(Trifluoromethyl)thiolation of 2-alkynylbenzoates: An efficient route to 4-[(trifluoromethyl)thio]-1H-isochromen-1-ones

Article abstract of DOI:10.1002/ejoc.201402629

The incorporation of the (trifluoromethyl)thio group into the isocoumarin scaffold through a Lewis-acid-mediated electrophilic cyclization reaction of 2-(2-alkynyl)benzoates with trifluoromethanesulfanylamide is reported. The transformation proceeds well

Full text of DOI:10.1002/ejoc.201402629

FULL PAPER
DOI: 10.1002/ejoc.201402629
(Trifluoromethyl)thiolation of 2-Alkynylbenzoates: An Efficient Route to
4-[(Trifluoromethyl)thio]-1H-isochromen-1-ones
Yuewen Li,[a] Guangming Li,*[b] and Qiuping Ding*[a]
Keywords: Fluorine / Sulfur / Cyclization / Alkynes / Oxygen heterocycles / Lewis acid catalysis
The incorporation of the (trifluoromethyl)thio group into the
proceeds well in the presence of BiCl3 and BF3·Et2O under
isocoumarin scaffold through a Lewis-acid-mediated electro- mild conditions to give 4-[(trifluoromethyl)thio]-1H-iso-
philic cyclization reaction of 2-(2-alkynyl)benzoates with tri-
fluoromethanesulfanylamide is reported. The transformation
chromen-1-ones regioselectively and in good yields.
Introduction
Fluorinated organic compounds often show unique and
important physical, chemical, and biological properties due
to the high electronegativity, low polarizability, and small
size of the fluorine atom, and the strength of the C–F bond.
Such compounds have been used to great effect in the phar-
maceutical and agrochemical industries.[1] Statistical analy-
sis of available data indicates that more than 20% of com-
mercial drugs contain a fluorine group. The trifluoro-
methylthio group (CF3S) has attracted increasing interest
because of its strong electron-withdrawing effects and high
lipophilicity.[2] The introduction of an SCF3 group into
small molecules can enhance their membrane permeability
and absorption rate and also their stability. This gives an
opportunity for the modification of known and new drugs
(Figure 1).[3]
Figure 1. Examples of approved drugs containing an SCF3 group.
Recently, several elegant approaches for the formation of
C–SCF3 bonds by direct trifluoromethylthiolation have
been described. Nucleophilic trifluoromethylthiolation
–
reagents (SCF3 ),[4] such as AgSCF3, NMe4SCF3, and
including trifluoromethanesulfanylamides,[5] trifluoro-
methylated thioperoxide,[6] trifluoromethanesulfonyl hyper-
valent iodonium ylide,[7] and N-trifluoromethylthiophthal-
imide,[8] have been developed to introduce the SCF3 group
into the target products. Recently, Qing and co-workers re-
ported a transition-metal-free oxidative trifluoromethyl-
thiolation of alkynes or arylboronic acids using elemental
sulfur and (trifluoromethyl)trimethylsilane (CF3TMS) as
the source of the (trifluoromethyl)thio group.[9] Daugulis
and co-workers reported the copper-catalysed single or
double trifluoromethylthiolation of 8-aminoquinoline benz-
amides through the auxiliary-assisted direct functionaliza-
tion of β-C–H bonds using bis(trifluoromethyl) disulfide
(CF3S)2 as the electrophile.[10] Radical aryltrifluoromethyl-
thiolation of activated alkenes using an AgSCF3/K2S2O8
system has also been developed.[11]
CsSCF3, have been used in combination with transition
metals (especially, palladium and copper) by Buchwald and
Vicic for the efficient formation of C–SCF3 bonds. Wu and
ourselves reported the introduction of the (trifluoromethyl)-
thio moiety into the scaffold of isoquinoline by using
AgSCF3 as the nucleophilic reagent.[4e] Meanwhile, several
electrophilic trifluoromethylthiolation reagents (SCF3+),
[a] Key Laboratory of Functional Small Organic Molecules,
Ministry of Education and College of Chemistry & Chemical
Engineering, Jiangxi Normal University,
Nanchang, Jiangxi 330022, China
E-mail: dqpjxnu@gmail.com
http://chem.jxnu.edu.cn/s/44/t/430/1b/48/info6984.htm
[b] Department of Gastroenterology, Xinhua Hospital, Medical
School of Shanghai Jiaotong University,
Shanghai, China
E-mail: ligm68@126.com
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402629.
Isocoumarin and its derivatives can be found in many
natural products and pharmaceuticals that show a wide
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Y. Li, G. Li, Q. Ding
FULL PAPER
range of physiological and biological activities, such as anti- Table 1. Initial studies for the cyclization of methyl 2-(phenyl-
ethynyl)benzoate (1a) with trifluoromethanesulfanylamide 2.[a]
bacterial, anti-inflammatory, and anticancer activities, or as
protease inhibitors or weedkillers.[12] Therefore, a lot of ef-
fort has been put into the synthesis of isocoumarins.[13]
However, the synthesis of fluorinated isocoumarins using
fluorinating reagents has not been reported. Prompted by
advances in trifluoromethylthiolation, and by our interest
in looking for small molecules for the inhibition of the acti-
vation and proliferation of hepatic stellate cells, and for the
inhibition of extracellular matrix production,[14] we envi-
sioned that functionalization of isocoumarin by incorpora-
tion of a trifluoromethylthio group under mild conditions
would be beneficial for our biological evaluations
(Scheme 1). Therefore, we initiated a program for the devel-
opment of methods that could be used for the synthesis of
a library of trifluoromethylthio-substituted isocoumarins.
Entry Pd(OAc)2 BiCl3 BF3·Et2O Solvent[b]
T
[°C]
Yield[c]
[%]
[mol-%] [equiv.]
[equiv.]
1
2
3
–
–
1.1
–
1.1
–
–
1.5
–
DCE
DCE
DCE
DCE
DCE
DCE
toluene
THF
DMA
dioxane
CH3CN
toluene
toluene
toluene
toluene
toluene
toluene
toluene
80
80
80
80
80
80
80
80
80
80
80
60
50
25
25
25
25
25
n.r.
n.d.
trace
n.d.
31
trace
38
10
10
10
10
10
10
10
10
10
10
10
10
–
4
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.0
1.5
1.5
5
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
1.1
0.5
0.1
6[d]
7
8
9
9
trace
trace
trace
39
39
37
97
75
73
trace
10
11
12
13
14
15
16
17
18
Scheme 1. Incorporation of an SCF3 moiety into the isocoumarin
core.
–
–
–
[a] Reaction conditions: methyl 2-(phenylethynyl)benzoate (1a)
(0.2 mmol), trifluoromethanesulfanylamide 2a (0.3 mmol), under
N2. [b] DMA = N,N-dimethylacetamide. [c] Isolated yield based on
1a; n.r. = no reaction; n.d. = no 3a detected. [d] Under air.
Results and Discussion
To examine this proposed trifluoromethylthiolation, we
started to explore the practicability of this transformation,
and chose the reaction of methyl 2-(phenylethynyl)benzoate
(1a) with trifluoromethanesulfanylamide 2 as the model.
Based on previous studies, which showed that Lewis acids
could promote the electrophilic addition of trifluoro-
methanesulfanylamide,[5] the reaction was initially at-
tempted in the presence of BiCl3 (1.1 equiv.) or BF3·Et2O
(1.5 equiv.) in ClCH2CH2Cl (DCE) at 80 °C (Table 1, En-
tries 1 and 2). However, no reaction took place at all. A
trace amount of the desired product (i.e., 3a) was obtained
when a combination of Pd(OAc)2 (10 mol-%) and BiCl3
(1.1 equiv.) was used (Table 1, Entry 3). The structure of
compound 3a was determined by X-ray diffraction analysis
(Figure 2). By adjusting the amounts of the three metal
salts Pd(OAc)2 (10 mol-%), BiCl3 (1.1 equiv.), and
BF3·Et2O (1.5 equiv.), the expected product (i.e., 3a) was
obtained in 31% yield (Table 1, Entry 4). We next examined
the effect of changing the solvent. The screening results
indicated that the reaction in toluene worked more ef-
ficiently to give 3a in 38% yield (Table 1, Entries 7–11). We
found that the temperature had little impact on the out-
come (Table 1, Entries 12–14). Surprisingly, the yield of 3a
increased dramatically to 97% in the absence of Pd(OAc)2
Figure 2. ORTEP representation of the structure of 4-[(trifluoro-
methyl)thio]-1H-isochromen-1-one 3a (30% probability ellipsoids).
Using the optimal conditions, we then explored the sub-
(Table 1, Entry 15). The yield could not be improved fur- strate scope of this transformation. The results are summa-
ther by changing the loading of BiCl3 or BF3·Et2O (Table 1, rized in Table 2. The substituents attached to the triple
Entries 16 and 17). No reaction occurred when 0.1 equiv. of bond of 2-(2-alkynyl)benzoates 1 were tolerated well in ge-
BiCl3 was used as the Lewis acid (Table 1, Entry 18).
neral. For instance, when 2-alkynylbenzoate 1d, with an n-
5018
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Eur. J. Org. Chem. 2014, 5017–5022

(Trifluoromethyl)thiolation of 2-Alkynylbenzoates
butyl group attached to the alkynyl moiety, was used as the worked well under the optimized conditions. Different func-
substrate, a high yield (94%) of product 3d was obtained. tional groups including fluoro, methyl, and methoxy groups
In contrast, substrate 1e, with a tert-butyl group, gave a were all compatible with the reaction process (leading to
44% yield of 3e, probably due to steric hindrance. Interest- 3j–3m). As expected, 3-phenyl-4-[(trifluoromethyl)thio]-1H-
ingly, a trimethylsilyl group attached to the triple bond was isochromen-1-one (3a) was obtained in almost the same
tolerated under the standard conditions, and substrate 1g yield when methyl 2-(phenylethynyl)benzoate (1a) was re-
gave the desired product (i.e., 3g) in 85% yield. Addi- placed by ethyl 2-(phenylethynyl)benzoate (1n) under the
tionally, various 2-alkynylbenzoates 1 with electron-with- standard conditions (Scheme 2).
drawing or electron-donating groups on the aromatic ring
Table 2. Synthesis of 4-[(trifluoromethyl)thio]-1H-isochromen-1-
ones 3 by cyclization of 2-alkynylbenzoates 1 with trifluoro-
methanesulfanylamide 2.[a]
Scheme 2. Reaction of ethyl 2-(phenylethynyl)benzoate (1n) with
trifluoromethanesulfanylamide 2.
To investigate the reaction mechanism, we ran the reac-
tion in the absence of trifluoromethanesulfanylamide 2 un-
der the conditions shown in Table 2 (Scheme 3). Isocouma-
rin 4 was obtained by the Lewis acid (BiCl3) catalysed intra-
molecular annulation of the internal alkyne in 85% yield.
Isocoumarin 4 was not transformed into the desired prod-
uct (i.e., 3a) under the optimized conditions (Scheme 4).
The formation of the trifluoromethylthio-substituted iso-
Scheme 3. Cyclization of methyl 2-(phenylethynyl)benzoate (1a) in
the absence of trifluoromethanesulfanylamide 2.
Scheme 4. Cyclization of 3-phenyl-1H-isochromen-1-one (4) with
trifluoromethanesulfanylamide 2.
[a] Isolated yield based on 2-alkynylbenzoate 1.
Scheme 5. Proposed pathway for the formation of 3a.
Eur. J. Org. Chem. 2014, 5017–5022
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Y. Li, G. Li, Q. Ding
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1 H), 8.18 (d, J = 8.1 Hz, 1 H), 7.91–7.84 (m, 1 H), 7.68 (dd, J =
7.6, 1.8 Hz, 2 H), 7.62 (dd, J = 11.2, 4.0 Hz, 1 H), 7.48–7.50 (m, 3
H) ppm. 19F NMR (376 MHz, CDCl3): δ = –42.41 (s) ppm. 13C
NMR (100 MHz, CDCl3): δ = 163.5, 160.5, 137.7, 135.4, 132.3,
130.5, 129.8, 129.1, 128.9 (q, JC,F = 310.0 Hz), 128.1, 127.3, 125.6,
120.3, 115.0 ppm. HRMS calcd. for C16H10F3O2S [M + H]+
323.0348; found 323.0322.
coumarin 3a instead of 4 is probably due to the strong inter-
action between the trifluoromethanesulfanyl cation (CF3S+)
and the carbon–carbon triple bond. Based on these prelimi-
nary results and previous studies,[5] we propose that the re-
action involves a cascade electrophilic activation/cyclization
process (Scheme 5). Initially, the additive BF3·Et2O pro-
motes the generation of a reactive CF3S+ cation and aniline
(which was observed by TLC) from trifluoromethanesulfan-
ylamide 2.[5d] Subsequently, intermediate A would be
formed by coordination between the carbon–carbon triple
bond and the trifluoromethanesulfanyl cation (CF3S+).
Then, the intermediate B would be produced by intramolec-
ular nucleophilic attack of oxygen. Finally, SN2 attack of
3-(p-Tolyl)-4-[(trifluoromethyl)thio]-1H-isochromen-1-one
(3b):
1
White solid. H NMR (400 MHz, CDCl3): δ = 8.35 (dd, J = 7.9,
0.9 Hz, 1 H), 8.17 (d, J = 8.1 Hz, 1 H), 7.88–7.84 (m, 1 H), 7.62–
7.58 (m, 3 H), 7.29 (d, J = 8.0 Hz, 2 H), 2.43 (s, 3 H) ppm. 19F
NMR (376 MHz, CDCl3): δ = –42.45 (s) ppm. 13C NMR
(100 MHz, CDCl3): δ = 163.8, 160.7, 141.0, 138.0, 135.4, 133.9,
131.7, 130.1, 129.9, 129.8, 129.0 (q, JC,F = 310.0 Hz), 128.8, 125.6,
the chloride ion coming from BiCl3 on the methyl group 120.3, 21.5 ppm. HRMS calcd. for C17H12F3O2S [M + H]+
generates the desired product (i.e., 3).[5k]
337.0505; found 337.0483.
3-(4-Chlorophenyl)-4-[(trifluoromethyl)thio]-1H-isochromen-1-one
1
(3c): White solid. H NMR (400 MHz, CDCl3): δ = 8.37 (dd, J =
Conclusions
7.6, 0.8 Hz, 1 H), 8.18 (d, J = 8.4 Hz, 1 H), 7.90 (t, J = 7.6 Hz, 1 H),
7.65–7.63 (m, 3 H), 7.48–7.46 (m, 2 H) ppm. 19F NMR (375 MHz,
We have reported a trifluoromethylthiolation/cyclization
protocol for the synthesis of 4-[(trifluoromethyl)thio]-1H-
isochromen-1-ones 3 through reaction of 2-(2-alkynyl)-
benzoates 1 with trifluoromethanesulfanylamide 2 in good
yields under mild conditions. The Lewis acids BiCl3 and
BF3·Et2O were found to be important as activators in the
transformation. The introduction of a (trifluoromethyl)thio
moiety (SCF3) into other heterocycles is currently underway
in our laboratory.
CDCl3): δ = 42.35 (s, 3 F) ppm. 13C NMR (100 MHz, CDCl3): δ
= 162.3, 160.3, 137.6, 136.9, 135.6, 131.3, 130.7, 130.0, 129.4, 128.8
(q, JC,F = 311 Hz), 128.5, 125.6, 120.4 ppm. HRMS calcd. for
C16H9ClF3O2S [M + H]+ 356.9958; found 356.9950.
3-Butyl-4-[(trifluoromethyl)thio]-1H-isochromen-1-one (3d): White
1
solid. H NMR (400 MHz, CDCl3): δ = 8.29 (dd, J = 7.9, 0.9 Hz,
1 H), 8.05 (d, J = 8.1 Hz, 1 H), 7.85–7.80 (m, 1 H), 7.57–7.53 (m,
1 H), 3.02 (s, 2 H), 1.79–1.72 (m, 2 H), 1.47–1.41 (m, 2 H), 0.97 (t,
J = 7.3 Hz, 3 H) ppm. 19F NMR (376 MHz, CDCl3): δ = –42.86
(s) ppm. 13C NMR (100 MHz, CDCl3): δ = 168.0, 160.9, 141.3,
137.6, 135.4, 129.8, 129.1 (q, JC,F = 310.0 Hz), 128.5, 125.0, 120.1,
32.6, 29.4, 22.4, 13.7 ppm. HRMS calcd. for C14H14F3O2S [M +
H]+ 303.0661; found 303.0660.
Experimental Section
General Information: Unless otherwise stated, commercially
sourced reagents were used as received. Solvents were dried and
distilled according to standard procedures. Flash column
chromatography was carried out using silica gel (60 Å pore size,
32–63 μm, standard grade). Analytical thin-layer chromatography
was carried out using glass plates precoated with 0.25 mm 230–
400 mesh silica gel impregnated with a fluorescent indicator
(254 nm). Thin-layer chromatography plates were visualized by ex-
posure to ultraviolet light. Organic solutions were concentrated in
rotary evaporators at ca. 20 Torr at 25–35 °C. 1H, 19F, and 13C
NMR spectra were recorded in CDCl3 with a Bruker DRX-400
3-(tert-Butyl)-4-[(trifluoromethyl)thio]-1H-isochromen-1-one (3e):
White solid. H NMR (400 MHz, CDCl3): δ = 8.73 (d, J = 8.1 Hz,
1
1 H), 7.96 (d, J = 7.6 Hz, 1 H), 7.76 (td, J = 7.9, 1.2 Hz, 1 H), 7.63
(td, J = 7.5, 0.7 Hz, 1 H), 1.44 (s, 9 H) ppm. 19F NMR (376 MHz,
CDCl3): δ = –41.26 (s) ppm. 13C NMR (100 MHz, CDCl3): δ =
165.1, 153.8, 138.9, 134.8, 131.0, 127. 8 [q, J(C,F) = 310.0 Hz],
127.4, 125.6, 118.7, 38.8, 30.4 ppm. HRMS calcd. for C14H14F3O2S
[M + H]+ 303.0661; found 303.0664.
3-(2-Methoxyphenyl)-4-[(trifluoromethyl)thio]-1H-isochromen-1-one
1
(3f): White solid. H NMR (400 MHz, CDCl3): δ = 8.37 (dd, J =
spectrometer operating at 400, 376, or 100 MHz, respectively. 7.9, 1.1 Hz, 1 H), 8.14 (d, J = 8.1 Hz, 1 H), 7.90–7.85 (m, 1 H),
Chemical shifts are reported in parts per million (ppm) from in-
ternal tetramethylsilane on the δ scale. Coupling constants are re-
ported in Hz. High-resolution mass spectra (HRMS) were obtained
with a micrOTOF II Instrument.
7.64–7.60 (m, 1 H), 7.51–7.46 (m, 1 H), 7.41 (d, J = 7.3 Hz, 1 H),
7.07 (t, J = 7.4 Hz, 1 H), 6.99 (d, J = 8.4 Hz, 1 H), 3.82 (s, 3 H)
ppm. 19F NMR (376 MHz, CDCl3): δ = –42.40 (s) ppm. 13C NMR
(100 MHz, CDCl3): δ = 161.2, 156.9, 137.7, 135.3, 132.0, 130.9,
129.9, 129.1 (q, J = 310.0 Hz), 129.0, 125.5, 121.9, 120.6, 120.3,
111.0, 55.6 ppm. HRMS calcd. for C17H12F3O3S [M + H]+
353.0454; found 353.0440.
General Procedure for the Synthesis of 4-[(Trifluoromethyl)thio]-1H-
isochromen-1-ones: BiCl3 (69.4 mg, 0.22 mmol) was added to a
solution of 2-alkynylbenzoate 1 (0.2 mmol), trifluoromethanesulf-
anylamide 2 (0.3 mmol) and BF3·Et2O (0.3 mmol) in toluene
(2.0 mL) under nitrogen. The mixture was stirred at 25 °C for 4–
6 h. After TLC showed that the reaction was complete, the mixture
was filtered through a thin layer of silica gel, which was then
washed with EtOAc (3ϫ 5.0 mL). The mixture was concentrated
in vacuo, and the residue was purified by column chromatography
on silica gel (eluting with petroleum ether/EtOAc, 20:1) to give
product 3.
4-[(Trifluoromethyl)thio]-3-(trimethylsilyl)-1H-isochromen-1-one
1
(3g): White solid. H NMR (400 MHz, CDCl3): δ = 8.31 (dd, J =
8.0, 1.0 Hz, 1 H), 8.10 (d, J = 8.0 Hz, 1 H), 7.84 (t, J = 7.6 Hz, 1
H), 7.61 (t, J = 7.6 Hz, 1 H), 0.46 (s, 9 H) ppm. 19F NMR
(375 MHz, CDCl3): δ = 41.93 (s, 3 F) ppm. 13C NMR (100 MHz,
CDCl3): δ = 174.64, 161.66, 136.49, 135.01, 128.74 (JC,F
=
310.0 Hz), 124.90, 121.84, 121.21, 115.10, –0.51 ppm. HRMS
calcd. for C13H14F3O2SSi [M + H]+ 319.0430; found 319.0434.
3-Phenyl-4-[(trifluoromethyl)thio]-1H-isochromen-1-one (3a): White 3-(4-Fluorophenyl)-4-[(trifluoromethyl)thio]-1H-isochromen-1-one
1
1
solid. H NMR (400 MHz, CDCl3): δ = 8.36 (dd, J = 7.9, 0.8 Hz,
(3h): White solid. H NMR (400 MHz, CDCl3): δ = 8.36 (dd, J =
5020
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5017–5022

(Trifluoromethyl)thiolation of 2-Alkynylbenzoates
D. Bonnet-Delpon (Eds.), Bioorganic and Medicinal Chemistry
of Fluorine, Wiley, Hoboken, 2008; e) I. Ojima (Ed.), Fluorine
in Medicinal Chemistry and Chemical Biology, Wiley, Chiches-
ter, 2009.
7.9, 1.0 Hz, 1 H), 8.18 (d, J = 8.2 Hz, 1 H), 7.91–7.87 (m, 1 H),
7.72–7.68 (m, 2 H), 7.66–7.61 (m, 1 H), 7.20–7.16 (m, 2 H) ppm.
19F NMR (376 MHz, CDCl3): δ = –42.42 (s), –108.99 (s) ppm. 13
C
NMR (100 MHz, CDCl3): δ = 163.8 (d, J = 252.3 Hz), 162.5, 160.4,
137.7, 135.5, 132.1 (d, J = 8.7 Hz), 129.9, 129.3, 128.8 (q, J =
310.0 Hz), 128.4, 125.7, 120.3, 115.4 (d, J = 22.0 Hz) ppm. HRMS
calcd. for C16H9F4O2S [M + H]+ 341.0254; found 341.0248.
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7-Methoxy-3-phenyl-4-[(trifluoromethyl)thio]-1H-isochromen-1-one
(3j): White solid. 1H NMR (400 MHz, CDCl3): δ = 8.10 (d, J =
8.8 Hz, 1 H), 7.76 (d, J = 2.8 Hz, 1 H), 7.68–7.66 (m, 2 H), 7.50–
7.43 (m, 4 H), 3.95 (s, 3 H) ppm. 19F NMR (376 MHz, CDCl3): δ
= –42.43 (s) ppm. 13C NMR (100 MHz, CDCl3): δ = 161.3, 160.8,
160.2, 132.3, 131.3, 130.3, 129.9, 129.0 (q, J = 310.0 Hz), 128.1,
127.5, 124.7, 123.4, 121.6, 110.4, 55.9 ppm. HRMS calcd. for
C17H12F3O3S [M + H]+ 353.0454; found 353.0457.
[4]
7-Methyl-3-phenyl-4-[(trifluoromethyl)thio]-1H-isochromen-1-one
1
(3k): White solid. H NMR (400 MHz, CDCl3): δ = 8.25 (d, J =
8.1 Hz, 1 H), 7.96 (s, 1 H), 7.68–7.65 (m, 2 H), 7.51–7.42 (m, 4 H),
2.57 (s, 3 H) ppm. 19F NMR (376 MHz, CDCl3): δ = –42.45 (s)
ppm. 13C NMR (101 MHz, CDCl3): δ = 163.7, 160.6, 146.8, 137.8,
132.4, 130.5, 129.9, 128.9 (q, JC,F = 310 Hz), 128.1, 125.7, 117.9,
22.3 ppm. HRMS calcd. for C17H12F3O2S [M + H]+ 337.0505;
found 337.0508.
[5]
7-Fluoro-3-phenyl-4-[(trifluoromethyl)thio]-1H-isochromen-1-one
1
(3l): White solid. H NMR (400 MHz, CDCl3): δ = 8.20 (dd, J =
8.9, 4.9 Hz, 1 H), 8.01 (dd, J = 8.1, 2.7 Hz, 1 H), 7.67 (dd, J = 7.9,
1.7 Hz, 2 H), 7.61–7.57 (m, 1 H), 7.52–7.46 (m, 3 H) ppm. 19F
NMR (376 MHz, CDCl3): δ = –42.41 (s, 3 F), –109.70 (s, 1 F) ppm.
13C NMR (100 MHz, CDCl3): δ = 162.9, 162.4 (d, J = 250.0 Hz),
159.6, 134.3, 131.9, 130.7, 129.9, 128.8 (q, J = 311.0 Hz), 128.5 (d,
J = 7.8 Hz), 128.2, 123.6 (d, J = 22.9 Hz), 122.1 (d, J = 8.3 Hz),
115.4 (d, J = 23.6 Hz) ppm. HRMS calcd. for C16H9F4O2S [M +
H]+ 341.0254; found 341.0252.
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a) X. Shao, X. Wang, T. Yang, L. Lu, Q. Shen, Angew. Chem.
Int. Ed. 2013, 52, 3457; Angew. Chem. 2013, 125, 3541; b) X.
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6-Fluoro-3-phenyl-4-[(trifluoromethyl)thio]-1H-isochromen-1-one
1
(3m): White solid. H NMR (400 MHz, CDCl3): δ = 8.39 (dd, J =
8.7, 5.6 Hz, 1 H), 7.84 (dd, J = 9.9, 2.2 Hz, 1 H), 7.71–7.65 (m, 2
H), 7.55–7.46 (m, 3 H), 7.31 (ddd, J = 8.7, 8.0, 2.4 Hz, 1 H) ppm.
19F NMR (376 MHz, CDCl3): δ = –42.4, –99.6 ppm. 13C NMR
(100 MHz, CDCl3): δ = 167.3 (d, J = 257.6 Hz), 165.0, 159.6, 141.2
(d, J = 10.4 Hz), 133.3 (d, J = 10.3 Hz), 131.9 (d, J = 17.6 Hz),
130.8, 129.8, 128.8 (q, JC,F = 311.0 Hz), 128.7, 117.5 (d, J =
23.4 Hz), 116.8, 112.0 (d, J = 25.3 Hz) ppm. HRMS calcd. for
C16H9F4O2S [M + H]+ 341.0254; found 341.0246.
[7]
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1
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Acknowledgments
Financial support from the National Natural Science Foundation
of China (21262016), the Project of Jiangxi Youth Scientist
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Received: May 25, 2014
Published Online: July 11, 2014
5022
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© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 5017–5022