Visible-Light-Mediated Synthesis of Trifluoromethylthiolated Arenes

Article abstract of DOI:10.1055/s-0037-1610322

The visible-light-mediated synthesis of trifluoromethylthiolated arenes in the presence of ruthenium-based photocatayst under mild reaction conditions is reported. The trifluoromethylthiolated arenes are obtained using the shelf-stable reagent trifluoromethyl toluenethiosulfonate at room temperature. The reaction proceeds selectively and does not require the presence of any additive. A mechanism is proposed based on the obtained results of EPR as well as luminescence.

Full text of DOI:10.1055/s-0037-1610322

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2018, 50, A–F
paper
A
en
C. Ghiazza et al.
Paper
Synthesis
Visible-Light-Mediated Synthesis of Trifluoromethylthiolated
Arenes
Clément Ghiazzaa
Cyrille Monnereaub
Lhoussain Khrouzb
Thierry Billard*a,c
O O
[RuPhen3(Cl2)]
(5 mol%)
SCF3
BF4
N2
S
SCF3
R
R
+
white LED
DMSO, N2, 16 h
0
0
0
0-0
0
0
2-2
9
3
7-9
5
2
3
11 examples
up to 77%
Anis Tlili*a
0
0
0
0-0
0
0
2-3
0
5
8-2
0
4
3
a Institute of Chemistry and Biochemistry (ICBMS–UMR CNRS 5246) Univ
Lyon, Université Lyon 1, CNRS, CPE-Lyon, INSA 43 Bd du 11 Novembre
1918, 69622 Villeurbanne, France
anis.tlili@univ-lyon1.fr
b Univ Lyon, Ens de Lyon, CNRS UMR 5182, Université Lyon 1, Laboratoire
de Chimie, 69342, Lyon, France
c CERMEP-In vivo Imaging, Groupement Hospitalier Est, 59 Bd Pinel,
69003, Lyon, France
Published as part of the Bürgenstock Special Section 2018 – Future Stars in Organic Chemistry
Received: 26.09.2018
Accepted after revision: 24.10.2018
Published online: 20.11.2018
sides, transition-metal-free procedures using ammonium
trifluoromethylthiolate salts with arenediazonium salts
have also been disclosed.6
DOI: 10.1055/s-0037-1610322; Art ID: ss-2018-z0634-op
We have recently demonstrated that the formation of
C(sp2)–SeCF3 could be performed selectively under visible
light catalysis involving radical intermediates starting from
the shelf stable reagent trifluoromethyl tolueneselenosul-
fonate.7 We questioned whether such a procedure could be
extrapolated to the formation of C(sp2)–SCF3.8 Consequent-
ly, a similar trifluoromethylthiolating reagent TsSCF3 (2) has
been synthesized in almost quantitative yield starting from
our second generation of trifluoromethanesulfenamide re-
agent BB23H (Scheme 1).9
Abstract The visible-light-mediated synthesis of trifluoromethylthio-
lated arenes in the presence of ruthenium-based photocatayst under
mild reaction conditions is reported. The trifluoromethylthiolated
arenes are obtained using the shelf-stable reagent trifluoromethyl tolu-
enethiosulfonate at room temperature. The reaction proceeds selec-
tively and does not require the presence of any additive. A mechanism
is proposed based on the obtained results of EPR as well as lumines-
cence
Key words visible light, trifluoromethylthiolation, arenediazonium,
radical, reaction mechanism
O
S
Direct formation of C–SCF3 chemical bond has recently
been the object of many research endeavors.1 Indeed, the
Hansch parameter of SCF3 (πR = 1.44)2 confers to trifluoro-
methylthiolated molecules a high lipophilicity, thus con-
tributing to a better transmembrane permeation of CF3S-
substituted molecules allowing improved bioavailability,
thus making it a much sought-after feature.3 Among the
most studied reactions, we can find the direct trifluoro-
methylthiolation of arenes or heteroarenes.
O
Na
O
O
O
O
S
S
SCF3
(1.2 equiv)
N
SCF3
H
AcOH
95%
BB23H
2
Scheme 1 Synthesis of 2
Analysis of the state of the art literature on the topic re-
veals two distinct families of reactions that differ by the na-
ture of the trifluoromethylthiolating reagent. On the one
hand, nucleophilic reagents (R4N+–SCF3 or σ-bonded metal-
SCF3) can be associated with electrophilic arene sources un-
der transition metal catalysis (including Pd, Ni, and Cu).1f–h,4
On the other hand, shelf-stable electrophilic trifluorometh-
ylthiolating reagents have been also successfully employed
in the presence of nucleophilic arene sources (e.g., arylbo-
ronic acid derivatives and aryl Grignard reagents).1e,f,h,5 Be-
With our continued interest to discover and develop
new synthetic methodologies, we turned our attention to
study the formation of C(sp2)–SCF3 bonds from arenediazo-
nium salts using this shelf-stable reagent. During this work,
similar results have been described.10
Initial attempt was devoted to study the influence of the
solvents on the reaction outcome. Indeed, our previous
studies on related selenide reagents had evidenced a crucial
influence of this parameter.7 While reaction using eosin Y
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

B
C. Ghiazza et al.
Paper
Synthesis
(5 mol%) as photocatalyst allowed 59% product formation to
be reached using DMSO as solvent at room temperature (Ta-
ble 1, entry 1), the use of other solvents showed the forma-
tion of desired products in lower yields (entries 2–5). Next,
the influence of the photocatalyst on the reaction outcome
was tested. Only marginal amount of the product was
formed when Rhodamine 6G was used as photocatalyst.
The use of transition-metal-based photocatalyst showed
good reactivity when Ir(ppy)3 was used (entry 7), but the
best yield was obtained with Ru(II) as photocatalyst as the
targeted product was formed in 67% yield (entry 8). We also
verified that the presence of the photocatalyst is primordial
for the formation of the product since only traces were ob-
served in the blank experiment (entry 9).
good yields (up to 77%). Halogenated products were also
tolerated since 3i and 3j could be formed in moderate to
good yields. Finally, we could demonstrate through the ex-
ample of product 3k that a heterocyclic starting material
could be also converted into its desired product although in
low reaction outcome (Scheme 2).
[RuPhen3(Cl2)]
(5 mol%)
O
O
SCF3
BF4
N2
S
+
SCF3
R
R
white LED
DMSO, N2, 16 h
1
2
3
OMe
SCF3
SCF3
SCF3
3c, 54% (64%)
SCF3
MeO
3b, 55% (68%)
HO
3a, 52% (69%)
Table 1 Reaction optimizationa
SMe
O
a
O
SCF3
SCF3
SCF3
3e, 53% (55%)
SCF3
O2N
3f, 47% (51%)
SCF3
N2 BF4
Eosin Y (5 mol%)
S
SCF3
+
DMSO
white LED
N2, 16 h, 25 °C
3d, 47% (51%)
SCF3
1a
2
3a
EtO2C
3h, 72% (77%)
F
NC
Entry
Deviation from standard conditions
Yield (%)b
3g, 59% (59%)
3i, (60%)
1
2
none
59
31
47
27
45
19
59
67
<5
<5
DMF instead of DMSO
EtOH instead of DMSO
THF instead of DMSO
MeCN instead of DMSO
rhodamine 6G instead of eosin Y
Ir(ppy)3 instead of eosin Y
[Ru(phen)3Cl2]·xH2O instead of eosin Y
no photocatalyst
SCF3
3
N
I
SCF3
3k, 24% (30%)
4
3j, (44%)
5
Scheme 2 Reactions were performed with TsSCF3 (2; 0.6 mmol, 3
6
equiv), arenediazonium salt 1 (0.2 mmol, 1 equiv), [Ru] (5 mol%), and
DMSO (2 mL). The reaction mixture was stirred at r.t. for 16 h under in-
ert conditions. Yields shown are those of isolated products; yields deter-
mined by 19F NMR spectroscopy with PhOCF3 as internal standard are
shown in parentheses.
7
8
9
10
no photocatalyst, no light
a Reactions were performed with TsSCF3 (0.3 mmol, 3 equiv), arenediazoni-
um salt (0.1 mmol, 1 equiv), photocatalyst (5 mol%), and solvent (1 mL).
The reaction mixture was stirred at r.t. for 16 h under inert conditions.
b Determined by 19F NMR spectroscopy with PhOCF3 as an internal stan-
dard.
Mechanistic details were further investigated using lu-
minescence spectroscopy. We first aimed at establishing
the occurrence of an electron transfer process between the
ruthenium catalyst and the tolyldiazonium reagent 1a by
following extinction of the former luminescence upon in-
cremental additions of the latter [see Supporting Informa-
tion (SI) for further experimental details]. Quite surprising-
ly, unlike previously observed in earlier works dealing with
Ru complexes,11 a plot of the resulting data using a Stern–
Volmer model did not lead to a straight line. Instead, we no-
ticed a distinct upward curvature of the plotted data. Such
behavior suggests that, while a photoinduced reaction is
clearly seen between the Ru catalyst and the diazonium
quencher, it cannot be fully rationalized based on a diffu-
sion-controlled charge transfer mechanism as postulated in
the Stern–Volmer theory. Indeed, such positive curvature
deviations from Stern–Volmer model have been largely doc-
umented in the past, on a variety of donor/acceptor (D/A)
pairs. Among the most currently admitted causes for this
With the best conditions in hand, we studied the reac-
tion scope. Initial attempts demonstrated that substrates
substituted with electron-donating groups could be trans-
formed to the desired products in moderate to very good
yields (up to 69%). No significant change was observed
when the starting arenediazonium salts 1c and 1d were
substituted in the ortho-position. Interestingly, taking ad-
vantage of the base-free conditions, free hydroxyl arenedia-
zonium salt was also tolerated, furnishing the desired prod-
uct 3e in 55% yield. Similarly, arenediazonium salts substi-
tuted with electron-withdrawing groups were also
successfully evaluated under our reaction conditions. Obvi-
ously, very strong electron-withdrawing substituted arenes
(including NO2, CN, and CO2Et) could be converted into their
trifluoromethylthiolated analogues in acceptable to very
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

C
C. Ghiazza et al.
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Synthesis
phenomenon, the occurrence of increased static quenching
at high quencher concentration ([Q]) is often mentioned.12
The latter adds to the dynamic, diffusion controlled process
encountered at low [Q], thus increasing the extent of
quenching at high [Q]. Accordingly, those effects can find
two distinct origins either in 1) the occurrence of a non-
emissive ground state luminophore-quencher complex,
which is highly favored at high [Q]13 or 2) in the so-called
‘sphere of action’ model,14 in which concentration-depen-
dent spatial proximity of the excited luminophore and the
quencher molecule ensures that diffusion is not a limiting
factor of the quenching process. The latter is also obviously
favored at high [Q] and is more prone to occur when slow
charge transfer processes are involved within the D/A pair.
Indeed, the latter model seems to account for the observed
trend in our case, as plotting ln(I0/If) versus [Q] affords a
quasi linear evolution as predicted by the aforementioned
model (see SI for details).
by elimination of SO2. Two other species of significant in-
tensity are observed, but their chemical nature is less
straightforward. The 5% species (aN = 8.1 G) and 15% species
(aN = 12.4 G) can both be attributed to oxidation products of
the aforementioned BPN-radical adduct as no hyperfine in-
teraction with the adjacent proton (Hβ) is observed (Figure
1).
Next, the reaction quantum yield (QY) was determined
in order to establish whether a step or chain mechanism
was more likely involved in the reaction. Using the Xenon
lamp of the fluorimeter as an irradiation source, we per-
formed controlled irradiation (435 nm) of a degassed 3 mL
sample of the reaction medium set in a 1 cm quartz cuvette,
and followed reactant-to-product conversion using 19F NMR
analysis on aliquots of the reaction mixture taken up at var-
ious reaction time. As for our previously reported example
using eosin as a catalyst, catalytic conversion was seen to
proceed in two stages: first a buildup of a dimeric CF3S–
SCF3 species, which was then consumed upon addition to
the diazonium reagent. Linearization of the data collected
in the initial stage of the reaction (first 30 min) allowed es-
tablishing a quantum yield ca. 1.5, following the general
methodology detailed in SI. This value, which clearly ex-
ceeds unity, is in line with a chain propagation mechanism,
consistent with what had been previously shown with the
selenium counterpart of the current sulfur reagent in the
presence of eosin (with a QY slightly exceeding 1 in the lat-
ter case).
By analogy with our previous work on related trifluoro-
methylselenosulfonate reagents, radicals formed upon irra-
diation of the ruthenium catalyst-free sample are attribut-
ed to the outcome of a light-induced homolytic cleavage of
the trifluoromethyl toluenethiosulfonate reagent 2. In this
case, a hallmark of the reaction is the production of a CF3S•
radical species that forms the most prominent adduct (65%)
Figure 1 EPR spin-trapping spectra on visible irradiation in the pres-
ence of PBN in DMSO at r.t. Blue: experimental, red simulated after 4
min with Ru (top) and 7 min without Ru (bottom) of irradiation.
When ruthenium catalyst is added to the mixture, EPR
signal obtained upon photoirradiation is enhanced by al-
most one order of magnitude. Moreover, species distribu-
tion pattern is largely different from that obtained in the
absence of catalyst. As a consequence of the electron trans-
fer taking place between Ru(II) catalyst and the diazonium
reactant 1a, decomposition of the latter by elimination of
nitrogen provides an Ar• tolyl radical (40% aN = 14.6G, aH =
2.8G) that is within error margin identical to the above-
mentioned evolution product of the Ts• radical, thereby ret-
with PBN radical trap, whose features (aN = 14.4G, aH
=
1.9G) are in good agreement with what we previously re-
ported for its CF3Se• counterpart. Formation of two other
readily attributable species can be observed in the EPR
spectrum: the first one (7% aN = 14.4G, aH = 1.2G) corre-
sponds to the second member of the homolytic cleavage,
the Ts• radical; the other by-product (8%, aN = 14.4G, aH
=
2.7G) most likely corresponds to an adduct of an Ar• radical
(tolyl) that evolves from this first Ts• radical intermediate,
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

D
C. Ghiazza et al.
Paper
Synthesis
O
O
hν
S
TolSO2
CF3S
SCF3
2
F3CS SCF3
F3C
S
N2
BF4
SCF3
SET
R
R
R
+
A
*
[Ru]
[Ru]
BF4
1
N2
BF4
CF3
R
S
Nu
SCF3
SCF3
BF4
R
R
3
NuSCF3
B
Scheme 3 Proposed mechanism
rospectively confirming the attribution of the latter. Sur-
prisingly, the two others adducts (40%, aN = 12.3G, 20%, aN =
8.2G) do not seem to correspond to the CF3S• radical as ob-
served in the absence of ruthenium, but to similar PBN oxi-
dation products as monitored in the absence of the rutheni-
um catalyst.
With these results in hand, we are able to propose a
plausible mechanism (Scheme 3). The diazonium salt is first
reduced through a single electron transfer (SET) by the trip-
let state ruthenium photocatalyst. The resulting aryl radical
could then react with the transient dimer CF3SSCF3, ob-
tained from the reagent 2 under light irradiation. The ob-
tained trivalent sulfur radical A is then oxidized by the di-
azonium salt furnishing the cationic species B and a new
aryl radical. Finally, the cationic intermediate could react
with a nucleophile from the reaction media (DMSO can also
play this role), yielding the desired product 3.
To conclude, the direct synthesis of trifluoromethylthio-
lated arenes could occur under visible light catalysis start-
ing with arenediazonium salts and a shelf-stable reagent
under mild reaction conditions. Furthermore, mechanistic
investigations were also performed to shed some light on
the reaction pathway. It turns out that trifluoromethylsul-
fur radical is a key intermediate in the reaction mechanism.
Further developments are under way in our laboratory.
a Bruker AV 500 spectrometer at 500 MHz (1H NMR), 126 MHz (13
C
NMR), 471 MHz (19F NMR). Multiplicities are indicated with standard
abbreviations. All coupling constants are reported in hertz (Hz).
Arenediazonium Salts 1a–d,f–k; General Procedure3
In a 25 mL round-bottomed flask were added aniline (10 mmol) and
aq 48% HBF4 (2.6 mL, 20 mmol) in absolute EtOH (3 mL). The mixture
was stirred until total homogeneity and cooled to 0 °C. t-BuONO
(90%; 2.7 mL, 20 mmol) was added dropwise to the solution. The re-
action mixture was stirred at r.t. for 30 min. Et2O (10 mL) was then
added to precipitate the salt. The solid was filtered and washed with
Et2O (3 ×) and dried under reduced pressure to afford the desired
product.
Characterization data of the products matched with that reported in
the literature.3
4-Hydroxybenzenediazonium Tetrafluoroborate (1e)4
In a 25 mL round-bottomed flask were added aniline (10 mmol) and
aq 48% HBF4 (2.6 mL, 20 mmol). The mixture was stirred until total
homogeneity and cooled to 0 °C. NaONO (1.38 mg, 20 mmol) dis-
solved in H2O (2 mL) was added dropwise to the solution. The reac-
tion mixture was stirred at r.t. for 30 min. Et2O (10 mL) was added to
precipitate the salt. The solid was filtered and washed with Et2O (3 ×)
and dried under reduced pressure to afford the desired product 1e.
Characterization data of the product matched with that reported in
the literature.4
1-Methyl-4-{[(trifluoromethyl)sulfanyl]sulfonyl}benzene (2)
To a flame-dried flask under N2 atmosphere equipped with a magnet-
ic stir bar were added 4-methyl-N-[(trifluoromethyl)sulfanyl]ben-
zene-1-sulfonamide9 (BB23H; 10 g, 37.2 mmol, 1 equiv), sodium p-
toluenesulfinate (7.95 g, 44.6 mmol, 1.2 equiv), and AcOH (70 mL).
The reaction mixture was stirred at 25 °C for 16 h. The mixture was
partitioned between EtOAc and brine. The aqueous layer was extract-
ed with EtOAc and the combined organic layers were dried (MgSO4),
filtered, and concentrated to dryness. The crude residue was purified
Commercial reagents and anhydrous solvents were used as supplied.
NMR spectra were recorded on a Bruker AV 400 spectrometer at 400
MHz (1H NMR), 101 MHz (13C NMR), 376 MHz (19F NMR), on a Bruker
AV 300 spectrometer at 300 MHz (1H NMR), 282 MHz (19F NMR), or on
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2018, 50, A–F

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Synthesis
by chromatography (eluent: cyclohexane/EtOAc 100:0 to 95:5) to af-
ford the desired product 2 as a colorless liquid; yield: 9.2 g (35.9
mmol, 97%).
19F NMR (282 MHz, CDCl3): δ = –43.94 (s, 3 F).
Characterization data matched with that reported in the literature.16
1H NMR (300 MHz, CDCl3): δ = 7.88 (d, J = 8.3 Hz, 2 H), 7.40 (d, J = 8.3
Hz, 2 H), 2.49 (s, 3 H).
19F NMR (282 MHz, CDCl3): δ = –38.48 (s, 3 F).
Characterization data matched with that reported in the literature.15
1-Nitro-4-[(trifluoromethyl)sulfanyl]benzene (3f)
Eluent: n-pentane/Et2O (98:2); yellow oil; yield: 21 mg (0.094 mmol,
47%).11H NMR (300 MHz, CDCl3): δ = 8.28 (m, 2 H), 7.83 (d, J = 8.8 Hz,
2 H).
19F NMR (282 MHz, CDCl3): δ = –41.32 (s, 3 F).
Characterization data matched with that reported in the literature.17
Trifluoromethylthiolation of Arenediazonium Salts; General Pro-
cedure
To a flame-dried flask under N2 atmosphere equipped with a magnet-
ic stir bar were added 2 (153.8 mg, 0.6 mmol, 3 equiv), arenediazoni-
um salt 1 (0.2 mmol, 1.0 equiv), [Ru(phen)3Cl2] (7.13 mg, 0.01 mmol,
5 mol%), and anhyd DMSO (2 mL). The reaction mixture was stirred at
25 °C under white LED irradiation for 16 h. Conversion was checked
by 19F NMR with PhOCF3 as internal standard. The mixture was parti-
tioned between Et2O and H2O. The aqueous layer was extracted with
Et2O and the combined organic layers were dried (MgSO4), filtered,
and concentrated to dryness. The crude residue was purified by chro-
matography to afford the desired product 3.
4-[(Trifluoromethyl)sulfanyl]benzonitrile (3g)
Eluent: n-pentane/Et2O (98:2); off-white solid; yield: 24 mg (0.118
mmol, 59%).1H NMR (300 MHz, CDCl3): δ = 7.77 (d, J = 8.5 Hz, 2 H),
7.71 (d, J = 8.5 Hz, 2 H).
19F NMR (282 MHz, CDCl3): δ = –41.49 (s, 3 F).
Characterization data matched with that reported in the literature.17
Ethyl 4-[(Trifluoromethyl)sulfanyl]benzoate (3h)
Eluent: n-pentane/Et2O (98:2); colorless liquid; yield: 36 mg (0.144
mmol, 72%).1H NMR (300 MHz, CDCl3): δ = 8.08 (m, 2 H), 7.71 (d, J =
8.3 Hz, 2 H), 4.40 (q, J = 7.1 Hz, 2 H), 1.40 (t, J = 7.1 Hz, 3 H).
Note: As the products are very volatile, solvents must be carefully re-
moved.
19F NMR (282 MHz, CDCl3): δ = –41.87 (s, 3 F).
Characterization data matched with that reported in the literature.18
1-Methyl-4-[(trifluoromethyl)sulfanyl]benzene (3a)
Eluent: n-pentane (100%); slightly yellow liquid; yield: 20 mg (0.104
mmol, 52%).1H NMR (300 MHz, CDCl3): δ = 7.54 (d, J = 8.0 Hz, 2 H),
7.23 (d, J = 8.0 Hz, 2 H), 2.39 (s, 3 H).
19F NMR (282 MHz, CDCl3): δ = –43.20 (s, 3 F).
8-[(Trifluoromethyl)sulfanyl]quinoline (3k)
Eluent: n-pentane/Et2O (90:1); yellow oil; yield: 11 mg (0.048 mmol,
24%).
1H NMR (300 MHz, CDCl3): δ = 9.07 (d, J = 3.7 Hz, 1 H), 8.25 (d, J = 8.3
Hz, 1 H), 8.11 (d, J
Characterization data matched with that reported in the literature.16
1-Methoxy-4-[(trifluoromethyl)sulfanyl]benzene (3b)
= 7.4 Hz, 1 H), 7.92 (d, J = 8.1 Hz, 1 H), 7.61 (t, J = 7.8 Hz, 1 H), 7.54 (dd,
J = 8.3, 4.3 Hz,
Eluent: n-pentane/Et2O (98:2); colorless oil; yield: 23 mg (0.110
mmol, 55%).1H NMR (300 MHz, CDCl3): δ = 7.58 (m, 2 H), 6.93 (m, 2
H), 3.84 (s, 3 H).
19F NMR (282 MHz, CDCl3): δ = –43.94 (s, 3 F).
1 H).
19F NMR (282 MHz, CDCl3): δ = –41.13 (s, 3 F).
Characterization data matched with that reported in the literature.8
Characterization data matched with that reported in the literature.16
1-Methoxy-2-[(trifluoromethyl)sulfanyl]benzene (3c)
Funding Information
Eluent: n-pentane/Et2O (98:2); colorless oil; yield: 23 mg (0.110
mmol, 54%).1H NMR (300 MHz, CDCl3): δ = 7.62 (d, J = 7.3 Hz, 1 H),
7.46 (td, J = 8.0, 1.7 Hz, 1 H), 7.02–6.96 (m, 2 H), 3.91 (s, 3 H).
19F NMR (282 MHz, CDCl3): δ = –42.39 (s, 3 F).
C.G. held a doctoral fellowship from la region Auvergne Rhône Alpes.
The authors are grateful to the CNRS, ICBMS (UMR 5246), and ICL (In-
stitut de Chimie de Lyon) for financial support. The French Fluorine
Network as well as the federation RENARD are also acknowledged for
their support.()
Characterization data matched with that reported in the literature.17
1-(Methylsulfanyl)-2-[(trifluoromethyl)sulfanyl]benzene (3d)
Eluent: n-pentane (100%); yellow oil; yield: 22 mg (0.098 mmol,
47%)1H NMR (300 MHz, CDCl3): δ = 7.64 (d, J = 7.7 Hz, 1 H), 7.45 (td,
J = 8.0, 1.5 Hz, 1 H), 7.22 (d, J = 8.1 Hz, 1 H), 7.17 (td, J = 7.6, 1.3 Hz, 1
H), 2.47 (s, 3 H).
Acknowledgment
We thank Dr. Maurice Médebielle (ICBMS) for cyclic voltametry mea-
surements.
13C NMR (101 MHz, CDCl3): δ = 146.9, 138.3, 131.8, 129.6 (q, 1JC,F = 310
Hz), 125.3, 125.2, 121.9 (q, 3JC,F = 2 Hz), 15.8.
19F NMR (282 MHz, CDCl3): δ = –42.02 (s, 3 F).
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610322.
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n
4-[(Trifluoromethyl)sulfanyl]phenol (3e)
Eluent: n-pentane/Et2O (80:20); orange oil; yield: 21 mg (0.108
mmol, 53%).1H NMR (300 MHz, CDCl3): δ = 7.53 (d, J = 8.6 Hz, 2 H),
6.87 (m, 2 H).
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References
(6) (a) Dong, T.; He, J.; Li, Z.-H.; Zhang, C.-P. ACS Sustain. Chem. Eng.
2018, 6, 1327. (b) Bertoli, G.; Exner, B.; Evers, M. V.; Tschulik, K.;
Gooßen, L. J. J. Fluorine Chem. 2018, 210, 132.
(7) Ghiazza, C.; Debrauwer, V.; Monnereau, C.; Khrouz, L.;
Medebielle, M.; Billard, T.; Tlili, A. Angew. Chem. Int. Ed. 2018,
57, 11781.
(8) (a) Bottecchia, C.; Wei, X.-J.; Kuijpers, K. P. L.; Hessel, V.; Noël, T.
J. Org. Chem. 2016, 81, 7301. (b) Straathof, N. J. W.; Tegelbeckers,
B. J. P.; Hessel, V.; Wang, X.; Noël, T. Chem. Sci. 2014, 5, 4768.
(9) Glenadel, Q.; Alazet, S.; Baert, F.; Billard, T. Org. Process Res. Dev.
2016, 20, 960.
(1) (a) Boiko, V. N. Beilstein J. Org. Chem. 2010, 6, 880. (b) Toulgoat,
F.; Alazet, S.; Billard, T. Eur. J. Org. Chem. 2014, 2415. (c) Zhang,
K.; Xu, X.; Qing, F. Chin. J. Org. Chem. 2015, 35, 556. (d) Xiong, H.-
Y.; Pannecoucke, X.; Besset, T. Chem. Eur. J. 2016, 22, 16734.
(e) Chachignon, H.; Cahard, D. Chin. J. Chem. 2016, 34, 445.
(f) Barata-Vallejo, S.; Bonesi, S.; Postigo, A. Org. Biomol. Chem.
2016, 14, 7150. (g) Zheng, H.; Huang, Y.; Weng, Z. Tetrahedron
Lett. 2016, 57, 1397. (h) Toulgoat, F.; Billard, T. Towards CF3S
Group: From Trifluoromethylation of Sulfides to Direct Trifluoro-
methylthiolation. In Modern Synthesis Processes and Reactivity of
Fluorinated Compounds: Progress in Fluorine Science; Groult, H.;
Leroux, F.; Tressaud, A., Ed.; Elsevier Science: London, 2017,
141.
(2) Leo, A.; Hansch, C.; Elkins, D. Chem. Rev. 1971, 71, 525.
(3) (a) Avdeef, A. Absorption and Drug Development: Solubility, Per-
meability, and Charge State; Wiley: Hoboken, 2012. (b) Johnson,
T. W.; Gallego, R. A.; Edwards, M. P. J. Med. Chem. 2018, 61, 6401.
(4) (a) Wu, W.; Wang, B.; Ji, X.; Cao, S. Org. Chem. Front. 2017, 4,
1299. (b) Nguyen, T.; Chiu, W.; Wang, X.; Sattler, M. O.; Love, J.
A. Org. Lett. 2016, 18, 5492. (c) Zhao, M.; Zhao, X.; Zheng, P.;
Tian, Y. J. Fluorine Chem. 2017, 194, 73.
(10) Zhao, X.; Zheng, X.; Tian, M.; Tong, Y.; Yang, B.; Wei, X.; Qiu, D.;
Lu, K. Org. Chem. Front. 2018, 5, 2636.
(11) (a) Arias-Rotondo, D. M.; McCusker, J. K. Chem. Soc. Rev. 2016,
45, 5803. (b) Stephenson, C. R. J.; Yoon, T. P.; MacMillan, D. W. C.
Visible Light Photocatalysis in Organic Chemistry; Wiley: Wein-
heim, 2018. (c) Romero, N. A.; Nicewicz, D. A. Chem. Rev. 2016,
116, 10075. (d) Shaw, M. H.; Twilton, J.; MacMillan, D. W. C.
J. Org. Chem. 2016, 81, 6898. (e) Angnes, R. A.; Li, Z.; Correia, C.
R. D.; Hammond, G. B. Org. Biomol. Chem. 2015, 13, 9152.
(12) Keizer, J. J. Am. Chem. Soc. 1983, 105, 1494.
(13) Li, X.; Yang, Z.; Bai, Y. Int. J. Biol. Macromol. 2018, 107, 144.
(14) Wei, X. L.; Xiao, J. B.; Wang, Y.; Bai, Y. Spectrochim. Acta, Part A
2010, 75, 299.
(15) Zhao, X.; Yang, B.; Wei, A.; Sheng, J.; Tian, M.; Li, Q.; Lu, K. Tetra-
hedron Lett. 2018, 59, 1719.
(5) (a) Zhang, M.; Weng, Z. Adv. Synth. Catal. 2016, 358, 386. (b) Xu,
J. C. P.; Ye, J.; Liu, G. Acta Chim. Sinica 2015, 73, 1294. (c) Zhang,
P.; Li, M.; Xue, X.-S.; Xu, C.; Zhao, Q.; Liu, Y.; Wang, H.; Guo, Y.;
Lu, L.; Shen, Q. J. Org. Chem. 2016, 81, 7486. (d) Shao, X.; Xu, C.;
Lu, L.; Shen, Q. Acc. Chem. Res. 2015, 48, 1227. (e) Billard, T.
Chim. Oggi/Chem. Today 2016, 34, 18. (f) Glenadel, Q.; Alazet, S.;
Billard, T. J. Fluorine Chem. 2015, 179, 89.
(16) Alazet, S.; Billard, T. Synlett 2015, 26, 76.
(17) Matheis, C.; Wagner, V.; Goossen, L. J. Chem. Eur. J. 2016, 22, 79.
(18) Yi, Y.; Long, X.; Siqi, Y.; Xiaoqiang, L.; Yu, Z.; Vicic, D. A. Chem.
Eur. J. 2016, 22, 858.
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