7.41 (m, 1H), 7.83 (dd, J = 1.4, 7.8 Hz, 1H), 7.98 (dd, J = 1.4,
7.8 Hz, 1H): anti-isomer, δ = 1.27 (d, J = 7.4 Hz, 3H), 2.65-2.74 (m, 1H), 3.81 (s, 3H), 6.37 (d, J
=3.7 Hz, 1H), 6.89-6.92 (m, 2H), 7.18 (ddd, J = 1.4, 7.8, 7.8 Hz, 1H), 7.30 (d, J =8.3 Hz, 2H), 7.44
(ddd, J = 1.4, 7.8, 7.8 Hz, 1H), 7.89 (dd, J =1.4, 7.8 Hz, 1H), 8.02 (dd, J = 1.4, 7.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ = 8.0, 10.8, 42.8 (q, J = 25.1 Hz), 44.3 (q, J = 25.1 Hz), 55.4, 55.4,
73.3, 75.1, 94.3, 94.5, 114.1, 127.0 (q, J = 280.3 Hz), 127.1 (q, J = 280.3), 127.6, 128.0, 128.1,
129.0, 129.1, 129.7, 131.0, 132.9, 133.0, 134.4, 134.5, 141.6, 141.7, 159.6, 160.0, 164.7; 19F
NMR (376 MHz, CDCl3): δ = –68.9 (d, J = 8.7 Hz, syn), –69.8 (d, J = 8.7 Hz, anti); IR (neat):
1732, 1613, 1513, 1463, 1243, 1126, 1015, 833, 740 cm-1; HRMS (ESI+): Calcd. for
[C18H16F3NO3+Na]+: m/z = 486.9994, Found: 486.9989.
4.3. Typical procedure for the oxy-trifluoromethylation of diene derivatives
CuI (3.8 mg, 10 mol%) and Togni’s reagent 1 (76 mg, 1.2 equiv.) were added to a Schlenk tube
which had been flame-dried under vacuum. The tube was evacuated and backfilled with nitrogen.
CH2Cl2 (1 mL) and 1-phenyl-1,3-butadiene 6a (26.0 mg, 0.2 mmol) were added to the tube. The
reaction mixture was stirred for 2 h at 40 °C, then diluted with EtOAc (5 mL) and quenched with
aqueous saturated NaHCO3. The mixture was extracted with EtOAc. The organic layer was
washed with brine and dried over MgSO4. After filtration, the filtrate was concentrated under
reduced pressure and the residue was purified by column chromatography on silica gel
(hexane/EtOAc = 30/1) to give product 7a (81.4 mg, 91%) as a colorless solid.
Page 13 of 21

4.3.1. (E)-5,5,5-trifluoro-1-phenylpent-2-en-1-yl 2-iodobenzoate (7a)
Colorless solid; 81.4 mg, 91%; 1H NMR (400 MHz, CDCl3): δ = 2.84–2.94 (m, 2H), 5.89–5.86 (m,
1H), 6.07 (dd, J = 6.0, 15.2 Hz, 1H), 6.54 (d, J = 6.0 Hz, 1H), 7.16 (m, 1H), 7.33–7.47 (m, 6H),
7.84 (dd, J = 1.8, 7.8 Hz, 1H), 8.00 (dd, J = 0.9, 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ =
37.0 (q, J = 30.8 Hz), 76.6, 94.2, 121.6 (q, J = 3.9 Hz), 125.6 (q, J = 277.4 Hz), 127.3, 127.9,
128.5, 128.7, 131.0, 132.8, 134.8, 135.2, 138.0, 141.4, 165.3; 19F NMR (376 MHz, CDCl3): δ =
–66.0 (t, J = 10.4 Hz); IR (neat): 3034, 1727, 1583, 1429, 1242, 1130, 1092, 1014, 968, 737, 696
cm-1; HRMS (ESI+): Calcd. for [C18H14F3IO2+Na]+: m/z = 468.9883, Found: 468.9880.
4.3.3. (E)-5,5,5-trifluoro-1-(4-methoxyphenyl)pent-2-en-1-yl 2-iodobenzoate (7b)
Colorless oil; 86.7 mg, 91%; 1H NMR (400 MHz, CDCl3): δ = 2.84–2.94 (m, 2H), 3.81 (s, 3H),
5.75-5.83 (m, 1H), 6.07 (dd, J = 6.0, 15.6 Hz, 1H), 6.50 (d, J = 6.0 Hz, 1H), 6.86–6.93 (m, 2 H),
7.14 (dd, J = 7.8 Hz, 1H), 7.34–7.43 (m, 3H), 7.80 (d, J = 7.8 Hz, 1H), 7.98 (d, J = 7.8 Hz, 1H);
13C NMR (100 MHz, CDCl3): δ = 37.0 (q, J = 29.9 Hz), 55.2, 76.2, 94.1, 114.0, 121.1 (q, J = 3.8
Hz), 125.6 (q, J = 276.5 Hz), 127.9, 128.9, 130.0, 130.9, 132.7, 134.9, 135.4, 141.4, 159.7, 165.3;
19F NMR (376 MHz, CDCl3): δ = –66.0 (t, J = 10.4 Hz); IR (neat): 2960, 1729, 1607, 1583, 1464,
1429, 1175 cm-1; HRMS (ESI+): Calcd. for [C19H16F3IO3+Na]+: m/z = 498.9994, Found:
498.9995.
4.3.4. (E)-5,5,5-trifluoro-1-(4-fluorophenyl)pent-2-en-1-yl 2-iodobenzoate (7c)
Colorless oil; 80.6 mg, 87%; 1H NMR (400 MHz, CDCl3): δ = 2.84–2.94 (m, 2H), 5.80 (dt, J = 7.3,
15.6 Hz, 1H), 6.03 (dt, J = 5.8, 15.6 Hz, 1H), 6.51 (d, J = 5.8 Hz, 1H), 7.05–7.18 (m, 3H),
7.39–7.45 (m, 3H), 7.78–7.81 (m, 1H), 7.98–8.00 (m, 1H); 13C NMR (100 MHz, CDCl3): δ = 36.9
(q, J = 29.9 Hz), 75.8, 94.0, 115.6 (d, J = 22.2 Hz), 121.7 (q, J = 2.9 Hz), 125.5 (q, J = 276.5 Hz),
127.9, 129.2 (d, J = 7.7 Hz), 130.9, 132.8, 133.8 (d, J = 2.9 Hz), 134.7, 135.0, 141.4, 162.7 (d, J =
247.6 Hz), 165.2; 19F NMR (376 MHz, CDCl3): δ = –113.0– –112.9 (m), –66.0 (t, J = 10.4 Hz); IR
(neat): 2933, 1605, 1583, 1562, 1465, 1429, 1042 cm-1; HRMS (ESI+): Calcd. for
[C18H13F4IO2+Na]+: m/z = 486.9794, Found: 486.9799.
4.3.5. (E)-1,1,1-trifluoroundec-3-en-5-yl 2-iodobenzoate (7d)
Colorless oil; 77.3 mg, 85%; 1H NMR (400 MHz, CDCl3): δ = 0.88 (t, J = 6.9 Hz, 3H), 1.29–1.42
(m, 8H), 1.68–1.88 (m, 2H), 2.79–2.91 (m, 2H), 5.50 (dt, J = 6.4, 6.4 Hz, 1H), 5.73–5.85 (m, 2H),
7.14 (ddd, J = 1.8, 7.8, 7.8 Hz, 1H), 7.40 (ddd, J = 0.9, 7.8, 7.8 Hz, 1H), 7.77 (dd, J = 1.8, 7.8 Hz,
1H), 7.99 (dd, J = 0.9, 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 14.0, 22.5, 25.0, 28.9, 31.6,
34.1, 37.0 (q, J = 29.9 Hz), 75.4, 93.9, 121.4 (q, J = 3.8 Hz), 125.6 (q, J = 276.5 Hz), 127.9, 130.7,
19
132.5, 135.4, 135.5, 141.3, 165.7; F NMR (376 MHz, CDCl3): δ = –66.1 (t, J = 10.4 Hz); IR
Page 14 of 21

(neat): 2928, 1727, 1465, 1430, 1347, 1285, 1043 cm-1; HRMS (ESI+): Calcd. for
[C18H22F3IO2+Na]+: m/z = 477.0514, Found: 477.0513.
4.3.6. (E)-1-cyclohexyl-5,5,5-trifluoropent-2-en-1-yl 2-iodobenzoate (7e)
Colorless oil; 73.7 mg, 92%; 1H NMR (400 MHz, CDCl3): δ = 1.02–1.29 (m, 5H), 1.66–1.86 (m,
6H), 2.76–2.94 (m, 2H), 5.32 (dd, J = 6.4, 6.4 Hz, 1H), 5.70–5.83 (m, 2H), 7.14 (ddd, J = 1.8, 7.8,
7.8 Hz, 1H), 7.41 (ddd, J = 0.9, 7.8, 7.8 Hz, 1H), 7.78 (dd, J = 1.4, 7.8 Hz, 1H), 7.99 (dd, J = 0.9,
7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 25.8, 25.8, 26.2, 28.5, 28.6, 37.0 (q, J = 29.9 Hz),
41.5, 79.4, 94.0, 122.1 (q, J = 3.8 Hz), 125.7 (q, J = 276.5 Hz), 127.9, 130.7, 132.5, 134.1, 135.3,
141.3, 165.6;19F NMR (376 MHz, CDCl3): δ = –66.1 (t, J = 10.4 Hz); IR (neat): 2927, 2854, 1583,
1464, 1450, 1429, 1281 cm-1; HRMS (ESI+): Calcd. for [C18H20F3IO2+Na]+: m/z = 475.0358,
Found: 475.0352.
4.3.7. (E)-5,5,5-trifluoro-2-methyl-1-phenylpent-2-en-1-yl 2-iodobenzoate (7f)
Colorless oil; 76.8 mg, 83%; 1H NMR (400 MHz, CDCl3): δ = 1.67 (s, 3H), 2.87–2.97 (m, 2H),
5.78 (t, J = 7.4 Hz, 1H), 6.46 (s, 1H), 7.14–7.18 (m, 1H), 7.32–7.43 (m, 6H), 7.85 (dd, J = 1.8, 7.8
Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 13.5, 32.7 (q, J = 29.9 Hz),
80.3, 94.2, 115.6 (q, J = 3.8 Hz), 126.1 (q, J = 276.5 Hz), 127.0, 127.9, 128.3, 128.5, 130.9, 132.8,
19
134.7, 137.5, 140.0, 141.5, 165.1; F NMR (376 MHz, CDCl3): δ = –65.7 (t, J = 10.4 Hz) ; IR
(neat): 2928, 1730, 1583, 1562, 1495, 1465, 1375, 1191 cm-1; HRMS (ESI+): Calcd. for
[C19H16F3IO2+Na]+: m/z = 483.0045, Found: 483.0040.
4.3.2. 5,5,5-trifluoro-1,1-diphenylpent-1-en-3-yl 2-iodobenzoate (8g)
Colorless solid; 506.5 mg, 97% 1H NMR (400 MHz, CDCl3): δ = 2.51–2.63 (m, 1H), 2.67–2.81
(m, 1H), 5.84–5.89 (m, 1H), 6.21 (d, J = 9.2 Hz, 1H), 7.12–7.16 (m, 1H), 7.24–7.31 (m, 7H),
7.36–7.45 (m, 4H), 7.74 (dd, J = 1.4, 7.8 Hz, 1H), 7.97 (d, J = 8.3 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δ = 38.7 (q, J = 27.9 Hz), 68.2 (q, J = 2.9 Hz), 93.9, 123.6, 125.2 (q, J = 277.4 Hz), 127.5,
127.9, 128.1, 128.3, 128.3, 128.6, 129.3, 130.8, 132.7, 135.0, 138.2, 140.8, 141.2, 146.9, 165.0;
19F NMR (376 MHz, CDCl3): δ = –62.7 (t, J = 10.4 Hz); IR (neat): 3058, 3026, 1730, 1583, 1494,
1445, 1429, 1387, 1281, 1237, 1129, 1090, 1015, 759, 739, 697 cm-1; HRMS (ESI+): Calcd. for
[C24H18F3IO2+Na]+: m/z = 545.0196, Found: 545.0199.
4.4. Typical procedure for the synthesis of -trifluoromethylstyrene derivatives
[(MeCN)4Cu]PF6 (7.5 mg, 10 mol%), p-TsOH･H2O (38 mg, 1 equiv.) and Togni’s reagent 1 (76
mg, 1.2 equiv.) were weighed and added to a Schlenk tube which had been flame-dried under
Page 15 of 21

vacuum. The tube was evacuated and backfilled with nitrogen. CH2Cl2 (1 mL) was added to the
tube, followed by addition of 4-methoxystyrene 9a (27 L, 0.2 mmol). The reaction mixture was
stirred for 1 h at 40 °C, then diluted with EtOAc (5 mL) and quenched with aqueous NaHCO3.
The mixture was extracted with EtOAc. The organic layer was washed with brine and dried over
MgSO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was
purified by column chromatography on silica gel (hexane/EtOAc = 30/1) to give 10a (36.6 mg,
90%) as a colorless solid.
4.4.1. (E)-1-methoxy-4-(3,3,3-trifluoroprop-1-en-1-yl)benzene (10a)
Colorless solid; 36.6 mg, 90%; 1H NMR (400 MHz, CDCl3): δ = 3.84 (s, 3H), 6.06 (dq, J = 6.9,
16.1 Hz, 1H), 6.91 (d, J = 8.7 Hz, 2H), 7.06–7.11 (m, 1H), 7.40 (d, J = 8.7 Hz, 2H); 13C NMR (100
MHz, CDCl3): δ = 55.3, 113.4 (q, J = 33.7 Hz), 114.3, 123.9 (q, J = 268.8 Hz), 126.0, 129.0, 137.1
(q, J = 6.7 Hz), 161.0; 19F NMR (376 MHz, CDCl3): δ = –62.7 (d, J = 6.9 Hz); IR (neat) 3036,
2966, 2937, 2846, 1664, 1606, 1514, 1290, 1258, 1177, 1131, 1108, 1029, 974, 810 cm-1; HRMS
(EI+): Calcd. for [C10H9F3O]+: m/z = 202.0605, Found: 202.0607.
4.4.2. (E)-5-(3,3,3-trifluoroprop-1-en-1-yl)benzo[d][1,3]dioxole (10b)
White solid; 37.8 mg, 87%; 1H NMR (400 MHz, CDCl3): δ = 6.00 (s, 2 H), 6.02 (dq, J = 6.9, 16.1
Hz, 1H), 6.80 (d, J = 8.3 Hz, 1H), 6.90–6.95 (m, 2H), 7.04 (ddd, J = 1.8, 1.8, 16.1 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ = 101.5, 106.2, 108.5, 113.8 (q, J = 33.7 Hz), 123.4, 123.8 (q, J =
268.8 Hz), 127.7, 137.2 (q, J = 6.7 Hz), 148.4, 149.3; 19F NMR (376 MHz, CDCl3): δ = –62.8 (d,
J = 6.9 Hz); IR (neat): 2910, 1664, 1621, 1607, 1451, 1362, 1285, 1113 cm-1; HRMS (EI+): Calcd.
for [C10H7F3O2]+: m/z = 216.0398, Found: 216.0391.
4.4.3. (E)-tert-butyldimethylsiloxy-4-(3,3,3-trifluoroprop-1-en-1-yl)benzene (10c)
Colorless oil; 37.8 mg, 62%; 1H NMR (400 MHz, CDCl3): δ = 0.21 (s, 6 H), 0.98 (s, 9H), 6.06 (dq,
J = 6.9, 16.1 Hz, 1H), 6.84 (d, J = 8.7 Hz, 2H), 7.08 (dq, J = 2.3, 16.1 Hz, 1H), 7.34 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ = –4.4, 18.2, 25.6, 113.6 (q, J = 33.7 Hz), 120.5, 123.9 (q, J = 268.8
Hz), 126.6, 129.0, 137.1 (q, J = 6.7 Hz), 157.5;19F NMR (376 MHz, CDCl3): δ = –62.8 (d, J = 6.9
Hz); IR (neat): 2957, 2932, 2860, 1421, 1391, 1363, 1205 cm-1; HRMS (EI+): Calcd. for
[C15H21F3OSi]+: m/z = 302.1314, Found: 302.1312.
4.4.4. (E)-2-methyl-5-(3,3,3-trifluoroprop-1-en-1-yl)thiophene (10d)
Colorless oil; 25.2 mg, 66%; 1H NMR (400 MHz, CDCl3): δ = 2.49 (s, 3 H), 5.87 (dq, J = 6.9, 15.6
Hz, 1H), 6.68–6.69 (m, 1H), 6.96 (d, J = 3.7 Hz, 1H), 7.15 (dq, J = 1.8, 15.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3): δ = 15.7, 113.0 (q, J = 33.7 Hz), 123.6 (q, J = 268.8 Hz), 126.2, 130.5, 130.8
(d, J = 6.7 Hz), 135.9, 143.0; 19F NMR (376 MHz, CDCl3): δ = –62.7 (d, J = 6.9 Hz); IR (neat):
Page 16 of 21

2927, 1731, 1542, 1475, 1350, 1305, 1206 cm-1; HRMS (EI+): Calcd. for [C8H7F3S]+: m/z =
192.0221, Found: 192.0220.
4.4.5. 1-acetyl-3-((E)- 3,3,3-trifluoroprop-1-enyl)-1H-indole (10e)
Colorless solid; 37.2 mg, 73 %; 1H NMR (400 MHz, CDCl3): δ = 2.66 (s, 3H), 6.34 (dq, J = 6.9,
16.1 Hz, 1H), 7.21–7.27 (m, 1H), 7.35–7.45 (m, 2H), 7.59 (s, 1H), 7.75 (d, J = 7.4 Hz, 1H), 8.47
(d, J = 8.3 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ = 23.9, 116.2 (q, J = 33.7 Hz), 116.9, 119.6,
123.6 (q, J = 268.8 Hz), 124.5, 126.1, 126.6, 127.6, 128.9 (q, J = 7.7 Hz), 136.4, 168.4; 19F NMR
(376 MHz, CDCl3): δ = –63.3 (d, J = 6.9 Hz); IR (neat): 3136, 3020, 2929, 1714, 1666, 1450,
1379, 1348, 1306, 1274, 1215, 1113, 1088, 1012, 970, 743 cm-1; HRMS (ESI+): Calcd. for
[C13H10F3NO+Na]+: m/z = 276.0607, Found: 276.0609.
4.4.6. ((1E,3E)-5,5,5-trifluoropenta-1,3-dien-1-yl)benzene (10f)
Colorless oil; 1H NMR (400 MHz, CDCl3): δ = 5.80 (dq, J = 6.9, 15.2 Hz, 1H), 6.73–6.93 (m, 3H),
7.29–7.38 (m, 3H), 7.43–7.45 (m, 2H); 13C NMR (100 MHz, CDCl3): δ = 118.3 (q, J = 33.7 Hz),
123.5 (q, J = 268.8 Hz), 124.9, 127.0, 128.8, 128.9, 135.8, 137.5 (q, J = 7.7 Hz), 139.3; 19F NMR
(376 MHz, CDCl3): δ = –63.1 (d, J = 6.9 Hz); IR (neat): 3030, 2918, 1737, 1498, 1450, 1156,
1030 cm-1; HRMS (EI+): Calcd. for [C11H9F3]+: m/z = 198.0656, Found: 198.0654.
4.5. Synthesis of (E)-2-(3,3,3-trifluoroprop-1-en-1-yl)phenol (10g)
[(MeCN)4Cu]PF6 (7.5 mg, 10 mol%), Et3N (40.5 mg, 2 equiv.) and Togni reagent 1 (76 mg, 1.2
equiv.) were weighed and added to a Schlenk tube which had been flame-dried under vacuum.
The tube was evacuated and backfilled with nitrogen. CH2Cl2 (1 mL) was added to the tube,
followed by addition of 4-methoxystyrene 9g (24.0 mg, 0.2 mmol). The reaction mixture was
stirred for 6 h at 23 °C, then diluted with EtOAc (5 mL) and quenched with aqueous NaHCO3.
The mixture was extracted with EtOAc. The organic layer was washed with brine and dried over
MgSO4. After filtration, the filtrate was concentrated under reduced pressure and the residue was
purified by column chromatography on silica gel (hexane/EtOAc = 10/1) to give 10g (24.6 mg,
66%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 5.19 (s, 1H), 6.38 (ddq, J = 2.3, 6.9, 16.1
Hz, 1H), 6.77–6.79 (m, 1H), 6.94–6.98 (m, 1H), 7.21–7.26 (m, 1H), 7.35–7.40 (m, 2H); 13C NMR
(100 MHz, CDCl3): δ = 116.1, 116.9 (q, J = 33.7 Hz), 120.8, 121.2, 128.3 (q, J = 268.8 Hz), 129.1,
130.9, 132.7 (q, J = 6.7 Hz), 154.1; 19F NMR (376 MHz, CDCl3): δ = –63.2 (d, J = 6.9 Hz); IR
(neat): 3609, 3416, 1664, 1607, 1500, 1210, 1178 cm-1; HRMS (EI+): Calcd. for [C9H7F3O]+: m/z
= 188.0449, Found: 188.0452.
Page 17 of 21

4.6. Synthesis of (E)-4-(3,3,3-trifluoroprop-1-en-1-yl)acetoaniline (10h)
To a solution of 11h (105 mg, 0.22 mmol) in CH2Cl2 (1.1 mL) was added TfOH (49.5 mg, 1.5
equiv.). The reaction mixture was stirred for 12 h at 40 °C, then diluted with CH2Cl2 (5 mL) and
quenched with aqueous NaHCO3. After extraction, the organic layer was dried over MgSO4 and
filtered, and the filtrate was evaporated under reduced pressure. The residue was purified by
column chromatography on silica gel (hexane/EtOAc = 20/1) to give 10h (49.7 mg, 99%) as a
colorless oil. 1H NMR (400 MHz, CD3OD): δ = 2.13 (s, 3H), 6.36 (dq, J = 6.9, 16.1 Hz, 1H),
7.10–7.15 (m, 1H), 7.42 (d, J = 8.7 Hz, 2H), 7.55 (d, J = 8.7 Hz, 2H); 13C NMR (100 MHz,
CD3OD): δ = 23.9, 115.4 (q, J = 33.7 Hz), 121.0, 125.5 (q, J = 267.8 Hz), 129.4, 130.4, 138.5 (d,
J = 6.7 Hz), 141.7, 171.7;19F NMR (376 MHz, CD3OD): δ = –64.5 (d, J = 6.9 Hz); IR (neat): 3305,
2967, 1458, 1414, 1371, 1208, 1181 cm-1; HRMS (ESI+): Calcd. for [C11H10F3NO+H]+: m/z =
230.0793, Found: 230.0793.
4.7. Synthesis of (E)-1-(tert-butyl)-4-(3,3,3-trifluoroprop-1-en-1-yl)benzene (10i)
To a solution of 11i (95.3 mg, 0.2 mmol) in THF (2 mL) was added a 1 M solution of NaHMDS in
THF (0.4 mL, 2 equiv.) in –78 °C. The reaction mixture was stirred for 1 h, and then quenched
with aqueous NH4Cl. The mixture was extracted with EtOAc. The organic layer was washed with
brine, dried over MgSO4 and filtered. The filtrate was concentrated under reduced pressure and
the residue was purified by column chromatography on silica gel (hexane/EtOAc = 20/1) to give
10i (29.2 mg, 64%) as a colorless oil. 1H NMR (400 MHz, CDCl3): δ = 1.32 (s, 9H), 6.16 (dq, J =
6.9, 16.1 Hz, 1H), 7.10–7.15 (m, 1H), 7.38–7.42 (m, 4H); 13C NMR (100 MHz, CDCl3): δ = 31.2,
34.8, 114.9 (q, J = 33.7 Hz), 123.8 (q, J = 268.8 Hz), 125.9, 127.3, 130.6, 137.4 (d, J = 6.7 Hz),
153.5; 19F NMR (376 MHz, CDCl3): δ = –63.0 (d, J = 6.9 Hz); IR (neat): 2967, 1665, 1334, 1312,
1272, 1215, 1107 cm-1; HRMS (EI+): Calcd. for [C13H15F3]+: m/z = 228.1126, Found: 228.1127.
Acknowledgement
This work was supported in part by funding from RIKEN.
References and notes
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