Regioselective C-S bond formation accomplished by copper-catalyzed regioselective C-F substitution of perfluoroarenes with aryl thioacetates or benzyl thioacetate

Article abstract of DOI:10.1016/j.tet.2012.03.091

Practical and straightforward method for regioselective C-S bond formation accomplished by copper-catalyzed regioselective C-F substitution of electron-deficient perfluoroarenes with aryl thioacetates or benzyl thioacetate has been developed. Because of its high reaction efficiency, good chemoselectivity and regioselectivity, and excellent functional-group compatibility, this protocol provides a useful and operationally simple access to polyfluoroaryl thioethers used for drugs and material chemistry.

Full text of DOI:10.1016/j.tet.2012.03.091

Tetrahedron 68 (2012) 4233e4241
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Regioselective CeS bond formation accomplished by copper-catalyzed
regioselective CeF substitution of perfluoroarenes with aryl thioacetates or benzyl
thioacetate
,
b
b
c
a
,
a,
Qizhong Zhou a , Bin Zhang , Tieqi Du , Haining Gu , Huajiang Jiang , Rener Chen
*
*
*
a Department of Chemistry, Taizhou University, Taizhou 317000, China
b College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China
c Department of Chemistry, Zhejiang University, Hangzhou 310027, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Practical and straightforward method for regioselective CeS bond formation accomplished by copper-
catalyzed regioselective CeF substitution of electron-deficient perfluoroarenes with aryl thioacetates
or benzyl thioacetate has been developed. Because of its high reaction efficiency, good chemoselectivity
and regioselectivity, and excellent functional-group compatibility, this protocol provides a useful and
operationally simple access to polyfluoroaryl thioethers used for drugs and material chemistry.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 2 November 2011
Received in revised form 18 March 2012
Accepted 22 March 2012
Available online 30 March 2012
1. Introduction
high yields, but 1,2,4-trifluorobenzene, 1,3,5-tifluorobenzene and
1,3-difluorobenzene did not react with thiophenol.13
Polyfluorobenzene derivatives are very useful and significant
compounds, which were widely used in drugs and materials.1
Polyfluorobenzene attract much interest in CeH functionaliza-
tions catalyzed by various transition metals in modern organic
synthesis. Fagnou,2 Daugulis,3 Hiyama,4 Su,5 Zhang,6 Shi,7 and
Miura8 et al. developed direct transition-metal-catalyzed CeH
bond functionalization of perfluoroarenes.
The direct use of thiols has intrinsic shortcomes due to their foul
smell, which could lead to a severe environmental problem. In
addition, they are sensitive to oxidation and are prone to undergo
oxidative homocoupling to produce disulfides as byproducts.
Lee developed Pd-catalyzed cross-couplings of aryl halides and
thioacetates.14a Daniels established Pd-catalyzed cross-coupling of
benzyl thioacetates and aryl halides.14b
Perutz reported that fluorinated organic derivatives could be
synthesized by nickel mediated CeF activation of heteroaromatics.9
Radius reported that CeF bond could be efficiently activated by
a novel N-heterocyclic carbeneenickel(0) complex,10a and that
catalytic CeC bond formation was accomplished by selective CeF
activation of polyfluoroarenes using N-heterocyclic carbene-
stabilized nickel complex as catalyst.10b
In this paper, we describe regioselective CeS bond formation in
mild to high yield accomplished by copper-catalyzed selective CeF
substitution of polyfluoroarenes with aryl thioacetates or benzyl
thioacetate.
2. Results and discussion
It was reported decades ago that several fluorine atoms of
hexafluorobenzene and pentafluorobenzene could be replaced by
thiophenol through nucleophilic aromatic substitution (SNAr),
which showing no regioselectivity.11,12 However, the reaction
gave monothiolation product in very low yield. We have found that
the regioselective nucleophilic aromatic substitution reaction of
pentafluorobenzene, methyl 2,3,4,5-tetrafluorobenzoic acid
ester, and 1,2,4,5-tetrafluorobene with substituted thiophenols
showed good regioselectivity while pentafluorobenzene gave
Pentafluorobenzene (1 mmol), paramethyl phenyl thioacetate
(1 mmol), silver carbonate (2 mmol), and potassium carbonate
(2 mmol) were placed in anhydrous dimethoxyethane (DME). The
reaction was stirred at reflux under nitrogen atmosphere for 24 h.
After work up, we obtained compound 3a in 17% yield (see Scheme
1 and entry 1, Table 2). Compound 3a was confirmed by 1H NMR, 13
C
NMR, 19F NMR, MS (EI), and HRMS.
We screened various kinds of solvents, such as MeOH, THF,
CH3CN, ClCH2CH2Cl, dioxane, toluene, DME, and DMF, as well as
various kinds of bases, such as K2CO3, K3PO4, KOAc, Na2CO3, and
Cs2CO3, as well as various copper catalyst, such as CuI, CuBr, CuCl,
Cu(OAc)2, and CuSO4, and as well as some ligands, such as
Phen, DMEDA, Xantphos, and BINAP (see Table 1).
L-proline,
* Corresponding authors. Tel.: þ86 576 5137169; e-mail addresses: qizhong-
chou@yahoo.com (Q. Zhou), jhj@tzc.edu.cn (H. Jiang), cre@tzc.edu.cn (R. Chen).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.03.091

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Q. Zhou et al. / Tetrahedron 68 (2012) 4233e4241
Scheme 1. Pd-catalyzed direct CeS bond formation by regioselective CeF substitution from pentafluorobenzene and paramethyl phenyl thioacetate.
Table 1
Optimization of the reaction conditions
Entry
1
Metal
Ligand
Base
Solvent
DME
Temp
Yield%
17
Pd(OAc)2
K2CO3
Ag2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K3PO4
KOAc
Na2CO3
Cs2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
K2CO3
Reflux
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuI
CuBr
CuCl
Cu(OAc)2
CuSO4
CuBr
CuBr
CuBr
CuBr
CuBr
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
L-Proline
MeOH
THF
Reflux
Reflux
Reflux
Reflux
Reflux
110 ꢀC
110 ꢀC
Reflux
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
110 ꢀC
39
26
60
9
CH3CN
ClCH2CH2Cl
Dioxane
Toluene
DMF
DME
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
34
27
79
25 (68a)
68
49
63
77
95
86
82
94
84
89
95
78
94b
78
L
-Proline
L-Proline
L-Proline
L-Proline
Phen
DMEDA
Xantphos
BINAP
DMF
DMF
DMF
Xantphos
The values in bold indicate the best reaction conditions.
a
DME (anhydrous) was distilled from sodium on benzophenone.
DMF (anhydrous) was distilled from CaH2.
b
Table 2
Substrate scope
Entry
Fluoroarenes
Thioester
Product
Yield (%)
1
95
3a
3b
2
82
3
79
3c

Q. Zhou et al. / Tetrahedron 68 (2012) 4233e4241
4235
Table 2 (continued )
Entry
Fluoroarenes
Thioester
Product
Yield (%)
4
5
6
87
85
86
3d
3e
3f
7
8
58
3g
29 (14)a
3h
9
24
3i
10
24
3j
11
32
3k
(continued on next page)

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Q. Zhou et al. / Tetrahedron 68 (2012) 4233e4241
Table 2 (continued )
Entry
Fluoroarenes
Thioester
Product
Yield (%)
12
19
3l
13
21
3m
14
6
3n
15
39
3o
3p
16
48
17
18
19
29
49
41
3q
3r
3s

Q. Zhou et al. / Tetrahedron 68 (2012) 4233e4241
4237
Table 2 (continued )
Entry
Fluoroarenes
Thioester
Product
Yield (%)
20
33
3t
21
59
3u
22
43
3v
23
24
59
3w
31
23
3x
3y
25
a
14% yield was obtained from reaction of 1,2,4,5-tetrafluorobenzene (1 mmol) and paramethyl phenyl thioacetate (2 mmol).
On the basis of these results, the optimal reaction condition
involved the following parameters: CuBr as catalyst, -proline
(cheaper than Xantphos) as ligand, potassium carbonate as base,
DMF as solvent, and reaction temperature at 110 ꢀC under nitrogen
atmosphere (see entry 14, Table 1).
Under the optimal reaction condition in hand, a study on the
substrate scope was carried out, and the results are summarized in
Table 2 (see Scheme 2 and Table 2).
When pentafluorobenzene and aryl thioacetates bearing elec-
tron donating group as well as electron withdrawing group were
used as starting materials, all products were obtained in high yield
(79e95%, see entries 1e6, Table 2). All the aryl thioacetates bearing
electron donating group as well as electron withdrawing group
replaced the third F atom of pentafluorobenzene and showed
similar reactivity to generate the corresponding product in high
yields. The reaction showed good regioselectivity. Aryl thioacetates
or benzyl thioacetate replaced the first and the forth F atoms of
1,2,4,5-tetrafluorobenzene in mild yields, which show regiose-
lectivity (see entries 8e14, Table 2). Aryl thioacetates replaced the
first F atom of 1,3,5-trifluorobenzene in mild yields, which show
good regioselectivity (see entries 15e18, Table 2). Aryl thioacetates
or benzyl thioacetate replaced the second F atom of 1,2,4-
trifluorobenzene in mild yields, which show good regioselectivity
(see entries 19e24, Table 2). Benzyl thioacetate replaced the first F
atom of 1,3-difluorobenzene, which show good regioselectivity (see
entry 25, Table 2). Compared with the aryl thioacetates, benzyl
L
Scheme 2. Synthesis of various polyfluoroaryl aryl thioethers.

4238
Q. Zhou et al. / Tetrahedron 68 (2012) 4233e4241
thioacetate gave lower yield. The reactivity of benzyl thioacetate
was lower than the aryl thioacetates.
pentafluorobenzene with 3 equiv of paramethyl phenyl thio-
acetate provided compound 3a in 2% yield and compound 4 in
80% yield (see entry 2, Table 3). Reaction of pentafluorobenzene
with 4 equiv of paramethyl phenyl thioacetate provided com-
pound 4 in 68% yield and compound 5 in 23% yield (see entry 3,
Table 3).
Although aryl thioacetates could directly replace the fluorine
atom via SNAr mechanism, Herein, copper really can activate
the CeF bond. It is reasonable to assume that the catalytic
reaction proceeds by copper-promoted formation of fluoroar-
ylcopper followed by the reaction of the copper species with
paramethylphenylthio anion, affording the coupling product
(Scheme 4).
We have reported that thiophenol showed mild to high re-
activity with pentfluorobenzene and tetrafluorobenzene. However,
thiophenol showed no reactivity with trifluorobenzene and 1,3-
difluorobenzene.13 Under this reaction condition, aryl thioacetates
showed mild reactivity with trifluorobenzene and 1,3-
difluorobenzene.
We have found that the reaction of pentafluorobenzene with
more paramethyl phenyl thioacetate was very complex (see
Scheme 3). Reaction of pentafluorobenzene with 2 equiv of par-
amethyl phenyl thioacetate provided compound 3a in 29% yield
and compound 4 in 47% yield (see entry 1, Table 3). Reaction of
Scheme 3. Reaction of pentfluorobenzene with more paramethyl phenyl thioacetate.
Table 3
Control experiment: reaction of pentfluorobenzene with more paramethyl phenyl thioacetate
Entry
Product A
Product B
A: Yield (%)
B: Yield (%)
1a
29
47
80
3a
4
2b
3a
4
2
3c
4
68
23
5
a
Pentafluorobenzene (1 mmol), paramethyl phenyl thioacetates (2 mmol).
Pentafluorobenzene (1 mmol), paramethyl phenyl thioacetates (3 mmol).
Pentafluorobenzene (1 mmol), paramethyl phenyl thioacetates (4 mmol).
b
c

Q. Zhou et al. / Tetrahedron 68 (2012) 4233e4241
4239
Scheme 4. Mechanistic considerations.
3. Conclusion
4.1.4. Compound 3d. White solid; mp 72e73 ꢀC; 1H NMR (CDCl3,
400 MHz): 7.71e7.86 (m, 4H), 7.37e7.48 (m, 3H), 7.02e7.10 (m, 1H);
13C NMR (CDCl3, 100 MHz): 148.0 (dm, J¼87.4 Hz), 145.5 (dm,
J¼89.7 Hz), 133.9, 132.8, 130.4, 130.1, 129.4, 128.0, 127.7, 127.1, 126.9,
115.2 (t, J¼19.7 Hz), 107.3 (t, J¼22.7 Hz); 19F NMR (CDCl3, 300 MHz):
ꢁ62.8 (d, J¼10.2 Hz, 2F), ꢁ67.6 (d, J¼6.6 Hz, 2F); MS (EI): 308; HRMS
calcd for C16H8F4S: 308.0283, found: 308.0281.
In summary, the copper-catalyzed coupling reaction of penta-
fluorobenzene with aryl thioacetates and benzyl thioacetate
showed good regioselectivity and gave mild to high yields. Mean-
while, the copper-catalyzed coupling reaction of 1,2,3,4-
tetrafluorobenzene, 1,3,5-trifluorobenzene, 1,2,4-trifluorobenzene,
and 1,3-difluorobenzene with aryl thioacetates and benzyl thio-
acetate showed good regioselectivity and gave mild yields. The
transition-metal-catalyzed cross-coupling reactivity of poly-
fluoroarene was on the progress.
4.1.5. Compound 3e. White solid; mp 60e62 ꢀC; 1H NMR (CDCl3,
400 MHz): 7.32e7.25 (m, 4H), 7.13e7.08 (m, 1H); 13C NMR (CDCl3,
100 MHz): 148.0 (dm, J¼75.3 Hz), 145.5 (dm, J¼76.8 Hz), 134.5,
132.4, 131.7, 129.8, 114.9 (t, J¼20.1 Hz), 107.5 (t, J¼22.4 Hz); 19F NMR
(CDCl3, 300 MHz): ꢁ62.2 (m, 2F), ꢁ66.8 (m, 2F); MS (EI): 292;
HRMS calcd for C12H5ClF4S: 291.9737, found: 291.9734.
4. Experimental section
4.1.6. Compound 3f. White solid; mp 56e58 ꢀC; 1H NMR (CDCl3,
400 MHz): 7.46e7.42 (m, 2H), 7.12e6.98 (m, 3H); 13C NMR (CDCl3,
100 MHz): 164.3, 161.8, 147.9 (dm, J¼67.7 Hz), 145.4 (dm,
J¼70.5 Hz), 134.2 (d, J¼7.9 Hz), 131.6 (d, J¼8.4 Hz), 128.1, 116.8 (d,
J¼21.6 Hz), 115.8 (t, J¼20.4 Hz), 107.2 (t, J¼22.6 Hz); 19F NMR (CDCl3,
300 MHz): ꢁ62.8 (m, 2F), ꢁ67.1 (m, 2F), ꢁ87.9 (m, 1F); MS (EI): 276;
HRMS calcd for C12H5F5S: 276.0032, found: 276.0036.
4.1. General procedure for the copper-catalyzed coupling
reaction of perfluoroarenes with aryl thioacetates and benzyl
thioacetate
Pentafluorobenzene (0.168 g, 1 mmol), paramethyl phenyl thi-
oacetates (0.166 g, 1 mmol), CuBr (14.3 mg, 0.1 mmol), L-proline
(11.5 mg, 0.1 mmol), and potassium carbonate (0.276 g, 2 mmol)
were placed in DMF (5 mL). The reaction was stirred at 110 ꢀC
under nitrogen atmosphere for 24 h. Till cooled, the reaction
mixture was filtered. The organic solvent was evaporated. The
mixture was dissolved with dichloromethane (10 mL). Then the
mixture was washed with 10% NaOH (10 mL). The organic phase
was dried over sodium sulfate. After evaporation of the solvent, the
mixture was subjected column chromatography with petroleum
ether as eluent.
4.1.7. Compound 3g. White solid; mp 51e53 ꢀC; 1H NMR (CDCl3,
400 MHz): 7.26 (s, 5H), 7.00e6.92 (m, 1H), 4.11 (s, 2H); 13C NMR
(CDCl3, 100 MHz): 147.9 (dm, J¼113.0 Hz), 145.4 (dm, J¼115.2 Hz),
136.7, 129.1, 128.9, 128.0, 115.2 (t, J¼20.4 Hz), 106.3 (t, J¼22.5 Hz),
77.3 (t, J¼32.5 Hz), 39.0 (t, J¼2.8 Hz); 19F NMR (CDCl3, 300 MHz):
ꢁ133.91 (m, 2F), ꢁ138.84 (m, 2F); MS (EI): 272; HRMS calcd for
C13H8F4S: 272.0283, found: 272.0284.
4.1.1. Compound 3a. Colorless gel; 1H NMR (CDCl3, 400 MHz):
7.32e7.25 (m, 2H), 7.11e7.03 (m, 3H), 2.32 (s, 3H); 13C NMR (CDCl3,
100 MHz): 148.0 (dm, J¼69.0 Hz), 145.5 (dm, J¼70.6 Hz), 138.6,
131.7, 130.4, 130.1, 129.6, 128.9, 116.0 (t, J¼19.5 Hz), 106.9 (t,
J¼23.0 Hz), 21.4; 19F NMR (CDCl3, 300 MHz): ꢁ62.5 (m, 2F), ꢁ67.2
(m, 2F); MS (EI): 272; HRMS calcd for C13H8F4S: 272.0283, found:
272.0281.
4.1.8. Compound 3h. White solid; mp 162e164 ꢀC; 1H NMR (CDCl3,
400 MHz): 7.33 (d, J¼8.0 Hz, 4H), 7.17 (d, J¼8.0 Hz, 4H), 6.68 (t,
J¼7.6 Hz, 2H), 2.36 (s, 6H); 13C NMR (CDCl3, 100 MHz): 157.4 (d,
J¼2.8 Hz), 155.0 (d, J¼2.7 Hz), 139.2, 133.6, 130.8, 128.2, 125.0 (dd,
J1¼12.6 Hz, J2¼11.4 Hz), 117.2 (m), 21.5; 19F NMR (CDCl3, 300 MHz):
ꢁ84.3 (t, J¼9.6 Hz, 2F); MS (EI): 358; HRMS calcd for C20H16F2S2:
358.0662, found: 358.0662.
4.1.2. Compound 3b. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.44 (d, J¼8.8 Hz, 2H), 6.97e7.05 (m,1H), 6.82 (d, J¼8.4 Hz, 2H), 3.77
(s, 3H); 13C NMR (CDCl3, 100 MHz): 160.4, 147.8 (dm, J¼44.7 Hz),
145.2 (dm, J¼76.2 Hz), 134.8, 123.1, 116.9 (t, J¼19.2 Hz), 115.2, 106.6
(t, J¼22.4 Hz), 55.6; 19F NMR (CDCl3, 300 MHz): ꢁ61.4 (m, 2F),
ꢁ65.7 (m, 2F); MS (EI): 288; HRMS calcd for C13H8F4OS: 288.0232,
found: 288.0234.
4.1.9. Compound 3i. White solid; mp 129.5e131.6 ꢀC; 1H NMR
(CDCl3, 400 MHz): 7.41 (d, J¼8.8 Hz, 4H), 6.91 (d, J¼8.8 Hz, 4H), 6.56
(t, J¼8.0 Hz, 2H), 3.82 (s, 6H); 13C NMR (CDCl3, 100 MHz): 160.8,
155.7 (dd, J1¼4.0 Hz, J2¼3.5 Hz), 136.3, 125.6 (q, J¼11.7 Hz), 121.6,
116.2 (q, J¼10.3 Hz), 115.7, 55.7; 19F NMR (CDCl3, 300 MHz): ꢁ83.6
(t, J¼8.1 Hz, 2F); MS (EI): 390; HRMS calcd for C20H16F2O2S2:
390.0560, found: 390.0557.
4.1.3. Compound 3c. White solid; mp 44e45 ꢀC; 1H NMR
(CDCl3, 400 MHz): 7.22e7.26 (m, 1H), 7.04e7.11 (m, 2H),
6.85e6.88 (m, 2H), 3.85 (s, 3H); 13C NMR (CDCl3, 100 MHz):
157.8, 148.0 (dm, J¼105.7 Hz), 145.5 (dm, J¼107.6 Hz), 130.9,
129.3, 121.5, 121.3, 114.4 (t, J¼19.2 Hz), 111.4, 106.8 (t,
J¼21.9 Hz), 56.2; 19F NMR (CDCl3, 300 MHz): ꢁ62.2 (m, 2F),
ꢁ67.4 (m, 2F); MS (EI): 288; HRMS calcd for C13H8F4OS:
288.0232, found: 288.0231.
4.1.10. Compound 3j. White solid; mp 132.5e134.5 ꢀC; 1H NMR
(CDCl3, 400 MHz): 7.35e7.24 (m, 4H), 6.94e6.91 (m, 4H), 6.73 (t,
J¼7.6 Hz, 2H), 3.87 (d, J¼14.0 Hz, 6H); 13C NMR (CDCl3, 100 MHz):
158.7, 156.8 (dd, J1¼3.2 Hz, J2¼3.2 Hz), 133.9, 130.4, 123.3 (q,
J¼12.2 Hz), 121.8, 120.0, 117.8 (m), 111.6, 56.2; 19F NMR (CDCl3,
300 MHz): ꢁ84.6 (t, J¼8.7 Hz, 2F); MS (EI): 390; HRMS calcd for
C20H16F2O2S2: 390.0560, found: 390.0564.

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Q. Zhou et al. / Tetrahedron 68 (2012) 4233e4241
4.1.11. Compound 3k. White solid; mp 161.5e162.9 ꢀC; 1H NMR
(CDCl3, 400 MHz): 7.94 (s, 2H), 7.83e7.76 (m, 6H), 7.52e7.42 (m,
6H), 6.82 (t, J¼7.6 Hz, 2H); 13C NMR (CDCl3, 100 MHz): 156.6 (dd,
J1¼3.4 Hz, J2¼3.4 Hz), 134.1, 133.2, 132.4, 129.8, 129.6, 129.4, 128.1,
127.9, 127.2 (d, 4C), 124.7 (q, J¼12.0 Hz), 118.1 (m), 30.0; 19F NMR
(CDCl3, 300 MHz): ꢁ85.5 (t, J¼7.1 Hz, 2F); MS (EI): 430; HRMS calcd
for C26H16F2S2: 430.0662, found: 430.0664.
116.3 (q, J¼8.9 Hz), 115.7 (m, 3C), 113.4 (q, J¼8.3 Hz), 55.7; 19F NMR
(CDCl3, 300 MHz): ꢁ118.5 (m, 1F), ꢁ119.2 (m, 1F); MS (EI): 252;
HRMS calcd for C13H10F2OS: 252.0420, found: 252.0424.
4.1.20. Compound 3t. White solid; mp 67e69 ꢀC; 1H NMR (CDCl3,
400 MHz): 7.37e7.28 (m, 2H), 7.03e6.92 (m, 3H), 6.86e6.82 (m,
1H), 6.71e6.66 (m, 1H), 3.84 (d, J¼2.4 Hz, 3H); 13C NMR (CDCl3,
100 MHz): 159.0 (dm, J¼236.4 Hz), 159.0, 155.6 (d, J¼1.5 Hz), 134.5,
130.6, 125.7 (q, J¼7.9 Hz), 121.8, 119.8, 117.6 (d, J¼25.2 Hz), 116.5 (q,
J¼8.7 Hz),114.5 (q, J¼7.9 Hz),111.7, 56.2; 19F NMR (CDCl3, 300 MHz):
ꢁ117.4 (m, 1F), ꢁ118.8 (m, 1F); MS (EI): 252; HRMS calcd for
C13H10F2OS: 252.0420, found: 252.0419.
4.1.12. Compound 3l. Colorless gel; 1H NMR (CDCl3, 400 MHz): 7.33
(s, 8H), 6.80 (t, J¼7.6 Hz, 2H); 13C NMR (CDCl3, 100 MHz): 157.8 (d,
J¼3.1 Hz), 155.4 (d, J¼3.6 Hz), 135.1, 134.0, 130.8, 130.2, 124.5 (dd,
J1¼12.5 Hz, J2¼12.2 Hz), 118.3 (m); 19F NMR (CDCl3, 300 MHz):
ꢁ86.0 (t, J¼7.5 Hz, 2F); MS (EI): 398; HRMS calcd for C18H10Cl2F2S2:
397.9569, found: 397.9566.
4.1.21. Compound 3u. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.95 (s, 1H), 7.84e7.75 (m, 3H), 7.52e7.43 (m, 3H), 7.05e7.00 (m,
1H), 6.89e6.76 (m, 2H), 13C NMR (CDCl3, 100 MHz): 158.8 (dd,
J1¼2.1 Hz, J2¼2.8 Hz), 155.2 (d, J¼2.5 Hz), 133.9, 132.9, 132.3, 129.6,
129.4, 129.2, 127.9, 127.7, 126.9 (d, J¼4.2 Hz), 126.2 (q, J¼8.0 Hz),
117.7 (d, J¼15.9 Hz), 116.5 (q, J¼8.8 Hz), 114.7 (q, J¼7.7 Hz); 19F NMR
(CDCl3, 300 MHz): ꢁ117.0 (m, 1F), ꢁ118.2 (m, 1F); MS (EI): 272;
HRMS calcd for C16H10F2S: 272.0471, found: 272.0469.
4.1.13. Compound 3m. White solid; mp 143e145 ꢀC; 1H NMR
(CDCl3, 400 MHz): 7.45e7.42 (m, 4H), 7.08 (t, J¼8.4 Hz, 4H), 6.69 (t,
J¼7.6 Hz, 2H); 13C NMR (CDCl3, 100 MHz): 164.6, 162.2, 157.4, 155.0
(d, J¼2.9 Hz), 135.7 (d, J¼8.1 Hz), 127.0, 125.0 (dd, J1¼11.7 Hz,
J2¼11.8 Hz), 117.4 (m); 19F NMR (CDCl3, 300 MHz): ꢁ112.1 (s, 2F),
ꢁ115.9 (s, 2F); MS (EI): 366; HRMS calcd for C18H10F4S2: 366.0160,
found: 366.0158.
4.1.22. Compound 3v. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.34 (s, 4H), 7.06e7.01 (m, 1H), 6.93e6.87 (m, 1H), 6.83e6.79 (m,
1H); 13C NMR (CDCl3, 100 MHz): 13C NMR (CDCl3, 100 MHz): 159.0
(dd, J1¼2.4 Hz, J2¼2.7 Hz), 156.9 (dd, J1¼2.9 Hz, J2¼2.9 Hz), 134.9,
133.9, 131.2, 130.1, 125.5 (q, J¼8.7 Hz), 118.4 (d, J¼25.5 Hz), 116.9 (q,
J¼8.0 Hz), 115.6 (q, J¼7.8 Hz); 19F NMR (CDCl3, 300 MHz): ꢁ116.4
(m, 1F), ꢁ117.9 (m, 1F); MS (EI): 256; HRMS calcd for C12H7ClF2S:
255.9925, found: 255.9927.
4.1.14. Compound 3n. White solid; mp 109e111 ꢀC; 1H NMR (CDCl3,
400 MHz): 7.29e7.21 (m, 10H), 6.92 (t, J¼8.0 Hz, 2H), 4.05 (s, 4H);
13C NMR (CDCl3, 100 MHz): 157.3 (dd, J1¼3.7 Hz, J2¼3.2 Hz), 136.7,
129.1, 128.9, 127.8, 123.4 (q, J¼12.2 Hz), 118.5 (m), 38.4; 19F NMR
(CDCl3, 300 MHz): ꢁ85.5 (t, J¼7.2 Hz, 2F); MS (EI): 358; HRMS calcd
for C20H16F2S2: 358.0662, found: 358.0663.
4.1.15. Compound 3o. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.39 (d, J¼8.0 Hz, 2H), 7.21 (d, J¼7.6 Hz, 2H), 6.64e6.51 (m, 3H), 2.38
(s, 3H); 13C NMR (CDCl3, 100 MHz): 163.4 (dd, J1¼13.3 Hz,
J2¼13.0 Hz), 143.3 (t, J¼9.5 Hz), 139.8, 134.8, 130.9, 128.0, 110.3 (q,
J¼7.8 Hz), 101.3 (t, J 25.4 Hz), 21.5; 19F NMR (CDCl3, 300 MHz):
ꢁ90.9 (t, J¼8.4 Hz, 2F); MS (EI): 236; HRMS calcd for C13H10F2S:
236.0471, found: 236.0470.
4.1.23. Compound 3w. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.48e7.25 (m, 2H), 7.10e6.98 (m, 3H), 6.87e6.82 (m, 1H), 6.70e6.65
(m, 1H); 13C NMR (CDCl3, 100 MHz): 163.4 (d, J¼248.9 Hz), 159.1
(dd, J1¼2.3 Hz, J2¼2.4 Hz), 156.3 (dd, J1¼1.9 Hz, J2¼2.7 Hz), 135.9 (d,
J¼8.4 Hz), 131.6 (d, J¼8.2 Hz), 126.9 (q, J¼8.0 Hz), 116.9 (m), 114.7 (q,
J¼7.7 Hz); 19F NMR (CDCl3, 300 MHz): ꢁ112.2 (m, 1F), ꢁ117.6 (m,
1F), ꢁ118.1 (m, 1F); MS (EI): 240; HRMS calcd for C12H7F3S:
240.0221, found: 240.0222.
4.1.16. Compound 3p. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.46 (d, J¼8.8 Hz, 2H), 6.95 (d, J¼8.8 Hz, 2H), 6.58e6.48 (m, 3H),
3.84 (s, 3H); 13C NMR (CDCl3, 100 MHz): 163.4 (dd, J1¼13.0 Hz,
J2¼13.2 Hz), 161.1, 144.3 (t, J¼9.3 Hz), 137.2, 121.6, 115.7, 109.5 (q,
J¼7.7 Hz), 100.9 (t, J¼25.3 Hz), 55.7; 19F NMR (CDCl3, 300 MHz):
ꢁ110.0 (t, J¼8.4 Hz, 2F); MS (EI): 252; HRMS calcd for C13H10F2OS:
252.0420, found: 252.0417.
4.1.24. Compound 3x. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.28e7.22 (m, 5H), 7.00e6.93 (m, 2H), 6.87e6.82 (m, 1H); 4.10 (s,
2H); 13C NMR (CDCl3, 100 MHz): 158.7 (dd, J1¼2.5 Hz, J2¼2.5 Hz),
157.6 (dd, J1¼2.7 Hz, J2¼2.7 Hz), 136.8, 129.1, 128.9, 127.8, 125.3 (q,
J¼8.2 Hz), 118.4 (d, J¼25.3 Hz), 116.5 (q, J¼8.9 Hz), 114.8 (q,
J¼8.1 Hz), 38.2 (d, J¼2.4 Hz); 19F NMR (CDCl3, 300 MHz): ꢁ116.4 (m,
1F), ꢁ118.7 (m, 1F); MS (EI): 236; HRMS calcd for C13H10F2S:
236.0471, found: 236.0470.
4.1.17. Compound 3q. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.43e7.38 (m, 2H), 6.98 (t, J¼6.4 Hz, 2H), 6.67e6.53 (m, 3H), 3.83 (s,
3H); 13C NMR (CDCl3, 100 MHz): 163.3 (dd, J1¼13.0 Hz, J2¼13.3 Hz),
159.5, 114.7 (t, J¼9.3 Hz), 136.1, 131.4, 121.8, 119.6, 111.9, 110.7 (q,
J¼7.1 Hz), 101.4 (t, J¼25.6 Hz), 56.2; 19F NMR (CDCl3, 300 MHz):
ꢁ110.2 (t, J¼6.9 Hz, 2F); MS (EI): 252; HRMS calcd for C13H10F2OS:
252.0420, found: 252.0422.
4.1.25. Compound 3y. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.30e7.16 (m, 6H), 7.06e6.97 (m, 2H), 6.87e6.82 (m, 1H), 4.11 (s,
2H); 13C NMR (CDCl3, 100 MHz): 163.0 (d, J¼246.7 Hz), 139.2 (d,
J¼7.4 Hz), 137.1, 130.3 (d, J¼8.0 Hz), 129.1, 128.9, 127.7, 125.0 (d,
J¼2.9 Hz), 116.2 (d, J¼22.8 Hz), 113.3 (d, J¼21.0 Hz), 38.8; 19F NMR
(CDCl3, 300 MHz): ꢁ88.0 (m, 1F); MS (EI): 218; HRMS calcd for
C13H11FS: 218.0566, found: 218.0561.
4.1.18. Compound 3r. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.51e7.47 (m, 2H), 7.11 (t, J¼8.8 Hz, 2H), 6.64e6.55 (m, 3H); 13C
NMR (CDCl3, 100 MHz): 163.5 (dt, J1¼16.9 Hz, J2¼17.2 Hz), 142.6 (t,
J¼10.0 Hz), 136.8 (d, J¼9.2 Hz), 131.6 (d, J¼7.8 Hz), 127.0 (d,
J¼3.1 Hz), 117.3 (d, J¼22.0 Hz), 110.6 (q, J¼7.1 Hz), 101.7 (t,
J¼25.8 Hz); 19F NMR (CDCl3, 300 MHz): ꢁ89.3 (m, 1F), ꢁ91.3 (t,
J¼7.8 Hz, 2F); MS (EI): 240; HRMS calcd for C12H7F3S: 240.0221,
found: 240.0216.
4.1.26. Compound 4. White solid; mp 129e130.2 ꢀC; 1H NMR
(CDCl3, 400 MHz): 7.39 (d, J¼8.0 Hz, 2H), 7.23 (t, J¼6.4 Hz, 2H), 7.15
(d, J¼8.0 Hz, 2H), 7.00e7.09 (m, 6H), 6.49 (dd, J1¼6.4 Hz, J2¼6.4 Hz,
1H), 2.38 (s, 3H), 2.28 (d, J¼9.6 Hz, 6H); 13C NMR (CDCl3, 100 MHz):
159.5 (dd, J1¼2.5 Hz, J2¼3.3 Hz), 155.4 (d, J¼242.7 Hz), 140.3, 137.3,
136.9, 135.2, 132.4, 131.8, 130.9, 130.4, 130.0 (d, J¼6.9 Hz), 129.7,
128.9,128.7,126.1,124.2,124.0,115.6 (dd, J1¼2.9 Hz, J2¼4.2 Hz), 21.6,
21.3 (d, J¼4.9 Hz); 19F NMR (CDCl3, 300 MHz): ꢁ104.63 (m, 1F),
ꢁ105.55 (m, 1F); MALDI (480.1); HRMS (MALDI) calcd for
C27H22F2S3: 480.0837, found: 480.0846.
4.1.19. Compound 3s. Colorless liquid; 1H NMR (CDCl3, 400 MHz):
7.47e7.44 (m, 2H), 6.99e6.92 (m, 3H), 6.79e6.73 (m,1H), 6.53e6.49
(m, 1H), 3.84 (s, 3H); 13C NMR (CDCl3, 100 MHz): 161.0, 159.2 (d,
J¼239.8 Hz), 155.4 (d, J¼238.3 Hz), 136.8, 129.0 (q, J¼8.4 Hz), 121.0,

Q. Zhou et al. / Tetrahedron 68 (2012) 4233e4241
4241
4.1.27. Compound 5. White solid; mp 168e170 ꢀC; 1H NMR (CDCl3,
400 MHz): 7.09 (d, J¼8.4 Hz, 4H), 6.94e7.00 (m, 12H), 6.91 (s, 4H),
6.22 (s, 1H), 2.36 (s, 6H), 2.27 (s, 6H), 2.23 (s, 3H); 13C NMR (CDCl3,
100 MHz): 152.0, 149.1, 139.3, 135.6 (t, J¼4.0 Hz), 134.8, 133.7, 130.9,
130.5, 129.9, 128.8, 128.0, 127.5, 123.8, 21.7, 21.3; MALDI (688.1);
HRMS (MALDI) calcd for C41H362S5: 688.1408, found: 688.1415.
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Acknowledgements
We thank the National Natural Science Foundation of China (No.
21172166) and Natural Science Foundation of Zhejiang Province
(Y4100783) for financial support.
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