Regioselective addition reactions of 3-phenylsulfonyl-2-trifluoromethyl-1, 3-butadiene with nucleophiles

Article abstract of DOI:10.1016/j.jfluchem.2012.06.014

Reactions of 3-phenylsulfonyl-2-trifluoromethyl-1,3-butadiene (1) with heteroatom nucleophiles such as pri-amines, pri-alcohols, and thiols afforded the addition products 2, 3, and 5 regioselectively formed via addition of nucleophiles toward double bond

Full text of DOI:10.1016/j.jfluchem.2012.06.014

Journal of Fluorine Chemistry 143 (2012) 198–203
Contents lists available at SciVerse ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Regioselective addition reactions of 3-phenylsulfonyl-2-trifluoromethyl-1,
3-butadiene with nucleophiles
*
Eun Joon Yang, Sung Lan Jeon, In Howa Jeong
Department of Chemistry, Yonsei University, Wonju 220-710, South Korea
A R T I C L E I N F O
A B S T R A C T
Article history:
Reactions of 3-phenylsulfonyl-2-trifluoromethyl-1,3-butadiene (1) with heteroatom nucleophiles such
as pri-amines, pri-alcohols, and thiols afforded the addition products 2, 3, and 5 regioselectively formed
via addition of nucleophiles toward double bond attaching phenylsulfonyl group. Cyclization of 2a in
2,2,2-trifluoroethanol at 60 8C for 2 h gave pyrrolidine 4a in good yield. Similarly, compound 1 was also
reacted with diethylmalonate in the presence of NaH to give addition product 7 in good yield.
ß 2012 Elsevier B.V. All rights reserved.
Received 13 April 2012
Received in revised form 13 June 2012
Accepted 14 June 2012
Available online 16 July 2012
Keywords:
3-Phenylsulfonyl-2-trifluoromethyl-1,3-
butadiene
Heteroatom nucleophiles
Carbon nucleophiles
Regioselective nucleophilic addition
reaction
1. Introduction
of this compound toward the dienophile [25]. Since the
trifluoromethyl and sulfonyl group attached to 2- and 3-positions
1,3-Butadienes have received much attention because they
have been widely used in the Diels–Alder reaction to give the
carbocyclic compounds [1]. The introduction of heterosubstituents
has a significant influence on the reactivity, regioselectivity, and
stereochemistry of the diene and also versatility in further
reactions [2–6]. Sulfur-substituent within the diene unit, in
particular, not only increases the reactivity of the diene but also
adds control to the regioselectivity of the cycloaddition or addition
reaction [7,8]. Numerous reactions related to the sulfur-substitut-
ed 1,3-butadienes have been well established in the previous
literatures [9–12]. In the past several decades, much effort has
been devoted to introduce the trifluoromethyl functionality into
organic molecules because of the dramatic effects of functionality
on their structure stability and reactivity of the resulting
compounds [13–17]. Consequently, a variety of methods for the
synthesis of trifluoromethylated dienes have been developed [18–
22], but only scarce examples of their reactions are known [23,24].
Recently, we developed the method for the preparation of novel
2-trifluoromethyl-3-phenylthio-1,3-butadiene as a new building
block which contains the trifluoromethyl and phenylthio func-
tionality in the diene unit and examined the Diels–Alder reaction
of the diene unit effects significant polarization of the double bond,
this compound should be highly reactive toward nucleophilic
addition because of its remarkably lowered LUMO energy level
compared to 1,3-butadiene. Although nucleophilic addition reac-
tions of doubly activated diene at the 2- and 3-positions have been
well documented previously [26–28], there has been no report on
the nucleophilic reaction of 3-phenylsulfonyl-2-trifluoromethyl-
1,3-butadiene. Herein, we wish to report on the reactivity
of 3-phenylsulfonyl-2-trifluoromethyl-1,3-butadiene toward the
nucleophiles and its regioselectivity.
2. Results and discussion
When 3-phenylsulfonyl-2-trifluoromethyl-1,3-butadiene (1)
was reacted with benzylamine in THF at the several reaction
temperature (À78, À20, 25 8C) for 1 h, a messy reaction mixture
was always obtained. However, treatment of 1 with benzylamine
in methylene chloride at room temperature for 0.5 h resulted in
the formation of addition product 2a in 83% yield regioselectively.
The use of co-solvent system (CH2Cl2:t-BuOH = 1:1) in this reaction
dramatically increased the yield of 2a up to 97% yield. There was no
addition product at the double bond bearing a trifluoromethyl
group. The other primary amines such as n-butylamine, s-
butylamine, and t-butylamine also produced the addition products
2b–d in 81–85% yields. The reaction of 1 with aniline in co-solvent
* Corresponding author. Tel.: +82 33 760 2240; fax: +82 33 763 4323.
E-mail address: jeongih@yonsei.ac.kr (I.H. Jeong).
0022-1139/$ – see front matter ß 2012 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.jfluchem.2012.06.014

E.J. Yang et al. / Journal of Fluorine Chemistry 143 (2012) 198–203
199
Table 1
Addition reaction of 2-trifluoromethyl-3-phenylsulfonyl-1,3-butadiene (1) with RNH2.
CF3
CF3
RNH2 (1.1 equiv)
Solvent, T(oC), t (h)
PhO2S
NHR
PhO2S
2
1
Compound no.
R
Solvent
T (8C)
t (h)
Yield (%)a
b
b
2a
2a
2a
2a
2b
2c
2d
2e
CH2C6H5
CH2C6H5
CH2C6H5
CH2C6H5
n-C4H9
s-C4H9
THF
25
1
1
–
–
THF
À78
25
MC
0.5
0.5
0.5
0.5
0.5
24
83
97
85
83
81
51
MC:t-BuOH = 1:1
MC:t-BuOH = 1:1
MC:t-BuOH = 1:1
MC:t-BuOH = 1:1
MC:t-BuOH = 1:1
25
25
25
t-C4H9
25
C6H5
Reflux
a
Isolated yield.
b
A messy reaction mixture was obtained.
system at reflux for 24 h afforded the addition product 2e in 51%
yield. In contrast to the reaction with primary amines, secondary
amines such as diethylamine, diisopropylamine, and pyrrolidine
did not undergo the addition reaction with 1 even at the reflux
temperature for 24 h. The results of these reactions were
summarized in Table 1.
according to the Baldwin rule [29], although the similar 5-endo-trig
cyclization of alkene with a CF3 group was reported previously
[30]. The result of cyclization reaction of 2a was summarized in
Table 2. These results indicate that 4a undergoes the elimination
reaction to give the diene 1 under the reaction condition, in which
diene 1 was attacked by alcohol to afford the addition product 3.
The results were summarized in Scheme 1.
Since we proposed the reaction process for the formation of 3 in
the cyclization of 2a in Scheme 1, we examined the addition
reaction of 1 with alcohols in the presence of amine. Treatment of 1
with excess of methanol in the presence of diisopropylamine
(5 equiv.) in MC at room temperature for 16 h produced the
addition product 3a in 80% yield. Similar reaction with ethanol and
2,2,2-trifluoroethanol also provided the addition products 3b–c in
71–74% yields. However, phenol, isopropyl alcohol and t-butyl
alcohol were not reacted with 1 under the same reaction condition.
The use of catalytic amount of NaH in this reaction resulted in the
formation of a messy reaction mixture. The results of these
reactions were summarized in Table 3.
The addition products 2 still have an activated double bond
which can be attacked by nitrogen nucleophile within 2. Therefore,
cyclization of 2a was performed under the different reaction
condition. Heating of 2a in methanol at 60 8C for 2 h produced
pyrrolidine derivative 4a in 25% yield along with diene 1 (10%) and
methanol addition product 3 (55%). Stereochemistry of 4a (trans)
was determined by 1H NMR. When 2a was heated for 10 h, 4a was
obtained in 16% yield, and diene 1 and 3 were obtained in 5% and
72% yields, respectively. The use of t-BuOH in this reaction
provided the only diene 1 in 72% yield. However, 2a was heated in
2,2,2-trifluoroethanol for 2 h to give 4a in 71% yield along with
diene 1 (6%) and 3 (15%). The longer reaction time (10 h)
dramatically decreased the yield of 4a (12%), but yield of 3 was
increased up to 69%. The facility of the 5-endo-trig cyclization of 2a
is particularly surprising to us because of a disfavored process
We have also examined the reaction of diene 1 with thiophenol
and found that the reaction proceeded smoothly in THF at 0 8C for
Table 2
Cyclization reaction of 2a in alcohols solvent.
PhO2S
CF3
CF3
CF3
CF3
ROH
T(oC), t (h)
N
Bn
4a
PhO2S
PhO2S
OR
PhO2S
NHBn
1
3
2a
Entry
R
T (8C)
t (h)
Yield (%)a
1
3
4a
1
2
3
4
5
6
CH3
25
60
60
60
60
60
10
2
45
10
5
36
55
72
0
0
25
16
0
CH3
CH3
10
2
t-C4H9
CF3CH2
CF3CH2
72
6
2
15
69
71
12
10
4
a
Isolated yield.
PhO2S
CF3
CF3
CF3
CF3
- BnNH2
ROH
N
Bn
4a
PhO2S
PhO2S
NHBn
PhO2S
OR
2a
1
3
Scheme 1.

200
E.J. Yang et al. / Journal of Fluorine Chemistry 143 (2012) 198–203
Table 3
Addition reaction of 2-trifluoromethyl-3-phenylsulfonyl-1,3-butadiene (1) with alcohols.
CF3
CF3
ROH (excess) / (i-Pr)2NH (5 equiv)
Solvent, T(oC), t (h)
PhO2S
OR
PhO2S
3
1
Compound no.
R
Solvent
T (8C)
t (h)
Yield (%)a
3a
3b
3c
3d
3e
3f
CH3
MC
MC
MC
MC
MC
MC
25
16
16
8
80
74
71
CH3CH2
CF3CH2
C6H5
25
25
b
Reflux
25
30
30
30
–
b
i-C3H7
t-C4H9
–
b
25
–
a
Isolated yield.
b
No reaction.
Table 4
12 h to give the trifluoromethylated olefin 6 (E/Z = 7/93) in 60%
yield (Scheme 2). Assignment of a E/Z isomer of 6 was based on the
H–F coupling constant between H and CF3. The 1H NMR of Z isomer
in which H and CF3 group are arranged at the same side, showed
that the H–F coupling constant is 1.6 Hz, whereas the H–F coupling
Addition reaction of 2-trifluoromethyl-3-phenylsulfonyl-1,3-butadiene (1) with
thiols.
CF3
CF3
RSH (1 equiv)
THF, T(oC), 0.5 h
constant of
E isomer is not observed. Usually, in olefinic
PhO2S
SR
4
PhO2S
compounds bearing a CF3 group, JH–F is ca. 2 Hz in the cis
arrangement between H and CF3 group and up to 1 Hz in the trans
arrangement [31].
5
1
Compound no.
R
T (8C)
Yield (%)a
Finally, we have examined the reaction of diene 1 with carbon
nucleophiles such as alkyllithium, aryllithium, alkynyllithium,
sodium diethyl malonate and found that only sodium diethyl
malonate underwent the addition reaction in THF at 0 8C for 0.5 h,
giving 78% yield of addition product 7 (Scheme 3). Other carbon
nucleophiles provided the messy reaction mixture even at low
temperature. The reaction of 7 with bases such as NaH, NaOMe, t-
BuOK for the cyclization of 7 did not provide a cyclization product 8
via 5-endo-trig cyclization which is considered as a disfavored
process [29], but caused to regenerate the diene 1.
b
5a
5a
5b
5b
C6H5
25
0
–
C6H5
72
b
n-C3H7
n-C3H7
0
–
À45
70
a
Isolated yield.
b
A messy reaction mixture was obtained.
PhS
F3C
CF3
PhSNa (2 equiv)
THF, reflux, 12 h
60%
3. Conclusion
PhO2S
H
SPh
SPh
6 (E/Z = 7:93)
5a
In conclusion, we found that 2-trifluoromethyl-3-phenylsulfo-
nyl-1,3-butadiene (1) underwent the addition reaction regiospeci-
fically with heteroatom nucleophiles such as pri-amines, pri-
alcohols, and thiols at the double bondattached withphenylsulfonyl
group. Amineadditionproduct 2aunderwent5-endo-trigcyclization
to givepyrrolidine derivatives 4a, but this compound underwent the
elimination reaction to provide the diene 1 at the prolong reaction
time. The diene 1 also reacted with diethylmalonate to afford the
addition product 7, but this compound did not undergo the 5-endo-
trig cyclization in the base condition.
Scheme 2.
0.5 h, giving 72% yield. The use of excess thiophenol did not cause
to increase the yield of 5a. When the same reaction was performed
at room temperature, a messy reaction mixture was obtained, but
regioisomers were not detected. The reaction of diene 1 with
alkanethiol was much faster than that with thiophenol and thus
was controlled by lowing the reaction temperature. Therefore,
diene 1 was reacted with 1-propanethiol in THF at À45 8C for 0.5 h
to afford the addition product 5b in 70% yield. The reaction at
higher temperature resulted in the formation of a messy reaction
mixture which does not include regioisomers. No addition
products were obtained from the reaction of 1 with 2-propanethiol
or 2-methyl-2-propanethiol. The result of these reaction was
summarized in Table 4. The addition product 5a was further
reacted with sodium thiophenoxide (2.0 equiv.) in THF at reflux for
4. Experimental
1H and 13C NMR spectra were recorded on a 400 MHz Bruker
AVANCEII++ NMR spectrometer with tetramethylsilane (TMS) as an
internal standard and 19F NMR spectra were also recorded on a
400 MHz Bruker AVANCEII++ NMR spectrometer with CFCl3 as an
internal standard and the upfield as negative. All chemical shifts (d)
Scheme 3.

E.J. Yang et al. / Journal of Fluorine Chemistry 143 (2012) 198–203
201
are expressed in parts per million and coupling constant (J) are
given in Hertz. Mass spectra were obtained by using Agilent
Technologies 6890N GC/5973 Network MSD (EI, 70 eV). Elemental
analysis data were obtained by using EA1110 elemental analyzer.
Melting points were determined in open capillary tubes and are
uncorrected.
(q, J = 32.2 Hz), 129.4, 129.3, 125.6 (q, J = 6.0 Hz), 124.0, 62.7, 53.9,
47.7, 29.7, 19.7, 10.3; MS, m/z (relative intensity) 335 (M+, 1), 320
(5), 306 (55), 164 (15), 150 (52), 141 (15), 125 (10), 96 (12), 86 (46),
77 (100), 56 (15), 51 (38). Anal. Calcd for C15H20F3NO2S: C, 53.72;
H, 6.01. Found: C, 53.52; H, 5.95.
Commercially available reagents were purchased from Aldrich,
Lancaster, Tokyo Kasei and Fluorochem. All solvents were dried by
general purification method. Flash chromatography was per-
4.1.4. 4-t-Butylamino-2-trifluoromethyl-3-phenylsulfonylbut-1-ene
(2d)
2d was prepared in 81% yield (0.206 g) from the reaction of
diene 1 with t-butylamine according to the general procedure. 2d:
yellow oil; 1H NMR (CDCl3)
d 7.85–7.83 (m, 2H), 7.68–7.64 (m, 1H),
formed on 40–60
mm silica gel (230–400 mesh).
4.1. General procedure for the preparation of 4-alkyl(or
7.56–7.53 (m, 2H), 6.19 (s, 1H), 6.10 (s, 1H), 3.93 (t, J = 6.4 Hz, 1H),
3.43 (dd, J = 12.4, 6.4 Hz, 1H), 3.06 (dd, J = 12.4, 6.4 Hz, 1H), 1.34
phenyl)amino-2-trifluoromethyl-3-phenylsulfonylbut-1-ene (2)
(bs, 1H), 1.06 (s, 9H); 19F NMR (CDCl3, internal standard CFCl3)
d
A 15 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with diene 1 (0.200 g, 0.76 mmol) and
4 mL of solvent (MC:t-BuOH = 1:1). The amine (0.84 mmol) was
added into the reaction mixture which was then stirred at room
temperature for 0.5 h (for alkylamine) or reflux for 24 h (for
aniline). After the reaction mixture was stirred, it was extracted
with methylene chloride twice, dried over anhydrous MgSO4 and
chromatographed on SiO2 column. Elution with a mixture of n-
hexane and ethyl acetate (4:1) provided the addition product 2.
À70.56 (s, 3F); 13C NMR (100 MHz, CDCl3)
d 138.0, 134.5, 131.7 (q,
J = 32.2 Hz), 129.5, 129.3, 125.6 (q, J = 6.0 Hz), 124.0, 64.2, 50.8,
44.0, 29.1; MS, m/z (relative intensity) 335 (M+, 1), 262 (8), 252 (9),
172 (34), 153 (95), 121 (61), 91 (30), 77 (100), 51 (71). Anal. Calcd
for C15H20F3NO2S: C, 53.72; H, 6.01. Found: C, 53.39; H, 6.07.
4.1.5. 4-Phenylamino-2-trifluoromethyl-3-phenylsulfonylbut-1-ene
(2e)
2e was prepared in 51% yield (0.138 g) from the reaction of
diene 1 with aniline according to the general procedure. 2e: yellow
oil; 1H NMR (CDCl3)
d 7.83–7.80 (m, 2H), 7.68–7.64 (m, 1H), 7.57–
4.1.1. 4-Benzylamino-2-trifluoromethyl-3-phenylsulfonylbut-1-ene
(2a)
7.53 (m, 2H), 7.20–7.16 (m, 2H), 6.78–6.75 (m, 1H), 6.56–6.54 (m,
2H), 6.23 (s, 1H), 6.16 (s, 1H), 4.24–4.20 (m, 1H), 4.18–4.12 (m, 1H),
4.07 (t, J = 6.0 Hz, 1H), 3.74–3.67 (m, 1H); 19F NMR (CDCl3, internal
2a was prepared in 97% yield (0.272 g) from the reaction of
diene 1 with benzylamine according to the general procedure. 2a:
standard CFCl3)
d
À69.65 (s, 3F); 13C NMR (100 MHz, CDCl3)
d
yellow oil; 1H NMR (CDCl3)
d
7.85–7.77 (m, 2H), 7.68–7.64 (m, 1H),
139.0, 137.2, 134.0, 131.3 (q, J = 32.2 Hz), 129.5, 129.1, 128.7,
128.3, 125.5 (q, J = 6.0 Hz), 124.1, 120.4, 62.0, 52.9; MS, m/z
(relative intensity) 355 (M+, 8), 228 (3), 214 (9), 174 (8), 141 (8),
106 (100), 77 (89), 65 (24), 91 (7), 51 (30). Anal. Calcd for
7.55–7.51 (m, 2H), 7.33–7.23 (m, 5H), 6.12 (s, 1H), 6.09 (s, 1H), 4.04
(t, J = 6.4 Hz, 1H), 3.79 (m, 2H), 3.51 (dd, J = 13.2, 6.4 Hz, 1H), 3.13
(dd, J = 13.2, 6.4 Hz, 1H), 1.86 (bs, 1H); 19F NMR (CDCl3, internal
standard CFCl3)
d
À69.53 (s, 3F); 13C NMR (100 MHz, CDCl3)
d
C17H16F3NO2S: C, 57.46; H, 4.54. Found: C, 57.19; H, 4.48.
139.3, 137.6, 134.2, 131.5 (q, J = 32.2 Hz), 129.2, 129.1, 128.5,
128.0, 127.2, 125.5 (q, J = 6.0 Hz), 123.7, 62.2, 53.1, 49.4; MS, m/z
(relative intensity) 369 (M+, 1), 228 (3), 141 (3), 120 (57), 106 (6),
104 (5), 91 (100), 77 (16), 65 (8), 51 (7). Anal. Calcd for
4.2. Preparation of N-benzyl-3-trifluoromethyl-4-
phenylsulfonylpyrrolidine (4a)
C
18H18F3NO2S: C, 58.53; H, 4.91. Found: C, 58.31; H, 4.94.
A 15 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with olefin 2a (0.185 g, 0.50 mmol) and
4 mL of 2,2,2-trifluoroethanol. The reaction mixture was heated at
60 8C for 2 h and then cooled down to room temperature. After
evaporation of solvent, it was chromatographed on SiO2 column.
Elution with a mixture of n-hexane and ethyl acetate (3:1)
provided the pyrrolidine 4a in 71% yield (0.131 g). 4a: yellow oil;
4.1.2. 4-n-Butylamino-2-trifluoromethyl-3-phenylsulfonylbut-1-ene
(2b)
2b was prepared in 85% yield (0.216 g) from the reaction of
diene 1 with n-butylamine according to the general procedure. 2b:
yellow oil; 1H NMR (CDCl3)
d 7.83–7.82 (m, 2H), 7.69–7.65 (m, 1H),
7.57–7.53 (m, 2H), 6.16 (s, 1H), 6.11 (s, 1H), 4.04 (t, J = 6.4 Hz, 1H),
3.53 (dd, J = 13.2, 6.4 Hz, 1H), 3.12 (dd, J = 13.2, 6.4 Hz, 1H), 2.59 (t,
J = 6.8 Hz, 2H), 1.55 (bs, 1H), 1.44 (m, 2H), 1.33 (m, 2H), 0.90 (t,
J = 7.6 Hz, 3H); 19F NMR (CDCl3, internal standard CFCl3)
(s, 3F); 13C NMR (100 MHz, CDCl3)
J = 32.2 Hz), 129.6, 129.5, 125.7 (q, J = 6.0 Hz), 124.0, 62.0, 50.3,
48.9, 32.0, 20.3, 13.9; MS, m/z (relative intensity) 335 (M+, 1), 292
(12), 150 (16), 141 (15), 122 (18), 86 (72), 82 (39), 77 (100), 51 (33).
Anal. Calcd for C15H20F3NO2S: C, 53.72; H, 6.01. Found: C, 53.48;
H, 5.98.
1H NMR (CDCl3)
d 7.91–7.89 (m, 2H), 7.71–7.67 (m, 1H), 7.60–7.56
(m, 2H), 7.32–7.20 (m, 6H), 3.79–3.75 (dt, J = 7.6, 4.8 Hz, 1H), 3.64
(d, J = 13.2 Hz, 1H), 3.56 (d, J = 13.2 Hz, 1H), 3.31–3.25 (m, 1H), 3.08
(dd, J = 10.4, 5.6 Hz, 1H), 2.94–2.84 (m, 2H), 2.70 (dd, J = 10.4,
d
À69.60
d
138.0, 134.5, 131.6 (q,
5.6 Hz, 1H); 19F NMR (CDCl3, internal standard CFCl3)
J = 11.3 Hz, 3F); 13C NMR (100 MHz, CDCl3)
d
À70.74 (d,
d
138.0, 137.8, 134.4,
131.5, 129.7, 129.1, 129.0, 128.7, 128.5, 127.6, 63.6, 58.9, 54.2,
53.60 (q, J = 7.0 Hz), 43.9 (q, J = 28.2 Hz), 31.2; MS, m/z (relative
intensity) 369 (M+, 1), 227 (81), 158 (100), 91 (90), 77 (22), 65 (10),
51 (8). Anal. Calcd for C18H18F3NO2S: C, 58.53; H, 4.91. Found: C,
58.21; H, 4.85.
4.1.3. 4-s-Butylamino-2-trifluoromethyl-3-phenylsulfonylbut-1-ene
(2c)
2c was prepared in 83% yield (0.211 g) from the reaction of
diene 1 with s-butylamine according to the general procedure. 2c:
yellow oil; 1H NMR (CDCl3)
d 7.85–7.83 (m, 2H), 7.68–7.65 (m, 1H),
4.3. General procedure for the preparation of 4-alkoxy-2-
trifluoromethyl-3-phenylsulfonylbut-1-ene (3)
7.57–7.53 (m, 2H), 6.17 (s, 1H), 6.11 (s, 1H), 4.00 (t, J = 6.4 Hz, 1H),
3.49 (dd, J = 13.2, 6.4 Hz, 1H), 3.15 (dd, J = 13.2, 6.4 Hz, 1H), 2.55 (m,
1H), 1.50 (bs, 1H), 1.41 (m, 1H), 1.29 (m, 1H), 0.98 (d, J = 6.4 Hz, 3H),
A 15 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with diene 1 (0.200 g, 0.76 mmol),
diisopropylamine (0.384 g, 3.80 mmol), alcohol (3.80 mmol), and
3 mL of methylene chloride. The reaction mixture was then stirred
0.87 (t, J = 7.2 Hz, 3H); 19F NMR (CDCl3, internal standard CFCl3)
d
À70.56 (s, 3F); 13C NMR (100 MHz, CDCl3)
d 138.0, 134.5, 131.8

202
E.J. Yang et al. / Journal of Fluorine Chemistry 143 (2012) 198–203
at room temperature for 8 h (2,2,2-trifluoroethanol) or 16 h (for
methanol or ethanol). It was extracted with ether twice, dried over
anhydrous MgSO4 and chromatographed on SiO2 column. Elution
with a mixture of n-hexane and ethyl acetate (4:1) provided the
addition product 3.
7.56–7.52 (m, 2H), 7.26–7.21 (m, 5H), 6.19 (s, 1H), 6.07 (s, 1H), 3.88
(dd, J = 11.6, 3.2 Hz, 1H), 3.82 (dd, J = 13.6, 3.2 Hz, 1H), 3.23 (dd,
J = 13.6, 11.6 Hz, 1H); 19F NMR (CDCl3, internal standard CFCl3)
d
À68.46 (s, 3F); 13C NMR (100 MHz, CDCl3)
d 137.2, 134.7, 133.8,
131.7 (q, J = 32.2 Hz), 130.5, 129.5, 129.4, 127.5, 126.4 (q,
J = 5.0 Hz), 62.3, 34.4; MS, m/z (relative intensity) 372 (M+, 1),
231 (100), 198 (10), 177 (9), 135 (8), 109 (80), 77 (52), 65 (16), 51
(21). Anal. Calcd for C17H15F3O2S2: C, 54.83; H, 4.06. Found: C,
54.55; H, 4.02.
4.3.1. 2-Trifluoromethyl-4-methoxy-3-phenylsulfonylbut-1-ene (3a)
3a was prepared in 80% yield (0.179 g) from the reaction of
diene 1 with methanol according to the general procedure. 3a:
yellow oil; 1H NMR (CDCl3)
d 7.88–7.85 (m, 2H), 7.68–7.65 (m,
1H), 7.57–7.53 (m, 2H), 6.15 (m, 2H), 4.07–3.99 (m, 2H), 3.85
4.4.2. 2-Trifluoromethyl-3-phenylsulfonyl-4-propylthiobut-1-ene
(5b)
5b was prepared in 70% yield (0.2180 g) from the reaction of
diene 1 with propanethiol according to the general procedure. 5b:
yellow oil; 1H NMR (CDCl3)
d 7.89–7.81 (m, 2H), 7.69–7.67 (m, 1H),
(dd, J = 10.0, 6.0 Hz, 1H), 3.28 (s, 3H); 19F NMR (CDCl3, internal
standard CFCl3)
d
À69.09 (s, 3F); 13C NMR (100 MHz, CDCl3)
d
138.6, 134.4, 130.5 (q, J = 32.2 Hz), 129.4, 129.3, 125.9 (q,
J = 5.0 Hz), 71.3, 62.6, 59.2; MS, m/z (relative intensity) 294 (M+,
1), 172 (13), 153 (44), 141 (12), 121 (28), 91 (13), 83 (10), 77
(100), 65 (10), 51 (65). Anal. Calcd for C12H13F3O3S: C, 48.98; H,
4.45. Found: C, 48.81; H, 4.42.
7.59–7.55 (m, 2H), 6.20 (s, 1H), 6.08 (s, 1H), 3.94 (dd, J = 11.2,
3.2 Hz, 1H), 3.38 (dd, J = 13.6, 3.2 Hz, 1H), 2.97 (dd, J = 13.6, 11.6 Hz,
1H), 2.46 (t, J = 7.2 Hz, 2H), 1.59–1.51 (m, 2H), 0.94 (t, J = 7.2 Hz,
3H); 19F NMR (CDCl3, internal standard CFCl3)
NMR (100 MHz, CDCl3) d 137.0, 134.4, 131.8 (q, J = 32.2 Hz), 129.4,
d
À68.76 (s, 3F); 13
C
4.3.2. 4-Ethoxy-2-trifluoromethyl-3-phenylsulfonylbut-1-ene (3b)
3b was prepared in 74% yield (0.173 g) from the reaction of
diene 1 with ethanol according to the general procedure. 3b:
yellow oil; 1H NMR (CDCl3)
d 7.87–7.86 (m, 2H), 7.68–7.64 (m, 1H),
129.1, 125.9 (q, J = 5.0 Hz), 123.4, 62.6, 34.7, 31.5, 22.5, 13.0; MS, m/
z (relative intensity) 338 (M+, 1), 197 (100), 155 (45), 153 (34), 141
(12), 115 (13), 77 (95), 51 (43). Anal. Calcd for C14H17F3O2S2: C,
49.69; H, 5.06. Found: C, 49.31; H, 4.99.
7.57–7.53 (m, 2H), 6.15 (s, 2H), 4.06 (q, J = 7.2 Hz, 2H), 3.88–3.83
(m, 1H), 3.43–3.40 (m, 2H), 1.05 (t, J = 7.2 Hz, 3H); 19F NMR (CDCl3,
internal standard CFCl3)
CDCl3)
d
À69.12 (s, 3F); 13C NMR (100 MHz,
4.5. Preparation of 1,4-bis(phenylthio)-2-trifluoromethylbut-2-ene
d
138.4, 134.2, 130.6 (q, J = 32.2 Hz), 129.3, 129.1, 125.8 (q,
(6)
J = 5.0 Hz), 71.0, 62.4, 60.1, 15.3; MS, m/z (relative intensity) 308
(M+, 1), 262 (3), 172 (15), 153 (51), 141 (13), 121 (26), 91 (14), 83
(12), 77 (100), 65 (11), 51 (64). Anal. Calcd for C13H15F3O3S: C,
50.64; H, 4.90. Found: C, 50.31; H, 4.84.
A 15 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to
an argon source was charged with NaH (1.0 mmol) and 3 mL of
THF. Then, thiophenol (0.110 g, 1.0 mmol) was added into the
mixture and then stirred at room temperature for 0.5 h. The
compound 5a (0.186 g, 0.5 mmol) added into the mixture and
then it was heated at reflux temperature for 12 h. After cooling the
reaction mixture, it was extracted with ether twice, washed with
10% NaOH, dried over anhydrous MgSO4 and chromatographed on
SiO2 column. Elution with n-hexane provided the product 6 (E/
4.3.3. 4-(2,2,2-Trifluoroethoxy)-2-trifluoromethyl-3-
phenylsulfonylbut-1-ene (3c)
3c was prepared in 71% yield (0.195 g) from the reaction of
diene 1 with 2,2,2-trifluoroethanol according to the general
procedure. 3c: yellow oil; 1H NMR (CDCl3)
d
7.88–7.85 (m, 2H),
7.70–7.67 (m, 1H), 7.59–7.55 (m, 2H), 6.18 (s, 2H), 4.25 (dd,
J = 10.0, 6.0 Hz, 1H), 4.13–4.03 (m, 2H), 3.82 (q, J = 8.4 Hz, 2H); 19
NMR (CDCl3, internal standard CFCl3)
À69.26 (s, 3F), À74.05 (t,
J = 9.4 Hz, 3F); 13C NMR (100 MHz, CDCl3)
138.1, 134.6, 129.9 (q,
F
Z = 93:7) in 60% yield (0.102 g). 6: yellow oil; 1H NMR (CDCl3)
d
d
7.40–7.26 (m, 10H), 6.28 (tq, J = 7.6, 1.6 Hz, 1H, E-isomer), 5.71 (t,
J = 7.6 Hz, 1H, Z-isomer), 3.62 (d, J = 7.6 Hz, 2H, Z-isomer), 3.56 (s,
2H, Z-isomer), 3.33 (s, 2H, E-isomer), 3.20 (dq, J = 7.6, 1.6 Hz, 2H, E-
d
J = 32.2 Hz), 129.4, 129.3, 126.5 (q, J = 5.2 Hz), 71.0, 69.0 (q,
J = 34.2 Hz), 62.7, 59.2; MS, m/z (relative intensity) 362 (M+, 2),
279 (7), 263 (14), 189 (13), 143 (10), 129 (13), 121(18), 113 (100),
101 (10), 97 (9), 83 (20), 77 (74), 51 (35). Anal. Calcd for
isomer); 19F NMR (CDCl3, internal standard CFCl3)
d
À60.53 (s, 3F,
Z-isomer), À67.88 (s, 3F, E-isomer); MS, m/z (relative intensity)
340 (M+, 1), 230 (52), 197 (32), 177 (20), 153 (15), 109 (100), 77
(10), 65 (41), 51 (10). Anal. Calcd for C17H15F3S2: C, 59.98; H, 4.44.
Found: C, 59.57; H, 4.39.
C
13H12F6O3S: C, 43.10; H, 3.34. Found: C, 42.91; H, 3.36.
4.4. General procedure for the preparation of 4-alkylthio(or arylthio)-
2-trifluoromethyl-3-phenylsulfonylbut-1-ene (5)
4.6. Preparation of diethyl 2-[3-trifluoromethyl-2-phenylsulfonylbut-
3-enyl]malonate (7)
A
15 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with diene 1 (0.200 g, 0.76 mmol) and
3 mL of THF. The reaction mixture was then cooled to 0 8C
(thiophenol) or À45 8C (propanethiol) and then thiol (0.76 mmol)
was added into the mixture. After stirring for 0.5 h, the reaction
mixture was extracted with ether twice, washed with 10% NaOH,
dried over anhydrous MgSO4 and chromatographed on SiO2
column. Elution with a mixture of n-hexane and ethyl acetate
(4:1) provided the addition product 5.
A 15 mL two-neck round bottom flask equipped with a
magnetic stirrer bar, a septum and nitrogen tee connected to an
argon source was charged with NaH (1.1 mmol) and 3 mL of THF.
Then, diethyl malonate (0.176 g, 1.1 mmol) was added into the
mixture and then stirred at room temperature for 0.5 h. Diene 1
(0.288 g, 1.1 mmol) was added into the mixture at 0 8C and then
the mixture was stirred at 0 8C for 0.5 h. The reaction mixture was
extracted with ether twice, dried over anhydrous MgSO4 and
chromatographed on SiO2 column. Elution with a mixture of n-
hexane and ethyl acetate (4:1) provided the addition product 7 in
4.4.1. 2-Trifluoromethyl-3-phenylsulfonyl-4-phenylthiobut-1-ene
(5a)
78% yield (0.362 g). 7: yellow oil; 1H NMR (CDCl3)
d 7.88–7.86 (m,
2H), 7.70–7.67 (m, 1H), 7.59–7.55 (m, 2H), 6.22 (s, 1H), 6.17 (s, 1H),
5a was prepared in 72% yield (0.204 g) from the reaction of
diene 1 with thiophenol according to the general procedure. 5a:
4.21 (m, 4H), 4.04 (dd, J = 10.4, 3.2 Hz, 1H), 3.44 (dd, J = 10.4, 4.8 Hz,
1H), 2.83–2.75 (m, 1H), 2.39–2.32 (m, 1H), 1.27–1.20 (m, 6H); 19
F
yellow oil; 1H NMR (CDCl3)
d
7.80–7.78 (m, 2H), 7.70–7.66 (m, 1H),
NMR (CDCl3, internal standard CFCl3)
d
À69.33 (s, 3F); 13C NMR

E.J. Yang et al. / Journal of Fluorine Chemistry 143 (2012) 198–203
203
[10] J.E. Backvall, S.K. Juntunen, Journal of Organic Chemistry 53 (1988) 2398–2400.
[11] A. Padwa, B. Harrison, S.S. Murphree, P.E. Yeske, Journal of Organic Chemistry 54
(1989) 4232–4235.
[12] J.E. Backvall, N.A. Plobeck, S.K. Juntunen, Tetrahedron Letters 30 (1989)
2589–2592.
[13] K. Uneyama, Organofluorine Chemistry, Blackwell, Oxford, 2006.
[14] R.D. Chambers, Fluorine in Organic Chemistry, Blackwell, Oxford, 2004.
[15] M. Hudlicky, A.E. Pavlath (Eds.), Chemistry of Organic Fluorine Compounds, ACS,
Washington, DC, 1996.
(100 MHz, CDCl3) d168.4, 168.0, 137.2, 134.6, 131.6 (q, J = 32.2 Hz),
129.5, 129.4, 126.5 (q, J = 5.0 Hz), 123.7, 62.2, 62.0, 60.3, 48.7, 29.5,
14.1; MS, m/z (relative intensity) 422 (M+, 1), 377 (10), 331 (10),
281 (100), 253 (13), 235 (11), 225 (12), 207 (81), 179 (30), 163 (27),
141 (28), 115 (70), 77 (90), 51 (32). Anal. Calcd for C18H21F3O6S: C,
51.18; H, 5.01. Found: C, 51.05; H, 5.04.
[16] R.P. Singh, J.M. Shreeve, Tetrahedron 56 (2000) 7613–7632.
[17] G.K.S. Prakash, A.K. Yudin, Chemical Reviews 97 (1997) 757–786.
[18] J. Ignatowska, W. Dmowski, Journal of Fluorine Chemistry 127 (2006) 720–729.
[19] Y. Shen, P. Li, J. Ni, J. Sun, Journal of Organic Chemistry 63 (1998) 9396–9398.
[20] F. Tellier, R. Sauvetre, Journal of Fluorine Chemistry 62 (1993) 183–189.
[21] B. Jiang, Y. Xu, Tetrahedron Letters 33 (1992) 511–514.
[22] T. Nagai, G. Nishioka, M. Koyama, A. Ando, T. Miki, I. Kumadaki, Journal of Fluorine
Chemistry 57 (1992) 229–237.
Acknowledgment
This work was supported by a grant from the Korea Sanhak
Foundation (2010-68).
References
[23] T. Nagai, G. Nishioka, M. Koyama, A. Ando, T. Miki, I. Kumadaki, Journal of Fluorine
Chemistry 57 (1992) 245–249.
[24] H. Abele, A. Haas, M. Lieb, M. Schelvis, Journal of Fluorine Chemistry 84 (1997)
75–78.
[25] K. Paul, J.H. Hwang, J.H. Choi, I.H. Jeong, Organic Letters 11 (2009) 4728–4731.
[26] A. Padwa, B.H. Norman, Journal of Organic Chemistry 55 (1990) 4801–4807.
[27] S.-S.P. Chou, T.-M. Yuan, Synthesis (1991) 171–173.
[28] A. Padwa, M.A. Filipkowski, M. Meske, S.S. Murphree, S.H. Watterson, Z. Ni, Journal
of Organic Chemistry 59 (1994) 588–596.
[29] J.E. Baldwin, Journal of the Chemical Society: Chemical Communications (1976)
734–735.
[30] J. Ichikawa, Journal of Synthetic Organic Chemistry Japan 68 (2010) 1175–1184.
[31] J.-P. Begue, D. Bonnet-Delpon, D. Mesureur, M. Ourevitch, Magnetic Resonance in
Chemistry 29 (1991) 675–678.
[1] W. Carruthers, Cycloaddition Reactions in Organic Synthesis, Pergamon, Oxford,
1990.
[2] M. Petrzilka, J.I. Grayson, Synthesis (1981) 753–786.
[3] B.M. Trost, W.C. Vladuchick, A.J. Bridges, Journal of the American Chemical Society
102 (1980) 3548–3554.
[4] S. Jeganathan, W.H. Okamura, Tetrahedron Letters 23 (1982) 4763–4764.
[5] P.J. Garratt, A. Tsotinis, Tetrahedron Letters 27 (1986) 2761–2762.
[6] E.L. Clennan, K. Nagraba, Journal of Organic Chemistry 52 (1987) 294–296.
[7] S. Oae (Ed.), Organic Chemistry of Sulfur, Plenum, New York, 1977.
[8] F. Bernardi, E. Mangini, Organic Sulfur Chemistry: Theoretical and Experimental
Advances, Elsevier, Amsterdam, 1985.
[9] J.E. Backvall, S.K. Juntunen, Journal of the American Chemical Society 109 (1987)
6396–6403.