Facile syntheses of various per- or polyfluoroalkylated internal acetylene derivatives

Article abstract of DOI:10.1016/S0040-4020(03)01199-2

Treatment of per- or polyfluoroalkylated vinyl iodides 5 with 2equiv. of n-BuLi in THF produced the corresponding lithium acetylides in situ, which were transformed into zinc acetylides by the addition of ZnCl₂· TMEDA complex into the reaction mixture. The in situ generated zinc acetylides were exposed to the cross-coupling conditions such as ArI/cat. Pd(PPh ₃)₄, reflux, 6-12 h, giving rise to the desired per- or polyfluoroalkylated acetylenes in high yields. In the case of trifluoromethylated acetylene, commercially available 2-bromo-3,3,3-trifluoropropene 6 could also be used instead of 5 as the starting material. In the acetylenes having a fluoroalkyl group and an aliphatic side chain, vinyl iodides 7, prepared by radical addition of perfluoroalkyl iodide to terminal acetylenes, were treated with t-BuOK at room temperature or at the reflux temperature of benzene, affording the desired compounds in good yields.

Full text of DOI:10.1016/S0040-4020(03)01199-2

Tetrahedron 59 (2003) 7571–7580
Facile syntheses of various per- or polyfluoroalkylated internal
acetylene derivatives
*
Tsutomu Konno, Jungha Chae, Masashi Kanda, Go Nagai, Kazushige Tamura, Takashi Ishihara
and Hiroki Yamanaka
Department of Chemistry and Materials Technology, Kyoto Institute of Technology, Sakyo-ku, Matsugasaki, Kyoto 606-8585, Japan
Received 10 June 2003; accepted 17 July 2003
Abstract—Treatment of per- or polyfluoroalkylated vinyl iodides 5 with 2 equiv. of n-BuLi in THF produced the corresponding lithium
acetylides in situ, which were transformed into zinc acetylides by the addition of ZnCl2·TMEDA complex into the reaction mixture. The in
situ generated zinc acetylides were exposed to the cross-coupling conditions such as ArI/cat. Pd(PPh3)4, reflux, 6–12 h, giving rise to the
desired per- or polyfluoroalkylated acetylenes in high yields. In the case of trifluoromethylated acetylene, commercially available 2-bromo-
3,3,3-trifluoropropene 6 could also be used instead of 5 as the starting material. In the acetylenes having a fluoroalkyl group and an aliphatic
side chain, vinyl iodides 7, prepared by radical addition of perfluoroalkyl iodide to terminal acetylenes, were treated with t-BuOK at room
temperature or at the reflux temperature of benzene, affording the desired compounds in good yields.
q 2003 Elsevier Ltd. All rights reserved.
1. Introduction
easy access to a variety of fluoroalkylated acetylenes 1–4
(Scheme 1).
In view of rapidly growing role of fluorine-containing
substances particularly in materials and pharmaceutical
science, the synthesis of fluorine-containing substances is
becoming more and more important.1 As one of the most
valuable synthetic intermediates for preparation of such
substances, fluoroalkylated acetylenes 1–4 (Fig. 1) have
recently been attracting much attention from organometallic
chemists,2 and synthetic chemists,3 polymer chemists,4
pharmaceutical scientists,5 etc. due to their potentially high
synthetic value.6 There have been several reports on the
preparation of fluoroalkylated acetylenes so far. For
example, the synthesis of trifluoromethylated acetylenes 1
has been achieved through the use of respective trifluoro-
propynyl lithium,7 Grignard8 or zinc reagents.9 However,
reliance upon trifluoropropyne as a precursor incurs
experimental difficulties, associated with the handling of a
gaseous reagent (bp 2478C), and has significant cost
implications. In addition to limited studies on the prep-
aration of 1,10 little attention has been paid on the synthesis
of per- or polyfluoroalkylated acetylenes 2.11 To the best of
our knowledge, no report has been appeared on the
preparation of acetylenes 3 and 4 which possess both per-
or polyfluoroalkyl group and an aliphatic chain R.12
Figure 1.
The path A is via the palladium-catalyzed coupling reaction
using various aryl iodides and zinc acetylide derived from
vinyl iodide 5 which was easily prepared from commer-
cially available per- or polyfluoroalkylcarbinol. The path B
is similar to the path A, in which the acetylenes are
synthesized from commercially available 2-bromo-3,3,3-
trifluoropropene 6 in a one-pot. The path C is for the
synthesis of fluoroalkylated acetylenes bearing an aliphatic
substituent via dehydroiodination of vinyl iodides 7.
2. Results and discussion
In this article we wish to describe three types of synthetic
methods (path A–C), all of which would provide us with
2.1. The palladium-catalyzed coupling reaction of zinc
acetylide with various aryl iodides (path A)
*
Corresponding author. Tel.: þ81-75-724-7573; fax: þ81-75-724-7580;
e-mail: konno@chem.kit.ac.jp
The starting vinyl iodides 5a–c could readily be prepared
0040–4020/$ - see front matter q 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4020(03)01199-2

7572
T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
case, ZnCl2·TMEDA was better than anhydrous ZnCl2
because it was less hydroscopic. After stirring of the
reaction mixture for 15 min, the mixture was allowed to
warm to room temperature and then stirred for 1 h. To this
reaction mixture was added 1 equiv. of aryl iodide and
5 mol% of tetrakis(triphenylphophine)palladium(0)
(Pd(PPh3)4) in this order. The whole mixture was heated
at 50–608C for 4–12 h, resulting in the formation of
fluoroalkylated acetylene derivative 1 or 2 in good to high
yields. The results are summarized in Table 1.
As shown in entries 1–6, various aryl iodides as well as
alkenyl iodides could participate nicely in the present
coupling reaction to give the corresponding fluoroalkylated
alkynes in high yields. Trifluoromethylated- and decafluor-
opentylated alkynes were also synthesized in the same
procedure (entries 7–12). However, the coupling reaction of
fluoroalkylated acetylide with alkyl iodide in the presence
of palladium catalyst did not proceed at all, giving the
complete recovery of the zinc acetylide. In this way, it was
found that the palladium-catalyzed coupling reaction of zinc
acetylide with various iodides was very effective for the
preparation of fluoroalkylated acetylenes bearing aromatic
substituents, not aliphatic ones.
Scheme 1.
from the corresponding polyfluoroalcohols 8 in three steps
(Scheme 2).13 Thus, commercially available 8 was treated
with p-toluenesulfonyl chloride (1.2 equiv.) and NaOH
(1.2 equiv.) at room temperature to give the corresponding
tosylate 9 in quantitative yield. The tosylate was subjected
to NaI/diethyleneglycol at room temperature, followed by
direct distillation, affording polyfluoroalkyl iodide 10. The
iodide was dissolved in DMSO, and to this solution was
added a 4N KOH solution. The whole was stirred at room
temperature overnight, giving rise to the desired Z-vinyl
iodide 5 in up to 56% yield for three steps.
2.2. The one-pot reaction for the preparation of
trifluoromethylated acetylenes (path B)
In seeking for more convenient methods for preparing
fluorine-containing acetylenes, we examined the one-pot
synthesis of trifluoromethylated acetylenes from commer-
cially available, easy-handling 2-bromo-3,3,3-trifluoropro-
pene 6 (bp 34–358C). Thus, 6 was treated with 2 equiv. of
LDA at 2788C,14 resulting in the formation of trifluor-
omethylated lithium acetylide in situ. To this reaction
mixture was added ZnCl2·TMEDA, Pd(PPh3)4 and ArI,
followed by refluxing the mixture, leading to the formation
of the desired alkynes 1. The results are summarized in
Table 2. Generally, the coupling reaction of zinc acetylide
with aryl iodides gave the corresponding acetylene
derivatives in excellent yields. As shown in entries 3–5,
aryl triflate as well as aryl bromide did not give the desired
Scheme 2.
The treatment of 5 with 2 equiv. of n-BuLi at 2788C for 1 h
produced the corresponding lithium acetylide in situ, which
was transmetallated into zinc acetylide by addition of
ZnCl2·TMEDA complex into the reaction mixture. In this
Table 1. Palladium-catalyzed coupling reaction of zinc acetylide with various aryl iodides
Entry
Rf
R
Temp. (8C)
Time (h)
Product
Yielda (%)
1
2
3
4
5
5
6
7
8
9
10
11
12
CHF2
CHF2
CHF2
CHF2
CHF2
CHF2
CHF2
CF3
CF3
CF3
CF3
CF3
Ph
o-MeOC6H4
m-NO2C6H4
p-EtO2COC6H4
p-ClC6H4
(E)-PhCHvCH
(E)-n-C6H13CHvCH
o-MeOC6H4
60
60
60
60
60
60
60
60
60
50
50
50
50
4
12
12
4
4
4
2a
2b
2c
2d
2e
2f
2g
1a
1b
1c
1d
1e
2h
62
74
80
76
70
85
74
78
76
73
75
81
77
4
12
12
4
4
4
m-NO2C6H4
p-EtO2COC6H4
(E)-PhCHvCH
(E)-n-C6H13CHvCH
m-NO2C6H4
H(CF2)5
4
a
Isolated yields.

T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
Table 2. The one-pot synthesis of trifluoromethylated acetylenes
7573
Entry
5 (equiv.)
RX
Time (h)
Product
Yielda (%)
1
2
3
4
5
6
7
8
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
2.0
2.0
1.5
2.0
2.0
2.0
PhI
6
6
6
6
6
6
6
6
6
6
6
12
6
12
6
24
24
24
1f
1g
–
–
–
99 (83)
99 (99)
tr
p-MeOC6H4I
p-MeOC6H4OTf
p-MeOC6H4OTf
p-MeOC6H4Br
p-MeOC6H4I
p-MeC6H4I
trb
tr
18c
–
1h
1i
1c
1j
1k
–
–
1a
–
99 (99)
81 (81)
94 (72)
51
99 (95)
60
85
p-ClC6H4I
9
p-EtO2CC6H4I
p-O2NC6H4I
m-MeOC6H4I
o-MeOC6H4I
o-MeOC6H4I
o-MeOC6H4I
o-ClC6H4I
o-ClC6H4I
o-ClC6H4I
o-ClC6H4I
10
11
12
13
14
15
16
17
18
99 (82)
27
77
–
–
1l
83d
96 (79)e
a
Determined by 19F NMR. Values in parentheses were of isolated yields.
NaI was used.
n-Bu3SnCl was used instead of ZnCl2·TMEDA.
10 mol% of Pd(PPh3)4 was used.
15 mol% of Pd(PPh3)4 was used.
b
c
d
e
coupling products at all. Furthermore, Stille coupling using
alkynylstannane instead of zinc acetylide afforded the
desired product in very low yield (entry 6). p-Methyliodo-
benzene, p-chloro-iodobenzene, and ethyl p-iodobenzoate
were found to be good substrates, while the reaction with p-
nitroiodobenzene proceeded very sluggishly, giving the
desired compound in only 51% yield together with
unidentified compounds and unreacted substrate after 6 h.
It was also found that the position of substituent on the
benzene ring influenced largely on the reaction. Meta-
substituted substrate gave the desired product in excellent
yield (entry 11), however, ortho-substituted one did not
afford the product in good yields (entries 12 and 16). After
several attempts, we found that the prolonged reaction time
and increase of the amount of catalyst improved the yields
(entries 14 and 18).
to terminal acetylenes in the presence of a catalytic amount
of Zn/TFA according to the literature (Scheme 3).15
Scheme 3.
In an initial experiment, vinyl iodide 7b (Rf¼n-C4F9, R¼n-
C6H13) was treated with 1.5 equiv. of n-BuLi at 2788C in
THF or Et2O, resulting in the recovery of the starting
material (see Table 3, entries 1 and 2). Use of LDA or t-
BuLi instead of n-BuLi gave no dramatic improvement
(entries 3–6). On the other hand, 7b was subjected to the
reaction conditions such as t-BuOK/THF at room tempera-
ture to produce the desired acetylene in 30% yield. When
the reaction was carried out in Et2O by using 3 equiv. of t-
BuOK, the yield was improved to 61%, while no starting
material was detected at all. No change was observed even
when the reaction was performed at 08C (entries 10 and 11).
As shown in entries 13–17, on the other hand, the reflux
conditions gave the satisfactory results. Eventually, we
found that the best yield was given when the reaction was
carried out in benzene at the reflux temperature for 2 h by
using 3 equiv. of t-BuOK (78% NMR yield, entry 17). The
optimized reaction conditions were applied for various
types of vinyl iodides 7. The results are summarized in
Table 4.
2.3. The synthesis of perfluoroalkylated acetylenes
bearing an alkyl side chain (path C)
In the preceding sections, we demonstrated two convenient
synthetic methods which enabled us to synthesize various
types of fluoroalkylated acetylenes bearing aromatic sub-
stituents. However, the palladium-catalyzed coupling reac-
tion of zinc acetylide with alkyl iodides failed, the starting
materials being recovered quantitatively. To the best of our
knowledge, the general synthetic methods for the fluor-
oalkylated acetylenes 3 and 4 (Fig. 1) which have an
aliphatic side chain, have not been reported so far. This
prompted us to develop the convenient access to such
fluoroalkylated acetylenes.
Our attempt was made to the synthesis of such acetylenes
via dehydroiodination from vinyl iodides 7 which were
prepared from the radical addition of perfluoroalkyl iodide

7574
T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
Table 3. The synthesis of fluoroalkylated acetylenes bearing an aliphatic substituent (Rf¼n-C4F9, R¼n-C6H13
)
Entry
Base
Equiv. of base
Solvent
Temp. (8C)
Time (h)
Yield a (%) of 4b
Recoverya (%) of 7b
1
2
3
4
5
6
7
8
n-BuLi
n-BuLi
LDA
LDA
t-BuLi
t-BuLi
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
3.0
1.5
3.0
3.0
1.5
3.0
3.0
1.5
3.0
THF
Et2O
THF
Et2O
THF
Et2O
THF
Et2O
Et2O
Et2O
Et2O
THF
THF
THF
THF
PhH
PhH
278
278
278
278
278
278
r.t.
r.t.
r.t.
0
2
2
2
2
2
2
2
2
2
2
2
2
2
2
4
2
2
tr
0
20
0
0
0
30
46
61
68
58
24
38
37
51
64
78
91
30
74
50
99
99
63
45
0
9
10
11
12
13
14
15
16
17
26
0
0
r.t.
54
60
52
41
13
0
Reflux
Reflux
Reflux
Reflux
Reflux
a
Determined by 19F NMR.
Table 4.
It was found that the amount of base was crucial for
obtaining the desired acetylenes in good yields. When the
reaction was carried out at room temperature by using
3.0 equiv. of t-BuOK, the product was given in only 30%
(entry 2). Use of 1.5 equiv. of base improved the yield from
30 to 66%. Eventually, the best yield was obtained when a
slight excess of base (1.2 equiv.) was employed at room
temperature. This reaction conditions were applied for
various types of trifluoromethylated vinyl iodides, as shown
in entries 5–7. Various vinyl iodides 7 having a branched
side chain as well as a straight side chain could also be
applied for the present reaction nicely.
Entry
Rf
R
Substrate Product Yielda (%) of 2–4
1
2
3
n-C8F17 n-C6H13
n-C4F9 n-C6H13
n-C4F9 n-C10H21
7a
7b
7c
4a
4b
4c
74 (49)
78 (44)
73
4
n-C4F9
7d
4d
81
5
6
7
8
9
n-C4F9 Ph
n-C4F9 p-MeC6H4
n-C3F7 n-C6H13
C5F5
CF3
7e
7f
2i
2j
74
77
7g
7h
7i
4g
4h
3i
74 (40)
65 (55)
24
n-C6H13
n-C6H13
a
Determined by 19F NMR. Values in parentheses are of isolated yields.
3. Summary
As seen in entries 1, 2, 7 and 8, the substrates bearing
various fluoroalkyl groups could participate well in the
reaction to give the corresponding acetylenes in good yields,
while the isolated yields were moderate owing to their
volatility. Additionally, various side chains R such as
aliphatic as well as aromatic groups did not influence on the
reaction. Interestingly, trifluoromethylated vinyl iodide 7i,
shown in entry 9, was subjected to the same reaction
conditions, affording the desired product in only 24% yield
with no recovery of the starting vinyl iodide. Therefore, the
reaction conditions for the dehydroiodination reaction of 7i
was re-examined in detail. The results are collected in Table 5.
In conclusion, we have demonstrated three types of synthetic
methods (path A–C). First, the palladium-catalyzed coupling
reactionbyusing variousaryliodidesand zincacetylidewhich
was readily prepared from the corresponding polyfluoroalco-
hol, was found to be effective for the preparation of acetylenes
substituted by fluoroalkyl group and an aromatic moiety.
Secondly, we also achieved the one-pot synthesis of
trifluoromethylated internal alkynes from commercially
available 2-bromo-3,3,3-trifluoropropene, leading to the
development of easy access to 1. Thirdly, we developed the
first synthesis of perfluoroalkylated acetylenes having an
Table 5. (Rf¼CF3)
Entrya
Eq of base
R
Substrate
Recoveryb (%) of 7
Product
Yieldb (%) of 3
1c
2
3
4
3
3
1.5
1.2
1.2
n-C6H13
n-C6H13
n-C6H13
n-C6H13
n-C10H21
7i
7i
7i
7i
7j
0
0
0
1
0
3i
3i
3i
3i
3j
24
30
66
73 (48)
84 (67)
5
6
1.2
1.2
7k
7l
0
0
3k
3l
86
74
7
a
All reaction was performed at the room temperature.
Determined by 19F NMR. Values in parentheses are of isolated yields.
Carried out at the reflux temperature of benzene.
b
c

T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
7575
aliphatic side chain, which could not be synthesized by the
palladium-catalyzed coupling reaction. As a result, these
methods enabled us to synthesize a wide variety of fluorine-
containing acetylenes in moderate to excellent yields.
39.8 Hz); 19F NMR (CDCl3) d 272.4 (3F, d, J¼13.2 Hz),
2108.44 (1F, m); IR (neat) 3105, 1674, 1346, 1157 cm21
HRMS (CI) calcd for C3HF4I 239.9059, found 239.9060.
;
4.1.4. (Z)-2,3,3,4,4,5,5,6,6,7,7-Decafluoro-1-iodoprop-1-
1
ene (5c). Yield 52%; H NMR (CDCl3) d 6.03 (1H, tt,
J¼52.01, 5.00 Hz), 6.64 (1H, d, J¼31.00 Hz); 13C NMR
(CDCl3) d 65.33 (d, J¼21.4 Hz), 107.58 (tt, J¼255.3,
32.1 Hz), 151.24 (dt, J¼264.0, 30.5 Hz); 19F NMR (CDCl3)
d 2102.89 to 2103.34 (1F, m), 2116.45 to 2116.92 (2F,
m), 2123.56 to 2124.27 (4F, m), 2130.13 to 2130.18 (2F,
m), 2137.17 to 2138.11 (2F, m); IR (neat) 3109, 1662,
4. Experimental
4.1. General methods
Infrared spectra (IR) were taken on a Shimadzu FTIR-
1
8200(PC) spectrometer as film on a NaCl plate. H NMR
1326, 1195 cm21
; HRMS (CI) calcd for C7H2F11I
spectra were measured with a General Electric QE-300
and/or Bruker DRX-500 NMR spectrometer in a chloro-
form-d (CDCl3) solution with tetramethylsilane (Me4Si) as
an internal reference. 13C NMR spectra were recorded with
a Bruker DRX-500 (125.75 MHz) NMR spectrometer in a
CDCl3 solution with Me4Si as an internal standard. A JEOL
JNM-EX90A (84.21 MHz) FT NMR spectrometer was used
for determining 19F NMR spectra in a CDCl3 solution with
the internal standard of trichlorofluoromethane. High-
resolution mass spectra (HRMS) were taken on a Hitachi
M-80B mass spectrometer by electron impact (EI), chemical
ionization (CI), and fast atom bombardment (FAB) method.
Thin-layer chromatography (TLC) was done on aluminium
sheets coated with silica gel (Merck 60 F254), and column
chromatography was carried out using silica gel (Wacogel
C-200) as absorbent.
421.9026, found 421.9032.
4.2. Typical procedure for the synthesis of difluoro-
methylated acetylene (path A)
To a THF solution of 5a (0.33 g, 1.5 mmol) was dropwise
added a 1.6 M hexane solution of n-BuLi (1.88 mL,
3.0 mmol) at 2788C. The reaction mixture was stirred at
that temperature for 30 min, followed by addition of
ZnCl2·TMEDA complex (0.30 g, 1.2 mmol). After stirring
of the reaction mixture for 15 min at 2788C and for 30 min
at room temperature, iodobenzene (0.20 g, 1.0 mmol) and
tetrakis(triphenylphosphine)palladium (58 mg, 5 mol%)
was added to a reaction mixture in this order, then heated
at 50–608C for 4–12 h. The reaction was quenched with sat.
NH4Cl aq. and the whole was extracted with ethyl acetate
three times. The combined organic layers were washed with
brine, dried over anhydrous sodium sulfate, and then
evaporated in vacuo. The residue was purified by flash
column chromatography to give the corresponding acety-
lene 2a (94 mg, 0.62 mmol) in 62% yield.
4.1.1. Typical procedure for the preparation of vinyl
iodide 5b. Polyfluoroalcohol (1.0 mol) and p-toluenesulfo-
nyl chloride (1.2 mol) was dissolved in water (350 mL), and
then the whole was heated at 508C. To this solution was
dropwise added a NaOH solution (150 mL, 1.2 mol). After
stirring of the reaction mixture for 3 h, the reaction mixture
was cooled to room temperature, followed by extraction with
ether three times. The combined organic layers were washed
with NH3 aq. (twice), then water (three times), and dried over
anhydrous Na2SO4. After evaporation of the organic
materials, the residue and NaI (180 g, 1.2 mol) was dissolved
in diethyleneglycol (350 mL). The solution was heated (bath
temperature ca. 1708C/760 mmHg) to distill the desired
iodide, which was washed with water six times. The crude
materials were dissolved in DMSO (250 mL), and to this
reaction mixture was added a KOH solution (100 mL,
0.9 mol) at 0–108C. After stirring of the reaction mixture for
24 h, the reaction mixture was heated at 80–1008C to obtain
the light-red oil, which was washed with water, dried over
anhydrous Na2SO4, then filtered to afford 5b.
1
4.2.1. 1-Phenyl-3,3-difluoropropyne (2a). Yield 62%; H
NMR (CDCl3) d 6.41 (1H, t, J¼55.01 Hz), 7.32–7.45 (3H,
m), 7.50–7.53 (2H, m); 13C NMR (CDCl3) d 79.75 (t,
J¼34.0 Hz), 88.40 (t, J¼7.6 Hz), 104.20 (t, J¼233.8 Hz),
119.87 (t, J¼3.4 Hz), 128.51, 130.11, 132.16; 19F NMR
(CDCl3) d 2105.8 (2F, d, J¼55.0 Hz); IR (neat) 2253,
2222, 1493, 1373 cm21; HRMS (EI) calcd for C9H6F2 m/z
152.0438, found 152.0443.
4.2.2. 1-(2-Methoxyphenyl)-3,3-difluoropropyne (2b).
1
Yield 74%; H NMR (CDCl3) d 3.89 (3H, s), 6.46 (1H, t,
J¼55.51 Hz), 6.90 (1H, d, J¼8.50 Hz), 6.93 (1H, t,
J¼7.50 Hz), 7.38 (1H, dt, J¼1.50, 8.00 Hz), 7.46 (1H, dt,
J¼1.00, 7.50 Hz); 13C NMR (CDCl3) d 55.76, 83.56 (t,
J¼33.1 Hz), 85.26 (t, J¼7.4 Hz), 104.36 (t, J¼230.8 Hz),
109.07, 110.76, 120.48, 131.69, 134.15, 160.80; 19F NMR
(CDCl3) d 2105.4 (2F, d, J¼55.1 Hz); IR (neat) 2245,
1736, 1596, 1492 cm21; HRMS (EI) calcd for C10H8F2O
182.0543, found 182.0545.
4.1.2. (Z)-2,3,3-Trifluoro-1-iodoprop-1-ene (5a). Yield
48%; 1H NMR (CDCl3) d 6.08 (1H, td, J¼53.50,
4.00 Hz), 6.28 (1H, d, J¼32.00 Hz); 13C NMR (CDCl3) d
61.25 (dt, J¼20.8, 6.9 Hz), 107.70 (td, J¼242.1, 40.8 Hz),
156.84 (dt, J¼262.5, 25.4 Hz); 19F NMR (CDCl3) d 2105.6
(1F, dtd, J¼33.0, 18.8, 3.3 Hz), 2123.2 (2F, dd, J¼52.8,
19.8 Hz); IR (neat) 3101, 1670, 1388 cm21; HRMS (CI)
calcd for C3H2F3I 221.9153, found 221.9149.
4.2.3. 1-(3-Nitrophenyl)-3,3-difluoropropyne (2c). Yield
1
80%; H NMR (CDCl3) d 6.45 (1H, t, J¼54.01 Hz), 7.61
(1H, t, J¼7.50 Hz), 7.86 (1H, d, J¼8.00 Hz), 8.29–8.32
(1H, m), 8.49 (1H, s); 13C NMR (CDCl3) d 81.82 (t,
J¼34.7 Hz), 85.42 (t, J¼7.2 Hz), 103.75 (t, J¼233.5 Hz),
121.64 (t, J¼2.5 Hz), 124.85, 127.06 (t, J¼2.2 Hz), 129.77,
137.70, 148.10; 19F NMR (CDCl3) d 2107.15 (2F, d,
4.1.3. (Z)-2,3,3,3-Tetrafluoro-1-iodoprop-1-ene (5b).
Yield 56%; 1H NMR (CDCl3)
d
6.59 (1H, d,
J¼35.00 Hz); 13C NMR (CDCl3) d 63.27 (d, J¼21.9 Hz),
J¼55.0 Hz); IR (neat) 2257, 2233, 1535, 1373, 1353 cm21
;
116.86 (qd, J¼272.3, 42.2 Hz), 152.24 (dq, J¼262.8,

7576
T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
HRMS (FAB) calcd for C9H5F2NO2 197.0288, found
197.0291.
MS (FAB) m/z (rel intensity) 215 (100, M) calcd for
C9H4F3NO2 215.0194, found 215.0189.
4.2.4. 1-(4-Ethoxycarbonyl)-3,3-difluoropropyne (2d).
1
4.2.10. Ethyl 4-(3,3,3-trifluoropropynyl)benzoate (1c).
1
Yield 76%; H NMR (CDCl3) d 1.40 (3H, t, J¼7.25 Hz),
Yield 73%; H NMR (CDCl3) d 1.41 (3H, t, J¼7.30 Hz),
4.39 (2H, q, J¼7.25 Hz), 6.43 (1H, t, J¼54.51 Hz), 7.58
(2H, d, J¼8.25 Hz), 8.04 (2H, d, J¼8.25 Hz); 13C NMR
(CDCl3) d 14.23, 61.38, 81.92 (t, J¼34.5 Hz), 87.28 (t,
J¼7.3 Hz), 103.97 (t, J¼232.7 Hz), 124.13, 129.54, 131.71,
132.06, 165.60; 19F NMR (CDCl3) d 2106.5 (2F, d,
J¼55.1 Hz); IR (neat) 2253, 2226, 1720, 1608, 1373,
1273 cm21; HRMS (FAB) calcd for C12H11F2O2 (MþH)
225.0727, found 225.0734.
4.40 (2H, q, J¼7.20 Hz), 7.63 (2H, d, J¼8.00 Hz), 8.07 (2H,
d, J¼8.00 Hz); 13C NMR (CDCl3) d 14.15, 61.43, 77.57 (q,
J¼53.2 Hz), 85.23 (q, J¼6.4 Hz), 114.55 (q, J¼257.3 Hz),
122.61, 128.24, 129.57, 132.30, 165.35; 19F NMR (CDCl3)
d 250.68 (3F, s); IR (neat) 2986, 2257, 1724, 1404, 1369,
1315 cm21; HRMS calcd for C12H9F3O2 m/z 242.0555,
found 242.0533.
4.2.12. 1,1,1-Trifluoro-5-phenylpent-4-en-2-yne (1d).
1
4.2.5. 1-(4-Chlorophenyl)-3,3-difluoropropyne (2e).
1
Yield 75%; H NMR (CDCl3) d 6.14 (1H, dq, J¼16.50,
Yield 70%; H NMR (CDCl3) d 6.40 (1H, t, J¼50.51 Hz),
3.00 Hz), 7.24 (1H, d, J¼5.50 Hz), 7.36–7.42 (5H, m); 13C
NMR (CDCl3) d 75.67 (q, J¼52.5 Hz), 86.07 (q, J¼6.2 Hz),
103.41, 114.83 (q, J¼256.5 Hz), 126.88, 128.03, 128.95,
130.12, 147.35; 19F NMR (CDCl3) d 250.1 (3F, s); IR
7.35 (2H, d, J¼8.50 Hz), 7.44 (2H, d, J¼8.50 Hz); 13C
NMR (CDCl3) d 80.60 (t, J¼34.0 Hz), 87.19 (t, J¼7.2 Hz),
104.05 (t, J¼232.7 Hz), 118.30, 128.96, 133.37, 136.45; 19F
NMR (CDCl3) d 2110.7 (2F, d, J¼50.5 Hz); IR (neat)
2253, 2226, 1489, 1373 cm21; HRMS (EI) calcd for
C9H355ClF2 186.0048, found 186.0034.
(neat) 3031, 2931, 2233, 1573, 1492, 1450, 1261 cm21
HRMS (EI) calcd for C11H7F3 196.0500, found 196.0500.
;
4.2.13. 1,1,1-Trifluoroundec-4-en-2-yne (1e). Yield 81%;
1H NMR (CDCl3) d 0.89 (3H, t, J¼6.75 Hz), 1.24–1.33
(6H, m), 1.41 (2H, sex, J¼7.12 Hz), 2.17 (2H, q,
J¼7.33 Hz), 5.5 (1H, m), 6.48 (1H, dt, J¼16.00, 7.00 Hz);
13C NMR (CDCl3) d 14.00, 22.53, 28.10, 28.71, 31.56,
33.33, 74.21 (q, J¼51.8 Hz), 85.78 (q, J¼6.5 Hz), 105.78,
114.84 (q, J¼256.0 Hz), 152.24; 19F NMR (CDCl3) d
250.7 (3F, s); IR (neat) 2931, 2858, 2237, 1631,
1465 cm21; HRMS (EI) calcd for C11H15F3 (MþH)
205.1204, found 205.1208.
4.2.6. 1-Phenyl-5,5-difluoro-1-penten-3-yne (2f). Yield
85%; 1H NMR (CDCl3) d 6.17 (1H, dt, J¼16.25,
4.00 Hz), 6.36 (1H, t, J¼55.01 Hz), 7.15 (1H, d,
J¼16.25 Hz), 7.33–7.45 (5H, m); 13C NMR (CDCl3) d
81.32 (t, J¼33.3 Hz), 87.81 (t, J¼7.4 Hz), 104.18 (t,
J¼233.0 Hz), 104.74 (t, J¼3.7 Hz), 126.69, 128.86,
129.68, 135.13, 145.58; 19F NMR (CDCl3) d 2105.32
(2F, dd, J¼4.4, 55.0 Hz); IR (neat) 2218, 1450, 1373 cm21
;
HRMS (EI) calcd for C11H8F2 178.0594, found 178.0593.
1
4.2.7. 1,1-Difluoro-4-dodecen-2-yne (2g). Yield 74%; H
NMR (CDCl3) d 0.89 (3H, t, J¼7.00 Hz), 1.22–1.33 (6H,
m), 1.35–1.43 (2H, m), 2.15 (2H, q, J¼7.00 Hz), 5.47–5.85
(1H, m), 6.28 (1H, t, J¼55.01 Hz), 6.38 (1H, dt, J¼15.00,
7.50 Hz); 13C NMR (CDCl3) d 14.04, 22.55, 28.25, 28.72,
31.58, 33.24, 78.28 (t, J¼33.5 Hz), 87.59 (t, J¼7.4 Hz),
104.22 (t, J¼231.0 Hz), 106.81 (t, J¼4.0 Hz), 150.15
(t, J¼3.7 Hz); 19F NMR (CDCl3) d 2105.0 (2F, d,
4.2.14. 1-(3-Nitrophenyl)-3,3,4,4,5,5,6,6,7,7-decafluoro-
1-heptyne (2h). Yield 77%; 1H NMR (CDCl3) d 6.08
(1H, tt, J¼10.00, 52.76 Hz) 7.64 (1H, t, J¼8.00 Hz), 7.89
(1H, d, J¼8.00 Hz), 8.36 (1H, d, J¼8.00 Hz), 8.43 (1H, s);
13C NMR (CDCl3) d 76.46–77.25 (overlap), 88.87 (t,
J¼6.28 Hz), 103–111 (5C, m), 120.26, 125.76, 127.37,
130.01, 137.97, 148.13; 19F NMR (CDCl3) d 2137.8 (2F, d,
J¼27.0 Hz), 2130.32 (2F, s), 2123.44 (4F, s), 299.1 (2F,
s); IR (neat) 2256, 1539, 1477 cm21; MS (FAB) m/z (rel
intensity) 397 (55) calcd for C13H5F10NO2 397.0161, found
397.0160.
J¼4.4, 55.0 Hz); IR (neat) 2932, 2858, 2226, 1373 cm21
;
HRMS (CI) calcd for C11H15F2 (M2H) 185.1142, found
185.1145.
4.2.8. 1-(2-Methoxyphenyl)-3,3,3-trifluoropropyne (1a).
1
Yield 78%; H NMR (CDCl3) d 3.90 (3H, s), 6.92 (1H, d,
4.3. Typical procedure for the synthesis of trifluoro-
methylated acetylene derivatives. To a solution of
diisopropylamine (0.46 mL, 3.3 mmol) in THF (3.0 mL)
was added 2.06 mL (3.3 mmol) of n-BuLi (1.6 M hexane
solution) at 2788C and the whole was stirred for 15 min. To
this solution was added dropwise 2-bromo-3,3,3-trifluor-
opropene (0.15 mL, 1.5 mmol), followed by addition of zinc
chloride tetramethylethylenediamine complex (ZnCl2·-
TMEDA) (0.417 g, 1.65 mmol) in one portion. The reaction
was stirred for 30 min at 2788C, then allowed to warm to
room temperature and stirred for 30 min. After the mixture
was stirred for 30 min at room temperature, iodobenzene
(0.204 g, 1.0 mmol) and tetrakis(triphenyl–phosphine)pal-
ladium(0) (Pd(PPh3)4) (0.058 g, 0.05 mmol) were added and
the whole was stirred for 6 h at the reflux temperature of
THF. The reaction mixture was quenched with NH4Cl aq.
and extracted with EtOAc three times. The organic layer
was dried over Na2SO4 and concentrated in vacuo. The
J¼8.50 Hz), 6.96 (1H, t, J¼7.80 Hz), 7.43 (1H, dt, J¼1.30,
7.90 Hz), 7.49 (1H, dd, J¼1.30, 7.80 Hz); 13C NMR
(CDCl3) d 55.75, 79.29 (q, J¼52.1 Hz), 83.76 (q,
J¼6.1 Hz), 107.74, 110.86, 115.03 (q, J¼256.4 Hz),
120.50, 132.49, 134.32, 161.29; 19F NMR (CDCl3) d
249.95 (3F, s); IR (neat) 2253, 1597, 1497, 1466,
1323 cm21; HRMS calcd for C10H7F3O m/z 200.0449,
found 200.0427.
4.2.9. 1-(3-Nitrophenyl)-3,3,3-trifluoropropyne (1b).
1
Yield 76%; H NMR (CDCl3) d 7.63 (1H, t, J¼8.20 Hz),
7.88 (1H, d, J¼7.50 Hz), 8.34 (1H, d, J¼10.00 Hz), 8.43
(1H, s); 13C NMR (CDCl3) d 76.74–77.4 (overlap), 83.39
(q, J¼6.2 Hz), 114.36 (q, J¼259.0 Hz), 113.30, 120.20,
125.60, 127.30, 129.90, 137.90; 19F NMR (CDCl3) d 251.0
(3F, s); IR (neat) 3089, 2858, 2268, 2237, 1535, 1477 cm21
;

T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
7577
residue was chromatographed on silica gel (hexane
only) to afford 1-phenyl-3,3,3-trifluoropropyne (0.142 g,
0.83 mmol).
129.69, 131.94, 134.21, 137.08; 19F NMR (CDCl3) d 250.6
(3F, s); IR (neat) 2260, 1475, 1436 cm21; HRMS calcd for
C9H345ClF3 203.9954, found 203.9952.
4.3.1. 1-Phenyl-3,3,3-trifluoropropyne (1f). Yield 83%;
1H NMR (CDCl3) d 7.40 (2H, t, J¼7.50 Hz), 7.49 (1H, t,
J¼7.50 Hz), 7.57 (2H, d, J¼7.50 Hz); 13C NMR (CDCl3) d
75.67 (q, J¼52.5 Hz), 86.50 (q, J¼6.2 Hz), 114.86 (q,
J¼256.8 Hz), 118.51, 128.64, 130.87, 132.43; 19F NMR
(CDCl3) d 250.3 (3F, s); IR (neat) 2928, 2855, 2257, 1493,
1447 cm21; HRMS (EI) calcd for C9H5F3 170.0343, found
170.0347.
4.4. Typical procedure for the preparation of vinyl
iodide 5 via radical addition of perfluoroalkyl iodide to
terminal acetylene
Zinc (powder, 10 mol%, 65 mg, 1.0 mmol) was placed in a
10 mL round-bottom flask followed by 2 mL of CH2Cl2 and
terminal alkyne (10.0 mmol). To this mixture were added
perfluoroalkyl iodide (10 mmol) and 20 mol% of TFA
slowly (228 mg, 2.0 mmol). The mixture was allowed to stir
overnight at room temperature, diluted with 10 mL of
CH2Cl2, and filtered to remove zinc. The solvent was
removed in vacuo to provide the crude materials which were
purified by column chromatography to give the correspond-
ing fluoroalkylated vinyl iodide with preferential E
selectivity (up to 95% selectivity). Only physical data of
E-vinyl iodides is described below.
4.3.2. 1-(4-Methoxyphenyl)-3,3,3-trifluoropropyne (1g).
1
Yield 99%; H NMR (CDCl3) d 3.84 (3H, s), 6.90 (2H, d,
J¼8.50 Hz), 7.49 (2H, d, J¼8.50 Hz); 13C NMR (CDCl3) d
55.37, 74.78 (q, J¼52.1 Hz), 87.05 (q, J¼6.8 Hz), 110.30,
114.30, 115.05 (q, J¼256.3 Hz), 134.15, 161.53; 19F NMR
(CDCl3) d 249.9 (3F, s); IR (neat) 2253, 1609, 1512,
1323 cm21; HRMS calcd for C10H7F3O m/z 200.0449,
found 200.0434.
4.4.1. (E)-9,9,10,10,11,11,12,12,13,13,14,14,15,15,16,16,16-
Heptadecafluoro-7-iodo-7-hexadecene (7a). Yield 62%; 1H
NMR (CDCl3) d 0.90 (3H, t, J¼6.70 Hz), 1.31–1.36 (6H, m),
1.55–1.59 (2H, m), 2.63 (2H, t, J¼7.50 Hz), 6.32 (1H, t,
J¼15.00 Hz); 13C NMR (CDCl3) d 13.89, 22.48, 28.13, 30.06,
31.48, 41.17, 108.12–121.88 (m), 123.04 (t, J¼6.5 Hz),
126.52 (t, J¼23.8 Hz); 19F NMR (CDCl3) d281.6 (3F, t,
J¼8.8 Hz), 2105.7 (2F, m), 2122.3 to 2124 (10F, m),
2126.7 (2F, m); IR (neat) 2935, 2862, 1635, 1465 cm21; MS
(CI) calcd for C16H14F17I 655.9869, found 655.9860.
4.3.3. 1-(4-Methylphenyl)-3,3,3-trifluoropropyne (1h).
1
Yield 99%; H NMR (CDCl3) d 2.39 (3H, s), 7.20 (2H,
d, J¼8.00 Hz), 7.45 (2H, d, J¼8.00 Hz); 13C NMR (CDCl3)
d 21.37, 75.20 (q, J¼52.0 Hz), 86.92 (q, J¼6.8 Hz),
114.92 (q, J¼256.6 Hz), 115.40, 129.39, 132.34, 141.45;
19F NMR (CDCl3) d 250.1 (3F, s); IR (neat) 2253, 1512,
1315 cm21; HRMS calcd for C10H7F3 m/z 184.0500, found
184.0490.
4.3.4. 1-(4-Chlorophenyl)-3,3,3-trifluoropropyne (1i).
1
Yield 81%; H NMR (CDCl3) d 7.39 (2H, d, J¼8.50 Hz),
4.4.2. (E)-1,1,1,2,2,3,3,4,4-Nonafluoro-6-iodo-5-dodecene
(7b). Yield 81%; 1H NMR (CDCl3) d 0.90 (3H, t,
J¼6.70 Hz), 1.31–1.36 (6H, m), 1.55–1.59 (2H, m), 2.63
(2H, t, J¼7.50 Hz), 6.32 (1H, t, J¼14.50 Hz); 13C NMR
(CDCl3) d 13.95, 22.47, 28.1, 30.02, 31.46, 41.16, 108.04–
121.52 (m), 123.14 (t, J¼7.5 Hz), 126.35 (t, J¼23.8 Hz);
19F NMR (CDCl3) d 280.3 (3F, m), 2104.3 to 2104.6 (2F,
m), 2123.1 to 2123.2 (2F, m), 2124.7 to 2125.0 (2F, m);
IR (neat) 2935, 2862, 1635 cm21; MS (CI) calcd for
C12H14F9I 455.9997, found 456.0000.
7.49 (2H, d, J¼8.00 Hz); 13C NMR (CDCl3) d 76.53
(q, J¼53.3 Hz), 85.30 (q, J¼6.2 Hz), 115.30 (q, J¼
256.9 Hz), 116.93, 129.14, 133.65, 137.36; 19F NMR
(CDCl3) d 249.9 (3F, s); IR (neat) 2257, 1593, 1493,
1400, 1312 cm21; HRMS calcd for C9H435ClF3 203.9954,
found 203.9929.
4.3.5. 1-(4-Nitrophenyl)-3,3,3-trifluoropropyne (1j).
1
Yield 51%; H NMR (CDCl3) d 7.75 (2H, d, J¼9.00 Hz),
8.28 (2H, d, J¼9.00 Hz); 13C NMR (CDCl3) d 79.32 (q,
J¼53.4 Hz), 83.64 (q, J¼6.3 Hz), 114.35 (q, J¼258.0 Hz),
123.82, 124.88, 133.47, 148.81; 19F NMR (CDCl3) d 251.2
(3F, s); IR (neat) 2260, 1535, 1353 cm21; HRMS calcd for
C9H4F3NO2 215.0194, found 215.0203.
4.4.3. (E)-1,1,1,2,2,3,3,4,4-Nonafluoro-6-iodo-5-hexade-
1
cene (7c). Yield 81%; H NMR (CDCl3) d 0.88 (3H, t,
J¼6.70 Hz), 1.27–1.30 (14H, m), 1.55–1.59 (2H, m), 2.63
(2H, t, J¼7.50 Hz), 6.32 (1H, t, J¼14.30 Hz); 13C NMR
(CDCl3) d 14.05, 22.68, 28.43, 29.28, 29.31, 29.44, 29.55,
30.05, 31.90, 41.15, 108.22–121.51 (m), 123.15 (t,
J¼6.0 Hz), 126.33 (t, J¼23.7 Hz); 19F NMR (CDCl3) d
280.8 (3F, t, m), 2105.1 (2F, m), 2123.8 (2F, m), 2125.3
(2F, m); IR (neat) 2927, 2858, 1635, 1465 cm21; MS (CI)
calcd for C16H22F9I 512.0622, found 512.0622.
4.3.6. 1-(3-Methoxyphenyl)-3,3,3-trifluoropropyne (1k).
Yield 95%; 1H NMR (CDCl3) d 3.82 (3H, s), 7.02 (1H, dd,
J¼2.50, 8.50 Hz), 7.06 (1H, s), 7.15 (1H, d, J¼7.50 Hz),
7.30 (1H, t, J¼8.0 Hz); 13C NMR (CDCl3) d 55.35, 75.35
(q, J¼52.6 Hz), 86.43 (q, J¼6.2 Hz), 114.82 (q,
J¼256.8 Hz), 117.01, 117.57, 119.38, 124.89, 129.79,
159.41; 19F NMR (CDCl3) d 250.3 (3F, s); IR (neat)
2264, 2241, 1597, 1489 cm21; HRMS calcd for C10H7F3O
m/z 200.0449, found 200.0434.
4.4.4. (E)-1,1,1,2,2,3,3,4,4-Nonafluoro-7-ethyl-6-iodo-5-
1
undecene (7d). Yield 55%; H NMR (CDCl3) d 0.84 (3H,
t, J¼7.50 Hz), 0.90 (3H, t, J¼7.20 Hz), 1.16–1.46 (8H, m),
1.91 (1H, m), 6.49 (1H, t, J¼14.75 Hz); 13C NMR (CDCl3)
d 11.13, 13.83, 22.73, 28.86, 29.24, 36.02, 47.27, 112.3–
121.83 (m), 127.32 (t, J¼22.0 Hz), 135.14 (t, J¼6.3 Hz);
19F NMR (CDCl3) d 281.8 (3F, t, J¼10.1 Hz), 2103.1 to
2104.6 (2F, m), 2124.4 to 2124.5 (2F, m), 2126.1 to
2126.3 (2F, m); IR (neat) 2935, 2862, 1624, 1458,
4.3.7. 1-(2-Chlorophenyl)-3,3,3-trifluoropropyne (1l).
1
Yield 79%; H NMR (CDCl3) d 7.30 (1H, t, J¼7.50 Hz),
7.41 (1H, t, J¼7.80 Hz), 7.46 (1H, d, J¼8.50 Hz), 7.58 (1H, d,
J¼7.50 Hz);13C NMR (CDCl3) d80.03 (q, J¼52.9 Hz), 83.03
(q, J¼6.4 Hz), 114.73 (q, J¼257.3 Hz), 118.82, 126.72,

7578
T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
1353 cm21; MS (CI) calcd for C13H16F9I 470.0153, found
470.0155.
4.4.11. (E)-1,1,1-Trifluoro-4-ethyl-3-iodo-2-octene (7k).
1
Yield 66%; H NMR (CDCl3) d 0.82 (3H, t, J¼7.20 Hz),
0.89 (3H, t, J¼7.20 Hz), 1.12–1.45 (8H, m), 1.84 (1H,
quint, J¼5 Hz), 6.54 (1H, q, J¼7.80 Hz); 13C NMR
(CDCl3) d 11.14, 13.88, 22.67, 28.84, 28.93, 35.73, 47.25,
122.09 (q, J¼274.1 Hz), 130.08 (q, J¼34.0 Hz), 132.64 (q,
J¼6.2 Hz); 19F NMR (CDCl3) d 255.6 (3F, d, J¼8.7 Hz);
IR (neat) 2962, 2931, 2862, 1631, 1461, 1315 cm21; MS
(EI) 320 (Mþ, 3.1), 264 (100), 193 (1.9), 174 (9.9), 137
(32.1), 59 (61.3); HRMS was not obtained due to the
instability of the corresponding molecular ion.
4.4.5. (E)-1-Phenyl-3,3,4,4,5,5,6,6,6-nonafluoro-1-iodo-1-
1
hexene (7e). Yield 62%; H NMR (CDCl3) d 6.59 (1H, t,
J¼13.75 Hz), 7.28–7.33 (5H, m); 13C NMR (CDCl3) d
112.77 (t, J¼6.3 Hz), 113.64–116.41 (m), 126.83, 126.89
(t, J¼21.9 Hz), 127.89, 129.28, 141.30; 19F NMR (CDCl3) d
281.6 (3F, t, J¼9.9 Hz), 2106.1 (2F, q, J¼12.1 Hz),
2124.2 to 2124.5 (2F, m), 2126.2 to 2126.7 (2F, m); IR
(neat) 1639, 1488, 1353, 1234 cm21; HRMS (CI) calcd for
C12H6F9I 447.9370, found 447.9362.
4.4.12. (E)-1,1,1-Trifluoro-4-cyclohexyl-3-iodo-2-octene
1
(7l). Yield 62%; H NMR (CDCl3) d 0.89–0.99 (2H, m),
4.4.6. (E)-1-(4-Methylphenyl)-3,3,4,4,5,5,6,6,6-nona-
fluoro-1-hexyne (7f). Yield 65%; 1H NMR (CDCl3) d
2.34 (3H, s), 6.56 (1H, t, J¼13.50 Hz), 7.13 (2H, d,
J¼8.00 Hz), 7.19 (2H, d, J¼8.00 Hz); 13C NMR (CDCl3) d
21.32, 113.38 (t, J¼6.2 Hz), 113.4–116 (m), 126.53 (t,
J¼22.6 Hz), 126.89, 128.66, 138.50, 139.51; 19F NMR
(CDCl3) d 281.6 (3F, t, J¼9.9 Hz), 2105.9 (2F, q,
J¼13.2 Hz), 2124.2 to 2124.5 (2F, m), 2126.3 to
2126.7 (2F, m); IR (neat) 1635, 1508, 1353 cm21; HRMS
(CI) calcd for C13H8F9I 461.9527, found 461.9517.
1.1–1.3 (3H, m), 1.6–1.7 (6H, m), 2.4 (2H, d, J¼5.50 Hz),
6.44 (1H, q, J¼7.80 Hz); 13C NMR (CDCl3) d 26.17, 32.07,
38.19, 47.24, 120.23 (q, J¼6.3 Hz), 121.87 (q,
J¼274.8 Hz), 129.77 (q, J¼34.1 Hz); 19F NMR (CDCl3) d
256.6 (3F, d, J¼8.8 Hz); IR (neat) 2927, 2854, 1639,
1450 cm21; MS (EI) calcd for C10H14F3I 318.0092, found
318.0085.
4.5. Typical procedure for path C
4.4.7. (E)-1-Perfluoroisopropyl-2-iodo-1-octene (7g).
1
Potassium t-butoxide (3.0 mmol, 336 mg) was suspended in
5 mL of benzene, and the reaction mixture was cooled to
08C. To this solution was added the mixture of fluoroalky-
lated vinyl iodide (1.0 mmol) in benzene (2 mL) at that
temperature, then stirred for 10 min. The reaction mixture
was allowed to warm gradually to the reflux temperature,
and stirred for 2 h. The mixture was cooled to room
temperature, and poured into sat. NH4Cl aq. The whole was
extracted with ethyl acetate three times. The combined
organic layers were washed with brine, dried over
anhydrous Na2SO4, and concentrated in vacuo. The
obtained crude materials were purified by silica gel column
chromatography to afford the corresponding fluoroalkylated
alkyne.
Yield 84%; H NMR (CDCl3) d 0.89 (3H, t, J¼6.70 Hz),
1.30–1.35 (6H, m), 1.54–1.58 (2H, m), 2.64 (2H, t,
J¼7.50 Hz), 6.15 (1H, d, J¼2.50 Hz); 13C NMR (CDCl3)
d 13.95, 22.48, 28.10, 29.99, 31.45, 41.32, 92–94 (m),
119.77 (dd, J¼27.9, 287.2 Hz), 121.95 (d, J¼13.8 Hz); 19F
NMR (CDCl3) d 276.5 (6F, d, J¼8.4 Hz), 2182.5 (1F, m);
IR (neat) 2931, 2862, 1635, 1458, 1303 cm21; MS (CI)
calcd for C11H14F7I 406.0028, found 406.0029.
4.4.8. (E)-1,1,1,2,2-Pentafluoro-4-iodo-3-decene (7h).
1
Yield 85%; H NMR (CDCl3) d 0.90 (3H, t, J¼6.70 Hz),
1.27–1.36 (6H, m), 1.53–1.60 (2H, m), 2.63 (2H, t,
J¼7.50 Hz), 6.29 (1H, t, J¼14.30 Hz); 13C NMR (CDCl3)
d 13.95, 22.46, 28.07, 29.94, 31.45, 41.08, 109.68–121.91
(m), 123.06 (t, J¼6.0 Hz), 126.19 (t, J¼23.4 Hz); 19F NMR
(CDCl3) d 284.7 (3F, t, J¼17.5 Hz), 2108.5 (2F, d,
4.5.1. 9,9,10,10,11,11,12,12,13,13,14,14,15,15,16,16,16-
Heptadecafluoro-7-hexadecyne (4a). Yield 49%; 1H
NMR (CDCl3) d 0.82 (3H, t, J¼7.00 Hz), 1.19–1.36 (6H,
m), 1.51 (2H, quint, J¼7.40 Hz), 2.28 (2H, quint,
J¼6.40 Hz); 13C NMR (CDCl3) d 13.85, 18.46, 22.38,
27.15, 28.25, 31.08, 67.38 (t, J¼36.6 Hz), 95.42 (t,
J¼6.3 Hz); 19F NMR (CDCl3) d 281.6 (3F, t, J¼8.8 Hz),
295.5 (2F, m), 2122.3 to 2126.7 (10F, m), 2163.3 to
J¼13.2 Hz); IR (neat) 2931, 2862, 1635, 1458, 1334 cm21
;
MS (CI) calcd for C10H14F5I 356.0060, found 356.0059.
4.4.9. (E)-1,1,1-Trifluoro-3-iodo-2-nonene (7i). Yield
1
78%; H NMR (CDCl3) d 0.90 (3H, t, J¼6.7 Hz), 1.32–
1.36 (6H, m), 1.51–1.58 (2H, m), 2.60 (2H, t, J¼7.50 Hz),
6.38 (1H, q, J¼7.83 Hz); 13C NMR (CDCl3) d 13.97, 22.48,
27.99, 29.59, 31.46, 40.72, 121.00 (q, J¼6.3 Hz), 121.92 (q,
J¼274.1 Hz), 128.95 (q, J¼34.1 Hz); 19F NMR (CDCl3) d
257.2 (d, J¼8.8 Hz); IR (neat) 2931, 2858, 1639,
1465 cm21; MS (CI) calcd for C9H14F3I 306.0092, found
306.0085.
2164.2 (2F, m); IR (neat) 2935, 2866, 2260, 1211 cm21
;
MS (CI) calcd for C16H12F17 (M2H) 527.0668, found
527.0663.
4.5.2. 1,1,1,2,2,3,3,4,4-Nonafluoro-5-dodecyne (4b). Yield
1
44%; H NMR (CDCl3) d 0.90 (3H, t, J¼7.00 Hz), 1.26–
1.43 (6H, m), 1.59 (2H, quint, J¼7.40 Hz), 2.35 (2H, quint,
J¼6.40 Hz); 13C NMR (CDCl3) d 13.89, 18.46, 22.4, 27.15,
28.26, 31.08, 67.25 (t, J¼35.8 Hz), 95.46 (t, J¼6.3 Hz); 19F
NMR (CDCl3) d 281.76 (3F, t, J¼9.9 Hz), 296.4 (2F, m),
2123.89 to 2124.4 (2F, m), 2125.75 to 2126.14 (2F, m);
IR (neat) 2935, 2862, 2260, 1353, 1238 (s), 1137 cm21; MS
(CI) calcd for C12H14F9 (MþH) 329.0952, found 329.0954.
4.4.10. (E)-1,1,1-Trifluoro-3-iodo-2-tridecene (7j). Yield
1
45%; H NMR (CDCl3) d 0.88 (3H, t, J¼7.00 Hz), 1.27–
1.30 (14H, m), 1.52–1.57 (2H, m), 2.6 (2H, t, J¼7.50 Hz),
6.38 (1H, q, J¼7.60 Hz); 13C NMR (CDCl3) d 14.09, 22.68,
28.32, 29.26, 29.30, 29.43, 29.54, 29.62, 31.89, 40.71,
121.05 (q, J¼6.9 Hz), 121.92 (q, J¼274.1 Hz), 128.92 (q,
J¼34.4 Hz); 19F NMR (CDCl3) d 257.8 (3F, d, J¼8.4 Hz);
IR (neat) 2927, 2854, 1639, 1465 cm21; MS (CI) calcd for
C13H22F3I 362.0718, found 362.0717.
4.5.3. 1,1,1,2,2,3,3,4,4-Nonafluoro-5-hexadecyne (4c).
1
Yield 70%; H NMR (CDCl3) d 0.81 (3H, t, J¼7.00 Hz),

T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
7579
1.20–1.34 (14H, m), 1.51 (2H, quint, J¼7.40 Hz), 2.28 (2H,
quint, J¼6.40 Hz); 13C NMR (CDCl3) d 14.06, 18.47,
22.66, 27.20, 28.60, 28.91, 29.28, 29.37, 29.48, 31.88, 67.29
(t, J¼36.5 Hz), 95.48 (t, J¼6.4 Hz); 19F NMR (CDCl3) d
280.8 (3F, m), 295.9 (2F, m), 2123.2 (2F, m), 2125.1
(2F, m); IR (neat) 2927, 2858, 2256, 1465, 1353 cm21; MS
(CI) calcd for C16H21F9 384.1500, found 384.1505.
4.5.9. 1,1,1-Trifluoro-2-nonyne (3i). Yield 48%; 1H NMR
(CDCl3) d 0.90 (3H, t, J¼7.00 Hz), 1.27–1.43 (6H, m), 1.58
(2H, quint, J¼7.37 Hz), 2.27–2.32 (2H, m); 13C NMR
(CDCl3) d 13.92, 18.10, 22.43, 27.22, 28.38, 31.14, 68.35
(q, J¼51.6 Hz), 89.31 (q, J¼6.3 Hz), 114.19 (q,
J¼256.1 Hz); 19F NMR (CDCl3) d 249.2 (t, J¼4.7 Hz);
IR (neat) 2935, 2862, 2264, 1720, 1465 cm21; MS (CI)
calcd for C9H12F3 (M2H) 177.0891, found 177.0896.
4.5.4. 1,1,1,2,2,3,3,4,4-Nonafluoro-7-ethyl-5-undecyne
(4d). Yield 81%; 1H NMR (CDCl3) d 0.91 (3H, t,
J¼7.25 Hz), 1.01 (3H, t, J¼7.50 Hz), 1.26–1.6 (8H, m),
2.42 (1H, quint, J¼6.9 Hz); 13C NMR (CDCl3) d 11.38,
13.82, 22.36, 26.96, 29.23, 33.15, 33.34, 68.42 (t,
J¼35.8 Hz), 98.68 (t, J¼6.9 Hz), 105–120 (m); 19F NMR
(CDCl3) d 280.8 (3F, t, J¼8.8 Hz), 296.1 (2F, m), 2123.4
(2F, m), 2125.3 (2F, m); IR (neat) 2935, 2866, 2252, 1647,
1461 cm21; MS (CI) calcd for C13H16F9 (MþH) 343.1108,
found 343.1125.
4.5.10. 1,1,1-Trifluoro-2-tridecyne (3j). Yield 67%; 1H
NMR (CDCl3) d 0.81 (3H, t, J¼6.75 Hz), 1.2–1.33 (14H,
m), 1.50 (2H, quint, J¼8.10 Hz), 2.2–2.25 (2H, m); 13C
NMR (CDCl3) d 14.07, 18.01, 22.66, 27.22, 28.69, 28.94,
29.27, 29.38, 29.50, 31.88, 68.33 (q, J¼52.8 Hz), 89.34 (q,
J¼6.3 Hz), 114.17 (q, J¼256.5 Hz); 19F NMR (CDCl3) d
248.8 (t, J¼4.7 Hz); IR (neat) 2927, 2858, 2268, 1720,
1465 cm21; MS (CI) calcd for C13H20F3 (M2H) 233.1517,
found 233.1521.
4.5.5. 3,3,4,4,5,5,6,6,6-Nonafluoro-1-phenyl-2-hexyne
(2i). Yield 74%; 1H NMR (CDCl3) d 7.39 (2H, t,
J¼7.80 Hz), 7.48 (1H, t, J¼7.50 Hz), 7.56 (2H, d,
J¼7.00 Hz); 13C NMR (CDCl3) d 74.63 (t, J¼36.5 Hz),
92.34 (t, J¼6.3 Hz), 107–118 (m), 128.67, 131.09, 132.48;
19F NMR (CDCl3) d 281.6 (3F, t, J¼9.9 Hz), 297.8 to
298.0 (2F, m), 2123.8 to 2124.2 (2F, m), 2125.8 to
2126.1 (2F, m); IR (neat) 2248, 1728, 1492 cm21; HRMS
(CI) calcd for C12H5F9 320.0248, found 320.0241.
4.5.11. 1,1,1-Trifluoro-4-ethyl-2-octyne (3k). Yield 86%;
1H NMR (CDCl3) d 0.86–1.02 (6H, m), 1.22–1.61 (8H, m),
2.37–2.44 (1H, m); 13C NMR (CDCl3) d 11.58, 13.87,
22.39, 26.93, 29.35, 32.93, 33.14, 69.15 (q, J¼51.5 Hz),
89.8 (q, J¼6.3 Hz), 114.13 (q, J¼255.2 Hz); 19F NMR
(CDCl3) d 249.1 (3F, s); IR (neat) 2935, 2866, 2272,
1458 cm21; HRMS (CI) calcd for C10H14F3 (M2H)
191.1048, found 191.1041.
4.5.12. 1,1,1-Trifluoro-4-cyclohexyl-2-butyne (3l). Yield
1
4.5.6. 3,3,4,4,5,5,6,6,6-Nonafluoro-1-(4-methylphenyl)-2-
1
74%; H NMR (CDCl3) d 1.01 (2H, q, J¼12.00 Hz), 1.1–
hexyne (2j). Yield 77%; H NMR (CDCl3) d 2.39 (3H, s),
1.19 (1H, m), 1.26 (2H, q, J¼12.50 Hz), 1.65–1.81 (6H, m),
2.18–2.21 (2H, m); 13C NMR (CDCl3) d 25.78, 25.92,
32.54, 36.36, 69.18 (q, J¼51.6 Hz), 88.38 (q, J¼6.3 Hz),
114.18 (q, J¼255.3 Hz); 19F NMR (CDCl3) d 247.2 (d,
7.19 (2H, d, J¼8.00 Hz), 7.44 (2H, d, J¼8.00 Hz); 13C
NMR (CDCl3) d 21.67, 74.15 (t, J¼35.8 Hz), 92.81 (t,
J¼6.3 Hz), 107.28–125.09 (m), 129.43, 132.41, 141.76; 19F
NMR (CDCl3) d 281.5 (3F, t, J¼9.9 Hz), 297.2 to 297.8
(2F, m), 2123.8 to 2124.0 (2F, m), 2125.7 to 2126.0 (2F,
m); IR (neat) 2245, 1512, 1353 cm21; HRMS (CI) calcd for
C13H7F9 334.0404, found 334.0402.
J¼4.4 Hz); IR (neat) 2931, 2854, 2260, 1720, 1450 cm21
;
MS (EI) calcd for C10H12F3 (M2H) 189.0891, found
189.0894.
4.5.7. 1-Heptafluoroisopropyl-1-octyne (4g). Yield 40%;
1H NMR (CDCl3) d 0.89 (3H, t, J¼7.00 Hz), 1.26–1.43
(6H, m), 1.58 (2H, quint, J¼7.25 Hz), 2.34 (2H, q,
J¼7.20 Hz); 13C NMR (CDCl3) d 13.85, 18.64, 22.39,
27.24, 28.19, 31.05, 65.43 (d, J¼26.4 Hz), 96.52 (d,
J¼8.8 Hz), 111.62–125.41 (m); 19F NMR (CDCl3) d
275.5 (6F, d, J¼11.0 Hz), 2163.6 (1F, m); IR (neat)
2935, 2866, 2256, 1647 cm21; MS (CI) calcd for C11H14F7
(MþH) 279.0984, found 279.0984.
References
1. (a) Banks, R. E. Organofluorine Chemistry: Principals and
Commercial Applications; Plenum: New York, 1994. (b)
Banks, R. E. Fluorine Chemistry at the Millenium: Fascinated
by Fluorine; Elsevier: Amsterdam, 2000; and references
therein.
2. (a) Fields, R.; Hazeldine, R. N.; Hubbard, A. F. J. Chem. Soc.
C 1971, 3838–3843. (b) Clark, H. C.; Fiess, P. L.; Wong, C. S.
Can. J. Chem. 1977, 55, 177–188. (c) Attig, T. G.; Clark,
H. C.; Wong, C. S. Can. J. Chem. 1977, 55, 189–198. (d)
Clark, H. S.; Ferguson, G.; Goel, A. B.; Janzen, E. G.;
Ruegger, H.; Siew, P. Y.; Wong, C. S. J. Am. Chem. Soc. 1986,
108, 6961–6972.
4.5.8. 1,1,1,2,2-Pentafluoro-3-decyne (4h). Yield 55%; 1H
NMR (CDCl3) d 0.89 (3H, t, J¼7.00 Hz), 1.25–1.43 (6H,
m), 1.55–1.61 (2H, m), 2.31–2.39 (2H, m); 13C NMR
(CDCl3) d 13.85, 18.64, 22.39, 27.25, 28.19, 31.05, 65.43
(d, J¼26.9 Hz), 96.52 (d, J¼8.4 Hz), 115.22–124.01 (m);
19F NMR (CDCl3) d 285.4 (3F, t, J¼4.4 Hz), 299.9 (2F,
3. Bumgardner, C. L.; Bunch, J. E.; Whangbo, M.-H. Tetra-
hedron Lett. 1986, 27, 1883–1886.
m); IR (neat) 2931, 2874, 1666, 1465, 1369, 1207 cm21
;
HRMS (CI) calcd for C10H13F5 (MþH) 229.1016, found
4. Bunch, J. E.; Bumgaradner, C. L. J. Fluorine Chem. 1987, 36,
313–317.
229.1021.
5. Kobayashi, Y.; Yamashita, T.; Takahashi, K.; Kuroda, H.;
Kumadaki, I. Tetrahedron Lett. 1982, 23, 343–344.
6. For the synthetic applications of nonfluorinated counterparts,
see (a) Smith, N. D.; Mancuso, J.; Lautens, M. Chem. Rev.
2000, 100, 3257–3282. (b) Sato, F.; Urabe, H.; Okamoto, S.
For the synthesis of trifluoromethylated alkynes, 3i–l, the
reaction was carried out in a similar manner as described
above except for the reaction temperature (2 h) and an
amount of t-BuOK (1.2 equiv.).

7580
T. Konno et al. / Tetrahedron 59 (2003) 7571–7580
Chem. Rev. 2000, 100, 2835–2886. (c) Yoshida, H.;
11. Only a few reports have been published on the synthesis of
perfluoroalkylated acetylenes in addition to trifluoro-methyl-
ated acetylenes. See (a) Hamper, B. C. J. Org. Chem. 1988, 53,
5558–5562. (b) Hamper, B. C. Org. Synth. 1991, 70,
246–253. (c) See Ref. 9.
Shirakawa, E.; Nakano, Y.; Honda, Y.; Hiyama, T. Bull.
Chem. Soc. Jpn 2001, 74, 637–647. (d) Shirakawa, E.;
Hiyama, T. Bull. Chem. Soc. Jpn 2002, 75, 1435–1450. (e)
Asao, N.; Yamamoto, Y. Bull. Chem. Soc. Jpn 2000, 73,
1071–1087.
12. We attempted the conventional method for the preparation of
internal acetylene derivatives. Thus the reaction of trifluoro-
methylated lithium acetylide with benzyl bromide at 2788C or
08C, however, no trace of the desired alkyne was detected.
This may be due to less nucleophilisity of the acetylide, which
is derived from an electronwithdrawing CF3 group.
13. Yamanaka, H.; Araki, T.; Kuwabara, M.; Fukunishi, K.;
Nomura, M. Nippon Kagaku Kaishi 1986, 1321–1328.
14. (a) Yamazaki, T.; Mizutani, K.; Kitazume, T. J. Org. Chem.
1995, 60, 6046–6056. (b) Mizutani, K.; Yamazaki, T.;
Kitazume, T. J. Chem. Soc., Chem. Commun. 1995, 51–52.
(c) Katritzky, A. R.; Qi, M.; Wells, A. P. J. Fluorine Chem.
1996, 80, 145–147.
7. Drakesmith, F. G.; Stewart, O. J.; Tarrant, P. J. Org. Chem.
1968, 33, 280–285.
8. (a) Henne, A. L.; Nager, M. J. Am. Chem. Soc. 1952, 74,
650–652. (b) Bruce, M. I.; Harbourne, A. L.; Waugh, F.;
Stone, F. G. A. J. Chem. Soc. (A) 1968, 356–359.
9. Yoneda, N.; Matsuoka, S.; Miyaura, N.; Fukuhara, T.; Suzuki,
A. Bull. Chem. Soc. Jpn 1990, 63, 2124–2126.
10. (a) Laurent, A. J.; Le Drean, I. M.; Selmi, A. Tetrahedron Lett.
1991, 32, 3071–3074. (b) Porta, P. L.; Capuzzi, L.; Bettarini,
F. Synthesis 1994, 287–290. (c) Meazza, G.; Capuzzi, L.;
Piccardi, P. Synthesis 1989, 331–334. (d) Hiyama, T.; Sato,
K.; Fujita, M. Bull. Chem. Soc. Jpn 1989, 62, 1352–1354. (e)
Finnegan, W. G.; Norris, W. P. J. Am. Chem. Soc. 1963, 85,
1139–1140. (f) Brisdon, A. K.; Crossley, I. R. Chem.
Commun. 2002, 2420–2421.
15. Jennings, M. P.; Cork, E. A.; Ramachandran, P. V. J. Org.
Chem. 2000, 65, 8763–8766.