Product Control in Alkene Trifluoromethylation: Hydrotrifluoromethylation, Vinylic Trifluoromethylation, and Iodotrifluoromethylation using Togni Reagent

Article abstract of DOI:10.1002/asia.201500359

Hydrotrifluoromethylation, vinylic trifluoromethylation, and iodotrifluoromethylation of simple alkenes have been achieved by using Togni reagent in the absence of any transition metal catalyst. These reactions were readily controllable by selection of appropriate salts and solvents. The addition of K₂CO₃ afforded the hydrotrifluoromethylation product, with DMF acting not only as a solvent, but also as the hydrogen source. In contrast, the use of tetra-n-butylammonium iodide (TBAI) in 1,4-dioxane resulted in vinylic trifluoromethylation, while the use of KI afforded the iodotrifluoromethylation product. The vinylic trifluoromethylation product was obtained by treatment of the iodotrifluoromethylation product with ammonium 2-iodobenzoate, indicating that it was formed through an elimination reaction of the in-situ-generated iodotrifluoromethylation product, and the solubility of the resulting 2-iodobenzoate salt plays a key role in the product switching. A radical-clock experiment showed that these reactions proceed via radical intermediates.

Full text of DOI:10.1002/asia.201500359

DOI: 10.1002/asia.201500359
Full Paper
Trifluoromethylation
Product Control in Alkene Trifluoromethylation:
Hydrotrifluoromethylation, Vinylic Trifluoromethylation, and
Iodotrifluoromethylation using Togni Reagent
Hiromichi Egami,[a, b, e] Yoshihiko Usui,[a, c] Shintaro Kawamura,[a, b, d] Sayoko Nagashima,[c] and
Mikiko Sodeoka*[a, b, c, d]
Abstract: Hydrotrifluoromethylation, vinylic trifluoromethyla-
tion, and iodotrifluoromethylation of simple alkenes have
been achieved by using Togni reagent in the absence of any
transition metal catalyst. These reactions were readily con-
trollable by selection of appropriate salts and solvents. The
addition of K2CO3 afforded the hydrotrifluoromethylation
product, with DMF acting not only as a solvent, but also as
the hydrogen source. In contrast, the use of tetra-n-butylam-
monium iodide (TBAI) in 1,4-dioxane resulted in vinylic tri-
fluoromethylation, while the use of KI afforded the iodotri-
fluoromethylation product. The vinylic trifluoromethylation
product was obtained by treatment of the iodotrifluorome-
thylation product with ammonium 2-iodobenzoate, indicat-
ing that it was formed through an elimination reaction of
the in-situ-generated iodotrifluoromethylation product, and
the solubility of the resulting 2-iodobenzoate salt plays
a key role in the product switching. A radical-clock experi-
ment showed that these reactions proceed via radical inter-
mediates.
have typically been used for the construction of the C(sp3)ÀCF3
bond by nucleophilic addition with Ruppert–Prakash reagent
or electrophilic trifluoromethylation through enolate forma-
tion.[2a,h–l] Trifluoromethylation of olefins with an electrophilic
trifluoromethylating reagent[3] is another approach towards
C(sp3)ÀCF3 bond formation.[4]
Introduction
Fluorine-containing functional groups are found in many types
of organic molecules used in the pharmaceutical, agrochemi-
cal, and materials science fields.[1] Particular attention has been
paid to trifluoromethylation reactions.[2] Carbonyl compounds
We have been investigating copper-catalyzed trifluorome-
thylation using Togni reagent.[5,6] Recently, carbotrifluoromethy-
lation through 1,2-aryl migration to afford a b-trifluoromethyl
carbonyl moiety was achieved using Fe(OAc)2 as a catalyst
(Scheme 1a),[7] and the research groups of Wu and Tu inde-
pendently reported a similar reaction using a copper catalyst.[8]
These reactions appear to proceed through a neophyl-type re-
arrangement of an alkyl radical intermediate. During our stud-
ies, we obtained the hydrotrifluoromethylation product as
a by-product when DMF was used as a solvent (Scheme 1b).
These preliminary results prompted us to examine trifluorome-
thylations via radical intermediates, including hydrotrifluoro-
methylation of simple alkenes.
[a] Dr. H. Egami, Y. Usui, Dr. S. Kawamura, Prof. Dr. M. Sodeoka
Synthetic Organic Chemistry Laboratory
RIKEN
2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)
E-mail: sodeoka@riken.jp
[b] Dr. H. Egami, Dr. S. Kawamura, Prof. Dr. M. Sodeoka
Sodeoka Live Cell Chemistry Project
ERATO, Japan Science and Technology Agency
2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)
[c] Y. Usui, Dr. S. Nagashima, Prof. Dr. M. Sodeoka
Graduate School of Science and Engineering
Saitama University
255 Shimo-okubo, Sakura-ku, Saitama 338-8570 (Japan)
[d] Dr. S. Kawamura, Prof. Dr. M. Sodeoka
RIKEN Center for Sustainable Resource Science
2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)
Seminal work on catalytic hydrotrifluoromethylation of unac-
tivated olefins[9] has been reported by the research groups of
Qing, Gouverneur, and Nicewicz in 2013.[10a–c] Qing and co-
workers operated the reaction using Ag catalyst and 1,4-cyclo-
hexadiene under oxidative conditions.[10a] Gouverneur used
photoredox catalysis with a Ru complex and Umemoto’s re-
agent in MeOH, which worked as not only a solvent, but also
as a hydrogen source.[10b] Nicewicz and co-workers studied the
photoredox catalysis of mesityl acridinium ion for this transfor-
mation using Langlois reagent (CF3SO2Na).[10c] Furthermore,
during the preparation of this paper, Scaiano and co-workers
[e] Dr. H. Egami
School of Pharmaceutical Sciences
University of Shizuoka
5-1 Yada, Suruga-ku, Shizuoka 422-8526 (Japan)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/asia.201500359.
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
This is an open access article under the terms of the Creative Commons At-
tribution-NonCommercial License, which permits use, distribution and re-
production in any medium, provided the original work is properly cited and
is not used for commercial purposes.
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been used for the reaction and various radical initiators have
been reported.[14] However, there are very few reports on halo-
trifluoromethylation using Togni reagent. Szabó and co-work-
ers reported the halotrifluoromethylation of vinylsilane and 4-
fluorostyrene with a stoichiometric amount of copper salts,
albeit in moderate yield.[15]
This background suggests that product control in alkene tri-
fluoromethylation using the Togni reagent is a challenging
task, especially in the case of trifluoromethylations of simple al-
kenes bearing an allylic proton, in which deprotonative trifluor-
omethylation may occur competitively (Scheme 1c). Here, we
describe base-promoted hydrotrifluoromethylation and iodide
ion-promoted vinylic trifluoromethylation and iodotrifluorome-
thylation of simple alkenes (Scheme 1d).
Results and Discussion
To screen the reaction conditions, we employed 2a as a test
substrate (Table 1). First, the reaction with Fe(OAc)2 in DMF
was examined, based on a preliminary result (Scheme 1b). The
desired hydrotrifluoromethylation product 3a was formed in
53% yield at 808C (Table 1, entry 1). However, the reaction of
2a was slower than that of 1,1-diphenyl-2-propen-1-ol
(Scheme 1b), and only 5% of 3a was obtained when the reac-
tion was carried out at 238C (Table 1, entry 2). The vinylic tri-
fluoromethylation product 4a was the major product in the
absence of K2CO3 (Table 1, entry 3). To our surprise, the iron
catalyst was not required for the hydrotrifluoromethylation.
The reaction without Fe(OAc)2 provided mainly the hydrotri-
Scheme 1. Trifluoromethylations of alkenes.
reported a hydrotrifluoromethylation using a combination of
Togni reagent and methylene blue under photo-irradiation,
though the vinylic trifluoromethylation product was simultane-
ously formed.[10d] Attack of a free trifluoromethyl radical at
a C=C bond and trapping of the resulting radical by a hydrogen
source are essential for these reactions. On the other hand,
Buchwald and Wang independently reported the deprotona-
tive trifluoromethylation of unactivated olefins using a combi-
nation of CuI and Togni reagent in 2011 (Scheme 1c).[11] In our
study on the trifluoromethylation of allylsilane, we also found
that deprotonative trifluoromethylation occurred when mono-
substituted allylsilane was used as a substrate.[6c] The hydrotri-
fluoromethylation of simple alkenes having allylic protons
using the Togni reagent is accordingly a challenging topic.
Moreover, the trifluoromethyl-substituted alkene unit is
a key structural motif for pharmaceutical chemistry and materi-
als science.[2] This unit has generally been synthesized from
pre-functionalized substrate by cross-coupling reactions,[12] and
direct trifluoromethylation of simple alkenes is still under de-
velopment. Our first work directed toward this type of trifluor-
omethylation was reported in 2012. In the study of copper-cat-
alyzed oxytrifluoromethylation of styrene derivatives, it was
found that addition of p-toluenesulfonic acid directly afforded
b-trifluoromethylstyrene derivatives instead of oxytrifluorome-
thylation products.[6d,i] Although many research groups have
recently reported the vinylic trifluoromethylation of various
types of alkenes, the reaction of simple alkenes with allylic pro-
tons is still rare.[13]
Table 1. Screening of reaction conditions for hydro-trifluoromethyla-
tion.[a]
Entry Catalyst Base
Solvent Yield of 3a [%][b] Yield of 4a [%][b]
1
Fe(OAc)2 K2CO3
Fe(OAc)2 K2CO3
DMF
DMF
DMF
DMF
DMF
53
5
9
40
58
7
0
16[d]
3
2[c]
3
Fe(OAc)2
–
4
5
6
7
8
9
10
11
12[j]
13
–
–
–
–
–
–
–
–
–
–
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
[e]
7
DMAc[f] 47
18[g]
20[i]
trace
trace
20[i]
trace
2
DEF[h]
DCE
43
1
3
51
28
75[k]
2
MeCN
Cs2CO3 DMF
KHCO3 DMF
[e]
K2CO3
–
DMF
DMF
2
[a] The reactions were carried out with Togni reagent 1 (2 equiv), catalyst
(15 mol%), and base (1 equiv) in solvent (1.2 mL, 0.2m) at 808C on
a 0.25 mmol scale, unless otherwise noted. [b] Determined by 19F NMR
analysis using fluorobenzene as an internal standard. [c] Run at 238C.
[d] The E/Z ratio was 7:1. [e] Fine powder was used. [f] DMAc=N,N-dime-
thylacetamide. [g] The E/Z ratio was 8:1. [h] DEF=N,N-diethylformamide.
[i] The E/Z ratio was 9:1. [j] Run with 3 equiv of 1 in DMF (0.05m) for 12 h.
[k] Yield of isolated product.
A typical example of alkene trifluoromethylation through an
atom transfer-type radical reaction is halotrifluoromethylation,
and this type of transformation has been studied for a long
time due to the utility of the products.[14] Classically, CF3I has
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fluoromethylation product in 40% yield (Table 1, entry 4). How-
ever, it was found that the iron catalyst somewhat accelerated
the hydrotrifluoromethylation. The reaction using fine powder
of K2CO3 afforded 3a in 58% (Table 1, entry 5). N,N-Dimethyla-
cetamide (DMAc) and N,N-diethylformamide (DEF) were also
good solvents. Although the reaction proceeded smoothly in
these solvents, the yields of 4a also increased and the product
selectivities were low (Table 1, entries 6 and 7). Among the
bases screened, K2CO3 gave the best result (Table 1, entries 4–
5, 10–11). When the reaction was carried out with 3 equiva-
lents of Togni reagent in 0.05m DMF solution for 12 h, 3a was
obtained in 75% yield, with only 2% of 4a (Table 1, entry 12).
The reaction without any catalyst or base gave negligible
amounts of 3a and 4a (Table 1, entry 13), suggesting that the
base was essential for the hydrotrifluoromethylation.
Scheme 2. Hydrogen source in the hydrotrifluoromethylation.
With the optimized conditions in hand, the substrate scope
of the hydrotrifluoromethylation was investigated (Table 2). It
energy and would be involved in the rate-determining step of
this reaction.
Inspired by the production of 4a as a by-product during the
hydrotrifluoromethylation (Table 1), we next planned to find
optimum conditions for the vinylic trifluoromethylation of
simple alkenes using the Togni reagent. Fortunately, TBAI was
found to promote the target vinylic trifluoromethylation.[17]
The results of screening of reaction conditions (reaction sol-
vent, iodide ion source) are summarized in Table 3. The reac-
tion in DMF gave 4a in 18% yield, together with a trace
amount of hydrotrifluoromethylation product 3a (entry 1).
Among the solvents tested (Table 3, entries 1–4), 1,4-dioxane
was found to be the best solvent for this reaction (Table 3,
entry 4), but the yield was still not satisfactory. Since NMR stud-
ies suggested the formation of CF3I during the reaction, Togni
Table 2. Hydrotrifluoromethylation of alkenes.[a]
Table 3. Screening of the reaction conditions using iodide salts.[a]
[a] The reactions were carried out with 1 (3 equiv) and K2CO3 (1 equiv) in
DMF (5 mL) at 808C for 12 h on a 0.25 mmol scale. [b] Run in DMF/1,4-di-
oxane (1:10).
Entry Iodide salts Equiv Solvent
Yield of 4a [%][b] Yield of 6a [%][b]
1
2
3
4
TBAI
TBAI
TBAI
TBAI
1.0
1.0
1.0
1.0
0.3
1.0
1.0
1.0
1.0
1.0
1.0
1.1
1.1
DMF
MeCN
MeOH
1,4-dioxane 37[f]
1,4-dioxane 78[e,j]
1,4-dioxane 0
1,4-dioxane trace
1,4-dioxane trace
1,4-dioxane trace
DMF
DMF
21[c]
19[d]
16[e]
0
was found that various functional groups, such as aryl halides,
ester and carbonyl groups, were tolerated, and the corre-
sponding products were obtained in good-to-high yields with
high selectivity. Interestingly, gem-di-substituted alkene 2g was
smoothly converted into the corresponding product 3g in
51% yield.
trace
3
0
0
3
50
61
72
0
0
88
92[j]
5[g,h,i] TBAI
6
7
8
9
10
11
I2
NaI
KI
CsI
KI
CsI
In the reaction of 2a, compound 5 was formed in 56% yield
(Scheme 2a), thus suggesting that the hydrogen source of this
hydrotrifluoromethylation is DMF.[16] To obtain further informa-
tion about this reaction, we also investigated the reaction in
deuterated solvent (Scheme 2b). As expected, deuterated
product [D]3a was obtained in 18% yield, together with 34%
yield of the vinylic trifluoromethylation product 4a. In this re-
action, no H-adduct was observed. When the reaction was per-
formed in 1:1 DMF/[D7]DMF under the standard conditions, the
hydrogen/deuterium ratio in the product was 92:8. These re-
sults indicate that hydrogen atom abstraction needs high
22[c]
30[k]
12[g] CsI
13[g,l] KI
1,4-dioxane 0
1,4-dioxane 0
[a] The reactions were carried out with Togni reagent 1 (1.2 equiv) and
additive on a 0.25 mmol scale, unless otherwise noted. [b] Determined by
19F NMR analysis using fluorobenzene as an internal standard. [c] The E/Z
ratio was 6:1. [d] The E/Z ratio was 17:2. [e] The E/Z ratio was 7:1. [f] The
E/Z ratio was 8:1. [g] Run with 1.5 equiv of Togni reagent 1. [h] Run for
12 h. [i] Run in 0.5m solution. [j] Yield of isolated product. [k] The E/Z ratio
was 13:2. [l] Run at 608C for 9 h.
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reagent appears to be decomposed by iodide ion. Thus, the
amount of TBAI was decreased. It is noteworthy that 4a was
selectively obtained in 78% yield when the reaction was oper-
ated with 0.3 equivalents of TBAI for 12 h (Table 3, entry 5). In
this case, the E/Z ratio of the product was as high as 9:1. Other
iodide sources were also examined (Table 3, entries 6–9). Mo-
lecular iodine (I2) did not work as a mediator for the trifluoro-
methylation (Table 3, entry 6). In contrast to TBAI, NaI in 1,4-di-
oxane selectively provided iodotrifluoromethylation product
6a in 50% yield (Table 3, entry 7). KI and CsI were found to be
better mediators, selectively affording 6a in 61% and 72%
yields, respectively (Table 3, entries 8 and 9). Contrary to the
result in 1,4-dioxane, the reactions using KI or CsI in DMF
again selectively provided vinylic trifluoromethylation product
4a (Table 3, entries 10 and 11). A higher yield of 6a was ob-
tained when 1.5 equivalents of Togni reagent was used with
CsI (Table 3, entry 12). The reaction with KI smoothly proceed-
ed even at 608C, and 6a was obtained in 92% yield when the
reaction time was prolonged to 9 h (Table 3, entry 13).
Table 5. Iodotrifluoromethylation of alkenes using KI.[a]
Having established the reaction conditions, we next investi-
gated the substrate scope for the vinylic trifluoromethylation
using TBAI in 1,4-dioxane (Table 4). Similar to that of the hydro-
[a] The reactions were carried out with 1 (1.5 equiv) and KI (1.1 equiv) in
1,4-dioxane (1.2 mL) at 608C for 9 h on a 0.25 mmol scale.
Table 4. Vinylic trifluoromethylation of alkenes using TBAI.[a]
mono-substituted alkenes 2b–2 f, but also gem-disubstituted
alkene 2g were successfully converted into iodotrifluoromethy-
lation products 6b–6g. Interestingly, allylic alcohol 2h could
be transformed into g-trifluoromethyl-b-iodo-alcohol 6h with-
out epoxide formation in 65% yield, albeit in a non-stereose-
lective manner (syn/anti=1:1); this product was expected to
be difficult to obtain, and has synthetic potential as a building
block.
Encouraged by these results, we next examined the use of
KBr [Eq. (1)]. The reaction in 1,4-dioxane resulted in very low
conversion. To our surprise, the iodotrifluoromethylation prod-
uct was obtained in moderate yield when the reaction was car-
ried out in alcoholic solvent and no bromotrifluoromethylation
product was detected. Although the reason for this is still un-
clear, the iodide source is presumably 2-iodobenzoate derived
from Togni reagent. Indeed, benzoic acid was formed during
the reaction.
[a] The reactions were carried out with 1 (1.5 equiv) and TBAI (0.3 equiv)
in 1,4-dioxane (0.5 mL) at 808C for 12 h on a 0.25 mmol scale.
trifluoromethylation, various functional groups were tolerated
in this reaction. Although the E/Z ratio depended on the sub-
strate, the reaction with mono-substituted alkenes proceeded
in a highly stereoselective manner. It should be noted that no
deprotonative trifluoromethylation product was detected
under these reaction conditions.[11]
The reactions of these substrates with KI were also examined
(Table 5). The iodotrifluoromethylation products were obtained
in good to high yields under these reaction conditions. As ex-
pected, functional group tolerance was broad. Although an in-
ternal alkene was unsuitable for this iodotrifluoromethylation
due to generation of regio- and stereo-isomers, not only
To extend these protocols, 4-chlorostyrene 7 was examined
as a substrate (Scheme 3). Conjugated olefins tend to polymer-
ize under radical conditions. However, contrary to our expecta-
tion, the vinylic trifluoromethylation and iodotrifluoromethyla-
tion products 8 and 9 were obtained in good yields, however,
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reduction with azobisisobutyronitrile (AIBN) and n-Bu3SnH (see
the Supporting Information), and the diastereomeric ratio of
11 was 1:1. The cationic ring-opening product 12 was also pro-
duced, albeit in only 8% yield. Possible reaction pathways to
give 12 would be 1) simple iodotrifluoromethylation and then
cyclopropane ring-opening reaction with CÀI bond cleavage,
and 2) direct trifluoromethylation with cyclopropane ring-
opening reaction. In any case, the radical pathway product 11
was mainly obtained, suggesting that the reaction intermedi-
ate should have a radical character.[19]
Scheme 3. Trifluoromethylations of a styrene derivative.
hydrotrifluoromethylation gave a complex mixture. Unfortu-
nately, an electron-rich substrate, 4-methoxystyrene, gave only
the oxytrifluoromethylation product even with these proto-
cols.[6d] Therefore, the electron-rich substrates are not suitable
for the present reaction. In our previous copper-catalyzed con-
ditions for oxy-trifluoromethylation and preparation of b-tri-
fluoromethylstyrene,[6d,h,15a] electron-deficient styrene deriva-
tives were unsuitable as substrates. Thus, the current reaction
conditions provide a complementary method for transforma-
tion of styrene derivatives to b-trifluoromethylated products.
To establish the reason for the observed product switching
depending on the iodide salts, crown ether was added to the
reaction using KI in 1,4-dioxane. In this case, vinylic trifluoro-
methylation product 4a was selectively obtained in 70% yield
(Scheme 4a). Based on this result, we anticipated that the solu-
Conclusions
We have demonstrated that three distinct products, hydrotri-
fluoromethylated, vinylic trifluoromethylated, and iodotrifluoro-
methylated, can be selectively obtained by the reaction of
simple alkenes with Togni reagent; a high level of product con-
trol is achieved simply by changing the salt and solvent. The
combination of K2CO3 with DMF provided the hydrotrifluoro-
methylation product, with DMF as the hydrogen source. On
the other hand, iodide ion was found to work as a catalyst or
a promoter for vinylic trifluoromethylation and iodotrifluoro-
methylation. Vinylic trifluoromethylation was catalyzed by
TBAI, and the use of KI resulted in iodotrifluoromethylation. In-
terestingly, KI could also mediate vinylic trifluoromethylation
when the reaction was operated in the presence of 18-crown-6
or in DMF, thereby suggesting that the vinylic trifluoromethyla-
tion proceeds through the iodotrifluoromethylation product.
The reaction using radical-clock substrate 10 indicated that the
reactions proceeded through a radical intermediate. Further
studies of the reactions and mechanism are in progress.
Scheme 4. Formation of vinylic trifluoromethylation product.
bility of 2-iodobenzoate would be crucial for the selectivity,
and a vinylic trifluoromethylation product would be obtained
through iodotrifluoromethylation and an E2 reaction. Thus,
treatment of 6a with potassium-2-iodobenzoate in DMF and
1,4-dioxane and the reaction with ammonium-2-iodobenzoate
were examined under the described conditions (Scheme 4b).
As expected, the reaction with the barely soluble potassium
salt in 1,4-dioxane gave a trace amount of 4a, whereas an
almost quantitative yield of 4a was obtained in DMF. The am-
monium salt efficiently transformed 6a to 4a.
To obtain information regarding the mechanism of the pres-
ent reactions, a radical-clock substrate 10 was exposed to io-
dotrifluoromethylation conditions [Eq. (2)].[18] The main product
was 11 (67% yield), which is expected to be produced by cy-
clopropane ring-opening reaction through a radical pathway.
The structure of 11 was determined after removal of iodine by
Experimental Section
General Procedures
All reactions were carried out under an atmosphere of nitrogen.
Togni reagent was prepared according to the literature method.[5]
Dehydrated solvents (DMF, 1,4-dioxane, DMAc, MeCN, and MeOH)
purchased from Kanto Chemical Co., Inc. were used. KI was pur-
chased from Junsei Chemical Co., Ltd. and CsI and K2CO3 were pur-
chased from Wako Pure Chemical Industries, Ltd. All other inorgan-
ic salts were obtained from commercial sources, and used as re-
ceived. Other reagents were purified by usual methods. New al-
kenes were prepared using reported methods, and the results of
characterization are given in the Supporting Information.
1H and 19F NMR spectra were measured on a JEOL JNM-ECS-400
spectrometer at 400 and 376 MHz, respectively. 13C NMR spectra
were recorded on a JEOL JNM-ECS-400 spectrometer at 100 MHz.
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Chemical shifts were reported downfield from TMS (d=0 ppm) or
CDCl3 for 1H NMR. For 13C NMR, chemical shifts were reported in
the scale relative to CDCl3. For 19F NMR, chemical shifts were re-
ported in the scale relative to a CFCl3 external standard (0 ppm). In-
frared spectra were measured on a Thermo Nicolet iS5; only diag-
nostic absorptions are listed below. ESI-MS was taken on a Bruker
micrOTOF-QII-RSL and Varian QFT-7. FI-MS was taken on a JEOL JMS-
T100GCV. Column chromatography was performed with silica gel
N-60 (40–100 mm) 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-molyb-
do(VI)phosphoric acid in ethanol as the developing agent.
2-(6,6,6-trifluorohexyl)isoindoline-1,3-dione (3d)
Colorless oil; 50.9 mg, 72% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl3): d=1.39–1.46 (m, 2H), 1.56–1.65 (m, 2H), 1.68–1.75 (m, 2H),
2.01–2.13 (m, 2H), 3.70 (t, J=7.4 Hz, 2H), 7.71–7.73 (m, 2H), 7.84–
7.86 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=21.6 (q, J=
2.9 Hz), 26.0, 28.3, 33.7 (q, J=28.9 Hz), 37.7, 123.3, 127.2 (q, J=
276.5 Hz), 132.2, 134.1, 168.5 ppm; 19F NMR (376 MHz, CDCl3): d=
À66.3 ppm (t, J=10.8 Hz); IR (neat): n˜ =2945, 1773, 1706, 1467,
1395, 1187 cmÀ1; HRMS (ESI): Calcd. for [C14H14F3NO2+Na]+: m/z=
308.0869, Found: 308.0871.
tert-butyl phenyl(6,6,6-trifluorohexyl)carbamate (3e)
Colorless oil; 56.0 mg, 67% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl3): d=1.32–1.40 (m, 2H), 1.42 (s, 9H), 1.51–1.59 (m, 4H), 1.98–
2.10 (m, 2H), 3.63 (t, J=7.4 Hz, 2H), 7.18 (m, 2H), 7.21 (tt, J=1.4,
7.4 Hz, 1H), 7.31–7.36 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=
21.8 (q, J=2.9 Hz), 26.0, 28.2, 28.5, 33.8 (q, J=28.9 Hz), 49.7, 80.2,
126.2, 127.3, 127.3 (q, J=276.5 Hz), 128.9, 142.6, 154.9 ppm;
19F NMR (376 MHz, CDCl3): d=À66.3 ppm (t, J=10.8 Hz); IR (neat):
n˜ =3042, 1698, 1301, 1255, 1150, 1073 cmÀ1; HRMS (ESI): Calcd. for
[C17H24F3NO2+Na]+: m/z=354.1651, Found: 354.1653.
Typical experimental procedure for hydrotrifluoromethyla-
tion (Tables 1 and 2)
Togni reagent 1 (240 mg, 3 equiv) and K2CO3 (36.4 mg, 1 equiv)
were added to a Schlenk flask. The flask was evacuated and backfil-
led with nitrogen. Then, degassed DMF (5 mL) and alkene 2a
(46.9 mg, 0.25 mmol) were added to the flask. The reaction mixture
was stirred for 12 h at 808C, and then diluted with EtOAc (5 mL).
The organic solution was washed with distilled water and brine,
dried over Na2SO4, 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 3a
(47.8 mg, 75%) as a colorless oil.
Triphenyl((5,5,5-trifluoropentyl)oxy)silane (3 f)
Colorless oil; 61.7 mg, 61% (0.25 mmol scale); 1H NMR (400 MHz,
1
CDCl3); H NMR (400 MHz, CDCl3): d=1.63–1.68 (m, 4H), 1.97–2.09
(m, 2H), 3.81 (t, J=6.0 Hz, 2H), 7.37–7.48 (m, 9H), 7.60–7.62 ppm
(m, 6H); 13C NMR (100 MHz, CDCl3): d=18.6 (q, J=2.9 Hz), 31.5,
33.5 (q, J=28.9 Hz), 63.1, 127.3 (q, J=276.5 Hz), 128.0, 130.2, 134.2,
135.5 ppm; 19F NMR (376 MHz, CDCl3): d=À66.3 ppm (t, J=
6,6,6-trifluorohexyl benzoate (3a)
Colorless oil; 47.8 mg, 75% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl3): d=1.50–1.57 (m, 2H), 1.62–1.69 (m, 2H), 1.78–1.84 (m, 2H),
2.05–2.17 (m, 2H), 4.34 (t, J=6.9 Hz, 2H), 7.43–7.47 (m, 2H), 7.57
(tt, J=1.8, 7.4 Hz, 1H), 8.03–8.05 ppm (m, 2H); 13C NMR (100 MHz,
CDCl3): d=21.8 (q, J=2.9 Hz), 25.4, 28.5, 33.8 (q, J=28.9 Hz), 64.7,
127.2 (q, J=276.5 Hz), 128.5, 129.7, 130.4, 133.1, 166.8 ppm;
19F NMR (376 MHz, CDCl3): d=À66.3 ppm (t, J=10.8 Hz); IR (neat):
n˜ =2950, 1716, 1585, 1315, 1206, 834 cmÀ1; HRMS (ESI): Calcd. for
[C13H15F3O2+Na]+: m/z=283.0916, Found: 283.0914.
10.8 Hz); IR (neat): n˜ =3069, 1428, 1257, 1115, 1037, 738 cmÀ1
;
HRMS (FI): Calcd. for [C23H23F3OSi]+: m/z=400.1470, Found:
400.1487.
5,5,5-trifluoro-3-methylpentyl benzoate (3g)
Colorless oil; 32.4 mg, 51% (0.24 mmol scale); 1H NMR (400 MHz,
CDCl3): d=1.21 (d, J=6.4 Hz, 3H), 1.66–1.75 (m, 1H), 1.89–2.27 (m,
4H), 4.37 (td, J=6.4, 11.5 Hz, 1H), 4.40 (td, J=6.4, 11.5 Hz, 1H),
7.43–7.47 (m, 2H), 7.57 (tt, J=1.4, 7.4 Hz, 1H), 8.02–8.05 ppm (m,
2H); 13C NMR (100 MHz, CDCl3): d=19.8, 25.2 (q, J=2.9 Hz), 35.4,
40.3 (q, J=27.0 Hz), 62.6, 127.1 (q, J=277.4 Hz), 128.5, 129.7, 130.3,
133.1, 166.7 ppm; 19F NMR (376 MHz, CDCl3): d=À63.2 ppm (t, J=
3-[(6,6,6-trifluorohexyl)oxy]iodobenzene (3b)
Colorless oil; 77.3 mg, 81% (0.27 mmol scale); 1H NMR (400 MHz,
CDCl3): d=1.50–1.67 (m, 4H), 1.76–1.83 (m, 2H), 2.05–2.17 (m, 2H),
3.93 (t, J=6.4 Hz, 2H), 6.85 (ddd, J=0.9, 2.3, 8.3 Hz, 1H), 6.97–7.00
(m, 1H), 7.23–7.29 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=
21.8 (q, J=2.9 Hz), 25.4, 28.9, 33.8 (q, J=28.9 Hz), 67.8, 94.5, 114.3,
123.7, 127.3 (q, J=276.5 Hz), 130.0, 130.9, 159.7 ppm; 19F NMR
(376 MHz, CDCl3): d=À66.3 ppm (t, J=10.8 Hz); IR (neat): n˜ =2945,
10.8 Hz); IR (neat): n˜ =2968, 1717, 1271, 1253, 1090, 710 cmÀ1
;
HRMS (ESI): Calcd. for [C13H15F3O2+Na]+: m/z=283.0916, Found:
283.0920.
(N-methylformamido)methyl 2-iodobenzoate (5)
1284, 1204, 1090, 1040, 970 cmÀ1
; HRMS (FI): Calcd. for
1
[C12H14F3IO]+: m/z=358.0041, Found:358.0022.
Yellow oil; H NMR (400 MHz, CDCl3): d=3.07 (s, 3H), 5.56 (s, 2H),
7.18–7.22 (m, 1H), 7.41–7.45 (m, 1H), 7.80 (dd, J=1.4, 7.8 Hz, 1H),
8.01–8.03 (m, 1H), 8.44 ppm (s, 1H); 13C NMR (100 MHz, CDCl3): d=
30.4, 74.9, 94.2, 128.2, 131.3, 133.4, 134.0, 141.7, 164.4, 166.1 ppm;
IR (neat): 2878, 1723, 1682, 1239, 1012 742 cmÀ1; HRMS (FI): Calcd.
for [C10H10NO3I]+: m/z=318.9705, Found: 318.9715.
N-(2-bromo-4-chlorophenyl)-6,6,6-trifluorohexanamide (3c)
White solid; 44.6 mg, 50% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl3): d=1.64–1.72 (m, 2H), 1.80–1.87 (m, 2H), 2.09–2.21 (m, 2H),
2.47 (t, J=7.4 Hz, 2H), 7.30 (dd, J=2.3, 8.7 Hz, 1H), 7.50–7.59 (bs,
1H), 7.55 (d, J=2.3 Hz, 1H), 8.31 ppm (d, J=8.7 Hz, 1H); 13C NMR
(100 MHz, CDCl3): d=21.7 (q, J=2.9 Hz), 24.4, 33.7 (q, J=28.9 Hz),
37.3, 113.5, 122.6, 127.1 (q, J=276.5 Hz), 128.6, 129.6, 131.8, 134.4,
170.5 ppm; 19F NMR (376 MHz, CDCl3): d=À66.2 ppm (t, J=
Typical experimental procedure for vinylic trifluoromethyla-
tion (Tables 3 and 4)
Tetrabutylammonium iodide (TBAI) (28.0 mg, 0.3 equiv) and Togni
reagent 1 (119 mg, 1.5 equiv) were added to a Schlenk flask. The
flask was evacuated and backfilled with nitrogen. Then, degassed
1,4-dioxane (0.5 mL) and 2a (46.7 mg, 0.25 mmol) were added to
10.8 Hz); IR (neat): n˜ =2945, 1660, 1468, 1259, 1147, 1033 cmÀ1
;
HRMS (ESI): Calcd. for [C12H12BrClF3NO+Na]+: m/z=379.9635,
Found: 379.9635.
Chem. Asian J. 2015, 10, 2190 – 2199
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2195 ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
the flask. After stirring for 12 h at 808C, the reaction mixture was
diluted with EtOAc (5 mL) and concentrated under reduced pres-
sure and the residue was purified by column chromatography on
silica gel (n-hexane/EtOAc=20:1) to give trifluoromethylated prod-
uct 4a (49.3 mg, 78%, E/Z=9/1, the E/Z ratio was determined by
19F NMR analysis of the crude mixture) as a colorless oil. E isomer
was isolated by further purification of a small portion of the prod-
uct using HPLC (SenshuPak PEGASIL Silica SP100).
6.7 Hz), 168.5 ppm; 19F NMR (376 MHz, CDCl3): d=À64.0 ppm (tdd,
J=2.3, 2.3, 6.4 Hz); IR (neat): n˜ =1708, 1396, 1274, 1104, 972,
719 cmÀ1
;
HRMS (ESI): Calcd. for [C14H12F3NO2+Na]+: m/z=
306.0712, Found: 306.0713. Z isomer: 19F NMR (376 MHz, CDCl3):
d=À58.1 ppm (td, J=2.2, 8.7 Hz).
(E)-tert-butyl phenyl(6,6,6-trifluorohex-4-en-1-yl)carbamate
(4e)
Colorless oil; 64.1 mg, 80%, E/Z=7:1 (0.24 mmol scale); E isomer
was isolated by HPLC (n-hexane/EtOAc=10:1); E isomer: 1H NMR
(400 MHz, CDCl3): d=1.42 (s, 9H), 1.69 (quintet, J=7.4 Hz, 2H),
2.12–2.19 (m, 2H), 3.66 (t, J=7.4 Hz, 2H), 5.56 (tqd, J=1.8, 6.4,
15.6 Hz, 1H), 6.34 (qtd, J=2.3, 6.9, 15.6 Hz, 1H), 7.18 (m, 2H), 7.21
(tt, J=1.4, 7.4 Hz, 1H), 7.32–7.37 (m, 2H); 13C NMR (100 MHz,
CDCl3): d=27.0, 28.4, 28.8, 49.3, 80.4, 119.0 (q, J=32.8 Hz), 123.1
(q, J=268.8 Hz), 126.3, 127.2, 129.0, 139.8 (q, J=6.7 Hz), 142.4,
154.8 ppm; 19F NMR (376 MHz, CDCl3): d=À63.9 ppm (tdd, J=2.3,
(E)-6,6,6-trifluorohex-4-en-1-yl benzoate (4a)
Colorless oil; 49.3 mg, 78%, E/Z=9:1 (0.25 mmol scale); E isomer
was isolated by HPLC (n-hexane/EtOAc=10:1); E isomer: 1H NMR
(400 MHz, CDCl3): d=1.91–1.98 (m, 2H), 2.32–2.38 (m, 2H), 4.36 (t,
J=6.4 Hz, 2H), 5.69 (tqd, J=1.8, 6.4, 15.6 Hz, 1H), 6.44 (qtd, J=2.3,
6.9, 15.6 Hz, 1H), 7.43–7.47 (m, 2H), 7.57 (tt, J=1.4, 7.4 Hz, 1H),
8.02–8.05 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=27.3, 28.3,
64.0, 119.4 (q, J=32.7 Hz), 123.0 (q, J=269.7 Hz), 128.6, 129.7,
130.2, 133.2, 139.5 (q, J=6.7 Hz), 166.6 ppm; 19F NMR (376 MHz,
CDCl3): d=À64.0 ppm (tdd, J=2.3, 2.3, 6.4 Hz); IR (neat): n˜ =2958,
2.3, 6.4 Hz); IR (neat): n˜ =2977, 1694, 1597, 1299, 1272, 1088 cmÀ1
;
HRMS (ESI): Calcd. for [C17H22F3NO2+Na]+: m/z=352.1495, Found:
352.1498; Z isomer: 19F NMR (376 MHz, CDCl3): d=À58.0 ppm (td,
J=2.2, 8.7 Hz).
1717, 1602, 1269, 1111, 710 cmÀ1
; HRMS (ESI): Calcd. for
[C13H13F3O2+Na]+: m/z=281.0760, Found: 281.0766; Z isomer:
19F NMR (376 MHz, CDCl3): d=À58.0 ppm (td, J=2.2, 8.7 Hz).
(E)-triphenyl((5,5,5-trifluoropent-3-en-1-yl)oxy)silane (4 f)
(E)-3-((6,6,6-trifluorohex-4-en-1-yl)oxy)iodobenzene (4b)
White solid; 63.3 mg, 62%, E/Z=6:1 (0.25 mmol scale); E isomer
was isolated by HPLC (n-hexane/EtOAc=25:1); E isomer: 1H NMR
(400 MHz, CDCl3): d=2.38–2.44 (m, 2H), 3.89 (t, J=6.0 Hz, 2H),
5.66 (tqd, J=1.4, 6.4, 15.6 Hz, 1H), 6.39 (qtd, J=2.3, 6.9, 15.6 Hz,
1H, 7.37–7.47 (m, 9H), 7.60–7.62 ppm (m, 6H); 13C NMR (100 MHz,
CDCl3): d=34.8, 62.1, 120.4 (q, J=33.7 Hz), 123.0 (q, J=268.8 Hz),
128.1, 130.3, 133.9, 135.5, 137.6 ppm (q, J=6.7 Hz); 19F NMR
(376 MHz, CDCl3): d=À64.1 ppm (tdd, J=2.3, 2.3, 6.4 Hz); IR (neat):
n˜ =1429, 1115, 1029, 972, 736, 699 cmÀ1; HRMS (ESI): Calcd. for
[C23H21F3OSi+Na]+: m/z=421.1206, Found: 421.1214; Z isomer:
19F NMR (376 MHz, CDCl3): d=À58.2 ppm (d, J=8.7 Hz).
Colorless oil; 68.1 mg, 76%, E/Z=7:1 (0.25 mmol scale); E isomer
was isolated by HPLC (n-hexane/EtOAc=25:1); E isomer: 1H NMR
(400 MHz, CDCl3): d=1.89–1.96 (m, 2H), 2.32–2.39 (m, 2H), 3.95 (t,
J=6.0 Hz, 2H), 5.69 (tqd, J=1.8, 6.4, 15.6 Hz, 1H), 6.42 (qtd, J=2.3,
6.9, 15.6 Hz, 1H), 6.85 (ddd, J=0.9, 2.3, 8.3 Hz, 1H), 7.00 (dd, J=
8.3, 8.3 Hz, 1H), 7.24–7.30 ppm (m, 2H); 13C NMR (100 MHz, CDCl3):
d=27.8, 28.2, 67.0, 94.5, 114.3, 119.3 (q, J=33.7 Hz), 123.1 (q, J=
268.8 Hz), 123.7, 130.1, 131.0, 139.7 (q, J=6.7 Hz), 159.4 ppm;
19F NMR (376 MHz, CDCl3): d=À63.9 ppm (tdd, J=2.3, 2.3, 6.4 Hz);
IR (neat): n˜ =2945, 1584, 1242, 1091, 1049, 971 cmÀ1; HRMS (FI):
Calcd. for [C12H12F3IO]+: m/z=355.9885, Found: 355.9873;
Z
isomer: 19F NMR (376 MHz, CDCl3): d=À58.0 ppm (td, J=2.2,
(E)-5,5,5-trifluoro-3-methylpent-3-en-1-yl benzoate (4g)
8.7 Hz).
Colorless oil; 59.5 mg, 94%, E/Z=2:1 (0.25 mmol scale); stereoiso-
mers were isolated by HPLC (n-hexane/EtOAc=10:1); E isomer:
1H NMR (400 MHz, CDCl3): d =1.98–2.00 (m, 3H), 2.55–2.58 (m, 2H),
4.47 (t, J=6.4 Hz, 2H), 5.57 (qq, J=1.4, 8.3 Hz, 1H), 7.43–7.47 (m,
2H), 7.57 (tt, J=1.4, 7.4 Hz, 1H), 8.00–8.03 ppm (m, 2H); 13C NMR
(100 MHz, CDCl3): d=17.8, 38.6, 62.0, 116.8 (q, J=33.7 Hz), 123.3
(q, J=270.7 Hz), 128.6, 129.7. 130.0, 133.3, 147.5 (q, J=5.8 Hz),
166.5 ppm; 19F NMR (376 MHz, CDCl3): d=À57.5 ppm (m); IR
(neat): n˜ =2958, 1719, 1602, 1266, 1101, 710 cmÀ1; HRMS (ESI):
Calcd. for [C13H13F3O2+Na]+: m/z=281.0760, Found: 281.0766; Z
isomer: 1H NMR (400 MHz, CDCl3): d =1.95–1.97 (m, 3H), 2.76 (t,
J=6.4 Hz, 2H), 4.46 (t, J=6.4 Hz, 2H), 5.59 (q, J=8.3 Hz, 1H), 7.42–
7.46 (m, 2H), 7.57 (tt, J=1.4, 7.4 Hz, 1H), 8.02–8.04 ppm (m, 2H);
13C NMR (100 MHz, CDCl3): d=23.9, 32.3, 62.4, 117.5 (q, J=33.7 Hz),
123.2 (q, J=271.6 Hz), 128.5, 129.7. 130.1, 133.2, 147.5 (q, J=
5.8 Hz), 166.6 ppm; 19F NMR (376 MHz, CDCl3): d=À56.7 ppm (d,
(E)-N-(2-bromo-4-chlorophenyl)-6,6,6-trifluorohex-4-enamide
(4c)
White solid; 52.3 mg, 58%, E/Z=8:1 (0.25 mmol scale);1H NMR
(400 MHz, CDCl3): d=2.56–2.66 (m, 4H), 5.69–5.77 (m, 1H), 6.40–
6.49 (m, 1H), 7.30 (dd, J=2.3, 8.7 Hz, 1H), 7.50–7.57 (bs, 1H), 7.55
(d, J=2.3 Hz, 1H), 8.29 ppm (d, J=8.7 Hz, 1H); 13C NMR (100 MHz,
CDCl3): d=26.9, 35.8, 113.6, 120.1 (q, J=33.7 Hz), 122.7, 122.9 (q,
J=269.7 Hz), 128.7, 129.8, 131.9, 134.3, 138.4 (q, J=6.7 Hz),
169.4 ppm; 19F NMR (376 MHz, CDCl3): d=À64.1 ppm (m); IR
(neat): n˜ =3274, 1661, 1276, 1108, 1071, 741 cmÀ1; HRMS (ESI):
Calcd. for [C12H10BrClF3NO+Na]+: m/z=377.9479, Found: 377.9480;
Z isomer: 19F NMR (376 MHz, CDCl3): d=À58.2 ppm (td, J=2.2,
8.7 Hz).
J=8.7 Hz); IR (neat): n˜ =1721, 1678, 1603, 1269, 1104, 710 cmÀ1
;
(E)-2-(6,6,6-trifluorohex-4-en-1-yl)isoindoline-1,3-dione (4d)
HRMS (ESI): Calcd. for [C13H13F3O2+Na]+: m/z=281.0760, Found:
White solid; 53.8 mg, 76%, E/Z=8:1 (0.25 mmol scale); E isomer
was isolated by HPLC (n-hexane/EtOAc=5:1); E isomer: 1H NMR
(400 MHz, CDCl3): d=1.86 (quintet, J=7.4 Hz, 2H), 2.19–2.27 (m,
2H), 3.73 (t, J=7.4 Hz, 2H), 5.66 (tqd, J=1.8, 6.4, 15.6 Hz, 1H), 6.36
(qtd, J=2.3, 6.9, 15.6 Hz, 1H), 7.72–7.74 (m, 2H), 7.84–7.86 ppm (m,
2H); 13C NMR (100 MHz, CDCl3): d=27.0, 28.9, 37.3, 119.4 (q, J=
33.7 Hz), 123.0 (q, J=268.8 Hz), 123.4, 132.1, 134.2, 139.2 (q, J=
281.0770.
(E)-b-trifluoromethyl-4-chlorostyrene (8)
Colorless oil; 37.4 mg, 77% (0.24 mmol scale); 1H NMR (400 MHz,
CDCl3): d=6.18 (qd, J=6.4, 16.0 Hz, 1H), 7.11 (qd, J=2.3, 16.0 Hz,
1H), 7.36–7.41 ppm (m, 4H); 13C NMR (100 MHz, CDCl3): d=116.6
Chem. Asian J. 2015, 10, 2190 – 2199
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2196 ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
(q, J=33.7 Hz), 123.6 (q, J=268.8 Hz), 128.9, 129.4, 132.0, 136.1,
136.6 ppm (q, J=6.7 Hz); 19F NMR (376 MHz, CDCl3): d=À63.3 ppm
(dd, J=2.3, 6.4 Hz); IR (neat): n˜ =2929, 1492, 1273, 1093, 970,
807 cmÀ1; HRMS (FI): Calcd. for [C9H6ClF3]+: m/z=206.0110, Found:
206.0105.
2.9 Hz), 28.8, 36.8, 36.8, 44.9 (q, J=27.9 Hz), 123.4, 125.5 (q, J=
278.4 Hz), 132.1, 134.1, 168.4 ppm; 19F NMR (376 MHz, CDCl3): d=
À63.8 ppm (t, J=10.1 Hz); IR (neat): n˜ =2940, 1771, 1705, 1468,
1396, 1143 cmÀ1; HRMS (ESI): Calcd. for [C14H13F3INO2+Na]+: m/z=
433.9835, Found: 433.9845.
Typical experimental procedure for the iodotrifluoromethy-
lation (Tables 3 and 5)
N-phenyl-N-(6,6,6-trifluoro-4-iodohexyl) tert-butyl carbamate
(6e)
1
Togni reagent 1 (118 mg, 1.5 equiv) and KI (46.6 mg, 1.1 equiv)
were added to a Schlenk flask. The flask was evacuated and backfil-
led with nitrogen. Then, degassed 1,4-dioxane (1.2 mL) and 2a
(46.8 mg, 0.25 mmol) were added to the flask. The reaction mixture
was stirred for 9 h at 608C, and then diluted with EtOAc (5 mL).
After filtration to remove the insoluble solid, the filtrate was con-
centrated under reduced pressure and the residue was purified by
column chromatography on silica gel (n-hexane/EtOAc=20:1) to
give the trifluoromethylated product 6a (87.4 mg, 92%) as a color-
less oil.
Colorless oil; 100.2 mg, 87% (0.25 mmol scale.); H NMR (400 MHz,
CDCl3): d=1.42 (s, 9H), 1.59–1.68 (m, 1H), 1.74–1.84 (m, 3H), 2.68–
2.96 (m, 2H), 3.64–3.74 (m, 2H), 4.16–4.22 (m, 1H), 7.16–7.19 (m,
2H), 7.21 (tt, J=1.4, 7.4 Hz, 1H), 7.32–7.37 ppm (m, 2H); 13C NMR
(100 MHz, CDCl3): d=21.0 (q, J=2.9 Hz), 28.4, 28.7, 36.8, 45.1 (q,
J=27.9 Hz), 48.6, 80.4, 125.6 (q, J=278.4 Hz), 126.3, 127.2, 129.0,
142.3, 154.9 ppm; 19F NMR (376 MHz, CDCl3): d=À63.7 ppm (t, J=
10.1 Hz); IR (neat): n˜ =2977, 1693, 1252, 1208, 1145, 757 cmÀ1
;
HRMS (ESI): Calcd. for [C17H23F3INO2+Na]+: m/z=480.0618, Found:
480.0621.
6,6,6-trifluoro-4-iodohexyl benzoate (6a)
Triphenyl [(5,5,5-trifluoro-3-iodopentyl)oxy]silane (6 f)
Colorless oil; 87.4 mg, 92% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl3): d=1.86–2.13 (m, 4H), 2.75–3.02 (m, 2H), 4.24–4.30 (m, 1H),
4.38 (t, J=6.0 Hz, 2H), 7.43–7.47 (m, 2H), 7.57 (tt, J=1.4, 7.4 Hz,
1H), 8.02–8.05 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=20.6 (q,
J=2.9 Hz), 29.0, 36.3, 45.0 (q, J=28.9 Hz), 63.7, 125.6 (q, J=
279.4 Hz), 128.6, 129.7, 130.2, 133.2, 166.6 ppm; 19F NMR (376 MHz,
CDCl3): d=À63.8 ppm (t, J=10.1 Hz); IR (neat): n˜ =2958, 1716,
1
Colorless oil; 115.4 mg, 87% (0.25 mmol scale); H NMR (400 MHz,
CDCl3): d =1.92–2.08 (m, 2H), 2.76–2.99 (m, 2H), 3.86–3.99 (m, 2H),
4.44–4.51 (m, 1H), 7.38–7.48 (m, 9H), 7.61–7.63 ppm (m, 6H);
13C NMR (100 MHz, CDCl3): d=17.9 (q, J=2.9 Hz), 42.3, 45.1 (q, J=
28.9 Hz), 63.2, 125.7 (q, J=278.4 Hz), 128.1, 130.3, 133.8,
135.5 ppm; 19F NMR (376 MHz, CDCl3): d=À63.5 ppm (t, J=
10.1 Hz); IR (neat): n˜ =3068, 2874, 1428, 1255, 1114, 699 cmÀ1
;
1584, 1270, 1216, 829 cmÀ1
;
HRMS (ESI): Calcd. for
HRMS (FI): Calcd. for [C23H22F3IOSi]+: m/z=526.0437, Found:
[C13H14F3IO2+Na]+: m/z=408.9883, Found: 408.9910.
526.0431.
3-[(6,6,6-trifluoro-4-iodohexyl)oxy]iodobenzene (6b)
5,5,5-trifluoro-3-iodo-3-methylpentyl benzoate (6g)
1
Colorless oil; 74.3 mg, 76% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl3): d=2.20–2.21 (m, 3H), 2.24–2.37 (m, 2H), 3.08 (q, J=
10.6 Hz, 2H), 4.56–4.68 (m, 2H), 7.43–7.47 (m, 2H), 7.58 (tt, J=1.4,
7.4 Hz, 1H), 8.03–8.05 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=
35.8, 40.0, 45.4, 51.2 (q, J=27.0 Hz), 65.5, 125.3 (q, J=280.3 Hz),
128.6, 129.7, 130.0, 133.3, 166.5 ppm; 19F NMR (376 MHz, CDCl3):
d=À60.0 ppm (t, J=10.8 Hz); IR (neat): n˜ =2966, 1717, 1602, 1251,
1108, 710 cmÀ1; HRMS (FI): Calcd. for [C13H14F3IO2]+: m/z=385.9991,
Found: 386.0016.
Colorless oil; 105.7 mg, 87% (0.25 mmol scale.); H NMR (400 MHz,
CDCl3): d=1.84–2.09 (m, 4H), 2.75–3.02 (m, 2H), 3.98 (t, J=6.0 Hz,
2H), 4.22–4.29 (m, 1H), 6.85 (ddd, J=0.9, 2.3, 8.3 Hz, 1H), 6.99 (dd,
J=8.3, 8.3 Hz, 1H), 7.24–7.30 ppm (m, 2H); 13C NMR (100 MHz,
CDCl3): d=20.9, 29.4, 36.4, 45.0 (q, J=28.9 Hz), 66.8, 94.5, 114.3,
123.7, 125.6 (q, J=278.4 Hz), 130.1, 130.9, 159.4 ppm; 19F NMR
(376 MHz, CDCl3): d=À63.8 ppm (t, J=10.1 Hz); IR (neat): n˜ =2928,
1284, 1241, 1111, 1060, 989 cmÀ1
;
HRMS (FI): Calcd. for
[C12H13F3I2O]+: m/z=483.9008, Found: 483.8993.
N-(2-bromo-4-chlorophenyl)-6,6,6-trifluoro-4-iodohexana-
6,6,6-trifluoro-4-iodo-1-phenylhexan-3-ol (6h)
mide (6c)
Colorless oil; 55.1 mg, 65%, syn/anti=1:1 (0.24 mmol scale);
1H NMR (400 MHz, CDCl3): d=1.61–1.64 (m, 1H), 1.78–1.96 (m, 4H),
1.97–1.99 (m, 1H), 2.67–2.84 (m, 6H), 2.85–2.95 (m, 2H), 2.98–3.12
(m, 1H), 3.42–3.47 (m, 1H), 4.27–4.32 (m, 2H), 7.19–7.24 (m, 6H),
7.29–7.33 ppm (m, 4H); 13C NMR (100 MHz, CDCl3): d=29.5 (q, J=
2.89 Hz), 31.8, 31.9, 32.0, 36.3, 39.9 (q, J=28.9 Hz), 40.7, 42.1 (q, J=
28.9 Hz), 72.4, 74.6, 125.8 (q, J=278.4 Hz), 125.9 (q, J=278.4 Hz),
126.4, 126.4, 128.5, 128.5, 128.7, 128.7, 140.9, 141.1 ppm; 19F NMR
(376 MHz, CDCl3): d=À63.9 (t, J=10.1 Hz), À64.2 ppm (t, J=
Colorless oil; 97.3 mg, 81% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl3): d=2.06–2.16 (m, 1H), 2.24–2.32 (m, 1H), 2.58–2.66 (m, 1H),
2.70–2.78 (m, 1H), 2.80–3.05 (m, 2H), 4.27–4.34 (m, 1H), 7.30 (dd,
J=2.3, 8.7 Hz, 1H), 7.56 (d, J=2.3 Hz, 1H), 7.57–7.66 (bs, 1H),
8.29 ppm (d, J=8.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): d=20.7,
34.9, 37.7, 45.2 (q, J=28.9 Hz), 113.6, 122.7, 125.5 (q, J=278.4 Hz),
128.6, 129.8, 131.9, 134.3, 169.3 ppm; 19F NMR (376 MHz, CDCl3):
d=À63.6 ppm (t, J=10.1 Hz); IR (neat): 3295, 1661, 1469, 1284,
1210, 1110 cmÀ1; HRMS (ESI): Calcd. for [C12H11BrClF3INO+Na]+: m/
z=505.8602, Found: 505.8612.
10.1 Hz); IR (neat): n˜ =3441, 1603, 1429, 1251, 1141, 751 cmÀ1
;
HRMS (FI): Calcd. for [C12H14F3IO]+: m/z=358.0041, Found:
358.0032.
2-(6,6,6-trifluoro-4-iodohexyl)isoindoline-1,3-dione (6d)
1-(4-chlorophenyl)-1-iodo-3,3,3-trifluoropropane (9)
Colorless oil; 90.4 mg, 89% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl): d=1.78–1.88 (m, 3H), 1.94–2.03 (m, 1H), 2.69–2.96 (m, 2H),
3.72–3.76 (m, 2H), 4.19–4.26 (m, 1H), 7.70–7.75 (m, 2H), 7.84–
7.88 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=20.2 (q, J=
Colorless oil; 65.8 mg, 80% (0.25 mmol scale); 1H NMR (400 MHz,
CDCl3): d=3.09–3.29 (m, 2H), 5.25–5.28 (m, 1H), 7.28–7.36 ppm (m,
4H); 13C NMR (100 MHz, CDCl3): d=16.3 (q, J=2.9 Hz), 45.8 (q, J=
Chem. Asian J. 2015, 10, 2190 – 2199
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2197 ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

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28.9 Hz), 124.9 (q, J=279.4 Hz), 128.3, 129.3, 134.4, 140.9 ppm;
19F NMR (376 MHz, CDCl3): d=À64.3 ppm (t, J=9.4 Hz); IR (neat):
n˜ =3028, 1490, 1244, 1202, 1092, 725 cmÀ1; HRMS (FI): Calcd. for
[C9H7ClF3I]+: m/z=333.9233, Found: 333.9224.
Keywords: additive effect · alkenes · difunctionalization ·
Togni reagent · trifluoromethylation
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Reaction with KI and 1-(2-methoxy-3-phenylcyclopropyl)-
ethene 10 [Eq. (2)]
Togni reagent 1 (121 mg, 1.5 equiv) and KI (47.2 mg, 1.1 equiv)
were added to a Schlenk flask. The flask was evacuated and backfil-
led with nitrogen. Then, degassed 1,4-dioxane (1.2 mL) and 10
(44.8 mg, 0.26 mmol) were added to the flask. The reaction mixture
was stirred for 9 h at 608C, diluted with EtOAc (5 mL), and filtered.
The filtrate was concentrated under reduced pressure and the resi-
due was purified by column chromatography on silica gel (n-
hexane/EtOAc=20:1) to give the radical pathway product 11
(63.8 mg, 67%) as the major product, together with the cationic
pathway product 12 (10.1 mg, 8%).
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1-iodo-1-phenyl-2-methoxy-6,6,6-trifluorohex-3-ene (11)
Colorless oil; 63.8 mg, 67%, syn/anti=1:1; 1H NMR (400 MHz,
CDCl3): d=2.63–2.82 (m, 2H), 2.88 (dq, J=6.0, 10.6 Hz, 2H), 3.29 (s,
3H), 3.40 (s, 3H), 3.78 (t, J=7.4 Hz, 1H), 3.82 (t, J=6.4 Hz, 1H), 4.96
(d, J=7.4 Hz, 1H), 5.08 (d, J=6.4 Hz, 1H), 5.43–5.48 (m, 1H), 5.53–
5.61 (m, 1H), 5.59–5.71 (m, 2H), 7.20–7.30 (m, 6H), 7.34–7.38 (m,
2H), 7.39–7.42 ppm (m, 2H); 13C NMR (100 MHz, CDCl3): d=35.3,
36.2, 37.0 (q, J=29.9 Hz), 37.1 (q, J=29.9 Hz), 57.2, 57.3, 85.4, 85.5,
123.1 (q, J=2.9 Hz), 124.0 (q, J=2.9 Hz), 125.5 (q, J=276.5 Hz),
125.8 (q, J=276.5 Hz), 128.2, 128.4, 128.5, 128.6, 128.7, 128.9,
134.5, 135.4, 140.3, 140.7 ppm; 19F NMR (376 MHz, CDCl3): d=
À66.1 (t, J=10.8 Hz), À66.3 ppm (t, J=10.8 Hz); IR (neat): n˜ =2933,
1252, 1133, 1101, 972, 696 cmÀ1; HRMS (FI): Calcd. for [C13H14F3IO]+:
m/z=370.0041, Found: 370.0036.
(E)-1-methoxy-2-phenyl-6,6,6-trifluorohex-3-en-1-yl 2-iodo-
benzoate (12)
1
Colorless oil; 10.1 mg, 8%, syn/anti=1:1; H NMR (400 MHz, CDCl3):
d=2.76–2.86 (m, 2H), 2.81–2.92 (m, 2H), 3.47 (s, 3H), 3.54 (s, 3H),
3.82 (dd, J=6.0, 7.4 Hz, 1H), 3.84 (dd, J=6.0, 8.7 Hz, 1H), 5.50 (dtd,
J=1.4, 7.4, 15.6 Hz, 1H), 5.58 (td, J=6.9, 15.6 Hz, 1H), 6.04 (dd, J=
8.7, 15.6 Hz, 1H), 6.12–6.19 (m, 2H), 6.23 (d, J=6.0 Hz, 1H), 7.13
(dt, J=1.8, 7.8 Hz, 1H), 7.17 (dt, J=1.4, 7.8 Hz, 1H), 7.26–7.40 (m,
12H), 7.49 (dd, J=1.4, 7.8 Hz, 1H), 7.73 (dd, J=1.8, 7.8 Hz, 1H),
7.97 (dd, J=0.9, 7.8 Hz, 1H), 8.01 ppm (dd, J=0.9, 7.8 Hz, 1H);
13C NMR (100 MHz, CDCl3): d=37.5 (q, J=29.9 Hz), 37.6 (q, J=
29.9 Hz), 53.2, 53.5, 58.0, 58.1, 94.3, 94.6, 101.7, 101.8, 121.6 (q, J=
2.9 Hz), 121.7 (q, J=3.8 Hz), 125.8 (q, J=276.5 Hz), 126.0 (q, J=
276.5 Hz), 127.4, 127.4, 128.0, 128.1, 128.8, 128.8, 131.0, 131.2,
133.0, 133.2, 134.1, 134.6, 135.1, 135.5, 138.5, 138.6, 141.4, 141.7,
166.0, 166.1 ppm; 19F NMR (376 MHz, CDCl3): d=À66.2 (t, J=
10.8 Hz), À66.2 ppm (t, J=10.8 Hz); IR (neat): n˜ =2937, 1732, 1287,
1252, 1138, 743 cmÀ1; HRMS (ESI): Calcd. for [C20H18F3IO3+Na]+: m/
z=513.0145, Found: 513.0146.
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Acknowledgements
This work was supported in part by Project Funding from
RIKEN. We are grateful to Prof. Teiji Chihara and Prof. Hideki
Kurokawa of Saitama University for helpful discussions.
Chem. Asian J. 2015, 10, 2190 – 2199
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2198 ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
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Manuscript received: April 7, 2015
Accepted Article published: May 9, 2015
Final Article published: June 16, 2015
Chem. Asian J. 2015, 10, 2190 – 2199
www.chemasianj.org
2199 ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim