Regio- and stereo-specific preparation of (E)-1-aryl-3,3,3-trifluoro-1-iodo-propenes and their palladium-catalyzed reaction with terminal alkynes

Article abstract of DOI:10.1016/j.jfluchem.2008.01.002

A new type of iodo-containing trifluoromethylated building blocks were synthesized. The reaction of 1-aryl-3,3,3-trifluoropropynes 1 with lithium iodide in acetic acid at 75 °C gave (E)-1-aryl-3,3,3-trifluoro-1-iodo-propenes 2 in high yield, which undergo the palladium-catalyzed Sonogashira reaction with terminal alkynes afforded trifluoromethyl-containing 1,3-enynes in high yield.

Full text of DOI:10.1016/j.jfluchem.2008.01.002

Available online at www.sciencedirect.com
Journal of Fluorine Chemistry 129 (2008) 335–342
www.elsevier.com/locate/fluor
Regio- and stereo-specific preparation of
(E)-1-aryl-3,3,3-trifluoro-1-iodo-propenes
and their palladium-catalyzed reaction
with terminal alkynes
b
b
Xing-Guo Zhang a,b, , Mu-Wang Chen , Ping Zhong
, Mao-Lin Hu
*
b,**
a College of Chemistry and Chemistry Engineering, Donghua University, 1882 West Yanan Road, Shanghai 200051, China
b College of Chemistry and Materials Engineering, Wenzhou University, Xueyuan Road, Wenzhou, Zhejiang 325027, China
Received 17 December 2007; received in revised form 9 January 2008; accepted 10 January 2008
Available online 17 January 2008
Abstract
A new type of iodo-containing trifluoromethylated building blocks were synthesized. The reaction of 1-aryl-3,3,3-trifluoropropynes 1 with
lithium iodide in acetic acid at 75 8C gave (E)-1-aryl-3,3,3-trifluoro-1-iodo-propenes 2 in high yield, which undergo the palladium-catalyzed
Sonogashira reaction with terminal alkynes afforded trifluoromethyl-containing 1,3-enynes in high yield.
# 2008 Published by Elsevier B.V.
Keywords: Trifluoromethyl; Stereospecific; Vinyl iodides; 1,3-Enynes; Sonogashira reaction
1. Introduction
synthetic precursors of furan derivatives [7] and some
macrolides [8]. The addition of trifluoropropynes with
LiAlH4/I2 [6,9] or CF3I to propynes [10], and the selective
trifluoro-methylation [11] of 1,2-diiodoalkenes are usual
methods for preparation of CF3-containing vinyl iodides.
However, most of the reported building blocks [12] are (Z)-
isomer. Qing et al. [13] reported (Z)-isomer of CF3-containing
vinyl iodides which were prepared in NaI/AcOH system, and
now we would like to describe the synthesis of analogical (E)-
isomer in LiI/AcOH system.
Recently, trifluoromethylated compounds have received
considerable attention and have been found diverse applications
in the areas of materials science [1], agrochemistry and
biomedical chemistry [2] due to their unique chemical, physical
and biological properties [3]. Although various new approaches
were recently proposed [4], the existing methods for direct
trifluoromethylation of organic compounds do not always allow
the introduction of a CF3 group in required position of the target
molecule [5]. As a result, the preparation and application of
trifluoromethylated building blocks [6] is an alternative
approach for constructing trifluoromethyl-substituted com-
pounds. Among these blocks, trifluoromethylated building
blocks bearing a vinyl iodide moiety are versatile intermediates
owing to the active C–I bond, which are widely used as
The 1,3-enyne moiety is an important structural unit for
biologically active [14] and natural compounds [15], and also
new functional materials [16]. Therefore, the introduction of
CF3 group into 1,3-enynes is so attractive to chemists [10,13].
The generation of 1,3-enyne moiety from vinylic systems and
terminal acetylenes is quite obvious by using a configuration-
retention stereospecific procedure such as the Sonogashira
methodology [17]. The 1,3-enynes bearing a trifluoromethyl
group in double bond are key intermediates in preparation of
trifluoromethyl-containing furans [18]. Such as 3,3,3-trifluoro-
1-iodopropenes [10,13] and 3,3,3-trifluoro-2-iodopropenes
[19] are often used to prepare them by coupling reaction with
terminal alkynes.
* Corresponding author at: College of Chemistry and Chemistry Engineering,
Donghua University, 1882 West Yanan Road, Shanghai 200051, China.
Tel.: +86 577 88373013; fax: +86 577 88373013.
** Corresponding author.
E-mail addresses: zxg@wzu.edu.cn, xgzhang99@yahoo.com.cn
(X.-G. Zhang).
0022-1139/$ – see front matter # 2008 Published by Elsevier B.V.
doi:10.1016/j.jfluchem.2008.01.002

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X.-G. Zhang et al. / Journal of Fluorine Chemistry 129 (2008) 335–342
Table 1
Herein, wewish to report a practical regio- and stereo-specific
The addition reaction of 1 with LiI in AcOH
Entry 1 Ar
Product 2a
route to new building blocks: (E)-1-aryl-3,3,3-trifluoro-1-
iodopropenes 2, which were obtained from 1-aryl-3,3,3-
trifluoropropynes 1 [20]. In addition, 1 can be conveniently
prepared from commercially available 1,1,1-trichloro-2,2,2-
trifluoroethane (freon-113a) [21]. In order to demonstrate
synthetic utilities of the above building blocks and to prepare
trifluoromethyl-containing 1,3-enynes, the palladium-catalyzed
coupling reaction of (E)-1-aryl-3,3,3-trifluoro-1-iodopropenes
with terminal alkynes was investigated.
Yield (%)b
81
1
2
3
4
C6H5 1a
2ac
p-MeC6H4 1b
86
80
85
2b
p-MeOC6H4 1c
2c
2. Results and discussion
In 1992, Lu and co-workers [22] reported a stereospecifical
reaction of 2-propynoic acids with lithium halides or sodium
halides in acetic acid to give Z-isomers. Trifluoromethyl is also
a strong electron-withdrawing group as carboxyl. However,
when 1-aryl-3,3,3-trifluoropropynes 1 were treated with lithium
iodide in acetic acid at 75 8C (Scheme 1), we were delighted to
found that (E)-1-aryl-3,3,3-trifluoro-1-iodopropenes 2 were the
exclusive products. At the same condition, the yields were very
low if lithium iodide was substituted by sodium iodide.
The reaction was monitored by 19F NMR. A mixture of 1-
aryl-3,3,3-trifluoropropynes 1 and lithium iodide (1.1 equiv.) in
acetic acid was stirred and heated at 75 8C. With the proceeding
of reaction, a new doublet peak (close—60 ppm) increased and
the singlet peak (close—50 ppm) decreased. After 16 h, the
singlet peak of the starting material disappeared completely.
The mixture was poured into water and neutralized with solid
K2CO3 until no CO2 evolved, then extracted with ether, washed
wish saturated NaHSO3 solution and brine. The solvent was
removed in vacuo after extracts were dried by MgSO4.
Purification of the residue and elution with 25:1 petroleum
ether/ethyl acetate gave E-isomers 2 in high yields. The results
were summarized in Table 1. The yields have not been affected
by the electronic effects of substituents, all trifluoro-propynes
with substituent groups of different electronic nature on aryl
ring afforded satisfactory results. However, the steric hindrance
of aryl group could notably reduce reaction yields.
1d
2d
5
p-FC6H4 1e
92
2e
2f
6
p-ClC6H4 1f
m-ClC6H4 1g
p-BrC6H4 1h
m-BrC6H4 1i
p-BuOC6H4 1j
1-Naphthyl 1k
o-BrC6H4 1l
o-AcOC6H4 1m
89
7
72
2g
8
90
2h
2i
9
78
10
11
12
13
82
2j
14
2k (Z/E = 38:62)
The structure and configuration of products was confirmed
1
by H NMR and 19F NMR spectra. The vinyl hydrogen is a
Trace
Trace
quartet peak in 1H NMR spectra and coupling constant (7.3 Hz)
is a typical value for 3JF–H of ArCI = CHCF3. The –CF3 group
is a doublet peak in 19F NMR spectra and coupling constant is
2l
3
also 7.3 Hz which is a typical value for JF–H. Therefore, the
2m
product was assigned to be ArCI = CHCF3. Following
the method [11] of stereospecific reduction of C–I bond, we
reduced the ArCI = CHCF3 2(a, c, j, k). Only single isomer was
obtained when 2(a, c, j) were reduced, and the coupling
14
No reaction
1n
a
b
c
All compounds were corfirmed by NMR, IR and MS.
Yields were based on 1.
The spectra data of this compoud are same to reference.
Scheme 1.

X.-G. Zhang et al. / Journal of Fluorine Chemistry 129 (2008) 335–342
337
Table 2
The Sonogashira reaction of 2 with terminal alkynes 4
Entry 2 Ar 4 R Product 5
p-ClC6H4 CH2N(CH2CH3)2 5a
Yield (%)
1
81
77
82
88
88
78
89
74
98
86
96
95
96
66
52
96
2
3
p-ClC6H4
CH2OH
5b
5c
5d
5e
5f
p-ClC6H4
C6H5
4
p-ClC6H4
C(CH3)2OH
CH2N(CH2CH3)2
CH2OH
5
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-MeOC6H4
p-BuOC6H4
p-BuOC6H4
p-BuOC6H4
p-BrC6H4
Scheme 2.
6
7
C6H5
5g
5h
5i
8
C(CH3)2OH
CH2N(CH2CH3)2
CH2OH
9
10
11
12
13
14
15
16
5j
C6H5
5k
5l
CH2N(CH2CH3)2
CH2OH
p-BrC6H4
5m
5n
5o
5p
p-MeC6H4
p-MeC6H4
p-MeC6H4
CH2N(CH2CH3)2
CH2OH
Scheme 3.
C6H5
constant (3JH–H) of Ha and Hb in reduced product 3(a, c, j) is
12.7 Hz (Scheme 2), which means cis-vinyl protons in double
bond (3JH–H of tran > 16 Hz [23]). On the basis of above
results, the E-configuration was designated to 2. The 1H NMR
and 19F NMR spectra of 2a are same to the reported [11].
Taniguchi et al. [24] had pointed that the Z-isomer converted to
E-isomer under the condition of high temperature and long
reaction time. Actually, Z-isomer could be obviously detected
by 19F NMR during the reaction. The weak doublet peak of Z-
isomer in about À64 ppm disappeared completely at last.
In our reaction system, furan ring were opened when 1-furyl-
3,3,3-trifluoropropynes reacted with HI. In addition, we have
not obtained the addition results of 1-pyridyl-3,3,3-trifluor-
opropynes and 1-alkyl-3,3,3-trifluoropropynes because they
cannot be prepared by conventional method [20]. It was
noteworthy that the mixture of Z- and E-2k was obtained in
14% yield when Ar– is 1-naphthyl. We think the steric
hindrance of 1-naphthyl caused low yield and low stereo-
selectivity. In order to prove our viewpoint, trifluoropropynes
bearing ortho-substituted phenyl were applied to this reaction
system. In entry 12, 13, Ar– is o-Br–Ph–, o-CH3COO–Ph–,
when we monitored the reaction with 19F NMR, only a very
weak doublet peak brought out and the singlet peak of material
never disappeared. In entry 14, both ortho-positions of Ar– are
occupied by chlorine atom, no product was monitored.
The corresponding E-isomers of 2l, 2m had not been separated
because of the too less products.
In order to develop synthetic utilities of these building
blocks, we applied them to research their coupling reaction
(Scheme 4). The Sonogashira reaction of 2 with terminal
alkynes 4 in the presence of Pd(PPh3)4 and CuI in triethylamine
at 50 8C afforded trifluoromethyl-containing 1,3-enynes 5 in
high yield. The results were summarized in Table 2. Significant
influence of electronic effects of Ar and R on yields had not
been observed. Only in the case of entry 15 (Ar p-MeC6H4,
R CH2OH), the yield was not as high as the others.
It is well known that the reactivity of sp2 species is vinyl
iodide > aryl bromide ꢀ aryl chloride in coupling reaction
[17]. So, 2h and 2f reacted with 1.0 equiv. of terminal alkynes
afforded target products 5. However, the bromide atom on aryl
was also substituted by alkynyl when 2h or 2i was treated with
1.5 equiv. of terminal alkynes. Compare with 2, the chemical
shift of vinyl proton in 5 decreased in 1H NMR and 19F NMR,
3
and the coupling constant of JF–H increased.
3. Conclusion
In summary, we have investigated the regio- and stereo-
specific addition reaction of 1-aryl-3,3,3-trifluoropropyne 1
with HI in LiI/AcOH system. (E)-1-Aryl-3,3,3-trifluoro-1-
iodopropenes 2 were prepared in high yields by this addition
reaction. The vinyl iodides 2 were used to prepare trifluor-
omethyl-containing 1,3-enynes 5 by palladium-catalyzed
coupling reaction with terminal alkynes.
Although Lu and co-workers [22] had discussed the
mechanism of regio- and stereo-specific addition of carbon-
carbon triple bond, we think the trace product of 2l, 2m, 2n
owing to the steric hindrance between R group and iodide anion
when iodide anion regio-specifically attack C-3 carbon atom of
the electrondeficient carbon–carbon triple bond (Scheme 3).
4. Experimental
1H NMR and 13C NMR were determined in a CDCl3
solution with a Bruker Avance300 (300 M Hz) spectrometer
using tetramethylsilane as the internal standard. 19F NMR
spectra were also obtained in a CDCl3 solution on Bruker
Avance300 (282.2 MHz) spectrometer using CFCl3 as external
standard. All chemical shifts (d) were expressed in parts per
Scheme 4.

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X.-G. Zhang et al. / Journal of Fluorine Chemistry 129 (2008) 335–342
million, and coupling constants (J) were given in Hertz. Mass
spectra were obtained using EI at 70 eV. IR spectra were
recorded on a Bruker Equinox 55 spectrometer.
128.9, 129.5, 130.2, 133.4, 148.4, 152.2; 19F NMR (282 MHz,
CDCl3): d À57.66 (d, J = 7.3 Hz); MS (EI, 70 eV) m/z: 342
(M+, 6), 215 (100), 146 (32); Anal. Calcd for C10H6F3IO2: C,
35.11; H, 1.77. Found: C, 35.31; H, 1.87.
4.1. General procedure for addition of 1-aryl-3,3,3-
trifluoropropynes with LiI in AcOH
4.1.5. (E)-1-Iodo-1-(4-fluorophenyl)-3,3,3-trifluoropropene
(E)-2e
A mixture of 1-phenyl-3,3,3-trifluoropropynes 1a (240 mg,
1.4 mmol) and lithium iodide (218 mg, 1.6 mmol) in acetic acid
(1.5 mL) was stirred at 75 8C, while the mixture was monitored
by TLC and 19F NMR. After 16 h, water (8 mL) was added. The
mixture was neutralized with solid K2CO3 until no CO2 evolved
and then extracted with ether (3Â 15 mL), washed with
saturated NaHSO3 solution and brine. The extracts were dried
by MgSO4, and the solvent was removed in vacuo. Purification
of the residue by silica-gel column chromatography eluted with
25:1 petroleum ether/ethyl acetate gave product 2a.
Yield 92% (pale yellow oil). IR (thin film): 2934, 1683,
1310,1266, 1135 cmÀ1; 1H NMR (300 MHz, CDCl3): d 7.10 (q,
J = 7.3 Hz, 1H, CHCF3), 7.22 (m, 2H, Ph), 7.74 (m, 2H, Ph);
13C NMR (75 MHz, CDCl3): d 115.4, 119.0, 122.6, 127.6,
129.3, 132.0, 163.3; 19F NMR (282 MHz, CDCl3): d À109.03
(s, 1F), À68.72 (d, J = 7.3 Hz, 3F,); MS (EI, 70 eV) m/z: 316
(M+, 16), 189 (100), 120 (28); Anal. Calcd for C9H5F4I: C,
34.20; H, 1.59. Found: C, 34.31; H, 1.66.
4.1.6. (E)-1-Iodo-1-(4-chlorophenyl)-3,3,3-
trifluoropropene (E)-2f
Yield 89% (pale yellow oil). IR (thin film): 2928, 1675,
4.1.1. (E)-1-Iodo-1-phenyl-3,3,3-trifluoropropene (E)-2a
Yield 81% (pale yellow oil). IR (thin film): 2928, 1631,
1
1307, 1263, 1133 cmÀ1; H NMR (300 MHz, CDCl3): d 6.56
1
1306, 1266, 1133 cmÀ1; H NMR (300 MHz, CDCl3): d 6.51
(q, J = 7.3 Hz, 1H, CHCF3), 7.35 (d, J = 8.6 Hz, 2H, Ph), 7.43
(d, J = 8.6 Hz, 2H, Ph); 13C NMR (75 MHz, CDCl3): d 120.3,
124.0, 127.5, 128.4, 130.5, 135.7, 136.0; 19F NMR (282 MHz,
CDCl3): d À60.24 (d, J = 7.3 Hz); MS (EI, 70 eV) m/z: 333
(M + 1, 33), 332 (M+, 100), 205 (12), 185 (52), 169 (32), 136
(18); Anal. Calcd for C9H5ClF3I: C, 32.51; H, 1.52. Found: C,
32.63; H, 1.60.
(q, J = 7.3 Hz, 1H, CHCF3), 7.28 (s, 5H, Ph); 13C NMR
(75 MHz, CDCl3): d 112.2, 120.4, 124.1, 126.0, 128.0, 128.4,
138.2; 19F NMR (282 MHz, CDCl3): d À60.10 (d, J = 7.3 Hz);
MS (EI, 70 eV) m/z: 298 (M+, 16), 171 (100), 151 (52), 127(7);
Anal. Calcd for C9H6F3I: C, 36.27; H, 2.03. Found: C, 36.38;
H, 2.11.
4.1.2. (E)-1-Iodo-1-p-tolyl-3, 3, 3-trifluoropropene (E)-2b
Yield 86% (pale yellow oil). IR (thin film): 2925, 1628,
1599, 1303, 1264, 1129 cmÀ1; 1H NMR (300 MHz, CDCl3): d
2.38 (s, 3H, CH3), 6.53 (q, J = 7.3 Hz, 1H, CHCF3), 7.15 (d,
J = 8.2 Hz, 2H, Ph), 7.40 (d, J = 8.2 Hz, 2H, Ph); 13C NMR
(75 MHz, CDCl3): d 21.1, 111.6, 119.8, 123.4, 125.8,
128.2,139.2, 140.6; 19F NMR (282 MHz, CDCl3): d À59.89
(d, J = 7.3 Hz); MS (EI, 70 eV) m/z: 312 (M+, 100), 185 (12),
165 (46), 115 (48); Anal. Calcd for C10H8F3I: C, 38.49; H, 2.58.
Found: C, 38.61; H, 2.65.
4.1.7. (E)-1-Iodo-1-(3-chlorophenyl)-3,3,3-
trifluoropropene (E)-2g
Yield 72% (pale yellow oil). IR (thin film): 2922, 1629,
1
1302, 1265, 1134 cmÀ1; H NMR (300 MHz, CDCl3): d 6.58
(q, J = 7.3 Hz, 1H, CHCF3), 7.34 (m, 3H, Ph), 7.47 (s, 1H, Ph);
13C NMR (75 MHz, CDCl3): d 120.5, 124.4, 127.6, 128.5,
129.2, 129.6, 129.9, 130.2, 134.9; 19F NMR (282 MHz,
CDCl3): d À60.36 (d, J = 7.3 Hz); MS (EI, 70 eV) m/z: 333
(M + 1, 38), 332 (M+, 100), 205 (40), 185 (75), 169 (52), 136
(18). Anal. Calcd for C9H5ClF3I: C, 32.51; H, 1.52. Found: C,
32.66; H, 1.63.
4.1.3. (E)-1-Iodo-1-(4-methoxyphenyl)-3,3,3-
trifluoropropene (E)-2c
4.1.8. (E)-1-Iodo-1-(4-bromophenyl)-3,3,3-
trifluoropropene (E)-2h
Yield 80% (pale yellow oil). IR (thin film): 2960, 1604,
1257, 1126 cmÀ1; 1H NMR (300 MHz, CDCl3): d 3.82 (s, 3H,
OCH3), 6.56 (q, J = 7.3 Hz, 1H, CHCF3), 6.85 (d, J = 8.6 Hz,
2H, Ph), 7.30 (d, J = 8.6 Hz, 2H, Ph); 13C NMR (75 MHz,
CDCl3): d 55.2, 113.5, 119.6, 123.3, 128.8, 129.2, 133.0, 160.4;
19F NMR (282 MHz, CDCl3): d À57.54 (d, J = 7.3 Hz); MS
(EI, 70 eV) m/z: 328 (M+, 6), 201 (100), 181 (22), 132 (26);
Anal. Calcd for C10H8F3IO: C, 36.61; H, 2.46. Found: C, 36.73;
H, 2.55.
Yield 90% (pale yellow oil). IR (thin film): 2920, 1630,
1484, 1213, 1134 cmÀ1; 1H NMR (300 MHz, CDCl3): d 6.56
(q, J = 7.3 Hz, 1H, CHCF3), 7.36 (d, J = 8.6 Hz, 2H, Ph), 7.50
(d, J = 8.6 Hz, 2H, Ph); 13C NMR (75 MHz, CDCl3): d 119.6,
123.3, 124.6, 129.7, 131.7, 133.9, 134.8; 19F NMR
(282 MHz, CDCl3): d À60.27 (d, J = 7.3 Hz); MS (EI,
70 eV) m/z: 376/378 (M+, 90), 249/251 (5), 170 (100), 101
(22); Anal. Calcd for C9H5BrF3I: C, 28.68; H, 1.34. Found:
C, 28.70; H, 1.39.
4.1.4. (E)-1-Iodo-1-(3-benzo [1,3] dioxol-5-yl)-3,3,3-
trifluoropropene (E)-2d
Yield 85% (pale yellow oil). IR (thin film): 2902, 1633,
1487, 1240, 1145 cmÀ1; 1H NMR (300 MHz, CDCl3): d 6.00 (s,
2H, OCH2O). 6.02 (q, J = 7.3 Hz, 1H, CHCF3), 6.80 (m, 3H,
Ph); 13C NMR (75 MHz, CDCl3): d 101.8, 114.3, 120.8, 124.1,
4.1.9. (E)-1-Iodo-1-(3-bromophenyl)-3,3,3-
trifluoropropene (E)-2i
Yield 78% (pale yellow oil). IR (thin film): 2981, 1630,
1
1562, 1264, 1132 cmÀ1; H NMR (300 MHz, CDCl3): d 6.58
(q, J = 7.3 Hz, 1H, CHCF3), 7.36 (m, 3H, Ph), 7.63 (s, 1H, Ph);

X.-G. Zhang et al. / Journal of Fluorine Chemistry 129 (2008) 335–342
339
13C NMR (75 MHz, CDCl3): d 120.0, 123.8, 127.2, 128.4,
4.2.3. (Z)-1-(4-Butoxyphenyl)-3, 3, 3-trifluoropropene
(Z)-3j
129.1, 129.5, 129.8, 130.1,134.6; 19F NMR (282 MHz, CDCl3):
d À60.37 (d, J = 7.3 Hz); MS (EI, 70 eV) m/z: 376/378 (M+,
15), 249/251 (60), 170 (100), 101 (28); Anal. Calcd for
C9H5BrF3I: C, 28.68; H, 1.34. Found: C, 28.74; H, 1.43.
Yield 91% (pale yellow oil).1H NMR (300 MHz, CDCl3):
1.03 (t, J = 7.4 Hz, 3H, CH3), 1.55 (m, 2H,
d
OCH2CH2CH2CH3), 1.82 (m, 2H, OCH2CH2CH2CH3),
4.02 (t, J = 6.5 Hz, 2H, OCH2 CH2CH2CH3), 5.67 (dq,
J = 7.3 Hz, 12.7 Hz, CHCF3), 6.84 (d, J = 12.7 Hz, 1H,
CH = CHCF3), 6.93 (d, J = 8.7 Hz, 2H, Ph), 7.42 (d,
J = 8.7 Hz, 2H, Ph).
4.1.10. (E)-1-Iodo-1-(4-butoxyphenyl)-3,3,3-
trifluoropropene (E)-2j
Yield 82% (pale yellow oil). IR (thin film): 2960, 1604,
1507, 1261, 1133 cmÀ1; 1H NMR (300 MHz, CDCl3): d 0.97 (t,
J = 7.4 Hz, 3H, CH3). 1.49 (m, 2H, OCH2CH2CH2CH3), 1.76
(m, 2H, OCH2CH2CH2CH3), 3.96 (t, J = 6.5 Hz, 2H,
OCH2CH2 CH2CH3), 6.56 (q, J = 7.3 Hz, 1H, CHCF3), 6.83
(d, 2H, J = 8.7 Hz, Ph), 7.27 (d, 2H, J = 8.7 Hz, Ph); 13C NMR
(75 MHz, CDCl3): d 13.8, 19.2, 31.2, 67.7, 113.9, 119.5, 123.2,
128.7, 129.3, 132.7, 160.0; 19F NMR (282 MHz, CDCl3): d
À57.50 (d, J = 7.3 Hz); MS (EI, 70 eV) m/z: 370 (M+, 11), 243
(100), 174 (26); Anal. Calcd for C13H14F3IO: C, 42.18; H, 3.81.
Found: C, 42.24; H, 3.85.
4.2.4. (Z/E)-1-(Naphthalen-1-yl)-3,3,3-trifluoropropene
(Z/E)-3k
1
Yield 77% (pale yellow oil). H NMR (300 MHz, CDCl3):
5.68 (dq, J = 7.3 Hz, 12.7 Hz, 0.62H, CHCF3), 6.02 (dq,
J = 7.3 Hz, 16.5 Hz, 0.38H, CHCF3), 6.86 (d, J = 12.7 Hz,
0.62H, CH = CHCF3), 7.12 (d, J = 16.5 Hz, 0.38H,
CH = CHCF3), 7.40 (m, 2H), 7.57 (m, 2H), 7.86 (m, 2H),
7.98 (m, 1H).
4.3. General procedure for preparation of (E)-2-aryl-3-
trifluoromethyl-1,3-enynes 5
4.1.11. (Z/E)-1-Iodo-1-(naphthalen-1-yl)-3,3,3-
trifluoropropene (Z/E)-2k
Yield 14% (pale yellow oil). IR (thin film): 2965, 1609,
To a three-necked, round-bottomed flask were added (E)-1-
aryl-1-iodo-3,3,3-trifluoropropene 2 (1 mmol), terminal alkyne
3 (1.5 mmol), CuI (0.05 mmol), Pd(PPh3)4 (0.01 mmol), and
triethylamine (6 mL) under nitrogen atmosphere. The reaction
mixture was stirred at 50 8C for 8 h and then filtered. The filtrate
was concentrated and flash chromatographed on silica gel
(hexanes/ether = 10:1) to yield 5.
1
1521, 1267, 1135 cmÀ1; H NMR (300 MHz, CDCl3): d 6.57
(d, J = 7.3 Hz, 0.62H, CHCF3), 6.91 (q, J = 7.3 Hz, 0.38H,
CHCF3), 7.42 (m, 2H), 7.58(m, 2H), 7.88(m, 2H), 7.99(m, 1H);
19F NMR (282 MHz, CDCl3): d À60.49 (d, J = 7.3 Hz, 1.86 F),
À59.25 (d, J = 7.3 Hz, 1.14 F); MS (EI, 70 eV) m/z: 348 (M+,
18), 221 (100), 152 (23); Anal. Calcd for C13H8F3I: C, 44.85; H,
2.32. Found: C, 44.89; H, 2.29.
4.3.1. (E)-4-(4-Chlorophenyl)-N,N-diethyl-6,6,6-
trifluorohex-4-en-2-yl-1-amine (E)-5a
Yield 81% (pale yellow oil). IR (film): 2972, 2821, 2219,
4.2. General procedure for reduction of (E)-1-aryl-3,3,3-
trifluoro-1-iodopropenes in AcOH
1
1622, 1491, 1267, 1135, 839, 729 cmÀ1; H NMR (300 MHz,
(E)-ArCI = CHCF3 (5 mmol), Zn (1.2 g, 20 mmol), and
AgOAc (0.1 g, 0.6 mmol) were mixed together in AcOH
(10 mL). Under vigorous stirring 1 mL of concentrated HCl
(37%) was added dropwise over a 5 min period. The mixture
was further stirred for 5 min, and then was filtered. The filtrate
was mixed with 30 mL of hexane and 10 mL of H2O. The
organic layer was separated, and the water solution was
extracted with hexane (20 mL Â 3). The combined organic
solution was washed with water (10 mL Â 3), dried, and
concentrated. Purification of the residue by flash column
chromatography gave product 3.
CDCl3): d 1.11 (t, J = 5.7Hz, 6H, CH3), 2.60 (q, J = 5.7 Hz, 4H,
CH2CH3), 3.73 (s, 2H, CH2N), 6.27 (q, J = 7.5Hz, 1H, CHCF3),
7.37 (d, J = 8.6 Hz, 2H, Ph), 7.57 (d, J = 8.6 Hz, 2H, Ph); 13C
NMR (75 MHz, CDCl3): d 12.4, 41.2, 47.2, 78.7, 97.8, 120.6,
124.2, 127.8, 128.6, 130.5, 135.8, 136.1; 19F NMR (282 MHz,
CDCl3): d À59.21 (d, J = 7.5 Hz); MS (EI, 70 eV) m/z: 316
(M + 1, 33), 315 (M+, 100), 285 (32); Anal. Calcd for
C16H17ClF3N: C, 60.86; H, 5.43; N, 4.44. Found: C, 60.74; H,
5.49; N, 4.38.
4.3.2. (E)-4-(4-Chlorophenyl)-6,6,6-trifluorohex-4-en-2-yl-
1-ol (E)-5b
Yield 77% (pale yellow oil). IR (thin film): 3364, 2924,
4.2.1. (Z)-1-Phenyl-3,3,3-trifluoropropene (Z)-3a
Yield 76% (pale yellow oil). 1H NMR (300 MHz, CDCl3): d
5.75 (dq, J = 7.3 Hz, 12.7Hz, CHCF3), 6.92 (d, J = 12.7 Hz,
1H, CH=CHCF3), 7.36 (m, 5H, PH).
2865, 2237, 1624, 1491, 1268, 817, 729 cmÀ1 1H NMR
;
(300 MHz, CDCl3): d 2.00 (s, 1H, OH), 4.55 (s, 2H, CH2OH),
6.30 (q, J = 7.5 Hz, 1H, CHCF3), 7.57 (d, J = 8.6 Hz, 2H, Ph),
7.38 (d, J = 8.6 Hz, 2H, Ph); 13C NMR (75 MHz, CDCl3): d
51.2, 79.2, 99.1, 121.4, 124.0, 127.8, 128.7, 130.6, 135.9,
136.2; 19F NMR (282 MHz, CDCl3): d À59.48 (d, J = 7.5 Hz);
MS (EI, 70 eV) m/z: 261 (M+ 1, 23), 260 (M+, 68), 243 (100);
Anal. Calcd for C12H8ClF3O: C, 55.30; H, 3.09; Found: C,
55.42; H, 3.16.
4.2.2. (Z)-1-(4-Methoxyphenyl)-3,3,3-trifluoropropene
(Z)-3c
1
Yield 82% (pale yellow oil). H NMR (300 MHz, CDCl3):
d = 3.83 (s, 3H, OCH3), 5.64 (dq, J = 7.3 Hz, 12.7 Hz, CHCF3),
6.83 (d, J = 12.7 Hz, 1H, CH = CHCF3), 6.91 (d, J = 8.7 Hz,
2H, Ph), 7.40 (d, J = 8.7 Hz, 2H, Ph).

340
X.-G. Zhang et al. / Journal of Fluorine Chemistry 129 (2008) 335–342
4.3.3. (E)-1-Phenyl-3-(4-chlorophenyl)-5,5,5-trifluoropent-
3-en-1-yl (E)-5c
Yield 82% (pale yellow oil). IR (thin film): 3061, 2926,
(300 MHz, CDCl3): d 3.86 (s, 3H, OCH3), 6.15 (q, J = 8.7 Hz,
1H, CHCF3), 6.93 (d, J = 8.8 Hz, 2H, Ph), 7.36 (m, 3H, Ph),
7.49 (m, 4H, Ph); 13C NMR (75 MHz, CDCl3): d 54.8, 88.8,
93.6, 114.0, 120.8, 122.2, 124.3, 127.2, 128.4, 129.1, 129.7,
131.9, 134.7, 160.1; 19F NMR (282 MHz, CDCl3): d À56.12 (d,
J = 8.7 Hz); MS (EI, 70 eV) m/z: 302 (M+, 65), 271 (100), 69
(12); Anal. Calcd for C18H13F3O: C, 71.52; H, 4.33; Found: C,
71.38; H, 4.41.
2204, 1620, 1489, 1270, 836, 755, 690 cmÀ1 1H NMR
;
(300 MHz, CDCl3): d 6.34 (q, J = 7.5 Hz, 1H, CHCF3), 7.35
(m, 5H, Ph), 7.56 (d, J = 8.5 Hz, 2H, Ph), 7.67 (d, J = 8.5 Hz,
2H, Ph); 13C NMR (75 MHz, CDCl3): d 88.8, 93.8, 119.8,
126.5, 128.3, 128.7, 129.0, 129.2, 130.8, 131.7, 132.3, 135.7,
136.5; 19F NMR (282 MHz, CDCl3): d À59.38 (d, J = 7.5 Hz);
MS (EI, 70 eV) m/z: 307 (M + 1, 41), 306 (M+, 100), 271 (28);
Anal. Calcd for C17H10ClF3: C, 66.57; H, 3.29; Found: C,
66.48; H, 3.35.
4.3.8. (E)-5-(4-Methoxyophenyl)-7,7,7-trifluoro-2-
methylhept-5-en-3-yl-2-ol (E)-5h
Yield 74% (pale yellow oil). IR (thin film): 3400, 2983,
1
2937, 2220, 1610, 1512, 1463, 1364, 1253, 837 cmÀ1; H
4.3.4. (E)-5-(4-Chlorophenyl)-7,7,7-trifluoro-2-
methylhept-5-en-3-yl-2-ol (E)-5d
NMR (300 MHz, CDCl3): d 1.56 (s, 6H, CH3), 1.63 (s, 1H,
OH), 3.84 (s, 3H, OCH3), 6.02 (q, J = 8.7 Hz, 1H, CHCF3),
Yield 88% (pale yellow oil). IR (thin film): 3389, 2984,
2223, 1623, 1492, 1358, 1268, 1134, 814, 727 cmÀ1; 1H NMR
(300 MHz, CDCl3): d 1.63 (s, 6H, CH3), 2.05 (s, 1H, OH), 6.29
(q, J = 7.5 Hz, 1H, CHCF3), 7.38 (d, J = 8.5 Hz, 2H, Ph), 7.56
(d, J = 8.5 Hz, 2H, Ph); 13C NMR (75 MHz, CDCl3): d 30.4,
65.2, 79.0, 98.8, 121.4, 124.2, 127.5, 128.4, 130.3, 135.7,
136.8; 19F NMR (282 MHz, CDCl3): d À59.47 (d, J = 7.5 Hz);
MS (EI, 70 eV) m/z: 289 (M + 1, 37), 288 (M+, 86), 261 (100);
Anal. Calcd for C14H12ClF3O: C, 58.25; H, 4.19; Found: C,
58.17; H, 4.11.
6.90 (d, J = 8.8 Hz, 2H, Ph), 7.39 (d, J = 8.8 Hz, 2H, Ph); 13
C
NMR (75 MHz, CDCl3): d = 30.5, 54.8, 65.3, 85.2, 91.8,
113.9, 121.1, 124.2, 127.0, 129.8, 133.9, 160.0; 19F NMR
(282 MHz, CDCl3): d À56.13 (d, J = 8.7 Hz); MS (EI, 70 eV)
m/z: 284 (M+, 65), 267 (100), 236 (55); Anal. Calcd
for C15H15F3O2: C, 63.38; H, 5.32; Found: C, 63.26; H,
5.19.
4.3.9. (E)-4-(4-Butoxyphenyl)-N,N-diethyl-6,6,6-
trifluorohex-4-en-2-yl-1-amine (E)-5i
4.3.5. (E)-4-(4-Methoxyphenyl)-N,N-diethyl-6,6,6-
trifluorohex-4-en-2-yl-1-amine (E)-5e
Yield 98% (pale yellow oil). IR (thin film): 2968, 2363,
1611, 1511, 1270, 1109 cmÀ1; 1H NMR (300 MHz, CDCl3): d
0.95 (t, J = 7.3 Hz, 3H, OCH2CH2CH2CH3), 1.07 (t,
J = 5.7 Hz, 6H, NCH2CH3), 1.46 (m, 2H, OCH2CH2CH2CH3),
1.73 (m, 2H, OCH2 CH2CH2CH3), 2.53 (q, J = 5.7 Hz, 4H,
NCH2CH3), 3.58 (s, 2H, CH2N), 3.93 (t, J = 6.5 Hz, 2H,
OCH2CH2 CH2CH3), 5.99 (q, J = 8.7 Hz, 1H, CHCF3), 6.85 (d,
J = 8.8 Hz, 2H, Ph), 7.38 (d, J = 8.8 Hz, 2H, Ph); 13C NMR
(75 MHz, CDCl3): d 12.5, 13.7, 19.1, 31.1, 41.1, 47.3, 67.5,
Yield 88% (pale yellow oil). IR (thin film): 2971, 2820,
2218, 1610, 1513, 1362, 1271, 1105, 835, 735 cmÀ1; 1H NMR
(300 MHz, CDCl3): d 1.11 (t, J = 5.7Hz, 6H, CH3), 2.58 (q,
J = 5.7 Hz, 4H, CH2CH3), 3.63 (s, 2H, CH2N), 3.83 (s, 3H,
OCH3), 6.02 (q, J = 8.7 Hz, 1H, CHCF3), 6.89 (d, J = 8.7 Hz,
2H, Ph), 7.39 (d, J = 8.7 Hz, 2H, Ph); 13C NMR (75 MHz,
CDCl3): d 11.9, 40.8, 47.0, 54.7, 84.7, 88.8, 113.5, 120.5, 123.8,
127.1, 129.3, 133.8, 159.8; 19F NMR (282 MHz, CDCl3): d
À56.15 (d, J = 8.7 Hz); MS (EI, 70 eV) m/z: 311 (M+, 65), 280
(100), 251 (24); Anal. Calcd for C17H20F3NO: C, 65.58; H,
6.47; N, 4.50. Found: C, 65.47; H, 6.41; N, 4.45.
84.9, 89.6, 113.8, 120.5, 124.2, 127.3, 129.6, 134.3, 159.8; 19
F
NMR (282 MHz, CDCl3): d À55.93 (d, J = 8.7 Hz); MS (EI,
70 eV) m/z: 354 (M + 1, 20), 353 (M+, 100), 221 (18); Anal.
Calcd for C20H26F3NO: C, 67.97; H, 7.42; N, 3.96. Found: C,
68.02; H, 7.49; N, 3.92.
4.3.6. (E)-4-(4-Methoxyphenyl)-6,6,6-trifluorohex-4-en-2-
yl-1-ol (E)-5f
Yield 78% (pale yellow oil). IR (thin film): 3401, 2934,
2844, 2052, 1610, 1513, 1463, 1271, 1111, 831, 679 cmÀ1; 1H
NMR (300 MHz, CDCl3): d 1.88 (s, 1H, OH), 3.83 (s, 3H,
OCH3), 4.43 (s, 2H, CH2OH), 6.05 (q, J = 8.7Hz, 1H, CHCF3),
6.90 (d, J = 8.8 Hz, 2H, Ph), 7.39 (d, J = 8.8 Hz, 2H, Ph); 13C
NMR (75 MHz, CDCl3): d 51.4, 54.8, 85.0, 91.6, 113.8, 120.9,
124.1, 126.9, 129.7, 133.9, 160.0; 19F NMR (282 MHz,
CDCl3): d À56.16 (d, J = 8.7 Hz); MS (EI, 70 eV) m/z: 256
(M+, 65), 239 (100), 208(63); Anal. Calcd for C13H11F3O2: C,
60.94; H, 4.33; Found: C, 60.82; H, 4.42.
4.3.10. (E)-4-(4-Butoxyphenyl)-6,6,6-trifluorohex-4-en-2-
yl-1-ol (E)-5j
Yield 86% (pale yellow oil). IR (thin film): 3345, 2961,
1
2206, 1611, 1511, 1271, 1131 cmÀ1; H NMR (300 MHz,
CDCl3): d 0.99 (t, J = 7.3 Hz, 3H, CH3). 1.52 (m, 2H,
OCH2CH2CH2CH3), 1.80 (m, 2H, OCH2CH2CH2CH3), 1.89
(s, 1H, OH), 3.99 (t, J = 6.5 Hz, 2H, OCH2CH2CH2CH3),
4.45 (s, 2H, CH2OH), 6.06 (q, J = 8.7 Hz, 1H, CHCF3), 6.89
(d, J = 8.8 Hz, 2H, Ph), 7.39 (d, J = 8.8 Hz, 2H, Ph); 13C
NMR (75 MHz, CDCl3): d 13.8, 19.2, 31.2, 51.4, 67.7, 85.2,
91.8, 114.1, 121.5, 124.4, 126.8, 129.7, 133.9, 160.0; 19F
NMR (282 MHz, CDCl3): d À55.95 (d, J = 8.7 Hz); MS (EI,
70 eV) m/z: 298 (M+, 100), 279 (28), 243 (23); Anal.
Calcd for C16H17F3O2: C, 64.42; H, 5.74; Found: C, 64.38;
H, 5.66.
4.3.7. (E)-1-Phenyl-3-(4-methoxyphenyl)-5,5,5-
trifluoropent-3-en-1-yl (E)-5g
Yield 89% (pale yellow oil). IR (thin film): 2962, 2840,
;
2206, 1611, 1512, 1259, 837, 756, 685 cmÀ1 1H NMR

X.-G. Zhang et al. / Journal of Fluorine Chemistry 129 (2008) 335–342
341
4.3.11. (E)-1-Phenyl-3-(4-butoxyphenyl)-5,5,5-
trifluoropent-3-en-1-yl (E)-5k
4.3.15. (E)-6,6,6-Trifluoro-4-p-tolylhex-4-en-2-yl-1-ol
(E)-5o
Yield 52% (pale yellow oil). IR (thin film): 3364, 2928,
2363, 1709, 1616, 1512, 1271, 1129 cmÀ1 1H NMR
Yield 96% (pale yellow oil). IR (thin film): 3060, 2960,
2206, 1611, 1511, 1267, 1131 cmÀ1
;
1H NMR (300 MHz,
;
CDCl3): d 1.06 (t, J = 7.3 Hz, 3H, CH3), 1.59 (m, 2H,
OCH2CH2CH2CH3), 1.86 (m, 2H, OCH2CH2CH2CH3), 4.04 (t,
J = 6.5 Hz, 2H, OCH2CH2 CH2CH3), 6.20 (q, J = 8.7 Hz, 1H,
CHCF3), 6.99 (d, J = 8.8 Hz, 2H, Ph), 7.41 (m, 3H, Ph), 7.55
(m, 4H, Ph); 13C NMR (75 MHz, CDCl3): d 13.8, 19.2, 31.2,
67.6, 89.0, 93.9, 114.1, 120.8, 122.1, 124.5, 127.2, 128.4, 129.2,
129.9, 131.8, 134.6, 160.1; 19F NMR (282 MHz, CDCl3): d
À55.91 (d, J = 8.7 Hz); MS (EI, 70 eV) m/z: 344 (M+, 28), 289
(100), 181 (17); Anal. Calcd for C21H19F3O: C, 73.24; H, 5.56;
Found: C, 73.12; H, 5.63.
(300 MHz, CDCl3): d 2.02 (s, 1H, OH), 2.41 (s, 3H, PhCH3),
4.57 (s, 2H, CH2OH), 6.31 (q, J = 7.7 Hz, 1H, CHCF3), 7.23 (d,
J = 8.2 Hz, 2H, Ph), 7.56 (d, J = 8.2 Hz, 2H, Ph); 13C NMR
(75 MHz, CDCl3): d = 21.2, 51.5, 80.0, 98.7, 120.8, 124.6,
126.6, 129.4, 131.9, 132.6, 140.4; 19F NMR (282 MHz,
CDCl3): d À59.16 (d, J = 7.7 Hz); MS (EI, 70 eV) m/z: 240
(M+, 8), 223 (44), 208 (25); Anal. Calcd for C13H11F3O: C,
65.00; H, 4.62; Found: C, 64.89; H, 4.54.
4.3.16. (E)-5,5,5-Trifluoro-1-phenyl-3-p-tolylpent-3-en-1-
yl (E)-5p
Yield 96% (pale yellow oil). IR (thin film): 3058, 2958, 2206,
4.3.12. (E)-4-(4-Bromophenyl)-N,N-diethyl-6,6,6-
trifluorohex-4-en-2-yl-1-amine (E)-5l
Yield 95% (pale yellow oil). IR (thin film): 2972, 2819,
1709, 1616, 1490, 1268, 1129 cmÀ1 1H NMR (300 MHz,
;
CDCl3): d 2.46 (s, 3H, PhCH3), 6.39 (q, J = 7.7 Hz, 1H, CHCF3),
7.29 (d, J = 8.2 Hz, 2H, Ph), 7.45 (m, 4H, Ph), 7.60 (m, 3H, Ph);
13C NMR (75 MHz, CDCl3): d 21.1, 88.6, 92.8, 119.5, 126.5,
2361, 2221, 1626, 1485, 1272, 1131 cmÀ1
;
1H NMR
(300 MHz, CDCl3): d 1.09 (t, J = 5.7 Hz, 6H, CH3), 2.56 (q,
J = 5.7 Hz, 4H, CH2CH3), 3.61 (s, 2H, CH2N), 6.12 (q,
J = 8.5 Hz, 1H, CHCF3), 7.30 (d, J = 8.4 Hz, 2H, Ph), 7.53 (d,
J = 8.4 Hz, 2H, Ph); 13C NMR (75 MHz, CDCl3): d 12.6, 41.4,
47.4, 84.1, 91.4, 120.4, 122.6, 124.0, 129.7, 131.4, 133.8,
134.5; 19F NMR (282 MHz, CDCl3): d À59.50 (d, J = 8.5 Hz);
MS (EI, 70 eV) m/z: 361/359 (M+, 45), 221 (40); Anal. Calcd
for C16H17BrF3N: C, 53.35; H, 4.76; N, 3.89. Found: C, 53.42;
H, 4.85; N, 3.85.
128.3, 128.7, 129.0, 129.2, 131.5, 131.7, 132.3, 132.7, 140.1; 19
F
NMR (282 MHz, CDCl3): d À59.11 (d, J = 7.7 Hz); MS (EI,
70 eV) m/z: 286 (M+, 100), 271 (34). Anal. Calcd for C18H13F3:
C, 75.51; H, 4.58; Found: C, 75.43; H, 4.63.
Acknowledgement
This work was supported by the National Natural Science
Foundation of China (No. 20572079).
4.3.13. (E)-4-(4-Bromophenyl)-6,6,6-trifluorohex-4-en-2-
yl-1-ol (E)-5m
Yield 96% (pale yellow oil). IR (thin film): 3274, 2968,
References
[1] (a) R.E. Banks, B.E. Smart, J.C. Tatlow, Organofluorine Chemistry:
P; rinciples and Commercial Applications, Plenum Press, New York, 1994
(b) T. Hiyama, Organofluorine Compounds: Chemistry and Properties,
Springer-Verlag, Berlin, 2000;
1
2363, 1486, 1511, 1274, 1109 cmÀ1; H NMR (300 MHz,
CDCl3): d 1.80 (s, 1H, OH), 4.46 (s, 2H, CH2OH), 6.15 (q,
J = 8.5 Hz, 1H, CHCF3), 7.29 (d, J = 8.4 Hz, 2H, Ph), 7.54
(d, J = 8.4 Hz, 2H, Ph); 13C NMR (75 MHz, CDCl3): d 51.3,
(c) J.T. Welch, Tetrahedron 43 (1987) 3123–3197;
(d) Y. Zhu, P. Zhao, X. Cai, W.-D. Meng, F.-L. Qing, Polymer 48 (2007)
3116–3124;
84.0, 93.1, 120.5, 123.5, 124.0,129.7,131.5, 133.8, 134.6; 19
F
NMR (282 MHz, CDCl3): d À59.52 (d, J = 8.5 Hz); MS (EI,
70 eV) m/z: 306/304 (M+, 100), 287/285 (30); Anal. Calcd
for C12H8BrF3O: C, 47.24; H, 2.64; Found: C, 47.36;
H, 2.71.
(e) K. Tsuchiya, Y. Shibasaki, M. Aoyagi, M. Ueda, Macromolecules 39
(2006) 3964–3966.
[2] (a) R. Filler, Y. Kobayashi, L.M. Yagulpolskii, Organofluorine Com-
pounds in Medicinal Chemistry and Biomedical Applications, Elsevier,
Amsterdam, 1993;
(b) A. Becker, Inventory of Industrial Fluoro-Biochemicals, Eyrolles,
Paris, 1996;
4.3.14. (E)-N,N-Diethyl-6,6,6-trifluoro-4-p-tolylhex-4-en-
2-yl-1-amine (E)-5n
(c) G. Magueur, B. Crousse, S. Charneau, P. Grellierm, J.-P. Begue, D.
Bonnet-Delpon, J. Med. Chem. 47 (2004) 2694–2699;
(d) A. Gryshuk, Y. Chen, L.N. Goswami, et al. J. Med. Chem. 50 (2007)
1754–1767;
Yield 66% (pale yellow oil). IR (thin film): 2972, 2220,
1618, 1512, 1269, 1132 cmÀ1; 1H NMR (300 MHz, CDCl3): d
1.14 (t, J = 5.7 Hz, 6H, CH2CH3), 2.40 (s, 3H, PhCH3), 2.64 (q,
J = 5.7 Hz, 4H, CH2CH3), 3.76 (s, 2H, CH2N), 6.28 (q,
J = 7.7 Hz, 1H, CHCF3), 7.20 (d, J = 8.2 Hz, 2H, Ph), 7.56 (d,
J = 8.2 Hz, 2H, Ph); 13C NMR (75 MHz, CDCl3): d 12.6, 21.2,
41.4, 47.4, 79.5, 97.1, 120.3, 126.6, 128.8, 129.3, 132.6, 133.2,
140.1; 19F NMR (282 MHz, CDCl3): d À59.14 (d, J = 7.7 Hz);
MS (EI, 70 eV) m/z: 296 (M + 1, 20), 295 (M+, 100); Anal.
Calcd for C17H20F3N: C, 69.13; H, 6.83; N, 4.74. Found: C,
69.06; H, 6.94; N, 4.68.
(e) D. Gimenez, C. Andreu, M. Olmo, et al. Bioorg. Med. Chem. 14
(2006) 6971–6978.
[3] (a) P. Kirsch, Modern Fluoroorganic Chemistry, Wiley-VCH, Weinheim,
Germany, 2004;
(b) R.D. Chambers, Fluorine in Organic Chemistry, Blackwell, Oxford,
2004;
(c) J.F. Liebman, A. Greenberg, W.R. Dolbier, Jr. (Eds.), Fluorine Con-
taining Molecules: Structure, Reactivity, Synthesis, and Applications,
VCH, New York, 1988;
(d) S. Large-Radix, T. Billard, B.R. Langlois, J. Fluorine Chem. 124
(2003) 147–149;

342
X.-G. Zhang et al. / Journal of Fluorine Chemistry 129 (2008) 335–342
(e) G.P. Stahly, D.R. Bell, J. Org. Chem. 54 (1989) 2873–2877;
(f) B.E. Smart, J. Fluorine Chem. 109 (2001) 3–11.
(d) L.M. Kacharova, A.D. Kacharov, I.I. Gerus, J. Fluorine Chem. 111
(2001) 29–31;
[4] (a) Y. Itoh, K.N. Houk, K. Mikami, J. Org. Chem. 71 (2006) 8918–8925;
(b) K. Mikami, Y. Tomita, Y. Ichikawa, K. Amikura, Y. Itoh, Org. Lett. 8
(2006) 4671;
(e) Y. Shen, G. Wang, Synthesis 13 (2005) 2183–2187.
[13] F.-L. Qing, W.-Z. Gao, J. Ying, J. Org. Chem. 65 (2000) 2003–2006.
[14] (a) H. Lee, H. Kim, T. Yoon, B. Kim, S. Kim, H.-D. Kim, D. Kim, J. Org.
Chem. 70 (2005) 8723–8729;
(c) V. Petrick, D. Cahard, Tetrahedron Lett. 48 (2007) 3327–3330;
(d) J.-J. Yang, R.L. Kirchmeier, J.M. Shreeve, J. Org. Chem. 63 (1998)
2656–2660;
(b) V. Fiandanese, D. Bottalico, G. Marchese, A. Punzi, Tetrahedron 60
(2004) 11421–11425.
(e) J.-A. Ma, D. Cahard, J. Org. Chem. 68 (2003) 8726–8729;
(f) B.R. Langlois, T. Billard, S. Roussel, J. Fluorine Chem. 126 (2005)
173–179;
[15] (a) Y. Koyama, M.J. Lear, F. Yoshimura, I. Ohashi, T. Mashimo, M.
Hirama, Org. Lett. 7 (2005) 267–270;
´ ´ ´ ´
(b) S. Lopez, F. Fernandez-Trillo, P. Midon, L. Castedo, C. Saa, J. Org.
(g) W. Xu, W.R. Dolbier Jr., J. Org. Chem. 70 (2005) 4741–4745;
(h) I. Nowak, M.J. Robins, J. Org. Chem. 72 (2007) 2678–2681;
(i) W. Tyrra, D. Naumann, S. Quadt, S. Buslei, Y.L. Yagupolskii, M.M.
Kremlev, J. Fluorine Chem. 128 (2007) 813–817.
[5] S.V. Druzhinin, E.S. Balenkova, V.G. Nenajdenko, Tetrahedron 63 (2007)
7753–7808.
Chem. 71 (2006) 2802–2810;
(c) V. Fiandanese, D. Bottalico, C. Cardellicchio, G. Marchese, A. Punzi,
Tetrahedron 61 (2005) 4551–4556.
[16] (a) Y. Takayama, C. Delas, K. Maruoka, F. Sato, Org. Lett. 5 (2003) 365–
368;
(b) A.S. Anderson, K. Qvortrup, E.R. Torbensen, J.-P. Mayer, J.-P.
˚
Gisselbrecht, C. Boudon, M. Gross, A. Kadziola, K. Kilsa, M.B. Nielsen,
[6] (a) T. Veber, J. Brunner, J. Am. Chem. Soc. 117 (1995) 3084–3095;
(b) T. Fuchigami, K. Yamamoto, Y. Nakagawa, J. Org. Chem. 56 (1991)
137–142;
Eur. J. Org. Chem. (2005) 3660–3671.
[17] R. Chinchilla, C. Najera, Chem. Rev. 107 (2007) 874–922.
[18] (a) J. Zhang, X. Zhao, Y. Li, L. Lu, Tetrahedron Lett. 47 (2006) 4737–
4739;
(c) F. Massicot, N. Monnier-Benoit, N. Deka, P. Plantier-Royon, C.
Portella, J. Org. Chem. 72 (2007) 1174–1180;
(d) T. Hanamoto, R. Anno, K. Yamada, K. Ryu, Tetrahedron Lett. 48
(2007) 3727–3730;
(b) J. Zhang, X. Zhao, L. Lu, Tetrahedron Lett. 48 (2007) 1911–1913.
[19] (a) J. Thibonnet, G. Prie, M. Abarbri, A. Duchene, J.-L. Parrain, Tetra-
hedron Lett. 40 (1999) 3151–3154;
(e) V. Wehner, H.-U. Stilz, S.N. Osipov, A.S. Golubev, J. Sieler, K.
Burger, Tetrahedron 60 (2004) 4295–4302;
(b) T. Konno, T. Daitoh, A. Noiri, J. Chae, T. Ishihara, H. Yamanaka,
Tetrahedron 61 (2005) 9391–9404;
(f) V. Michault, F. Metz, J.-M. Paris, J.-C. Plaquevent, J. Fluorine Chem.
128 (2007) 889–895.
(c) T. Konno, T. Daitoh, A. Noiri, J. Chae, T. Ishihara, H. Yamanaka, Org.
Lett. 6 (2004) 933–936;
[7] F.-L. Qing, Z.-X. Jiang, J. Fluorine Chem. 114 (2002) 177–180.
[8] A. Rivkin, K. Biswas, T.-C. Chou, S.J. Danishefsky, Org. Lett. 4 (2002)
4081–4084.
(d) F.-L. Qing, J. Ying, Y. Zhang, J. Fluorine Chem. 101 (2000) 31–
33;
[9] F.-L. Qing, W.-Z. Gao, Tetrahedron Lett. 41 (2000) 7727–7730.
[10] M.P. Jennings, E.A. Cork, P.V. Ramachandran, J. Org. Chem. 65 (2000)
8763–8766.
(e) G. Prie, J. Thibonnet, M. Abarbri, A. Duchene, J.-L. Parrain, Synlett 8
(1998) 839–840.
[20] T. Hiyama, K. Sato, M. Fujita, Bull. Chem. Soc. Jpn. 62 (1989) 1352–
1354.
[11] J. Duan, W.R. Dolbier Jr., Q.-Y. Chen, J. Org. Chem. 63 (1998) 9486–
9489.
[21] (a) V.N. Korotchenko, A.V. Shastin, V.G. Nenajdenko, E.S. Balenkova,
Tetrahedron 57 (2001) 7519–7527;
[12] (a) T. Yamazaki, T. Yamamoto, R. Ichihara, J Org. Chem. 71 (2006)
6251–6253;
(b) M. Fujita, T. Hiyama, Tetrahedron Lett. 31 (1986) 3655–3658.
[22] S. Ma, X. Lu, Z. Li, J. Org. Chem. 57 (1992) 709–713.
[23] T. Fuchikami, M. Yatabe, I. Ojima, Synthesis 5 (1981) 365–366.
[24] M. Taniguchi, S. Kobayashi, M. Nakagawa, T. Hino, Tetrahedron Lett. 39
(1986) 4763–4766.
(b) P. Wang, M. Deng, R. Pan, S. Zhang, J. Fluorine Chem. 124 (2003)
93–97;
(c) T. Konno, J. Chae, T. Tanaka, T. Ishihara, H. Yamanaka, J. Fluorine
Chem. 127 (2006) 36–43;