Highly regio- and stereoselective hydrometallation reactions of fluorine-containing internal alkynes: Novel approaches to fluoroalkylated alkenes

Article abstract of DOI:10.1016/j.jfluchem.2005.09.015

Hydroalumination, hydrocupration, and hydroboration reactions of various fluorine-containing alkynes were investigated. The alkyne reacted smoothly with 2.0 equiv. of Red-Al at -78°C to give the hydroaluminated adduct in a highly regio- and stereoselectiv

Full text of DOI:10.1016/j.jfluchem.2005.09.015

Journal of Fluorine Chemistry 127 (2006) 36–43
www.elsevier.com/locate/fluor
Highly regio- and stereoselective hydrometallation reactions of
fluorine-containing internal alkynes: Novel approaches
to fluoroalkylated alkenes
*
Tsutomu Konno , Jungha Chae, Tomoo Tanaka, Takashi Ishihara, Hiroki Yamanaka
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan
Received 7 September 2005; received in revised form 26 September 2005; accepted 28 September 2005
Available online 11 November 2005
Abstract
Hydroalumination, hydrocupration, and hydroboration reactions of various fluorine-containing alkynes were investigated. The alkyne reacted
smoothly with 2.0 equiv. of Red-Al at ꢀ78 8C to give the hydroaluminated adduct in a highly regio- and stereoselective manner, which was treated
with iodine, the corresponding vinyliodide being produced in moderate yield. Hydrocupration of the alkynes also took place, but the resulting
vinylmetal reacted with various electrophiles sluggishly. In sharp contrast, the reaction with dicyclohexylborane proceeded smoothly to afford the
cis-addition products preferentially, which were subjected to Suzuki-Miyaura cross-coupling reaction, leading to trisubstituted alkenes in high
yields.
# 2005 Elsevier B.V. All rights reserved.
Keywords: Fluorine-containing alkynes; Hydroalumination; Hydrocupration; Hydroboration; Suzuki-Miyaura cross-coupling
1. Introduction
retention of configuration [5]. Despite of such great utility, little
attention has been paid to such reaction of fluorine-containing
alkynes so far [6]. Herein, we wish to describe highly regio- and
stereoselective hydrometallation reactions of various fluoroalky-
lated alkynes in detail.
Recently, much interest has been focused on organofluorine
compounds as pharmaceutical and agrochemical agents because
the fluorine atom often alters the physiochemical properties of
organic compounds, thereby modifying biological activities [1].
Accordingly, the development of novel and convenient methods
for the synthesis of fluorine-containing molecules has been
becoming more and more important in fluorine chemistry [2].
Among various types of fluorinated molecules, alkenes
possessing a fluoroalkyl group are well known as one of the
most important synthetic targets because they are often found in
the framework of biologically active compounds, such as
panomifene [3]. Although several synthetic methods for such
molecules have been reported thus far [4], the hydrometallation
of fluoroalkylated alkynes is potentially very attractive because
the hydrometallation reaction very often proceeds in a highly
regio- and stereoselective fashion and the resulting vinylmetal
intermediates can be converted further to variously substituted
ethenes under the influence of transition metal catalyst with
2. Results and discussion
2.1. Hydroalumination [7]
Initially,thehydroaluminationreactionoftrifluoromethylated
internalalkyne1a[8]withRed-Alwasexamined(Table1). Thus,
treatmentof 1awith 1.2equiv. of Red-Alin tolueneat ꢀ78 8C for
4 h, followed by quenching the reaction with H2O, gave the
corresponding trifluoromethylated alkene 2H-trans in 56% yield
asasoleproduct,togetherwith44%ofthestartingmaterial(Entry
1).Inthiscase,nostereoisomer2H-cis(Fig.1)wasdetectedatall.
Changing the solvent from toluene to ether led to a significant
increase of theyieldas shown in Entry 3, thoughno influencewas
observedinthereactioninTHF(Entry2). Thereactionatꢀ45 8C
was also found to be satisfactory (Entry 4), but higher reaction
temperature resulted in a decrease of the yield (Entry 5). The
use of 2.0 equiv. of Red-Al brought about the optimum yield,
* Corresponding author.
0022-1139/$ – see front matter # 2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2005.09.015

T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 36–43
37
Table 1
Hydroalumination of trifluoromethylated internal alkyne with Red-Al
Entry
Equiv. of
Red-Al
Solvent
Temperature
Time 1 (h)
Electrophile
(equiv.)
Temperature 2
Time 2
(h)
Yielda
Recoverya
Yielda
1 (8C)
(8C)
(%) of 2H-trans
(%) of 1a
(%) of 2I-trans
1
2
1.2
1.2
1.2
1.2
1.2
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
Ph–Me
THF
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
Et2O
ꢀ78
ꢀ78
ꢀ78
RT
4
4
4
4
4
4
8
4
4
4
4
4
4
H2O (excess)
H2O (excess)
H2O (excess)
H2O (excess)
H2O (excess)
H2O (excess)
H2O (excess)
I2 (6.0)
ꢀ78
1
1
1
1
1
1
1
2
2
2
2
6
6
56
47
86
64
83
95
94
82
56
33
33
32
36
44
–
ꢀ78
0
–
3
ꢀ78
14
–
4
RT
0
–
5
ꢀ45
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ45
3
–
6
ꢀ78
4
–
7
ꢀ78
1
–
8
ꢀ50 ! RT
RT
Trace
Trace
Trace
Trace
Trace
Trace
15
32
48
55
66
50
9
I2 (6.0)
10
11
12
13
I2 (6.0)
RT ! refl.
Refl.
I2 (6.0)
I2 (6.0)
Refl.
I2 (12.0)
Refl.
a
Determined by 19F NMR.
2H-trans being afforded in 95% yield, though 4% of 1a still
remained unreacted. The prolonged reaction time did not lead to
the complete consumption of the starting alkyne (Entry 7).
With this optimized reaction conditions, we next examined
the iodination of the hydroaluminated intermediate Int-1 as
described in Entries 8–13. Treatment of Int-1 with 6.0 equiv.
of iodine at ꢀ50 8C, followed by warming the reaction from
ꢀ50 8C to RT over 2 h, gave the desired vinyliodide 2I-trans,
exclusively, in only 15% yield, together with 82% recovery of
the protonated 2H-trans (Entry 8). The iodination at room
temperature resulted in the increase of the yield from 15% to
32% yield (Entry 9). Additionally, the refluxing conditions
(Entries 10 and 11) as well as the prolonged reaction time
(Entry 12) led to the increase of the yield. It should be noted
that the use of 12.0 equiv. of iodine caused a slight decrease of
the yield from 66% to 50% (Entry 13). Further investigation
to improve the yield of 2I-trans did not lead to the
satisfactory results. In all cases, 2H-trans and 2I-trans were
inseparable by silica gel column chromatography. Addition-
ally, the regioisomers, 3I-cis and 3I-trans, were not detected
at all (Fig. 1).
2.2. Hydrocupration [9]
We next examined the hydrocupration reaction with copper
hydride, which was prepared from copper bromide and Red-Al
(Table 2). As described in Entry 1, copper hydride was found to
be inactive, the starting material being recovered quantitatively.
On the other hand, the reaction with [CuH2]ꢀ at ꢀ45 8C for 4 h
took place in a preferential cis-addition manner to give 2H-
trans and 2H-cis in 59% yield in a ratio of 22:78, after
quenching the reaction with H2O (Entry 2). Changing the
reaction temperature from ꢀ45 8C to ꢀ78 8C caused an
increase of the stereoselectivity, 2H-cis being obtained as a
single isomer, though the chemical yield was decreased
significantly (Entry 3). The use of 2.4 equiv. of [CuH2]ꢀ at
ꢀ78 8C brought about a dramatical improvement of the yield
from 19% to 69% (Entry 4). Though the prolonged reaction
time did not lead to a satisfactory result, the reaction with 3.6
equiv. of [CuH2]ꢀ at ꢀ78 8C for 4 h gave a good yield as well as
an excellent stereoselectivity (Entry 6).
With this reaction conditions, we attempted the reaction of
Int-2 with various electrophiles as shown in Entries 7–9.
Treatment of Int-2 with 9.6 equiv. of iodine at ꢀ78 8C for 4 h
gave the corresponding vinyl iodide 3I-cis in 41% yield. In
sharp contrast to the hydroalumination reaction, only the
compounds possessing the iodine atom at the carbon attached
with a CF3 group were obtained exclusively. No other
regioisomers were detected at all. Similarly, the allylation
reaction of Int-2 using allyl bromide proceeded sluggishly to
afford the corresponding allylated product 3C-cis in only 31%
yield, whereas benzyl bromide was found to be completely
inactive.
Fig. 1. The regio- and stereoisomers.

38
T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 36–43
Table 2
Hydrocupration reaction of trifluoromethylated alkynes
Entry Copper reagent Equiv. Temperature (8C) Time (h) EX (equiv.)
Yielda (%) of 2 or 3 Ratio (trans:cis) Yielda (%) of 4 Recoverya (%) of 1a
1
2
3
4
5
6
7
8
9
CuH
1.2
1.2
1.2
2.4
2.4
3.6
3.6
3.6
3.6
ꢀ45
ꢀ45
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
ꢀ78
4
4
4
4
8
4
4
4
4
H2O (excess)
H2O (excess)
H2O (excess)
H2O (excess)
H2O (excess)
H2O (excess)
I2 (9.6)
0
59
19
69
58
69
41
0
–
0
100
5
CuH2
CuH2
CuH2
CuH2
CuH2
CuH2
CuH2
CuH2
22:78
0:100
4:96
8:92
1:99
1:99
1:99
1:99
10
1
66
12
3
1
7
8
0
N.D.
N.D.
N.D.
0
BnBr (9.6)
0
Allylbromide (9.6) 31
0
Determined by 19F NMR.
a
2.3. Hydroboration [10]
Prolonged reaction time led to the significant decrease of the
yield (Entry 2). Switching the palladium catalyst from
Pd(PPh3)4 to Pd(PPh3)2Cl2 brought about a slight increase of
the yield (Entry 3). It is interesting to note that the base used
in this reaction was crucial for the high yield. Thus, changing
the base from NaOEt to NaOH resulted in the dramatical
increase of the yield as described in Entry 4. In this case, 10%
of 2H-cis was recovered unchanged. The use of 10.0 mol% of
the palladium catalyst led to the complete consumption of the
vinylborane Int-3, giving the desired product in 89% yield
(Entry 5). In Entries 4 and 5, the high regioselectivity (5a-
trans + 5a-cis:6a-cis = 94:6) and the high stereoselectivity
(5a-trans:5a-cis = 2:98) were observed.
Additionally, we investigated the hydroboration reaction
of 1a with dicyclohexylborane was examined. On treating 1a
with 1.2 equiv. of dicyclohexylborane (prepared by the
reaction of cyclohexene (2.4 equiv.) with borane THF
complex (1.2 equiv.) in benzene at room temperature for
2 h), the vinylborane Int-3 was formed selectively, together
with a small amount of other isomers (<10%). This
encouraged us to examine the subsequent cross-coupling
reaction without isolation of vinylborane Int-3 (Table 3).
Thus, a benzene solution of the vinylborane Int-3 was treated
with 1.2 equiv. of iodobenzene, 5 mol% of Pd(PPh3)4, and 3.0
equiv. of NaOEt, and the whole was refluxed for 4 h. After
quenching the reaction with acetic acid, 19F NMR analysis
indicated that the desired coupling products 5a and 6a was
formed in 23% yield, together with 76% of 2H-cis (Entry 1).
With the optimized reaction conditions in hand, the scope of
the one-pot reaction was investigated with various alkynes in
detail (Table 4). As shown in Entries 1–4 and 6, various types of
alkynes carrying an electron-donating group (Me, MeO) or an
Table 3
Hydroboration reaction of trifluoromethylated alkyne
Entry
Catalysta
Base
Time (h)
Yieldb,c (%) of 5a + 6a
Ratiob 5a (trans:cis):6a-cis
Yieldb (%) of 2H-cis
1
2
3
4
5
Pd(PPh3)4
NaOEt
NaOEt
NaOEt
NaOH
NaOH
4
20
4
23
N.D.a
76
35
63
10
0
Pd(PPh3)4
7
N.D.a
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
Pd(PPh3)2Cl2
37
N.D.a
4
80
94 (2:98):6
94 (2:98):6
d
4
89 (64)
a
Unless otherwise noted, all reaction were employed in the presence of 5 mol% of catalyst.
Determined by 19F NMR.
b
c
d
Value in parentheses is of isolated yield.
Ten mol% of Pd(PPh3)2Cl2 was employed.

T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 36–43
39
Table 4
The synthesis of a variety of trisubstituted alkenes
Entry
Rf
R
R1
Yielda (%) of 5 + 6
Product
5 (cis:trans):6
1
2
CF3
Ph
Ph
85 (73)
89 (64)
83 (66)
99 (88)
25
b
a
c
d
e
f
g
h
i
j
k
l
m
n
o
P
95 (0:100):5
94 (2:98):6
CF3
p-ClC6H4
p-MeC6H4
p-MeOC6H4
p-O2NC6H4
p-EtO2CC6H4
p-MeOC6H4CH2
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
p-ClC6H4
Ph
3
CF3
Ph
94 (0:100):6
96 (0:100):4
88 (0:100):12
95 (0:100):5
58 (0:100):42
92 (0:100):8
93 (0:100):7
96 (0:100):4
94 (1:99):6
4
CF3
Ph
5
CF3
Ph
6
CF3
Ph
99
62b
53c
7
CF3
Ph
8
CF3
o-ClC6H4
m-ClC6H4
p-ClC6H4
p-MeC6H4
p-MeOC6H4
p-O2NC6H4
p-EtO2CC6H4
Ph
9
CF3
74
10
11
12
13
14
15
16
CF3
83 (74)
86 (55)
68 (56)
54
CF3
CF3
98 (7:93):2
CF3
100 (9:91):0
91 (0:100):9
84 (0:100):16
83 (0:100):17
CF3
99
CHF2
HCF2CF2CF2
67
Ph
78
a
Determined by 19F NMR. Values in parentheses are of isolated yields.
The product 6 was obtained in 26% yield, together with 8% of 1.
The dimmer 7 was obtained in 20% yield.
b
c
electron-withdrawing group (EtO2C) on the benzene ring
could participate well in the reaction to give the corresponding
trisubstituted alkenes in high yields. However, a significant
decrease of the yield was observed when the alkyne having a
nitro group on the benzene ring was used (Entry 5). The
regioselectivity was also decreased slightly. Additionally, the
fluoroalkylated alkyne having an aliphatic side chain ( p-
MeOC6H4CH2–) was not a good substrate, the low regios-
electivity (5:6 = 58:42) being obtained and 7 being produced in
26% yield (Entry 7, Fig. 2). We also examined the effect of the
coupling reagents (R1I) on the reaction as shown in Entries 8–
14. The position of the substituent on the benzene ring
significantly influenced on the coupling reaction. Thus, the
dimer 8 was formed in 20% yield when o-chloroiodobenzene
was used as R1I (Entry 8, Fig. 2), while the satisfactory result
was obtained in the case of m-chloroiodobenzene. The reaction
using the coupling reagents having various types of
substituents, such as chloro, methyl, methoxy, and ethox-
ycarbonyl groups, proceeded smoothly to afford the trisub-
stituted alkenes in a highly regio- and stereoselective manner
(Entries 10–12 and 14). However, the use of p-nitroiodoben-
zene resulted in the decrease of the yield (Entry 13). It should
also be noted that changing the fluoroalkyl group from a
trifluoromethyl group to a difluoromethyl or hexafluoropropyl
group did not cause the significant influence on the reaction
(Entries 15 and 16).
2.4. Stereochemistry
The stereochemical outcome of the reactions was made as
follows (Scheme 1). Thus, 19F NMR analysis of 2I-trans
(prepared readily from the hydroalumination of 1a and the
subsequent iodination) showed a doublet peak, indicating that
the iodine atom is attached to a carbon distal to a CF3 group.
Additionally, the analysis of the 1H NMR of 2H-trans (obtained
by the hydroalumination followed by quenching the reaction
with H2O) showed the coupling constant of Ha and Hb to be
16.5 Hz. This strongly indicates that 2H-trans has the E
configuration. Similarly, 19F NMR analysis of 3I-cis (prepared
by the hydrocupration of 1a) and Int-3 showed a singlet peak,
strongly suggesting that the iodine atom or a dicyclohexylboryl
group is attached to a carbon possessing a CF3 group.
Furthermore, the acid hydrolysis of Int-2 or Int-3 led to the
corresponding alkene, which showed the Ha–Hb coupling
constant to be 12.5 Hz, indicating that the hydrolysis products
have the Z configuration.
Accordingly, it was revealed that the hydroalumination
proceeded in a high trans addition manner, whereas the
hydrocupration and hydroboration took place in a high cis
addition manner. Furthermore, the hydroalumination was found
Fig. 2. The byproducts 7 and 8.

40
T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 36–43
CDCl3 solution with internal CFCl3 too. 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. Gas chromatography (GC) was taken on a Shimadzu
GC-7AG. Gas chromatography mass spectra (GS–MS) were
taken on a Shimadzu GCMS-QP1000.
4.1.1. Materials
Tetrahydrofuran (THF), copper bromide and iodine were
commercially available from Wako Chemicals Co. Red-Al
(1.6 M hexane solution) was purchased from Aldrich Chemi-
cals Co. Toluene, benzene, Et2O, and cyclohexene were freshly
distilled from calcium hydride (CaH2). 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 a previous literature
procedure.
4.2. The reaction of hydroaluminated adduct with iodine
Scheme 1. Determination of the stereochemistry.
To a solution of Red-Al (0.12 mL, 0.40 mmol, 3.3 M toluene
solution) in ether (2 mL) was added 1-(4-chlorophenyl)-3,3,3-
trifluoropropyne (41 mg, 0.20 mmol) at ꢀ78 8C and the whole
was stirred for 4 h at ꢀ78 8C. Then, a THF solution of I2
(305 mg, 1.20 mmol) (2.4 mL) was added to the reaction
mixture at ꢀ78 8C and gradually warmed up to the reflux
temperature. The whole was refluxed for 6 h and then cooled to
room temperature. Then the mixture was quenched with
aqueous NaHCO3 and Na2SO3, extracted with ethyl acetate
three times. The combined organic layers were dried over
anhydrous Na2SO4 and concentrated in vacuo. The residue was
chromatographed on silica gel to give the corresponding vinyl
iodide with some impurities.
to be opposite to the hydrocupration and the hydroboration in
the regioselectivity.
3. Conclusion
In summary, we have investigated three types of hydro-
metallation reactions of various fluorine-containing alkynes in
detail. Hydroalumination or hydrocuprataion proceeded
smoothly in a trans or cis addition manner, respectively, to
give the corresponding vinyl metal intermediates. The
intermediates reacted smoothly with H+, trans-, or cis-
disubstituted alkenes being obtained in good to high yields.
However, the reaction of the intermediates with the other
electrophiles, such as allylbromide, benzylbromide, and so on,
took place sluggishly. On the other hand, hydroboration
occurred in a highly regio- and stereoselective fashion,
followed by the subsequent Suzuki-Miyaura cross-coupling
reaction, affording the trisubstituted alkenes in excellent yields.
4.2.1. (Z)-1-(4-Chlorophenyl)-3,3,3-trifluoro-1-iodo-1-
propene (2I-trans)
Only identified peaks were noted as follows. 1H NMR
(CDCl3) d 6.56 (1H, q, J = 7.22 Hz), 7.35 (2H, d, J = 8.60 Hz),
7.43 (2H, d, J = 8.64 Hz); 19F NMR; d ꢀ60.8 (3F, d,
J = 6.50 Hz).
4.2.2. The reaction of hydrocuprated adduct with iodine
To a solution of copper bromide (144 mg, 1.00 mmol) in
THF (4 mL) was added 0.30 mL of Red-Al (1.00 mmol, 3.3 M
toluene solution) at ꢀ45 8C. The whole was stirred for 30 min,
then cooled to ꢀ78 8C. To this mixture was added 1-(4-
chlorophenyl)-3,3,3-trifluoropropyne (57 mg, 0.28 mmol) and
the solution was stirred at ꢀ78 8C. After stirring for 4 h, a THF
solution of I2 (683 mg, 2.69 mmol) (2 mL) was added to the
reaction mixture and the whole was stirred for 4 h at ꢀ78 8C,
followed by addition of a mixture of MeOH (2 mL) and
25 wt.% aqueous NH3 solution (2 mL). The whole was stirred
for 30 min, then gradually warmed up to room temperature. The
reaction was quenched with aqueous NaHCO3 and Na2SO3, and
4. Experimental
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 used for determining regioselectivity and
stereoselectivity and was used for taking 19F NMR spectra in a

T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 36–43
41
the whole was extracted with ethyl acetate three times. The
combined organic layers were dried over anhydrous Na2SO4,
concentrated in vacuo. The residue was chlomatographed on
silica gel to give the corresponding vinyl iodide.
organic layer was dried over anhydrous Na2SO4 and
concentrated in vacuo. The residue was chromatographed on
silica gel or TLC plate to afford 5 and 6.
4.2.4.1. (Z)-1,2-Diphenyl-3,3,3-trifluoropropene (5b-ci-
1
4.2.2.1. (E)-1-(4-Chlorophenyl)-3,3,3-trifluoro-2-iodo-1-pro-
pene (3I-cis). Yield 69% (determined by 19F NMR); 1H NMR
(CDCl3) d 7.20 (d, J = 8.50 Hz, 2H), 7.34 (d, J = 8.50 Hz, 2H),
7.73 (s, 1H); 13C NMR (CDCl3) d 84.5 (q, J = 37.4 Hz), 120.6
(q, J = 273.9 Hz), 128.6, 129.4 (q, J = 2.5 Hz), 134.1, 135.2,
148.7 (q, J = 3.1 Hz); 19F NMR (CDCl3) d ꢀ56.9 (s, 3F); IR
(neat) 2928, 2854, 1591, 1491, 1354, 1304 cmꢀ1; MS (FAB) m/
z 221, 205.
s). Yield 84%; mp 55–57 8C; H NMR (CDCl3) d 7.01 (s,
1H), 7.27–7.40 (m, 10 H); 13C NMR (CDCl3) d 123.4 (q,
J = 275.8 Hz), 128.1, 128.2, 128.38, 128.40, 128.60, 128.62,
131.8 (q, J = 30.3 Hz), 134.8, 136.5, 138.9 (q, J = 3.3 Hz); 19
F
NMR (CDCl3) d ꢀ56.8 (s, 3F); IR (KBr) 2360, 1373, 1218,
1164 cmꢀ1; HRMS calcd. for C15H11F3: 248.0813, found:
248.0818.
4.2.4.2. (Z)-1-(4-Chlorophenyl)-2-phenyl-3,3,3-trifluoropro-
1
pene (5a-cis). Yield 68%; H NMR (CDCl3) d 6.89 (s, 1H),
4.2.3. The coupling reaction of hydrocuprated adduct with
allylbromide
7.22–7.36 (m, 9H); 13C NMR (CDCl3)
d 123.2 (q,
To a solution of copper bromide (144 mg, 1.00 mmol) in
THF (4 mL) was added 0.30 mL of Red-Al (1.00 mmol, 3.3 M
toluene solution) at ꢀ45 8C. The whole was stirred for 30 min,
then cooled to ꢀ78 8C. To the solution was added 1-(4-
chlorophenyl)-3,3,3-trifluoropropyne (57 mg, 0.28 mmol) and
the whole was stirred for 4 h at ꢀ78 8C. Then allyl bromide
(0.23 mL, 2.69 mmol) in THF (2 mL) was added to the reaction
mixture and the whole was stirred for 4 h at ꢀ78 8C, followed
by addition of a mixture of MeOH (2 mL) and 25 wt.% of
aqueous NH3 solution (2 mL). The whole was stirred for
30 min, then gradually warmed up to room temperature,
quenched with aqueous NaHCO3, and extracted with ethyl
acetate three times. The combined organic layers were dried
over anhydrous Na2SO4, concentrated in vacuo. The residue
was chlomatographed on silica gel to give the corresponding
trisubstituted alkene.
J = 275.6 Hz), 128.1, 128.41, 128.44, 128.6, 130.0, 132.4 (q,
J = 30.2 Hz), 133.1, 134.4, 136.2, 137.4 (q, J = 3.2 Hz); 19F
NMR (CDCl3) d ꢀ56.84 (s, 3F); IR (neat) 1429, 1377, 1272,
1218, 1168 cmꢀ1; HRMS calcd. for C15H1035ClF3: 282.0423,
found: 282.0431.
4.2.4.3. (Z)-1-(4-Methylphenyl)-2-phenyl-3,3,3-trifluoropro-
1
pene (5c-cis). Yield 79%; H NMR (CDCl3) d 2.39 (s, 3H),
7.05 (s, 1H), 7.19–7.23 (m, 2H), 7.31–7.35 (m, 2H), 7.37–7.39
(m, 5H); 13C NMR (CDCl3) d 21.3, 123.5 (q, J = 278.3 Hz),
128.2, 128.4, 128.7, 128.9, 130.9 (q, J = 30.2 Hz), 131.8, 136.8,
138.5, 139.0 (q, J = 3.2 Hz); 19F NMR (CDCl3) d ꢀ56.8 (s, 3F);
IR (neat) 3028, 1639, 1512, 1447, 1381 cmꢀ1; HRMS calcd. for
C16H13F3: 262.0969, found: 262.0974.
4.2.4.4. (Z)-1-(4-Methoxyphenyl)-2-phenyl-3,3,3-trifluoropro-
1
pene (5d-cis). Yield 88%; H NMR (CDCl3) d 3.85 (s, 3H),
4.2.3.1. (1E)-1-(4-Chlorophenyl)-2-trifluoromethylpenta-1,4-
diene (3C-cis). Yield 31% (determined by 19F NMR); 1H
NMR (CDCl3) d 3.08 (2H, dd, J = 6.76 Hz, 5.48 Hz), 5.20 (1H,
t), 5.23 (1H, m), 5.87 (1H, m), 6.71 (1H, s), 7.20 (2H, d,
J = 8.42 Hz), 7.30 (2H, d, J = 8.51 Hz); 13C NMR (CDCl3) d
36.44 (q, J = 2.44 Hz), 118.29, 123.59 (q, J = 275.81 Hz),
128.28, 129.76 (q, J = 2.52 Hz), 129.95 (q, J = 28.55 Hz),
133.46, 133.81, 13.99, 134.52 (q, J = 3.77 Hz); 19F NMR; d
ꢀ60.1 (3F, s); IR (neat) 3084, 2984, 2918, 1655, 1643, 1595,
6.91–6.96 (m, 2H), 7.00 (s, 1H), 7.36–7.40 (m, 7H); 13C NMR
(CDCl3) d 55.2, 113.6, 122.5 (q, J = 275.0 Hz), 126.9, 128.1,
128.26, 128.33, 129.8 (q, J = 30.3 Hz), 130.6, 137.0, 138.8 (q,
J = 3.4 Hz), 159.8; 19F NMR (CDCl3) d ꢀ56.9 (s, 3F); IR (neat)
3063, 2936, 1639, 1512 cmꢀ1; HRMS calcd. for C16H13F3O:
278.0918, found: 278.0912.
4.2.4.5. (Z)-1-(4-Nitrophenyl)-2-phenyl-3,3,3-trifluoropropene
(5e-cis). Yield 25% (determined by 19F NMR); 1H NMR
(CDCl3) d 7.09 (s, 1H), 7.43–7.48 (m, 5H), 7.55 (d, J = 8.50 Hz,
2H), 8.26 (d, J = 8.50 Hz, 2H); 13C NMR (CDCl3) d 122.92 (q,
J = 276.1 Hz), 123.4, 128.0, 128.6, 129.1, 129.36, 129.38,
1493, 1435 cmꢀ1
.
4.2.4. General procedure for the hydroboration-coupling
reaction
134.8 (q, J = 30.2 Hz), 135.9 (q, J = 3.4 Hz), 141.5, 147.5; 19
F
To a solution of cyclohexene (0.12 mL, 1.2 mmol) in
benzene (2.0 mL) was added 0.58 mL (0.6 mmol) of borane at
0 8C and the whole solution was stirred for 20 min. The color of
reaction mixture became white. To this solution was added
dropwise 1 (0.5 mmol), and allowed to warm to RT, then stirred
for 2 h. After the reaction mixture became clear, iodobenzene
(0.12 g, 0.6 mmol), dichlorobis(triphenylphosphine)palladium
(0.034 g, 0.05 mmol) and 2.5 M sodium hydroxide (0.57 mL,
1.5 mmol) were added to the reaction mixture and the whole
solution was stirred for 4 h at reflux. Then the mixture was
quenched with water, and extracted with Et2O three times. The
NMR (CDCl3) d ꢀ56.9 (s, 3F); IR (neat) 3109, 2932, 1724,
1601, 1524 cmꢀ1; HRMS calcd. for C15H10F3NO2: 293.0664,
found: 293.0666.
4.2.4.6. (Z)-Ethyl 4-(3,3,3-trifluoro-2-phenylpropen-1-yl)-
benzoate (5f-cis). Yield 88% (chromatographed on TLC
1
plate); H NMR (CDCl3) d 1.41 (t, 3H, J = 7.50 Hz), 4.4 (q,
2H, J = 7.50 Hz), 7.10 (s, 1H), 7.36–7.50 (m, 6H), 8.03–8.10
(m, 2H); 13C NMR (CDCl3) d 14.3, 61.0, 123.1 (q,
J = 275.4 Hz), 128.1, 128.5, 128.7, 129.4, 129.5, 130.2,
133.3 (q, J = 31.4 Hz), 136.0, 137.5 (q, J = 3.3 Hz), 139.3,

42
T. Konno et al. / Journal of Fluorine Chemistry 127 (2006) 36–43
166.2; 19F NMR (CDCl3) d ꢀ56.9 (s, 3F); IR (neat) 2986, 1720,
1609, 1369, 1281 cmꢀ1; HRMS calcd. for C18H15F3O2:
321.1102 (M + H), found: 321.1103.
IR (KBr) 2963, 1639, 1570, 1489 cmꢀ1; HRMS calcd. for
C16H1235ClF3O: 312.0529, found: 312.0534.
4.2.4.13. (Z)-1-(4-Chlorophenyl)-2-(4-nitrophenyl)-3,3,3-tri-
fluoropropene (5m-cis). Yield 59% (chromatographed on
4.2.4.7. (Z)-4,4,4-Trifluoro-1-(4-methoxyphenyl)-3-phenyl-2-
1
1
butene (5g-cis). Yield 62% (determined by 19F NMR); H
TLC plate); mp 73–76 8C; H NMR (CDCl3) d 7.11 (s, 1H),
7.33–7.41 (m, 4H), 7.63 (d, J = 8.50 Hz, 2H), 8.28 (d,
NMR (CDCl3) d 3.71 (s, 2H), 3.78 (s, 3H), 6.13 (t, 1H,
J = 7.95 Hz), 6.86 (d, 2H, J = 8.65 Hz), 7.15 (d, 2H,
J = 8.55 Hz), 7.27–7.33 (m, 5H); 13C NMR (CDCl3) d 35.9,
55.3, 114.2, 117.2 (q, J = 33.7 Hz), 123.4 (q, J = 271.0 Hz),
126.9, 128.2, 128.5, 129.3, 131.4, 140.0, 140.6 (q, J = 3.1 Hz),
158.3; 19F NMR (CDCl3) d ꢀ57.1 (s, 3F); IR (neat) 2910, 1651,
1512, 1494 cmꢀ1; HRMS calcd. for C17H15F3O: 292.1075,
found: 292.1081.
J = 9.00 Hz, 2H); 13C NMR (CDCl3)
d
122.4 (q,
J = 276.6 Hz), 123.8, 128.7, 128.9, 129.1, 130.1, 131.1,
132.0, 134.4 (q, J = 36.1 Hz), 135.3, 139.8 (q, J = 3.4 Hz);
19F NMR (CDCl3) d ꢀ56.7 (s, 3F); IR (KBr) 2933, 1668, 1512,
1442 cmꢀ1; HRMS calcd. for C15H1035ClF3NO2: 328.0352
(M + H), found: 328.0357.
4.2.4.14. (Z)-Ethyl 4-(1,1,1-trifluoro-3-(4-chlorophenyl)pro-
pen-2-yl)benzoate (5n-cis). Yield 83% (chromatographed on
TLC plate); mp 66–67 8C; H NMR (CDCl3) d 1.41 (t, 3H,
4.2.4.8. (Z)-1-(4-Chlorophenyl)-2-(2-chlorophenyl)-3,3,3-tri-
1
fluoropropene (5h-cis). Yield 54%; H NMR (CDCl3) d 6.90
1
(s, 1H), 7.31–7.41 (m, 8H); 13C NMR (CDCl3) d 122.5 (q,
J = 275.0 Hz), 126.7, 128.6, 129.5 (q, J = 31.4 Hz), 129.8,
130.0, 130.1, 131.4, 132.3, 134.2, 134.9, 135.0, 139.7 (q,
J = 3.8 Hz); 19F NMR (CDCl3) d ꢀ57.7 (s, 3F); IR (neat) 2928,
1643, 1593, 1493 cmꢀ1. HRMS calcd. for C15H935Cl2F3:
316.0033, found: 316.0031.
J = 7.25 Hz), 4.41 (d, 2H, J = 7.00 Hz), 7.06 (s, 1H), 7.32–7.40
(m, 4H), 7.52 (d, 2H, J = 8.00 Hz), 8.09 (d, 2H, J = 8.00 Hz);
13C NMR (CDCl3) d 14.3, 61.2, 123.0 (q, J = 275.9 Hz), 128.1,
128.5, 129.7, 130.1, 130.6, 131.7 (q, J = 31.2 Hz), 132.6, 134.8,
138.5 (q, J = 3.0 Hz), 140.5, 166.0; 19F NMR (CDCl3) d ꢀ56.9
(s, 3F); IR (KBr) 2963, 1635, 1562, 1492 cmꢀ1; HRMS calcd.
for C19H1535ClF3O2: 355.0713 (M + H), found: 355.0712.
4.2.4.9. (Z)-1-(4-Chlorophenyl)-2-(3-chlorophenyl)-3,3,3-tri-
fluoropropene (5i-cis). Yield 94% (chromatographed on TLC
4.2.4.15. (Z)-1-(4-Chlorophenyl)-3,3-difluoro-2-phenyl-1-pro-
pene (5o-cis). Yield 85% (chromatographed on TLC plate);
1H NMR (CDCl3) d 6.57 (t, 1H, J = 54.41 Hz), 7.10 (s, 1H),
7.30 (d, 2H, J = 8.3 Hz), 7.38–7.43 (m, 5H), 7.58 (d, 2H,
J = 7.3 Hz); 13C NMR (CDCl3) d 112.9 (t, J = 236.2 Hz), 127.8,
128.36, 128.41, 128.9, 130.2, 132.9, 134.5, 135.4 (t,
J = 9.9 Hz), 135.6, 135.9 (t, J = 21.9 Hz); 19F NMR (CDCl3)
d ꢀ111.0 (d, J = 54.2 Hz); IR (neat) 3030, 1593, 1490,
1388 cmꢀ1; HRMS calcd. for C15H1135ClF2: 264.0517, found:
264.0521.
plate); 1H NMR (CDCl3) d 7.02 (s, 1H), 7.31–7.49 (m, 8H); 13
C
NMR (CDCl3) d 122.9 (q, J = 275.5 Hz), 126.4, 128.4, 128.5,
128.7, 129.7, 130.1, 131.2 (q, J = 30.3 Hz), 132.6, 134.4, 134.8,
137.8, 138.4 (q, J = 3.1 Hz); 19F NMR (CDCl3) d ꢀ56.9 (s, 3F);
IR (neat) 2927, 1643, 1593, 1492, 1377 cmꢀ1; HRMS calcd. for
C15H935Cl2F3: 316.0033, found: 316.0031.
4.2.4.10. (Z)-1,2-Bis(4-chlorophenyl)-3,3,3-trifluoropropene
1
(5j-cis). Yield 74%; H NMR (CDCl3) d 6.99 (s, 1H), 7.32–
7.39 (m, 8H); 13C NMR (CDCl3) d 123.0 (q, J = 275.6 Hz),
128.5, 128.7, 129.5, 129.97, 129.99, 131.3 (q, J = 31.1 Hz),
132.8, 134.7, 134.8, 137.9 (q, J = 2.6 Hz); 19F NMR (CDCl3) d
4.2.4.16. (Z)-1-(4-Chlorophenyl)-3,3,4,4,5,5-hexafluoro-2-
phenyl-1-pentene (5p-cis). Yield 80% (chromatographed on
TLC plate); 1H NMR (CDCl3) d 5.89 (tt, 1H, J = 52.31,
5.65 Hz), 7.41 (s, 1H), 7.22–7.50 (m, 9H); 13C NMR (CDCl3) d
107.8 (tt, J = 253.7, 30.9 Hz), 116.0 (tt, J = 253.7, 32.8 Hz),
128.1, 128.3, 128.6, 129.5, 131.8 (t, J = 19.9 Hz), 133.7, 133.9,
136.9 (t, J = 2.1 Hz), 141.1 (t, J = 4.1 Hz), 152.8 (t, J = 4.0 Hz);
19F NMR (CDCl3) d ꢀ104.6 to ꢀ104.8 (m, 2F), ꢀ127.5 to
ꢀ128.0 (m, 2F), ꢀ136.7 to ꢀ138.0 (m, 2F); IR (neat) 1492,
1400, 1137, 1091 cmꢀ1; HRMS calcd. for C17H1135ClF6:
364.0453, found: 364.0455.
ꢀ57.0 (s, 3F); IR (neat) 2927, 1639, 1596, 1492, 1377 cmꢀ1
;
HRMS calcd. for C15H935Cl2F3: 316.0033, found: 316.0031.
4.2.4.11. (Z)-1-(4-Chlorophenyl)-2-(4-methylphenyl)-3,3,3-
trifluoropropene (5k-cis). Yield 62%; mp 44–46 8C; 1H NMR
(CDCl3) d 2.37 (s, 3H), 7.00 (s, 1H), 7.18–7.23 (m, 2H), 7.21–
7.37 (m, 6H); 13C NMR (CDCl3) d 123.3 (q, J = 275.8 Hz),
128.0, 128.4, 129.1, 129.98, 130.00, 132.6 (q, J = 30.5 Hz),
133.3, 134.3, 136.9 (q, J = 2.5 Hz), 138.6; 19F NMR (CDCl3) d
ꢀ56.9 (s, 3F); IR (KBr) 2924, 1643, 1593, 1489 cmꢀ1; HRMS
calcd. for C16H1235ClF3: 296.0580, found: 296.0572.
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