Highly stereoselective one-pot synthesis of tetrasubstituted alkenes via carbopalladation reaction of fluorine-containing acetylene derivatives

Article abstract of DOI:10.1016/j.jfluchem.2006.04.012

Treatment of fluoroalkylated alkynes with various aryl halides and arylboronic acids in the presence of Pd(0) in DMF/H₂O at 100 °C for 2 h led to the smooth three-component coupling reaction, the corresponding tetrasubstituted alkenes being obt

Full text of DOI:10.1016/j.jfluchem.2006.04.012

Journal of Fluorine Chemistry 127 (2006) 966–972
www.elsevier.com/locate/fluor
Highly stereoselective one-pot synthesis of tetrasubstituted
alkenes via carbopalladation reaction of fluorine-containing
acetylene derivatives
*
Tsutomu Konno , Ken-ichi Taku, Takashi Ishihara
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Received 22 March 2006; received in revised form 27 April 2006; accepted 27 April 2006
Available online 2 May 2006
Abstract
Treatment of fluoroalkylated alkynes with various aryl halides and arylboronic acids in the presence of Pd(0) in DMF/H2O at 100 8C for 2 h led
to the smooth three-component coupling reaction, the corresponding tetrasubstituted alkenes being obtained in high yields stereoselectively.
# 2006 Elsevier B.V. All rights reserved.
Keywords: A fluoroalkyl group; Carbopalladation; One-pot reaction; Tetrasubstituted alkenes; Fluorine-containing alkynes
1. Introduction
leading to the corresponding tetrasubstituted alkenes stereo-
selectively.
Partially fluorinated organic molecules often possess
properties that make them suitable for diverse applications
in the area of materials science, agrochemistry, and pharma-
ceutical industry [1]. Consequently, much attention has been
focused on the development of the efficient and practical
synthetic methods for the preparation of such molecules [2].
Among various types of fluorinated compounds, tetrasub-
stituted alkenes 1 possessing a fluoroalkyl group, shown in
Fig. 1, are recognized as one of the most important synthetic
targets because of their physically as well as chemically unique
properties [3]. Although several synthetic approaches to the
fluoroalkylated alkenes have been reported thus far, they
sometimes suffer from multi-step manipulations, low stereo-
selectivities, harsh reaction conditions, etc [4].
2. Results and discussion
2.1. One-pot synthesis of fluorine-containing
tetrasubstituted alkenes
Initially, the reaction of trifluoromethylated internalalkyne2a
[10] with iodobenzene and phenylboronic acid in the presence of
palladium catalyst was examined (Table 1) [11]. Thus, treatment
of 2a with 2.0 equiv. of PhI and 3.0 equiv. of PhB(OH)2 in DMF/
H2O in the presence of 10 mol% of PdCl2(PhCN)2 and 3.0 equiv.
of K2CO3 at 100 8C for 2 h gave the corresponding tetrasub-
stituted alkene 1a in 73% yield as a sole product (Entry 1). In this
case, neither stereoisomer 3 nor the Suzuki-Miyaura cross-
coupling product 4 was detected at all (Fig. 2). Reducing the
amount of the catalyst from 10 mol% to 5 mol% led to an
increase of the yield as shown in Entry 2. Additionally, the
reaction with 2.0 equiv. each of PhI and PhB(OH)2 gave 1a in
93% yield (Entry 3). The use of 1.2 equiv. of PhI, on the other
hand, resulted in an appreciable decrease of the yield (Entry 4).
With this optimized reaction conditions, we next examined
the reaction with various fluoroalkylated alkynes, aryl iodides
and arylboronic acids as summarized in Table 2.
Recently, we have developed highly regio- and stereo-
selective hydrostannation [5], hydroboration [6], carbocupra-
tion [7], and carbostannylation reactions [8] of fluoroalkylated
acetylene derivatives 2, which realized the efficient as well as
practical approaches to 1 [9]. Herein we wish to describe the
practical one-step coupling reaction of three components, such
as aryl iodides, fluoroalkylated alkynes, and arylboronic acids,
As shown in Entries 1–3, various aryl halides or arylboronic
acids, such as p-methoxyphenyl, p-methylphenyl iodides or
* Corresponding author. Tel.: +81 75 724 7517; fax: +81 75 724 7580.
E-mail address: konno@chem.kit.ac.jp (T. Konno).
0022-1139/$ – see front matter # 2006 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2006.04.012

T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 966–972
967
Table 3
Examination of the regioselectivity
Fig. 1. Fluoroalkylated tetrasubstituted alkenes.
Table 1
Investigation of the reaction conditions for three-component coupling
Entry
R2
R3
Yielda of
(1 + 10)/%
Ratio
(1:10)a
1
2
3
4
5
6
Ph
p-MeOC6H4
76 (A)
80
40:60
63: 37b
39:61
71:29
57:43
62:38
p-MeOC6H4
p-MeC6H4
p-EtO2CC6H4
m-MeOC6H4
o-MeOC6H4
Ph
Ph
Ph
Ph
Ph
Entry
Phl/equiv.
PhB(OH)2/equiv.
Pd/mol%
Yielda/%
89 (B)
76 (C)
84 (D)
60 (E)
1
2
3
4
2.0
2.0
2.0
1.2
3.0
3.0
2.0
2.0
10
5
73
84
5
93 (85)
80
Determined by 19F NMR.
Ratio = 1A:10A.
a
5
b
a
Determined by 19F NMR. Value in parentheses is of isolated yield.
(Entries 4, 7, 8). The alkyne having an alkyl group as R1 was
also found to be effective for the reaction (Entry 9), though the
benzyl group as R1 did not give any desired product (Entry 10).
Switching a fluoroalkyl group from a trifluoromethyl to a
difluoromethyl or hexafluoropropyl group did not cause any
significant change for the reaction (Entries 11 and 12).
We next examined the regioselectivity in this three-
component coupling reaction as described in Table 3.
Fig. 2. A stereoisomer 3 and biphenyl (4).
boronic acids could participate nicely in the coupling reaction
to give the corresponding tetrasubstituted alkenes in high
yields. Various substituents on the benzene ring of 2, such as a
chloro, methoxy, methyl and ethoxycarbonyl group, did not
influence the reaction at all (Entries 1, 4–6). Additionally, the
alkynes having an ortho-or meta-substituted aromatic ring as R1
were also applied for the coupling reaction successfully
Even when R2 and R3 were different, the reaction proceeded
smoothly in a highly cis-selective manner, giving the
corresponding tetrasubstituted alkenes 1 and 10 in high yields.
However, the regioselectivity was found to be substantially low.
Changing R2 from an electron-donating group to an electron-
withdrawing group did not lead to a high regioselectivity (Entry
4). Additionally, no influence of the position of the substituent
Table 2
Three-component coupling reaction using various fluoroalkylated alkynes
Entry
Rf
R1
Substrate
R2
Product
Yielda/%
1
2
CF3
p-ClC6H4
2a
2a
2a
2b
2c
2d
2e
2f
Ph
1a
1b
1c
1d
1e
1f
1g
1h
1i
93 (85)
86
CF3
p-ClC6H4
p-MeOC6H4
3
CF3
p-ClC6H4
p-MeC6H4
85 (82)
88
4
CF3
p-MeOC6H4
p-MeC6H4
p-EtO2CC6H4
m-MeOC6H4
o-MeOC6H4
Ph(CH2)3
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
5
CF3
85 (81)
69
6
CF3
7
CF3
87(71)
85
8
CF3
9
CF3
2g
2h
2i
83
10
11
12
CF3
p-MeOC6H4CH2
p-ClC6H4
-
0
CHF2
CHF2CF2CF2
1j
1k
81 (80)
87 (73)
p-C1C6H4
2j
a
Determined by 19F NMR. Values in parentheses are of isolated yield.

968
T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 966–972
Scheme 1. Stereochemical assignment of 1A.
on R2 was observed (Entries 5 and 6). In order to improve the
regioselectivity, we examined various types of catalysts, such as
PdCl2(PPh3)2, Pd(OAc)2, Pd2(dba)3 + P(o-Tol)3, Pd2(dba)3 +
P(c-Hex)3, Pd2(dba)3 + dppe, and so on. All reactions took
place smoothly to give the corresponding tetrasubstituted
alkenes in good to high yields but with low regioselectivity (ca.
60:40). On the other hand, the use of other metal catalyst, such
as Ni(COD)2, RhCl(PPh3)3, and Rh(COD)2BF4 did not give the
desired compounds at all.
2.2. Stereochemistry
The stereochemical outcome of the reactions in Table 3 was
determined as follows. Thus, treatment of2awith Ph2Cu(CN)Li2
in THF at ꢀ45 8C for 4 h followed by the addition of an excess
amount of I2 gave the corresponding vinyl iodide 5a (Scheme 1).
The subsequent Suzuki-Miyaura cross-coupling reaction of 5a
proceeded smoothly to afford the corresponding tetrasubstituted
alkene. This alkene was found to be totally identical to the minor
Scheme 2. Stereochemical assignment of 10A.

T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 966–972
969
isomer 1A in the three-component coupling reaction of 2a
with PhI and ( p-MeOC6H4)B(OH)2, on the basis of 1H and 19
0.25 mmol) in DMF (2 mL) at room temperature. The whole
was heated at 100 8C for 2 h, and allowed to cool to room
temperature. The reaction mixture was poured into sat. NH4Cl
aq. and the whole was extracted with ether three times. The
combined organic layers were washed with sat. NaCl aq., dried
over anhydrous Na2SO4, and then concentrated in vacuo. The
residue was purified by silica gel column chromatography to
give the corresponding (Z)-1-(4-chlorophenyl)-1,2-diphenyl-
3,3,3-trifluoropropene (1a) (83 mg, 0.21 mmol, 85% yield).
F
NMR analysis. On the other hand, the reaction of 2a with
( p-MeOC6H4)2Cu(CN)(MgBr)2 in THF at ꢀ45 8C for 2 h
followed by the addition of an excess amount of I2 afforded
the vinyl iodide 6a (Scheme 2). The following Suzuki-
Miyaura cross-coupling reaction gave the corresponding
tetrasubstituted alkene in 82% yield. 1H and 19F NMR analyses
showed that the alkene derived from 2a via carbocupration was
totally identical to the 10A. The stereochemical assignments of
the other products were determined with the comparison of the
chemical shift in 19F NMR.
4.3.1. (Z)-1-(4-Chlorophenyl)-1,2-diphenyl-3,3,3-
trifluoropropene (1a)
1
Yield: 85%; M.P. 92–94 8C; H NMR (CDCl3) d = 6.87–
3. Conclusion
6.89 (m, 2H), 7.04–7.05 (m, 3H), 7.19–7.25 (m, 7H), 7.34 (d,
J = 8.4 Hz, 2H); 13C NMR (CDCl3) d = 123.5 (q,
J = 275.5 Hz), 127.6, 127.8, 128.0, 128.3, 129.6, 129.93,
129.94, 130.1 (q, J = 28.9 Hz), 131.3, 134.0, 134.7, 138.9,
140.5, 149.1 (q, J = 3.4 Hz); 19F NMR (CDCl3) d = –55.8 (s,
3F); IR (KBr) 1606, 1490, 1444, 1326, 1309 cmꢀ1; HRMS
calcd. for C21H14ClF3 (M+) 358.0736; found, 358.0743.
In summary, we have developed the practical one-pot
method for the preparation of fluoroalkylated tetrasubstituted
alkenes, starting from a variety of fluoroalkylated alkynes.
Various types of alkynes were demonstrated to be suitable for
the present reaction, affording the desired compounds in high
yields. In all cases, a complete stereoselectivity was observed.
4.3.2. (Z)-1-(4-Chlorophenyl)-1,2-bis(4-methoxyphenyl)-
3,3,3-trifluoropropene (1b)
4. Experimental
Yield: 86% (Determined by 19F NMR); M.P. 99–101 8C; 1H
NMR (CDCl3) d = 3.69 (s, 3H), 3.76 (s, 3H), 6.58 (d, J = 8.8 Hz,
2H), 6.76 (d, J = 8.8 Hz, 2H), 6.79 (d, J = 8.8 Hz, 2H), 7.15 (d,
J = 8.4 Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.4 Hz,
2H); 13C NMR (CDCl3) d = 55.05, 55.12, 113.2, 113.6, 123.7 (q,
J = 275.3 Hz), 127.3, 128.2, 128.5(q, J = 28.7 Hz), 130.2, 131.5,
132.7, 133.0, 133.8, 139.5, 148.1 (q, J = 3.4 Hz), 158.8, 159.1;
19F NMR (CDCl3) d = –56.1 (s, 3F); IR (KBr) 2835, 1606, 1571,
1510, 1461 cmꢀ1; HRMS calcd. for C23H18ClF3O2 (M+)
418.0947; found, 418.0947.
4.1. General experimental procedures
1H NMR spectra were measured with a Bruker DRX
(500.13 MHz) spectrometer in a chloroform-d (CDCl3)
solution with tetramethylsilane (Me4Si) as an internal
reference. 13C NMR spectra were recorded on a Bruker
DRX (125.77 MHz). A JEOL JNM-EX90F (84.21 MHz, FT)
spectrometer was used for determining 19F NMR yield with
internal C6F6. It was also used for determining regioselectivity
and stereoselectivity and for taking 19F NMR spectra in a
CDCl3 solution with internal CFCl3. CFCl3 was used (dF = 0) as
an internal standard for 19F NMR. Infrared spectra (IR) were
recorded on a Shimadzu FTIR-8200A (PC) spectrophotometer.
Mass spectra (MS) were taken on a JEOL JMS-700.
4.3.3. (Z)-1-(4-Chlorophenyl)-1,2-bis(4-methylphenyl)-
3,3,3-trifluoropropene (1c)
Yield: 82%; 1H NMR (CDCl3) d = 2.20 (s, 3H), 2.30 (s, 3H),
6.79 (d, J = 8.0 Hz, 2H), 6.87 (d, J = 7.9 Hz, 2H), 7.04 (d,
J = 7.9 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 7.24 (d, J = 8.3 Hz,
2H), 7.34 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3) d = 55.05,
55.12, 113.15, 113.56, 123.72 (q, J = 275.3 Hz), 127.32,
128.18, 128.51 (q, J = 28.7 Hz), 130.15, 131.46, 132.66,
133.01, 133.78, 139.46, 148.14 (q, J = 3.4 Hz), 158.76,
159.10; 19F NMR (CDCl3) d = ꢀ56.12 (s, 3F); IR (neat)
3028, 2922, 2868, 1905, 1610, 1593 cmꢀ1; HRMS calcd. for
C23H18ClF3 (M+) 386.1049; found, 386.1048.
4.2. Materials
Tetrahydrofuran (THF) and copper cyanide were commer-
cially available from Wako chemicals Co. All chemicals were of
reagent grade and, if necessary, were purified in the usual manner
prior to use. Thin layer chromatography (TLC) was done with
Merck silica gel 60 F254 plates and column chromatography was
carried out with Wako gel C-200. All acetylenes were prepared
according to the previous literature procedure [10].
4.3.4. (Z)-1-(4-Methoxyphenyl)-1,2-diphenyl-3,3,3-
trifluoropropene (1d)
1
4.3. Typical procedure for the Palladium-catalyzed
reaction of fluoroalkylated acetylene derivatives with
arylboronic acid and aryl iodide
Yield: 88% (Determined by 19F NMR); H NMR (CDCl3)
d = 3.83 (s, 3H), 6.88–6.92 (m, 4H), 7.03–7.04 (m, 3H), 7.18–
7.30 (m, 7H); 13C NMR (CDCl3) d = 55.2, 113.4, 123.7 (q,
J = 275.1 Hz), 127.3, 127.6, 127.7, 127.8, 128.8 (q,
J = 28.5 Hz), 129.8, 130.0, 131.5, 132.8, 135.3, 141.4, 150.2
(q, J = 3.0 Hz), 159.3; 19F NMR (CDCl3) d = ꢀ56.2 (s, 3F); IR
(KBr) 3003, 2908, 2837, 1608, 1573, 1510 cmꢀ1; HRMS calcd.
for C22H17F3O (M+) 354.1232; found, 354.1228.
To a solution of K2CO3 (104 mg, 0.75 mmol), PhI (102 mg,
0.50 mmol), PhB(OH)2 (61 mg, 0.50 mmol) and PdCl2(PhCN)2
(5 mg, 0.05 mmol) in DMF (2 mL)/H2O (1 mL) was added a
solution of 1-(4-chlorophenyl)-3,3,3-trifluoropropyne (51 mg,

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T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 966–972
4.3.5. (Z)-1-(4-Methylphenyl)-1,2-diphenyl-3,3,3-
4.3.10. (Z)-1-(4-Chlorophenyl)-1,2-diphenyl-3,3-
difluoropropene (1j)
trifluoropropene (1e)
Yield: 81%; M.P. 118–120 8C; 1H NMR (CDCl3) d = 2.37 (s,
3H), 6.90–6.92 (m, 2H), 7.02–7.04 (m, 3H); 13C NMR (CDCl3)
d = 21.3, 123.5 (q, J = 275.6 Hz), 127.2, 127.6, 127.7, 127.9,
128.5, 128.7, 129.1 (q, J = 28.7 Hz), 129.7, 131.5, 135.1, 137.6,
137.7, 141.2, 150.5 (q, J = 3.2 Hz); 19F NMR (CDCl3) d = ꢀ56.2
(s, 3F); IR (KBr) 3082, 3020, 2914, 2866, 1606 cmꢀ1; HRMS
calcd. for C22H17F3 (M+) 338.1282; found, 338.1284.
Yield: 80%; M.P. 126–128 8C; 1H NMR (CDCl3) d = 6.40 (t,
J = 55.1Hz, 1H), 6.90–6.91 (m, 2H), 7.06–7.09 (m, 3H), 7.21–
7.25 (m, 7H), 7.38–7.40 (m, 2H); 13C NMR (CDCl3) d = 113.9
(t, J = 234.7 Hz), 127.6, 127.8, 127.9, 128.8, 130.2, 131.1,
131.2, 133.2 (t, J = 22.5 Hz), 133.4, 134.4, 134.5, 137.8, 140.0,
147.4 (t, J = 9.4 Hz); 19F NMR (CDCl3) d = ꢀ111.3 (d,
J = 55.0 Hz, 2F); IR (KBr) 3022, 1591, 1573, 1490, 1442,
1398, 1369 cmꢀ1.; HRMS calcd. for C21H15ClF2 (M+)
340.0830; found, 340.0835.
4.3.6. Ethyl 4-((Z)-1,2-diphenyl-3,3,3-
trifluoropropenyl)benzoate (1f)
Yield: 69% (Determined by 19F NMR); M.P. 93–95 8C; 1H
NMR (CDCl3) d = 1.40 (t, J = 7.1 Hz, 3H), 4.39 (q, J = 7.1 Hz,
2H), 6.89–6.90 (m, 2H), 7.04–7.05 (m, 3H), 7.21–7.23 (m, 5H),
7.39 (d, J = 8.2 Hz, 2H), 8.05 (d, J = 8.3 Hz, 2H); 13C NMR
(CDCl3) d = 14.3, 61.1, 123.4 (q, J = 275.7 Hz), 127.6, 127.8,
128.00, 128.03, 128.5, 129.3, 129.6, 129.9, 130.1 (q,
J = 29.4 Hz), 131.2, 134.5, 140.1, 145.0, 149.2 (q,
J = 3.4 Hz), 166.2; 19F NMR (CDCl3) d = ꢀ56.2 (s, 3F); IR
(KBr) 2981, 1714, 1606, 1490, 1463 cmꢀ1; HRMS calcd. for
C24H19F3O2 (M+) 396.1337; found, 396.1330.
4.3.11. (Z)-1-(4-Chlorophenyl)-1,2-diphenyl-3,3,4,4,5,5-
hexafluoropentene (1k)
Yield: 73%; 1H NMR (CDCl3) d = 5.79 (tt, J = 52.3, 5.7 Hz,
1H), 6.90–6.92 (m, 2H), 7.01–7.05 (m, 3H), 7.17–7.18 (m, 3H),
7.23–7.26 (m, 4H), 7.31–7.33 (m, 2H); 13C NMR (CDCl3)
d = 107.8(tt, J = 253.2, 31.0 Hz), 110–120(m, 2C), 127.3, 127.8,
127.9, 128.1, 129.15, 129.18, 131.7, 133.4, 134.9, 139.3, 141.3,
151.6 (t, J = 4.1 Hz); 19F NMR (CDCl3) d = ꢀ138.0 ꢁ ꢀ137.1
(m. 2F), ꢀ126.7 ꢁ ꢀ126.5 (m, 2F), ꢀ102.9 ꢁ ꢀ102.8 (m, 2F);
IR (neat) 3058, 1492, 1444, 1398, 1271 cmꢀ1; HRMS calcd. for
C23H15ClF6 (M+) 440.0766; found, 440.0760.
4.3.7. (Z)-1-(3-Methoxyphenyl)-1,2-diphenyl-3,3,3-
trifluoropropene (1g)
4.3.11.1. (Z)-1-(4-Chlorophenyl)-1-(4-methoxyphenyl)-2-phe-
nyl-3,3,3-trifluoropropene (1A0) (Z)-1-(4-chlorophenyl)-2-(4-
methoxyphenyl)-1-phenyl-3,3,3-trifluoropropene (1A)
(1A + 1A0). Yield: 76% (determined by 19F NMR); The
physical data was described below.
1
Yield: 71%; M.P. 91–93 8C; H NMR (CDCl3) d = 3.81 (s,
3H), 6.87–6.96 (m, 5H), 7.04–7.05 (m, 3H), 7.20–7.26 (m, 5H),
7.29 (t, J = 7.8 Hz, 1H); 13C NMR (CDCl3) d = 55.2, 113.2,
114.3, 121.0, 123.6 (q, J = 275.3 Hz), 127.3, 127.7, 127.8,
127.9, 129.0, 129.4 (q, J = 29.7 Hz), 129.5, 131.4, 134.9, 140.7,
141.7, 150.1 (q, J = 3.4 Hz), 159.2; 19F NMR (CDCl3)
d = ꢀ56.4 (s, 3F); IR (KBr) 1575, 1487, 1458, 1446,
1429 cmꢀ1; HRMS calcd. for C22H18F3O (M + H) 355.1310;
found, 355.1315.
4.3.12. (Z)-1-(4-Chlorophenyl)-2-(4-methylphenyl)-1-
phenyl-3,3,3-trifluoropropene (1B0)
1H NMR (CDCl3) d = 2.27 (s, 3H), 7.01 (d, J = 7.9 Hz, 2H),
7.10 (d, J = 7.9 Hz, 2H); 19F NMR (CDCl3) d = –56.3 (s, 3F);
13C NMR (CDCl3) d = 21.2, 123.5 (q, J = 275.7 Hz), 148.7 (q,
J = 3.5 Hz).
4.3.8. (Z)-1-(2-Methoxyphenyl)-1,2-diphenyl-3,3,3-
trifluoropropene (1h)
Yield: 85% (Determined by 19F NMR); M.P. 91–93 8C; 1H
NMR (CDCl3) d = 3.75 (s, 3H), 6.90 (d, J = 8.3 Hz, 1H), 6.95–
6.97 (m, 1H), 6.98–7.32 (m, 12H); 13C NMR (CDCl3) d = 55.6,
111.1, 120.2, 123.6 (q, J = 275.2 Hz), 127.0, 127.4, 127.7,
127.8, 129.2, 129.3, 129.4, 129.76, 130.3 (q, J = 28.7 Hz),
131.3, 134.9, 140.5, 146.1 (q, J = 3.5 Hz), 156.1; 19F NMR
(CDCl3) d = ꢀ58.8 (s, 3F); IR (KBr) 3003, 2837, 1596, 1583,
1490 cmꢀ1; HRMS calcd. for C22H17F3O (M+) 354.1232;
found, 354.1223.
4.3.13. (Z)-1-(4-Chlorophenyl)-1-(4-methylphenyl)-2-
phenyl-3,3,3-trifluoropropene (1B)
1H NMR (CDCl3) d = 2.17 (s, 3H), 6.75 (d, J = 8.2 Hz, 2H),
6.84 (d, J = 8.0 Hz, 2H); 19F NMR (CDCl3) d = ꢀ56.1 (s, 3F);
13C NMR (CDCl3) d = 21.1, 148.9 (q, J = 3.1 Hz).
(1B + 1B0). Yield: 89% (Determined by 19F NMR); 1H NMR
(CDCl3) d = 6.88–7.34 (m, 18H); 13C NMR (CDCl3) d = 127.5,
127.8, 127.9, 128.0, 128.23, 128.26, 128.29, 128.5, 128.7,
129.66, 129.70, 130.0, 131.1, 131.29, 131.33, 131.7, 133.9,
134.9, 135.6, 137.5, 137.8, 139.1, 139.2, 140.7; IR (neat) 3028,
2923, 2868, 1903, 1593, 1577, 1512 cmꢀ1; HRMS calcd. for
C22H16ClF3 (M+) 372.0893; found, 372.0888.
4.3.9. (Z)-2,3,6-Triphenyl-1,1,1-trifluoro-2-hexene (1i)
1
Yield: 83% (Determined by 19F NMR); H NMR (CDCl3)
d = 1.64 (m, 2H), 2.62 (t, J = 7.9 Hz, 2H), 2.78–2.82 (m, 2H),
6.89–6.91 (m, 2H), 6.97–6.99 (m, 2H), 7.05–7.10 (m, 7H), 7.15–
7.17 (m, 1H), 7.22–7.25 (m, 3H); 13C NMR (CDCl3) d = 29.7,
34.9, 35.7, 124.1 (q, J = 275.9 Hz), 125.8, 127.0, 127.15, 127.20,
127.23, 127.6, 127.7, 128.26, 128.29, 128.4, 128.7, 129.2 (q,
J = 29.2 Hz), 130.7, 151.8 (q, J = 3.1 Hz); 19F NMR (CDCl3)
4.3.14. Ethyl 4-((Z)-1-(4-chlorophenyl)-2-phenyl-3,3,3-
trifluoropropenyl)benzoate (1C)
1H NMR (CDCl3) d = 1.36 (t, J = 7.2 Hz, 3H), 4.34 (q,
J = 7.1 Hz, 2H), 7.36 (d, J = 8.5 Hz, 3H), 7.89 (d, J = 8.3 Hz,
2H); 19F NMR (CDCl3) d = –56.0 (s, 3F); 13C NMR (CDCl3)
d = 14.2, 61.1, 123.2 (q, J = 275.5 Hz), 129.1 (q, J = 28.8 Hz),
150.0 (q, J = 3.0 Hz), 166.1.
d = ꢀ56.0 (s, 3F); IR (KBr) 3060, 3026, 2939, 2864, 1633 cmꢀ1
;
HRMS calcd. for C24H21F3 (M+) 366.1595; found, 366.1604.

T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 966–972
971
4.3.15. Ethyl 4-((Z)-2-(4-chlorophenyl)-2-phenyl-1-
trifluoromethyl-ethenyl)benzoate (1C0)
4.4. Determination of the stereochemistry
1H NMR (CDCl3) d = 1.32 (t, J = 7.1 Hz, 3H), 4.28 (q,
J = 7.1 Hz, 2H), 7.31 (d, J = 8.1 Hz, 3H), 7.73 (d, J = 8.3 Hz,
2H); 19F NMR (CDCl3) d = –56.6 (s, 3F); 13C NMR (CDCl3)
d = 14.2, 61.0, 123.2 (q, J = 276.2 Hz), 148.1 (q, J = 3.0 Hz),
165.9.
(1C + 1C0). Yield: 76% (determined by 19F NMR); 1H NMR
(CDCl3) d = 6.87–7.25 (m, 16H); 13C NMR (CDCl3) d = 127.9,
128.0, 128.1, 128.2, 128.3, 128.4, 128.5, 129.1, 129.2, 129.4,
129.5, 129.6, 129.82, 129.84, 129.88, 129.90, 131.1, 131.3,
134.1, 134.2, 134.3, 138.1, 138.5, 139.4, 140.0, 145.0; IR (neat)
2983, 2906, 1716, 1608, 1593 cmꢀ1; HRMS calcd. for
C24H18O2ClF3 (M+) 430.0947; found, 430.0948.
4.4.1. General procedure for the reaction of
fluoroalkylated acetylene derivatives with organocopper
reagents
To a solution of CuCN (94 mg, 1.05 mmol) and 1-(4-
chlorophenyl)-3,3,3-trifluoropropyne (175 mg, 0.86 mmol) in
THF (8 mL) was added Grignard reagent (2.10 mmol) at
ꢀ45 8C. After stirring for 10 min, the reaction mixture was
allowed to warm to ꢀ5 8C and then stirred for 30 min. The
reaction mixture was again cooled to ꢀ45 8C. After stirring at
that temperature for 2 h, iodine (533 mg, 2.50 mmol) in THF
(4 mL) was added slowly. After 1h, the reaction was quenched
with MeOH/NH3 aq. and a few drops of Na2SO3 were added
until the color of the reaction mixture changed. The whole was
extracted with EtOAc three times. The combined organic layers
were washed with NaCl aq., dried over anhydrous Na2SO4, and
concentrated in vacuo. The residue was purified by silica gel
column chromatography to give the corresponding vinyl iodide.
4.3.16. (Z)-1-(4-Chlorophenyl)-1-(3-methoxyphenyl)-2-
phenyl-3,3,3-trifluoropropene (1D)
1H NMR (CDCl3) d = 3.69 (s, 3H), 6.81 (d, J = 7.6 Hz, 1H);
19F NMR (CDCl3) d = ꢀ56.1 (s, 3F); 13C NMR (CDCl3)
d = 55.1, 123.4 (q, J = 275.9 Hz), 149.0 (q, J = 3.0 Hz), 159.1.
4.4.1.1. (Z)-1-(4-Chlorophenyl)-2-iodo-1-phenyl-3,3,3-tri-
fluoropropene (5a). 1H NMR (CDCl3) d = 3.81 (3H, s), 6.87
4.3.17. (Z)-1-(4-Chlorophenyl)-2-(3-methoxyphenyl)-1-
phenyl-3,3,3-trifluoropropene (1D0)
(2H, d, J = 8.2 Hz), 7.13–7.17 (4H, m), 7.30–7.31 (3H, m); 19
F
NMR (CDCl3) d = –54.21 (3F, s); 13C NMR (CDCl3) d = 55.2,
85.2 (q, J = 34.2 Hz), 113.7, 121.4 (q, J = 270.5 Hz), 128.1,
128.1, 129.8, 137.7, 139.7, 158.6 (q, J = 3.2 Hz), 160.8; IR
(neat) 1604, 1508, 1461 cmꢀ1; HRMS (FAB) calcd. for
C16H12F3IO (M+) 403.9885; found, 403.9889; Anal. calcd.
C, 47.55; H, 2.99; found, C, 47.54; H, 2.71.
1H NMR (CDCl3) d = 3.54 (s, 3H), 6.46 (d, J = 7.7 Hz, 1H),
6.59 (dd, J = 8.2, 2.5 Hz, 1H), 6.96 (t, J = 7.9 Hz, 1H); 19F
NMR (CDCl3) d = –56.2 (s, 3F); 13C NMR (CDCl3) d = 55.0,
123.4 (q, J = 275.4 Hz), 148. (q, J = 3.4 Hz), 158.8.
(1D + 1D0). Yield: 84% (Determined by 19F NMR); 1H
NMR (CDCl3) d = 6.41–7.35 (m, 22H); 13C NMR (CDCl3)
d = 112.8, 113.4, 113.7, 115.3, 117.0, 122.3, 123.8, 127.6,
127.8, 128.0, 128.3, 128.8, 128.9, 129.4, 129.9, 131.2, 134.0,
134.7, 135.0, 135.8, 138.7, 138.8, 140.5, 141.6; IR (neat) 2914,
2835, 1577, 1488, 1465 cmꢀ1; HRMS calcd. for C22H16OClF2
(M+) 388.0842; found, 388.0844.
4.4.1.2. (Z)-1-(4-Chlorophenyl)-2-iodo-1-(4-methoxyphenyl)-
1
3,3,3-trifluoropropene (6a). Yield: 46%; H NMR (CDCl3)
d = 3.82 (s, 3H), 6.89 (d, J = 8.6 Hz, 2H), 7.13 (t, J = 8.9 Hz,
4H), 7.30 (d, J = 8.4 Hz, 2H); 13C NMR (CDCl3) d = 55.2, 85.7
(q, J = 34.3 Hz), 113.8, 121.3 (q, J = 273.9 Hz), 128.4, 129.5,
129.9, 134.6, 137.2, 138.0, 157.3 (q, J = 3.4 Hz), 159.9; 19F
NMR (CDCl3) d = ꢀ54.1 (s, 3F); IR (neat) 2960, 2839, 1604,
1589, 1508, 1487 cmꢀ1; HRMS calcd. for C16H11ClF3IO (M+)
437.9495; found, 437.9495.
4.3.18. (Z)-1-(4-Chlorophenyl)-1-(2-methoxyphenyl)-2-
phenyl-3,3,3-trifluoropropene (1E)
1H NMR (CDCl3) d = 3.65 (s, 3H), 6.61 (d, J = 8.3 Hz,
1H), 6.68 (t, J = 7.4 Hz, 1H), 6.88 (d, J = 7.5 Hz, 1H); 19F
NMR (CDCl3) d = ꢀ56.4 (s, 3F); 13C NMR (CDCl3)
d = 55.1, 123.3 (q, J = 275.5 Hz), 131.2 (q, J = 28.8 Hz),
146.5 (q, J = 3.5 Hz).
4.4.2. General procedure for the Suzuki-Miyaura cross-
coupling reaction
To a solution of the vinyl iodide (0.37 mmol) and Pd(PPh3) 4
(45 mg, 0.036 mmol) in benzene (7 mL) was added Na2CO3
(97 mg, 0.91 mmol), aryl boronic acid (1.46 mmol), H2O
(0.45 mL), and EtOH (0.45 mL). The reaction mixture was
refluxed for 12 h, and then quenched with sat. NH4Cl aq. The
whole was extracted with EtOAc three times. The combined
organic layers were washed with NaCl aq., dried over
anhydrous Na2SO4, and then concentrated in vacuo. The
residue was purified by silica gel column chromatography to
give the corresponding fluorine-containing tetrasubstituted
alkene.
4.3.19. (Z)-1-(4-Chlorophenyl)-2-(2-methoxyphenyl)-1-
phenyl-3,3,3-trifluoropropene (1E0)
1H NMR (CDCl3) d = 1.76 (s, 3H); 19F NMR (CDCl3)
d = ꢀ56.93 (s, 3F); 13C NMR (CDCl3) d = 55.5, 131.7 (q,
J = 28.4 Hz).
(1E + 1E0). Yield: 60% (determined by 19F NMR); 1H
NMR (CDCl3) d = 6.77–7.34 (m, 23H); 13C NMR (CDCl3)
d = 110.6, 110.8, 120.2, 120.2, 124.1, 127.5, 127.6, 127.8,
127.9, 128.2, 128.5, 129.0, 129.5, 129.9, 130.0, 130.1, 132.1,
133.4, 133.8, 134.8, 138.3, 138.7, 140.8, 155.5, 158.2; IR
(neat) 3058, 3026, 3004, 2937, 2837, 1596, 1581, 1487,
981 cmꢀ1; HRMS calcd. for C22H16OClF3 (M+) 388.0842;
found, 388.0838.
4.4.2.1. (Z)-1-(4-Chlorophenyl)-2-(4-methoxyphenyl)-1-phe-
nyl-3,3,3-trifluoropropene (1A). Yield: 77% (determined by
1
19F NMR); M.P. 131–133 8C; H NMR (CDCl3) d = 3.75 (s,

972
T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 966–972
(c) Drugs Fut. 10 (1985) 395;
3H), 6.74 (d, J = 8.7 Hz, 2H), 6.88–6.91 (m, 2H), 7.05–7.08 (m.
3H), 7.14 (d, J = 8.3 Hz, 2H), 7.23 (d, J = 8.4 Hz, 2H), 7.34 (d,
J = 8.5 Hz, 2H); 13C NMR (CDCl3) d = 55.1, 113.5, 123.6 (q,
J = 275.5 Hz), 126.9, 127.4, 127.8, 128. 25, 128.31, 129.5 (q,
J = 28.9 Hz), 129.7, 130.0, 132.6, 133.9, 139.1, 140.7, 148.7 (q,
J = 3.5 Hz), 159.2; 19F NMR (CDCl3) d = –56.4 (s, 3F); IR
(KBr) 3003, 1610, 1577, 1512, 1487, 1465 cmꢀ1; HRMS calcd.
for C22H16ClF3O (M+) 388.0842; found, 388.0845.
(d) Drugs Fut. 11 (1986) 426;
(e) Drugs Fut. 12 (1987) 497;
(f) Drugs Fut. 13 (1988) 480.
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Am. Chem. Soc. 123 (2001) 6947–6948;
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´ ˆ
(e) J. Thibonnet, G. Prie, M. Abarbri, A. Duchene, J.-L. Parrain, Tetra-
hedron Lett. 40 (1999) 3151–3154;
4.4.2.2. (Z)-1-(4-Chlorophenyl)-1-(4-methoxyphenyl)-2-phe-
nyl-3,3,3-trifluoropropene (1A0). Yield: 82%; 1H NMR
(CDCl3) d = 3.68 (s, 3H), 6.55 (d, J = 8.8 Hz, 2H), 6.78 (d,
J = 8.8 Hz, 2H), 7.21–7.23 (m, 7H), 7.33 (d, J = 8.4 Hz, 2H);
13C NMR (CDCl3) d = 55.0, 113.1, 123. (q, J = 275.2 Hz),
127.9, 128.1, 128.2, 128.3, 128.8 (q, J = 28.5 Hz), 130.1, 131.4,
132.7, 133.9, 135.1, 139.3, 148.5 (q, J = 3.0 Hz), 158.9; 19F
NMR (CDCl3) d = ꢀ55.8 (s, 3F); IR (neat) 2935, 2910, 2839,
1604, 1573 cmꢀ1; HRMS calcd. for C22H16ClF3O (M+)
388.0842; found, 388.0846.
(f) T.E. Nickson, J. Org. Chem. 53 (1988) 3870–3872.
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