Nucleophilic trifluoromethylthiolation of allylic bromides: A facile preparation of allylic trifluoromethyl thioethers

Article abstract of DOI:10.1002/cjoc.201300415

A facile preparation of allylic trifluoromethyl thioethers was achieved by using a copper reagent. The reaction of (bpy)Cu(SCF₃) with various allylic bromides afforded the desired trifluoromethylthiolation products in good to excellent yields with high stereo- and regioselectivity. Common functional groups such as alkyl, alkoxy, trifluoromethyl, nitro, halides and geranyl are well tolerated. A facile preparation of allylic trifluoromethyl thioethers was achieved by the reaction of (bpy)Cu(SCF₃) with allylic bromides. This protocol afforded the desired trifluoromethylthiolation products in good to excellent yields with high stereo- and regioselectivity. Important functional groups such as alkyl, alkoxy, trifluoromethyl, nitro, halides and geranyl are well tolerated. Copyright

Full text of DOI:10.1002/cjoc.201300415

FULL PAPER
DOI: 10.1002/cjoc.201300415
Nucleophilic Trifluoromethylthiolation of Allylic Bromides: A
Facile Preparation of Allylic Trifluoromethyl Thioethers
Jianwei Tan, Guoting Zhang, Yangli Ou, Yaofeng Yuan, and Zhiqiang Weng*
Department of Chemistry, Fuzhou University, Fuzhou, Fujian 350108, China
A facile preparation of allylic trifluoromethyl thioethers was achieved by using a copper reagent. The reaction
of (bpy)Cu(SCF3) with various allylic bromides afforded the desired trifluoromethylthiolation products in good to
excellent yields with high stereo- and regioselectivity. Common functional groups such as alkyl, alkoxy, trifluoro-
methyl, nitro, halides and geranyl are well tolerated.
Keywords trifluoromethylthiolation, allylic halides, copper
Introduction
However, these processes require the use of high-cost
electrophilic trifluoromethylating reagents or an excess
of oxidants to promote the reaction effectively.
The organic molecules containing trifluoromethyl-
thio group (－SCF3) are key structural motifs in a num-
ber of pharmaceuticals and agrochemicals.[1,2] Therefore,
the development of efficient synthetic methods for their
synthesis is desirable. Numerous synthetic methodolo-
gies for the introduction of this substitution to molecules
have been developed in the past decades.
The traditional reaction procedures involve either the
nucleophilic reaction of trifluoromethylthiolate with aryl
halides,[3] or the nucleophilic[4] and radical[5] trifluo-
romethylation of aryl sulfides and disulfides, thiocy-
anates, and thiols as well as electrophilic trifluoro-
methylations of thiolates.[6]
Recently, the transition-metal-catalyzed or mediated
trifluoromethylthiolation has presented an attractive and
powerful strategy for the generation of aryl trifluoro-
methylthio ethers. Remarkable examples include the
palladium[7]/nickel[8]-catalyzed Ar-SCF3 bond-forming
reaction with aryl halides, the copper-catalyzed trifluo-
romethylthiolation of aryl boronic acids[9-11] or
arenes.[12]
On the other hand, allylic compounds are useful
synthons which can be transformed to a variety of more
complex molecules.[13] Compounds containing allylic
trifluoromethyl groups constitute particularly useful
building blocks for the synthesis of fluorine-containing
compounds.[14]
Meanwhile, nucleophilic allylic trifluoromethylation
of allylic halides mediated by transition-metal com-
plexes also constitutes a powerful reaction in synthesis
of these compounds. This reaction has been traditionally
performed using stoichiometric amount of CuCF3 re-
agent or its complex[18] and more recently, using readily
available and less expensive CF3SiMe3 as the trifluoro-
methylating reagent under copper catalysis.[19]
Although various methods are available for the ally-
lic trifluoromethylation, a completely general approach
to the formation of allylic trifluoromethyl thioethers has
not yet been developed. A perusal of the literature re-
vealed that only one example had been reported for the
synthesis of allyl trifluoromethyl thioether from the re-
actions of allyl bromides with [NMe4](SCF3) or
Cs(SCF3).[3a]
In our continuing efforts to develop copper-cata-
lyzed trifluoromethylation[20] and trifluoromethyl-thio-
lation reactions, we recently reported that an air-stable
copper reagent displayed excellent reactivity in the nu-
cleophilic trifluoromethylthiolation of aryl halides.[21]
Herein, we describe the first nucleophilic trifluoro-
methylation of allylic halides using copper reagent to
form allylic trifluoromethyl thioethers.
Results and Discussion
The development of the copper-catalyzed electro-
philic or oxidative allylic trifluoromethylation of termi-
nal alkenes using Umemoto’s[15] and Togni’s reagents[16]
and CF3SiMe3 (Ruppert-Prakash reagent)[17] has pro-
vided a robust and efficient approach to the synthesis of
molecules containing allylic CF3 functional groups.
We started our investigation on (E)-cinnamyl bro-
mide 1a as substrate, using (bpy)Cu(SCF3) 2 as
trifluoromethylthiolation reagent and CH3CN as solvent
(Table 1). The reaction was performed under ambient
temperature (25 ℃) for 15 h. We were gratified to ob-
*
E-mail: zweng@fzu.edu.cn; Tel.: 0086-0591-22866121; Fax: 0086-0591-22866121
Received May 22, 2013; accepted June 20, 2013; published online July 5, 2013.
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/cjoc.201300415 or from the author.
Chin. J. Chem. 2013, 31, 921—926
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Tan et al.
FULL PAPER
serve that trifluoromethylthiolation proceeded smoothly
and generated the desired cinnamyl(trifluoromethyl)-
sulfane 3a with an E/Z ratio of 3∶1 in 63% yield (Entry
1). It is noteworthy that no branched isomer was pro-
duced in this reaction. Heating of the reaction at 70 ℃
to facilitate trifluoromethylthiolation significantly im-
proved the yield as compared to reacting at room tem-
perature (Entry 2). Of particular importance, only ther-
modynamically more stable E-isomer of 3a was formed
in 80% yield under the reaction conditions.
ceeded to afford the corresponding allylic trifluoro-
methyl thioethers in moderate to good yields and with
excellent stereo- and regioselectivity.
Table
2
Trifluoromethylthiolation of allylic halides by
(bpy)Cu(SCF3)a
CH3CN
R
+ (bpy)Cu(SCF3)
Br
70 oC, 8 h
1
2
R
SCF3
Table 1 Optimization of the trifluoromethylthiolation of cin-
namyl bromide (1a)a
3
Yieldb/
%
Entry
1
Allylic halide
Product
solvent
+ (bpy)Cu(SCF3)
Br
temp.
1a
2
Br
SCF3
SCF3
SCF3
SCF3
86
89
80
64
84
78
36
96
67
53
54
3a
1a
SCF3
3a
Br
Entry Solvent
Temp./℃
Time/h
Yieldb/%
2
1b
1c
3b
1
2
CH3CN
CH3CN
Toluene
THF
25
70
70
70
15
8
63 (E/Z=3∶1)
80 (only E)
Br
3
8
76 (E/Z=3∶1)
68 (E/Z=4∶1)
66 (E/Z=4∶1)
25 (only E)
3
4
8
3c
5
Diglyme 70
8
6
MeOH
DMF
70
70
70
8
Br
4
7
8
76 (E/Z=5∶1)
56 (E/Z=19∶1)
75 (E/Z=4∶1)
82 (E/Z=5∶1)
i-Pr
t-Bu
F3C
i-Pr
t-Bu
F3C
3d
1d
8
DMSO
8
9
Dioxane 70
CH2Cl2 40
8
Br
Br
SCF3
SCF3
5
10
8
a Conditions: 1a (0.050 mmol), 2 (0.050 mmol), solvent (0.8 mL),
3e
1e
1f
b
under N2 atmosphere. Yields were determined by the 19F NMR
analysis of the crude reaction mixture with (trifluoromethoxy)-
benzene as internal standard.
6
3f
Encouraged with the reactivity, we then evaluated
various solvents in trifluoromethylthiolation under
similar reaction conditions. As shown in Table 1, per-
forming the trifluoromethylthiolation with other sol-
vents such as toluene, DMF, dioxane and CH2Cl2 gave
results almost comparable to CH3CN with moderate
stereoselectivities (Entries 3, 7, 9 and 10). Using THF,
diglyme and DMSO (instead of CH3CN) resulted in
inferior yields (Entries 4, 5 and 8). Additionally, the
reaction conducted in alcoholic solvents, such as
methanol giving a substantial decrease in the yield of
products but with little effect on the stereoselectivities
(Entry 6). Thus, CH3CN was found to be the optimal
solvent for the trifluoromethylthiolation with respect to
reactivity and stereoselectivity.
SCF3
SCF3
Br
Br
7
NO2
NO2
1g
3g
8
OMe
OMe
1h
3h
MeO
MeO
SCF3
Br
9
1i
3i
Br
SCF3
SCF3
10
11
Cl
Cl
Cl
Cl
3j
1j
Under the optimized reaction conditions, the scope
and generality of the trifluoromethylthiolation of allylic
bromide was evaluated and the results are summarized
in Table 2. Generally, the reactions of (bpy)Cu(SCF3) 2
with a variety of cinnamyl bromides successfully pro-
Br
3k
1k
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© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 921—926

Nucleophilic Trifluoromethylthiolation of Allylic Bromides
Continued
could also be used for further transformation.
Although the detailed mechanism still remains to be
clarified,[13a,22] the reaction is envisioned to take place
via oxidative addition of cinnamyl bromide 1a to
(bpy)Cu(SCF3) 2 to give an allylcopper(III) species
A[23,19] (Scheme 1). The intermediate A then undergoes
reductive elimination to give the expected trifluoro-
methylthiolated product as well as (bpy)CuBr.
Yieldb/
%
Entry
Allylic halide
Product
12
62
Br
F3CS
1l
3l
SCF3
Cl
13
77c
Scheme 1 Plausible reaction pathway leading to the allylic
trifluoromethyl thioethers
1a'
3a
a Reaction conditions: 1 (0.40 mmol), 2 (0.48 mmol), 8 h, 70 ℃,
under N2 atmosphere. b Isolated yield. c 19F NMR yield.
Br
N
N
N
N
SCF3
1a
Cu SCF3
Cu
The cinnamyl bromides 1a－1e with alkyl substitu-
tions at the para position of the aromatic rings yielded
the desired compounds 3a－3e in 64%－89% yields
(Table 2, Entries 1－5). The reaction of cinnamyl bro-
mide 1f with a trifluoromethyl group also proceeded
smoothly and the corresponding product 3f was ob-
tained in 78% yield (Entry 6). The cinnamyl bromide 1g
having a nitro substitution at the ortho position of the
phenyl ring provided the desired product 3g in a lower
yield (36%; Entry 7). The electron-donating group such
as ortho- and para-methoxy-substituted cinnamyl bro-
mides 1h and 1i also participated in the reaction afford-
ing desired products 3h and 3i in 96% and 67% yields,
respectively (Entries 8 and 9). Furthermore, chlorine
functionality was well tolerated under the reaction con-
ditions. Thereby, the para- and meta-chlorine-substi-
tuted cinnamyl bromides 1j and 1k produced the corre-
sponding trifluoromethylthiolated products 3j and 3k in
yields of 53% and 54%, respectively (Entries 10 and 11).
It was worthwhile to note that the chloro group can be
used as an active functionality in palladium-catalyzed
cross-coupling reactions, thus allowing additional modi-
fications. The geranyl bromide 1l containing no conju-
gated aromatic ring also provided a 62% isolated yield
for the corresponding allylic trifluoromethyl thioether 3l
(Entry 12). Moreover, cinnamyl chloride 1a' could also
be employed as substrate to give the desired product 3a,
albeit in a slightly lower yield of 77% (Entry 13).
Ph
2
A
(bpy)CuBr
Ph
SCF3
+
Conclusions
In summary, an efficient synthetic method for the
preparation of allylic trifluoromethyl thioethers has been
developed by nucleophilic trifluoromethylthiolation of
allylic bromides. The use of copper reagent (bpy)Cu-
(SCF3) provides a convenient protocol for the synthesis
of this important class of trifluoromethylthiolate com-
pounds in good to excellent yields with high stereo- and
regioselectivity. A number of functional groups such as
alkyl, alkoxy, trifluoromethyl, nitro, halides and geranyl
were tolerated under the reaction conditions. Further
efforts to expand the application to other distinctive
substrates and substituents are subjects of current re-
search efforts.
Experimental
1H NMR, 19F NMR and 13C NMR spectra were re-
corded using Bruker AVIII 400 spectrometer. H NMR
1
and 13C NMR chemical shifts were reported in parts per
million (ppm) downfield from tetramethylsilane and 19F
NMR chemical shifts were determined relative to CFCl3
as the external standard and low field is positive. Cou-
pling constants (J) are reported in Hertz (Hz). The re-
sidual solvent peak was used as an internal reference:
1H NMR (chloroform δ 7.26) and 13C NMR (chloroform
δ 77.0). The following abbreviations were used to ex-
plain the multiplicities: s＝singlet, d＝doublet, t＝
triplet, q＝quartet, m＝multiplet, br＝broad. Allylic
bromides 1b－1k, 1m[24] and (bpy)Cu(SCF3)[21] were
prepared according to the published procedures. Other
reagents were received from commercial sources. Sol-
vents were freshly dried and degassed according to the
procedures in Purification of Laboratory Chemicals
prior to use. Column chromatography purifications were
performed by flash chromatography using Merck silica
gel 60.
To examine the chemoselectivity of trifluoromethyl-
thiolation, cinnamyl bromide 1m possessing an allylic
and an aryl reactive sites was chosen as substrate (Eq. 1).
The reaction of 1m with 2 gave allylic trifluoromethyl
thioether product 3m exclusively in 58% yield and left
the aryl-Br bond unaffected. Therefore, this procedure
provides a highly chemoslective method for preparation
of halogenated allylic trifluoromethyl thioethers. Of
additional note, the bromo group on the phenyl ring
CH3CN
Br
+ 2
70 oC, 8 h
Br
1m
SCF3
(1)
Br
3m (58%)
Chin. J. Chem. 2013, 31, 921—926
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Tan et al.
FULL PAPER
General procedure for trifluoromethylthiolation of
allylic bromides using (bpy)Cu(SCF3)
J＝7.4 Hz, 2H), 2.94 (hept, J＝6.9 Hz, 1H), 1.29 (d, J＝
6.9 Hz, 6H); 19F NMR (376 MHz, CDCl3) δ: −40.86 (s,
3F); 13C NMR (101 MHz, CDCl3) δ: 149.1 (s), 134.3 (s),
133.8 (s), 130.8 (q, J＝306.9 Hz), 126.8 (s), 126.6 (s),
122.0 (s), 33.9 (s), 32.8 (q, J＝2.3 Hz), 23.9 (s); IR
(KBr) ν: 3087, 3027, 2964, 2931, 2873, 1650, 1610,
1513, 1461, 1240, 1111, 965, 827 cm−1; GC-MS m/z
260 (M＋), 159 (M＋−SCF3 100%). HRMS (EI) calcd for
C13H15F3S: 260.0847, found 260.0842.
Allylic bromide 1 (0.40 mmol), (bpy)Cu(SCF3) (154
mg, 0.48 mmol, 1.2 equiv.) and CH3CN (2.0 mL) were
added to a reaction tube equipped with a magnetic stir
bar. The tube was sealed and the solution was placed
into a preheated 70 ℃ oil bath for 8 h. The tube was
removed from the oil bath and allowed to cool. The re-
action mixture was then filtered through celite to re-
move metal salts. Water (10.0 mL) was added to the
mixture at 0 ℃. The resulting mixture was extracted
with diethyl ether (6.0 mL×3), and the combined or-
ganic layers were dried over magnesium sulfate. The
solvent was removed by rotary evaporation in an ice
bath and the resulting product was purified by column
chromatography on silica gel with pentane.
(E)-(3-(4-(tert-Butyl)phenyl)allyl)(trifluorometh-
yl)sulfane (3e) Obtained as a colorless oil in 84%
1
yield (92 mg), Rf (pentane): 0.79; H NMR (400 MHz,
CDCl3) δ: 7.43 (d, J＝8.0 Hz, 2H), 7.38 (d, J＝8.0 Hz,
2H), 6.65 (d, J＝15.7 Hz, 1H), 6.29－6.21 (m, 1H),
3.77 (d, J＝7.4 Hz, 2H), 1.39 (s, 9H); 19F NMR (376
MHz, CDCl3) δ: －40.82 (s, 3F); 13C NMR (101 MHz,
CDCl3) δ: 151.4 (s), 134.2 (s), 133.4 (s), 130.9 (q, J＝
306.2 Hz), 126.3 (s), 125.6 (s), 122.1 (s), 34.6 (s), 32.8
(q, J＝2.4 Hz), 31.3 (s); IR (KBr) ν: 3089, 3032, 2965,
2905, 2870, 1650, 1609, 1515, 1460, 1240, 1112, 965,
823 cm−1; GC-MS m/z: 274 (M＋ ), 173 (M＋ −SCF3
100%). HRMS (EI) calcd for C14H17F3S: 274.1003,
found 274.0999.
(E)-(Trifluoromethyl)(3-(4-(trifluoromethyl)-
phenyl)allyl)sulfane (3f) Obtained as a colorless oil
in 78% yield (89 mg), Rf (pentane): 0.65; 1H NMR (400
MHz, CDCl3) δ: 7.61 (d, J＝8.1 Hz, 2H), 7.49 (d, J＝
8.1 Hz, 2H), 6.66 (d, J＝15.7 Hz, 1H), 6.45－6.26 (m,
1H), 3.76 (d, J＝7.3 Hz, 2H); 19F NMR (376 MHz,
CDCl3) δ: −40.83 (s, 3F), −62.62 (s, 3F); 13C NMR (101
MHz, CDCl3) δ: 139.5 (s), 132.8 (s), 130.7 (q, J＝307.0
Hz), 130.0 (q, J＝32.5 Hz), 126.7 (s), 126.0 (s), 125.6
(q, J＝3.9 Hz), 124.1 (q, J＝271.9 Hz), 32.4 (q, J＝2.4
Hz); IR (KBr) ν: 2938, 1617, 1326, 1240, 1109, 967,
831 cm−1; GC-MS m/z: 286 (M＋ ), 185 (M＋ −SCF3
100%). HRMS (EI) calcd for C11H8F6S: 286.0251,
found 286.0255.
(E)-Cinnamyl(trifluoromethyl)sulfane (3a) Ob-
tained as a colorless oil in 86% yield (75 mg), Rf (pen-
1
tane): 0.70; H NMR (400 MHz, CDCl3) δ: 7.42－7.29
(m, 5H), 6.64 (d, J＝15.7 Hz, 1H), 6.31－6.21 (m, 1H),
3.76 (d, J＝7.4 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ:
－40.86 (s, 3F); 13C NMR (101 MHz, CDCl3) δ: 136.1
(s), 134.4 (s), 130.8 (q, J＝306.9 Hz), 128.7 (s), 128.1
(s), 126.5 (s), 123.0 (s), 32.7 (q, J＝2.0 Hz); IR (KBr) ν:
3086, 3032, 2931, 1647, 1112, 963, 749, 693 cm−1;
GC-MS m/z: 218 (M＋), 117 (M＋−SCF3 100%). HRMS
(EI) calcd for C10H9F3S: 218.0377, found 218.0376.
(E)-(3-(p-Tolyl)allyl)(trifluoromethyl)sulfane (3b)
Obtained as a colorless oil in 89% yield (82 mg), Rf
(pentane): 0.77; 1H NMR (400 MHz, CDCl3) δ: 7.33 (d,
J＝7.7 Hz, 2H), 7.20 (d, J＝7.7 Hz, 2H), 6.63 (d, J＝
15.6 Hz, 1H), 6.27－6.19 (m, 1H), 3.77 (d, J＝7.4 Hz,
2H), 2.41 (s, 3H); 19F NMR (376 MHz, CDCl3) δ:
−40.86 (s, 3F); 13C NMR (101 MHz, CDCl3) δ: 138.1
(s), 134.3 (s), 133.4 (s), 130.9 (q, J＝306.8 Hz), 129.4
(s), 126.5 (s), 121.9 (s), 32.8 (q, J＝2.3 Hz), 21.2 (s); IR
(KBr) ν: 3088, 3028, 2925, 2866, 1650, 1613, 1514,
1240, 1111, 965, 798 cm−1; GC-MS m/z: 232 (M＋), 131
(M＋−SCF3 100%). HRMS (EI) calcd for C11H11F3S:
232.0534, found 232.0531.
(E)-(3-(2-Nitrophenyl)allyl)(trifluoromethyl)-
sulfane (3g) Obtained as a yellow oil in 36% yield (38
1
mg), Rf (pentane/Et2O 13∶1 (V/V)): 0.63; H NMR
(400 MHz, CDCl3) δ: 7.99 (d, J＝8.3 Hz, 1H), 7.64－
7.59 (m, 2H), 7.48－7.43 (m, 1H), 7.13 (d, J＝15.5 Hz,
1H), 6.26－6.19 (m, 1H), 3.77 (d, J＝7.3 Hz, 2H); 19F
NMR (376 MHz, CDCl3) δ: −40.65 (s, 3F); 13C NMR
(101 MHz, CDCl3) δ: 147.7 (s), 133.3 (s), 131.9 (s),
130.7 (q, J＝307.1 Hz), 129.6 (s), 128.9 (s), 128.7 (s),
128.6 (s), 124.6 (s), 32.4 (q, J＝2.2 Hz); IR (KBr) ν:
3073, 2936, 2862, 1647, 1608, 1520, 1347, 1241, 1109,
963, 743 cm−1; GC-MS m/z: 262 (M＋−H), 162 (M＋
−SCF3 100%). HRMS (EI) calcd for C10H8F3NO2S:
263.0228, found 263.0227.
(E)-(3-(m-Tolyl)allyl)(trifluoromethyl)sulfane (3c)
Obtained as a pale yellow oil in 80% yield (74 mg), Rf
(pentane): 0.73; H NMR (400 MHz, CDCl3) δ: 7.30－
1
7.22 (m, 3H), 7.15 (d, J＝7.2 Hz, 1H), 6.62 (d, J＝15.7
Hz, 1H), 6.32－6.20 (m, 1H), 3.76 (d, J＝7.4 Hz, 2H),
2.41 (s, 3H); 19F NMR (376 MHz, CDCl3) δ: −40.84 (s,
3F); 13C NMR (101 MHz, CDCl3) δ: 138.3 (s), 136.1 (s),
134.5 (s), 130.9 (q, J＝306.9 Hz), 129.0 (s), 128.6 (s),
127.3 (s), 123.7 (s), 122.8 (s), 32.8 (q, J＝2.4 Hz), 21.4
(s); IR (KBr) ν: 3098, 3033, 2925, 2864, 1650, 1605,
1485, 1246, 1111, 963, 779, 685 cm−1; GC-MS m/z: 232
(M＋), 131 (M＋−SCF3 100%). HRMS (EI) calcd for
C11H11F3S: 232.0534, found 232.0533.
(E)-(3-(4-Isopropylphenyl)allyl)(trifluoromethyl)-
sulfane (3d) Obtained as a colorless oil in 64% yield
(67mg), Rf (pentane): 0.77; 1H NMR (400 MHz, CDCl3)
δ: 7.35 (d, J＝8.1 Hz, 2H), 7.24 (d, J＝8.1 Hz, 2H),
6.62 (d, J＝15.7 Hz, 1H), 6.27－6.16 (m, 1H), 3.75 (d,
(E)-(3-(2-Methoxyphenyl)allyl)(trifluoromethyl)-
sulfane (3h) Obtained as a white solid in 96% yield
1
(95 mg), m.p. 30－31 ℃, Rf (pentane): 0.51; H NMR
(400 MHz, CDCl3) δ: 7.44 (d, J＝7.6 Hz, 1H), 7.28 (t,
J＝2.9 Hz, 1H), 6.97－6.89 (m, 2H), 6.90 (d, J＝8.3 Hz,
1H), 6.34－6.18 (m, 1H), 3.88 (s, 3H), 3.77 (d, J＝7.4
Hz, 2H); 19F NMR (376 MHz, CDCl3) δ: −40.89 (s, 3F);
924
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© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 921—926

Nucleophilic Trifluoromethylthiolation of Allylic Bromides
13C NMR (101 MHz, CDCl3) δ: 156.8 (s), 130.9 (q, J＝
306.9 Hz), 129.4 (s), 129.2 (s), 127.1 (s), 125.1 (s),
123.5 (s), 120.7 (s), 110.9 (s), 55.5 (s), 33.2 (q, J＝2.4
Hz); IR (KBr) ν: 3047, 3006, 2940, 2839, 1644, 1599,
1489, 1247, 1109, 970, 751 cm−1; GC-MS m/z: 248
(M＋), 147 (M＋−SCF3 100%). HRMS (EI) calcd for
C11H11F3OS: 248.0483, found 248.0485.
(E)-(3-(3-Methoxyphenyl)allyl)(trifluoromethyl)-
sulfane (3i) Obtained as a colorless oil in 67% yield
(66 mg), Rf (pentane): 0.31; 1H NMR (400 MHz, CDCl3)
δ: 7.27 (t, J＝7.9 Hz, 1H), 6.99 (d, J＝7.9 Hz, 1H), 6.93
(s, 1H), 6.85 (dd, J＝7.9, 2.4 Hz, 1H), 6.60 (d, J＝15.6
Hz, 1H), 6.28－6.21 (m, 1H), 3.85 (s, 3H), 3.74 (d, J＝
7.4 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ: −40.87 (s,
3F); 13C NMR (101 MHz, CDCl3) δ: 159.8 (s), 137.5 (s),
134.3 (s), 130.8 (q, J＝307.0 Hz), 129.6 (s), 123.3 (s),
119.2 (s), 113.7 (s), 111.9 (s), 55.2 (s), 32.6 (q, J＝2.4
Hz); IR (KBr) ν: 3006, 2940, 2838, 1652, 1600, 1584,
1492, 1266, 1114, 963, 775, 694 cm−1; GC-MS m/z: 248
(M＋), 147 (M＋−SCF3 100%). HRMS (EI) calcd for
C11H11F3OS: 248.0483, found 248.0481.
(E)-(3-(4-Bromophenyl)allyl)(trifluoromethyl)-
sulfane (3m) Obtained as a pale yellow oil in 58%
yield (69 mg), Rf (pentane): 0.69; H NMR (400 MHz,
1
CDCl3) δ: 7.48 (d, J＝8.5 Hz, 2H), 7.26 (d, J＝8.5 Hz,
2H), 6.56 (d, J＝15.7 Hz, 1H), 6.33－6.16 (m, 1H),
3.73 (d, J＝7.3 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ:
−40.84 (s, 3F); 13C NMR (101 MHz, CDCl3) δ: 135.0
(s), 133.1 (s), 131.8 (s), 130.7 (q, J＝307.0 Hz), 128.0
(s), 123.9 (s), 122.0 (s), 32.5 (q, J＝2.4 Hz); IR (KBr) ν:
3034, 2930, 1648, 1589, 1488, 1240, 1111, 964, 841,
618 cm−1; GC-MS m/z: 298 (M＋). HRMS (EI) calcd for
C10H8BrF3S: 295.9482, found 295.9483.
Acknowledgement
This work was supported by National Natural Sci-
ence Foundation of China (No. 21072030), Research
Fund for the Doctoral Program of Higher Education of
China (No. 20123514110003), the Scientific Research
Foundation for the Returned Overseas Chinese Scholars,
State Education Ministry (No. 2012-1707), and Fuzhou
University (Nos. 022318, 022494).
(E)-(3-(4-Chlorophenyl)allyl)(trifluoromethyl)-
sulfane (3j) Obtained as a colorless oil in 53% yield
(54 mg), Rf (pentane): 0.69; 1H NMR (400 MHz, CDCl3)
δ: 7.37－7.30 (m, 4H), 6.58 (d, J＝15.7 Hz, 1H), 6.28－
6.18 (m, 1H), 3.73 (d, J＝7.3 Hz, 2H); 19F NMR (376
MHz, CDCl3) δ: −40.84 (s, 3F); 13C NMR (101 MHz,
CDCl3) δ: 134.6 (s), 133.8 (s), 133.1 (s), 130.8 (q, J＝
306.6 Hz), 128.8 (s), 127.7 (s), 123.8 (s), 32.5 (q, J＝
2.2 Hz); IR (KBr) ν: 3035, 2928, 2855, 1649, 1594,
1492, 1239, 1114, 965, 823 cm−1. GC-MS m/z: 252
(M＋), 151 (M＋−SCF3 100%). HRMS (EI) calcd for
C10H8ClF3S: 251.9987, found 251.9986.
References
[1] (a) Leroux, F.; Jeschke, P.; Schlosser, M. Chem. Rev. 2005, 105, 827;
(b) Manteau, B.; Pazenok, S.; Vors, J.-P.; Leroux, F. R. J. Fluorine
Chem. 2010, 131, 140.
[2] (a) Becker, A. Inventory of Industrial Fluoro-Biochemicals, Eyrolles,
Paris, 1996; (b) Langlois, B. R.; Billard, T.; Large, S.; Roques, N.
Fluorinated Bio-active Compounds, Fluorine Technology Ltd,
Cheshire, 1999, Paper 24.
[3] (a) Tyrra, W.; Naumann, D.; Hoge, B.; Yagupolskii, Y. L. J.
Fluorine Chem. 2003, 119, 101; (b) Adams, D. J.; Clark, J. H. J. Org.
Chem. 2000, 65, 1456; (c) Adams, D. J.; Goddard, A.; Clark, J. H.;
Macquarrie, D. J. Chem. Commun. 2000, 987; (d) Chen, Q.-Y.;
Duan, J.-X. J. Chem. Soc., Chem. Commun. 1993, 918; (e) Remy, D.
C.; Rittle, K. E.; Hunt, C. A.; Freedman, M. B. J. Org. Chem. 1976,
41, 1644; (f) Yagupolskii, L. M.; Kondratenko, N. V.; Sambur, V. P.
Synthesis 1975, 721.
[4] (a) Pooput, C.; Dolbier, W. R.; Médebielle, M. J. Org. Chem. 2006,
71, 3564; (b) Blond, G.; Billard, T.; Langlois, B. R. Tetrahedron
Lett. 2001, 42, 2473; (c) Roques, N. J. Fluorine Chem. 2001, 107,
311; (d) Billard, T.; Langlois, B. R. Tetrahedron Lett. 1996, 37,
6865.
[5] (a) Harsányi, A.; Dorkó, É.; Csapó, Á.; Bakó, T.; Peltz, C.; Rábai, J.
J. Fluorine Chem. 2011, 132, 1241; (b) Pooput, C.; Medebielle, M.;
Dolbier, W. R. Org. Lett. 2004, 6, 301; (c) Billard, T.; Roques, N.;
Langlois, B. R. J. Org. Chem. 1999, 64, 3813; (d) Quiclet-Sire, B.;
Saicic, R. N.; Zard, S. Z. Tetrahedron Lett. 1996, 37, 9057; (e)
Wakselman, C.; Tordeux, M.; Clavel, J.-L.; Langlois, B. J. Chem.
Soc., Chem. Commun. 1991, 993; (f) Wakselman, C.; Tordeux, M. J.
Org. Chem. 1985, 50, 4047.
[6] (a) Kieltsch, I.; Eisenberger, P.; Togni, A. Angew. Chem., Int. Ed.
2007, 46, 754; (b) Teruo, U.; Sumi, I. Tetrahedron Lett. 1990, 31,
3579; (c) Umemoto, T.; Ishihara, S. J. Am. Chem. Soc. 1993, 115,
2156.
[7] Teverovskiy, G.; Surry, D. S.; Buchwald, S. L. Angew. Chem., Int.
Ed. 2011, 50, 7312.
[8] Zhang, C.-P.; Vicic, D. A. J. Am. Chem. Soc. 2011, 134, 183.
[9] Zhang, C.-P.; Vicic, D. A. Chem. Asian J. 2012, 7, 1756.
[10] Chen, C.; Xie, Y.; Chu, L.; Wang, R.-W.; Zhang, X.; Qing, F.-L.
Angew. Chem., Int. Ed. 2012, 51, 2492.
(E)-(3-(3-Chlorophenyl)allyl)(trifluoromethyl)-
sulfane (3k) Obtained as a pale yellow oil in 54%
1
yield (55 mg), Rf (pentane): 0.72; H NMR (400 MHz,
CDCl3) δ: 7.40－7.36 (m, 1H), 7.28－7.24 (m, 3H),
6.57 (d, J＝15.7 Hz, 1H), 6.32－6.21 (m, 1H), 3.73 (d,
J＝7.3 Hz, 2H); 19F NMR (376 MHz, CDCl3) δ: −40.82
(s, 3F); 13C NMR (101 MHz, CDCl3) δ: 138.0 (s), 134.7
(s), 132.9 (s), 130.7 (q, J＝307.0 Hz), 129.9 (s), 128.1
(s), 126.5 (s), 124.8 (s), 124.7 (s), 32.4 (q, J＝2.4 Hz);
IR (KBr) ν: 3064, 3037, 2937, 1595, 1568, 1476, 1240,
1106, 962, 778, 675 cm−1; GC-MS m/z: 252 (M＋), 151
(M＋−SCF3 100%). HRMS (EI) calcd for C10H8ClF3S:
251.9987, found 251.9988.
(E)-(3,7-Dimethylocta-2,6-dien-1-yl)(trifluorometh-
yl)sulfane (3l) Obtained as a pale yellow oil in 62%
1
yield (59 mg), Rf (pentane): 0.97; H NMR (400 MHz,
CDCl3) δ: 5.30 (t, J＝7.8 Hz, 1H), 5.09 (t, J＝6.7 Hz,
1H), 3.59 (d, J＝7.9 Hz, 2H), 2.14－2.03 (m, 4H), 1.72
(s, 6H), 1.63 (s, 3H); 19F NMR (376 MHz, CDCl3) δ:
−41.40 (s, 3F); 13C NMR (101 MHz, CDCl3) δ: 142.1
(s), 131.9 (s), 131.0 (q, J＝306.7 Hz), 123.6 (s), 117.0
(s), 39.5 (s), 28.0 (s), 26.2 (s), 25.6 (s), 17.6 (s); IR (KBr)
ν: 2971, 2929, 2859, 1662, 1449, 1379, 1244, 1114 cm−1;
GC-MS m/z: 238 (M＋). HRMS (EI) calcd for C11H17F3S:
238.1003, found 238.0999.
[11] Shao, X.; Wang, X.; Yang, T.; Lu, L.; Shen, Q. Angew. Chem., Int.
Chin. J. Chem. 2013, 31, 921—926
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
www.cjc.wiley-vch.de
925

Tan et al.
FULL PAPER
Ed. 2013, 52, 3457.
[12] Tran, L. D.; Popov, I.; Daugulis, O. J. Am. Chem. Soc. 2012, 134,
18237.
[20] (a) Weng, Z.; Lee, R.; Jia, W.; Yuan, Y.; Wang, W.; Feng, X.;
Huang, K.-W. Organometallics 2011, 30, 3229; (b) Weng, Z.; Li, H.;
He, W.; Yao, L.-F.; Tan, J.; Chen, J.; Yuan, Y.; Huang, K.-W.
Tetrahedron 2012, 68, 2527; (c) Huang, Y.; Fang, X.; Lin, X.; Li, H.;
He, W.; Huang, K.-W.; Yuan, Y.; Weng, Z. Tetrahedron 2012, 68,
9949; (d) Lin, X.; Wang, G.; Li, H.; Huang, Y.; He, W.; Ye, D.;
Huang, K.-W.; Yuan, Y.; Weng, Z. Tetrahedron 2013, 69, 2628; (e)
Zheng, H.; Huang, Y.; Wang, Z.; Li, H.; Huang, K.-W.; Yuan, Y.;
Weng, Z. Tetrahedron Lett. 2012, 53, 6646.
[21] Weng, Z.; He, W.; Chen, C.; Lee, R.; Tan, D.; Lai, Z.; Kong, D.;
Yuan, Y.; Huang, K.-W. Angew. Chem., Int. Ed. 2013, 52, 1548.
[22] (a) Shintani, R.; Takatsu, K.; Takeda, M.; Hayashi, T. Angew. Chem.,
Int. Ed. 2011, 50, 8656; (b) Falciola, C. A.; Alexakis, A. Eur. J. Org.
Chem. 2008, 3765.
[23] (a) Bartholomew, E. R.; Bertz, S. H.; Cope, S.; Murphy, M.; Ogle, C.
A. J. Am. Chem. Soc. 2008, 130, 11244; (b) Yoshikai, N.; Zhang,
S.-L.; Nakamura, E. J. Am. Chem. Soc. 2008, 130, 12862.
[24] (a) van Zijl, A. W.; Arnold, L. A.; Minnaard, A. J.; Feringa, B. L.
Adv. Synth. Catal. 2004, 346, 413; (b) Vyas, D. J.; Oestreich, M.
Chem. Commun. 2010, 46, 568.
[13] (a) Harutyunyan, S. R.; den Hartog, T.; Geurts, K.; Minnaard, A. J.;
Feringa, B. L. Chem. Rev. 2008, 108, 2824; (b) Pacheco, M. C.;
Purser, S.; Gouverneur, V. Chem. Rev. 2008, 108, 1943; (c) Trost, B.
M.; Crawley, M. L. Chem. Rev. 2003, 103, 2921.
[14] Isanbor, C.; O’Hagan, D. J. Fluorine Chem. 2006, 127, 303.
[15] Xu, J.; Fu, Y.; Luo, D.-F.; Jiang, Y.-Y.; Xiao, B.; Liu, Z.-J.; Gong,
T.-J.; Liu, L. J. Am. Chem. Soc. 2011, 133, 15300.
[16] (a) Parsons, A. T.; Buchwald, S. L. Angew. Chem., Int. Ed. 2011, 50,
9120; (b) Shimizu, R.; Egami, H.; Hamashima, Y.; Sodeoka, M.
Angew. Chem., Int. Ed. 2012, 51, 4577; (c) Wang, X.; Ye, Y.; Zhang,
S.; Feng, J.; Xu, Y.; Zhang, Y.; Wang, J. J. Am. Chem. Soc. 2011,
133, 16410.
[17] Chu, L.; Qing, F.-L. Org. Lett. 2012, 14, 2106.
[18] Chen, Q.-Y.; Duan, J.-X. J. Chem. Soc., Chem. Commun. 1993,
1389.
[19] Miyake, Y.; Ota, S.-i.; Nishibayashi, Y. Chem.-Eur. J. 2012, 18,
13255.
(Cheng, F.)
926
www.cjc.wiley-vch.de
© 2013 SIOC, CAS, Shanghai, & WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Chin. J. Chem. 2013, 31, 921—926