Stereoselective synthesis of (E)-1-fluoro-1,3-enynes

Article abstract of DOI:10.1016/S0040-4020(01)00683-4

1-Fluoro-1,3-enynes were stereoselectively prepared by the cross-coupling reaction of 1-alkynes with β-fluoroalkenyliodides obtained from (β-fluoroalkenyl)iodonium salts. As the reaction proceeds under mild conditions, polyfunctionalized 1-fluoro-1,3-enyn

Full text of DOI:10.1016/S0040-4020(01)00683-4

TETRAHEDRON
Pergamon
Tetrahedron 57 ,2001) 7143±7148
Stereoselective synthesis of ꢀE)-1-¯uoro-1,3-enynes
Masanori Yoshida, Shuhei Yoshikawa, Tsuyoshi Fukuhara, Norihiko Yoneda and Shoji Harap
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo 060-8628, Japan
Received 25 April 2001; accepted 22 June 2001
AbstractÐ1-Fluoro-1,3-enynes were stereoselectively prepared by the cross-coupling reaction of 1-alkynes with b-¯uoroalkenyliodides
obtained from ,b-¯uoroalkenyl)iodonium salts. As the reaction proceeds under mild conditions, polyfunctionalized 1-¯uoro-1,3-enynes
could be prepared, and the synthesis of a ¯uorinated analog of a natural compound was achieved using this method. q 2001Elsevier Science
Ltd. All rights reserved.
1. Introduction
was examined.9 In the presence of a Pd catalyst, the reaction
of 1a with 1-hexyne took place to provide the desired ¯uoro-
enynes 2a along with a signi®cant amount of p-tolylhexyne
,3) ,Eq. ,2)).
Fluorinated compounds have been of great interest to
synthetic and medicinal chemists due to the unique physical
and biological properties imparted by ¯uorine.1 Signi®cant
efforts have been exerted to achieve the synthesis of
¯uorinated enynes for their use as building blocks in the
preparation of the ¯uorinated analogs of natural
compounds.2 Though the stereoselective syntheses of
di¯uoro-1,3-enynes3a±c and 2-¯uoro-1,3-enynes3d,e have
been reported, selective methods for the 1-¯uoro-1,3-enynes
had been unknown. Recently, Mestdagh et al. reported the
stereoselective synthesis of ,E)-1-¯uoro-1,3-enynes;4
however, they prepared only simple substrates and, for
application to the ¯uorinated analogs of natural
compounds, the synthesis of polyfunctionalized substrates
is necessary.5
ꢀ2†
Application of hexynylstannane instead of hexyne gave a
similar result, and the formation of 3 could not be
suppressed.10 As iodotoluene is formed in the reaction of
1a with 1-hexyne and the cross-coupling reaction of iodo-
toluene with 1-hexyne proceeds under mild conditions,11 the
formation of 3 is unavoidable as long as 1a is used. There-
fore, we converted 1a to ,E)-2-¯uoro-1-iodo-1-alkenes ,4a)6
,Eq. ,3)) and examined the cross-coupling reaction with
1-hexyne ,Table 1).
2. Results and discussion
Quite recently, we found that iodotoluene di¯uoride stereo-
and regioselectively adds to 1-alkynes to give ,E)-,b-¯uoro-
alkenyl),4-methylphenyl)iodonium ¯uorides ,1) ,Eq. ,1)),6
and then applied them to the synthesis of ,E)-b-¯uoro-a,b-
unsaturated esters7 and ,E,E)-d-¯uoro-a,b,g,d-unsaturated
carbonyl compounds.8
ꢀ3†
ꢀ1†
When 8 mol% of CuI to 4a was used, a signi®cant amount
of the 1-hexyne dimer was formed ,entry 1) and 2 equiv. of
1-hexyne was necessary to obtain 2a in a good yield ,entry
2).12 By using 16 mol% of CuI, the formation of the dimer
could be suppressed, and 2a was obtained in good yield with
1.2 equiv. of 1-hexyne ,entries 3±7). The best result was
obtained when Pd,OAc)2 and 2PPh3 were used as the
catalyst, and Et2NH was used as the solvent ,entry 6).
In order to develop a new methodology for 1-¯uoro-1,3-
enynes, the cross-coupling reaction of 1 with 1-alkynes
Keywords: coupling reactions; ¯uorine and compounds; hypervalent
elements.
p
Corresponding author. Tel./fax: 181-11-706-6556;
e-mail: hara@org-mc.eng.hokudai.ac.jp
0040±4020/01/$ - see front matter q 2001Elsevier Science Ltd. All rights reserved.
PII: S0040-4020,01)00683-4

7144
M. Yoshida et al. / Tetrahedron 57 ,2001) 7143±7148
Table 1. Cross-coupling reaction of 4a with 1-hexyne using various catalysts and amines
Entry
So1vent
Catalyst
Aminea
CuI/4a
Hexyne/4a
Yield of 2a ,%)b
c
1DMF
Pd
DMF
DMF
Et3N
Et3N
Et2NH
Et2NH
2dba314PPh3
Pd2dba314PPh3
Pd2dba314PPh3
Pd2dba314PPh3
Pd,OAc)212PPh3
Pd,OAc)212PPh3
Pd2dba314PPh3
Et3N
Et3N
Et3N
±
±
±
0.08
0.08
0.16
0.16
0.16
0.16
0.16
1.2
2
±
2
3
4
5
6
7
80
80
80
77
85
80
1.2
1.2
1.2
1.2
1.2
±
a
1.5 equiv. of amine to 4a was used.
Isolated yield based on 4a.
Most of 4a remained unchanged.
b
c
Table 2. Stereoselective synthesis of ,E)-,2-¯uoroalkenyl)alkynes
Entry
Alkyne
Product
Yield ,%)a

M. Yoshida et al. / Tetrahedron 57 ,2001) 7143±7148
7145
Table 2. ,continued)
Entry
Alkyne
Product
Yield ,%)a
If not otherwise mentioned, the reaction was carried out at room temperature for 12 h.
* Entry 13: The reaction was carried out at room temperature for 2.5 days.
Isolated yield based on 4a.
a
Under these reaction conditions, various 1-¯uoro-1,3-
enynes 2 could be stereoselectively prepared ,.98%)
from ¯uoroalkenyliodides 4 and 1-alkynes as shown in
Table 2. As both the preparation of 4 and the cross-coupling
reaction proceed under mild condtions, the introduction of
various functional groups into 2 is possible. In order to show
the usefulness of our method, the ¯uorinated analog of a
biologically active compound was synthesized. Recently,
an 11,12-dehydrocoriolic acid ,5) was found to have stron-
ger inhibitory activity than the natural coriolic acid against
rice blast fungus.13 We planned to synthesize the ¯uorinated
analog of the dehydrocoriolic acid using our method. The
reaction of methyl ,E)-10-iodo-9-¯uoro-9-decenoate ,7),
prepared from methyl 9-decynoate, with 1-octyn-3-ol ,8)
Scheme 1.

7146
M. Yoshida et al. / Tetrahedron 57 ,2001) 7143±7148
was carried out in the presence of a Pd catalyst and CuI to
provide the ,^)-9-¯uorodehydrocoriolic acid methyl ester
,6) in 91% yield directly ,Scheme 1).
the crude ,E)-,2-¯uoro-10-methoxycarbonyl-1-decenyl),4-
methylphenyl)iodonium ¯uoride ,1a), which was dissolved
in CH2Cl2 ,25 ml), and CuI ,3.81g, 20 mmol) and KI
,3.32 g, 20 mmol) were then added. The reaction mixture
was stirred at room temperature for 3 d and then extracted
with CH2Cl2. The compound 4a was isolated by column
chromatography ,silica gel/hexane±ether) in 80% yield as
a pale yellow oil: IR ,neat): 1735 ,CvO), 1645
3. Conclusion
The stereoselective synthesis of ,E)-1-¯uoro-1,3-enynes
was carried out by the cross-coupling reaction of 1-alkynes
with ,b-¯uoroalkenyl)iodides obtained from ,b-¯uoro-
alkenyl)iodonium salts. As the reaction proceeds under
mild conditions, polyfunctionalized 1-¯uoro-1,3-enynes
could be prepared. We also applied our method to the
synthesis of a ¯uorinated analog of a natural compound.
1
,CvC) cm21. H NMR dˆ5.67 ,1H, d, Jˆ17.8 Hz), 3.67
,3H, s), 2.50 ,2H, dt, Jˆ22.5, 7.3 Hz), 2.31,2H, t,
Jˆ7.3 Hz), 1.64±1.51 ,4H, m), 1.39±1.28 ,8H, brs). 19F
NMR dˆ282.36 ,1F, dt, Jˆ17.8, 22.5 Hz). HRMS ,EI)
Calcd for C11H17FIO ,M12OMe) 300.0308, Found
300.0321.
4.1.2. ꢀE)-11-Chloro-2-¯uoro-1-iodo-1-undecene ꢀ4b).
1
Pale yellow oil: IR ,neat): 1649 ,CvC) cm21. H NMR
4. Experimental
4.1. General
dˆ5.67 ,1H, d, Jˆ17.8 Hz), 3.53 ,2H, t, Jˆ6.6 Hz), 2.50
,2H, dt, Jˆ22.4, 7.3 Hz), 1.81±1.73 ,2H, m), 1.59±1.52
,2H, m), 1.44±1.30 ,10H, m). 19F NMR dˆ282.35 ,1F,
dt, Jˆ17.8, 22.4 Hz). HRMS ,EI) Calcd for C11H19ClFI
332.0204, Found 332.0204.
The IR spectra were recorded using a JASCO FT/IR-410.
The 1H NMR ,400 MHz) and 19F NMR ,376 MHz) spectra
were recorded in CDCl3 on a JEOL JNM-A400II FT NMR
and the chemical shift, d, are referred to TMS ,1H) and
CFCl3 ,19F), respectively. The EI-low and high-resolution
mass spectra were measured on a JEOL JMS-700TZ, JMS-
FABmate or JMS-HX110. The elemental micro-analyses
were done using a Yanagimoto CHN Corder MT-5. The
Et3N±5HF was prepared by the addition of freshly distilled
Et3N to anhydrous HF in Te¯one PFA vessel at 08C,14 and
can be kept in a Te¯one PFA vessel. It is less corrosive
and has a higher boiling point than anhydrous HF itself,
but should be used in a bench hood with Te¯one PFA
apparatus. ,Trimethylsilyl)acetylene, Pd,OAc)2, Pd2dba3,
PPh3, 1-hexyne, phenylacetylene, and 1-ethynylcyclo-
hexenol were purchased from Tokyo Kasei Co. Ltd. Pro-
pargyl alcohol, 10-undecynoic acid, and 10-undecyn-1-ol
were also purchased from Tokyo Kasei Co. Ltd. and
converted to the corresponding THP ether, methyl ester,
and acetate, respectively. 1-Ethynylcyclohexene,15 11-
chloro-1-dodecyne,15 1-octyn-3-ol,15 and methyl 9-decyno-
ate16 were prepared from 1-ethynylcyclohexenol, 10-unde-
cyn-1-ol, hexanal, and 9-decenoic acid, respectively,
according to the literature. Ethyl 2,2-dimethyl-4-pentynoate
was prepared from ethyl isobutyrate and propargyl
bromide.17
4.1.3. ꢀE)-11-Acetoxy-2-¯uoro-1-iodo-1-undecene ꢀ4c).
Pale yellow oil: IR ,neat): 1740 ,CvO), 1649
,CvC) cm21
.
1H NMR dˆ5.67 ,1H, d, Jˆ17.8 Hz),
4.05 ,2H, t, Jˆ6.8 Hz), 2.50 ,2H, dt, Jˆ22.7, 7.3 Hz),
2.05 ,3H, s), 1.64±1.53 ,4H, m), 1.39±1.28 ,10H, m).
19F NMR dˆ282.48 ,1F, dt, Jˆ17.8, 22.7 Hz). HRMS
,EI) Calcd for C13H22IO2 ,M12F) 337.0649, Found
337.0665.
4.1.4. ꢀE)-1-Fluoro-1-phenyl-2-iodoethene ꢀ4d). Pale
yellow oil: IR ,neat): 1637 ,CvC) cm21
.
1H NMR
dˆ7.81±7.78 ,2H, m), 7.43±7.41 ,3H, m), 6.14 ,1H, d,
Jˆ19.5 Hz). 19F NMR dˆ276.58 ,1F, d, Jˆ19.5 Hz).
HRMS ,EI) Calcd for C8H6FI 247.9498, Found 247.9523.
4.1.5. ꢀE)-2-Fluoro-1-iodo-1-dodecene ꢀ4e). Pale yellow
.
oil: IR ,neat): 1645 ,CvC) cm21
1H NMR dˆ5.63
,1H, d, Jˆ17.7 Hz), 2.46 ,2H, dt, Jˆ23.0, 7.6 Hz),
1.56±1.44 ,2H, m), 1.32±1.20 ,14H, m), 0.85 ,3H, t,
Jˆ6.5 Hz). 19F NMR dˆ282.25 ,1F, dt, Jˆ17.7,
23.0 Hz). HRMS ,EI) Calcd for C12H22FI 312.0750,
Found 312.0742.
4.2. Cross-coupling reaction of 1-hexyne with ꢀE)-ꢀ2-
¯uoro-10-methoxycarbonyl-1-decenyl)ꢀ4-methyl-
phenyl)iodonium ¯uoride ꢀ1a)
4.1.1. Methyl ꢀE)-11-iodo-10-¯uoro-10-undecenoate ꢀ4a).
p-Iodotoluene di¯uoride was prepared from iodotoluene by
an electrochemical method in a divided cell made of
Te¯one PFA ,25 ml£2) with a Na®one 117 cation
exchange membrane. Each cell was equipped with a smooth
platinum electrode ,20£20 mm) and a magnetic stirrer bar.
Et3N±5HF ,22 ml) was introduced into both cells, and
p-iodotoluene ,654 mg, 3 mmol) was added to the anodic
cell. By passing 2 Fmol21 of electricity at a constant current
,50 mA h21) at room temperature, the reaction was
completed. The resulting Et3N±5HF solution of p-iodo-
toluene di¯uoride was added at 08C to a CH2Cl2 ,6 ml)
solution of methyl 10-undecynoate ,392 mg, 2 mmol) in a
reaction vessel made of Te¯one PFA. After stirring for 1h
at 08C, the mixture was extracted with CH2Cl2, dried over
MgSO4, and concentrated under reduced pressure to give
A mixture of PPh3 ,26 mg, 0.1mmol) and Pd,OAc) 2
,11 mg, 0.05 mmol) in DMF ,10 ml) was stirred at room
temperature under an atmosphere of nitrogen for 10 min.
To the reaction mixture, 1-hexyne ,98 mg, 1.2 mmol), 1a
prepared from methyl 10-undecynoate ,196 mg, 1 mmol),
Et3N ,150 mg, 1.5 mmol), and CuI ,15 mg, 0.08 mmol)
were successively added. The mixture was stirred at room
temperature overnight and then poured into an aqueous
NH4Cl solution. The mixture was extracted with ether and
the organic phase was dried over MgSO4. Puri®cation by
column chromatography ,silica gel/hexane±ether) gave 2a
in 59% yield with 41% of 3.

M. Yoshida et al. / Tetrahedron 57 ,2001) 7143±7148
7147
4.3. Cross-coupling reaction of 1-alkyne with 2-¯uoro-1-
iodo-1-alkene ꢀ4)
dˆ292.71,1F, dt, Jˆ13.9, 21.4 Hz). Anal. C, 63.44; H,
9.32. Found: C, 63.68; H, 9.22.
4.3.7. ꢀE)-1-Acetoxy-22-chloro-13-¯uoro-12-docosen-10-
yne ꢀ2g). Pale yellow oil: IR ,neat): 1741 ,CvO), 1239
4.3.1. Methyl ꢀE)-10-¯uoro-10-heptadecen-12-ynoate
ꢀ2a). A mixture of 4a ,342 mg, 1mmol), PPh 3 ,26.2 mg,
0.1mmol), Pd,OAc) 2 ,11.3 mg, 0.05 mmol), CuI ,32 mg,
0.16 mmol), 1-hexyne ,98 mg, 1.2 mmol) in Et2NH
,10 ml) was stirred overnight at room temperature under
an atmosphere of nitrogen. The reaction mixture was poured
into an aqueous NH4Cl solution and extracted with ether.
The organic phase was dried over MgSO4 and concentrated
under reduced pressure. Puri®cation by column chromato-
graphy ,silica gel/hexane±ether) gave 2a in 85% yield as a
1
,C±OR) cm21. H NMR dˆ5.16 ,1H, dt, Jˆ14.4, 2.2 Hz),
4.05 ,2H, t, Jˆ6.8 Hz), 3.53 ,2H, t, Jˆ6.8 Hz), 2.44 ,2H, dt,
Jˆ22.2, 7.4 Hz), 2.30 ,2H, t, Jˆ6.8Hz), 2.04 ,3H, s), 1.80±
1.73 ,2H, m), 1.65±1.31 ,26H, m). 19F NMR dˆ297.67
,1F, dt, Jˆ14.4, 22.2 Hz). HRMS ,EI) Calcd for
C24H40ClFO2 414.2701, Found 414.2715.
4.3.8. ꢀE)-13-Chloro-4-¯uoro-1-phenyl-3-tridecen-1-yne
ꢀ2h). Pale yellow oil: IR ,neat): 2207 ,CuC), 1489
1
pale yellow oil: IR ,neat): 1741 ,CvO) cm21. H NMR
1
,CvC) cm21. H NMR dˆ7.42±7.39 ,2H, m), 7.33±7.29
dˆ5.16 ,1H, dt, Jˆ14.0, 2.2 Hz), 3.67 ,3H, s), 2.43 ,2H,
dt, Jˆ22.0, 7.3 Hz), 2.31,2H, t, Jˆ7.3 Hz), 1.64±1.32
,18H, m), 0.92 ,3H, t, Jˆ7.3 Hz). 19F NMR dˆ298.65
,1F, dt, Jˆ14.0, 22.0 Hz). HRMS ,EI) Calcd for
C18H29FO2 296.2151, Found 296.2146.
,3H, m), 5.41,1H, d, Jˆ13.9 Hz), 2.54 ,2H, dt, Jˆ22.0,
7.3 Hz), 2.43 ,2H, t, Jˆ7.3 Hz), 1.64±1.49 ,2H, m), 1.36±
1.21 ,2H, m), 1.11 ,10H, brs). 19F NMR dˆ293.32 ,1F, dt,
Jˆ13.9, 22.0 Hz). HRMS ,EI) Calcd for C19H24ClF
306.1551, Found 306.1542.
4.3.2. Methyl ꢀE)-10-¯uoro-13-ꢀtrimethylsilyl)-10-tri-
decen-12-ynoate ꢀ2b). Pale yellow oil: IR ,neat): 2142
4.3.9. ꢀE)-1-Acetoxy-10-¯uoro-13-ꢀ1-cyclohexenyl)-10-tri-
decen-12-yne ꢀ2i). Pale yellow oil: IR ,neat): 1741 ,CvO),
,CuC), 1742 ,CvO) cm21
.
1H NMR dˆ5.21,H1, d,
1
1238 ,C±OR) cm21. H NMR dˆ6.05±6.07 ,1H, m), 5.30
Jˆ14.2 Hz), 3.67 ,3H, s), 2.47 ,2H, dt, Jˆ22.0, 7.3 Hz),
2.31,2H, t, Jˆ7.6 Hz), 1.64±1.53 ,4H, m), 1.32 ,8H, brs),
0.18 ,9H, s). 19F NMR dˆ292.74 ,1F, dt, Jˆ14.2, 22.0 Hz).
HRMS ,EI) Calcd for C17H29FO2Si 312.1921, Found
312.1927.
,1H, d, Jˆ14.2 Hz), 4.05 ,2H, t, Jˆ6.8 Hz), 2.46 ,2H, dt,
Jˆ21.9, 7.3 Hz), 2.13±2.10 ,4H, m), 2.04 ,3H, s), 1.67±
1.53 ,8H, m), 1.31 ,10H, brs). 19F NMR dˆ295.41,1F,
dt, Jˆ14.2, 21.9 Hz). HRMS ,EI) Calcd for C21H31FO2
334.2308, Found 334.2324.
4.3.3. Methyl ꢀE)-10-¯uoro-13-phenyl-10-tridecen-12-
ynoate ꢀ2c). Pale yellow oil: IR ,neat): 2209 ,CuC),
4.3.10. ꢀE)-1-Acetoxy-10-¯uoro-13-phenyl-10-tridecen-
12-yne ꢀ2j). Pale yellow oil: IR ,neat): 1739 ,CvO),
1739 ,CvO) cm21
.
1H NMR dˆ7.42±7.39 ,2H, m),
1240 ,C±OR) cm21
.
1H NMR dˆ7.42±7.39 ,2H, m),
7.33±7.30 ,3H, m), 5.41,1H, d, Jˆ13.9 Hz), 3.66 ,3H, s),
2.54 ,2H, dt, Jˆ22.0, 7.4 Hz), 2.28 ,2H, t, Jˆ7.6 Hz), 1.62±
1.55 ,4H, m), 1.38±1.31 ,8H, m). 19F NMR dˆ293.34 ,1F,
dt, Jˆ13.9, 22.0 Hz). HRMS ,EI) Calcd for C20H25FO2
316.1838, Found 316.1844.
7.33±7.26 ,3H, m), 5.41,1H, d, Jˆ13.9 Hz), 4.03 ,2H, t,
Jˆ6.8 Hz), 2.55 ,2H, dt, Jˆ21.9, 7.3 Hz), 2.03 ,3H, s),
1.68±1.56 ,4H, m), 1.38±1.30 ,10H, m). 19F NMR
dˆ293.29 ,1F, dt, Jˆ13.9, 21.9 Hz). HRMS ,EI) Calcd
for C21H27FO2 330.1995, Found 330.1991.
4.3.4. Methyl ꢀE)-10-¯uoro-14-ꢀ2-tetrahydropyranyl-
oxy)-10-tetradecen-12-ynoate ꢀ2d). Pale yellow oil: IR
4.3.11. ꢀE)-1-Fluoro-1-phenyl-5-ꢀ2-tetrahydropyrany-
loxy)-1-penten-3-yne ꢀ2k). Pale yellow oil: IR ,neat):
,neat): 2220 ,CuC), 1740 ,CvO) cm21
.
1H NMR
2216 ,CuC) cm21
.
1H NMR dˆ8.01±7.98 ,2H, m),
dˆ5.22 ,1H, dt, Jˆ13.9, 2.2 Hz), 4.82 ,1H, t, Jˆ3.4 Hz),
4.44±4.33 ,2H, m), 3.88±3.82 ,1H, m), 3.67 ,3H, s), 3.56±
3.45 ,1H, m), 2.45 ,2H, dt, Jˆ21.9, 7.3 Hz), 2.30 ,2H, t,
Jˆ7.6 Hz), 1.87±1.53 ,10H, m), 1.31 ,8H, brs). 19F NMR
dˆ293.50 ,1F, dt, Jˆ13.9, 21.9 Hz). HRMS ,EI) Calcd for
C20H31FO4 354.2206, Found 354.2203.
7.43±7.33 ,3H, m), 5.62 ,1H, dt, Jˆ2.4, 17.6 Hz), 4.85
,1H, t, Jˆ3.6 Hz), 4.51±4.41 ,2H, m), 3.89±3.83 ,1H, m),
3.56±3.53 ,1H, m), 1.89±1.51 ,m, 6H). 19F NMR
dˆ2102.19 ,1F, d, Jˆ17.6 Hz). HRMS ,EI) Calcd for
C16H17FO2 260.1212, Found 260.1206.
4.3.12. Ethyl ꢀE)-7-¯uoro-2,2-dimethyl-7-phenyl-6-
hepten-4-ynoate ꢀ2l). Pale yellow oil: IR ,neat): 1731
4.3.5. Ethyl ꢀE)-7-¯uoro-15-methoxycarbonyl-2,2-di-
methyl-6-pentadecen-4-ynoate ꢀ2e). Pale yellow oil:
1
,CvO) cm21. H NMR dˆ8.02±7.98 ,2H, m), 7.42±7.38
IR ,neat): 1735 ,CvO) cm21
.
1H NMR dˆ5.16 ,1H,
,3H, m), 5.59 ,1H, dt, Jˆ18.1, 2.7 Hz), 4.14 ,2H, q,
Jˆ7.2 Hz), 2.66 ,2H, s), 1.30 ,6H, s), 1.23 ,3H, t,
Jˆ7.2 Hz). 19F NMR dˆ2105.34 ,1F, d, Jˆ18.1 Hz).
HRMS ,EI) Calcd for C17H19FO2 274.1369, Found
274.1397.
dt, Jˆ13.9, 2.2 Hz), 4.14 ,2H, q, Jˆ7.1Hz), 3.67 ,3H,
s), 2.56 ,2H, s), 2.42 ,2H, dt, Jˆ22.2, 7.6 Hz), 2.30 ,2H,
t, Jˆ7.6 Hz), 1.64±1.52 ,4H, m), 1.31±1.24 ,17H, m).
19F NMR dˆ296.62 ,1F, dt, Jˆ13.9, 22.2 Hz).
HRMS ,EI) Calcd for C21H33FO4 368.2363, Found
368.2356.
4.3.13. Methyl ꢀE)-13-¯uoro-13-phenyl-12-tridecen-10-
ynoate ꢀ2m). Pale yellow oil: IR ,neat): 2215 ,CuC),
4.3.6. ꢀE)-13-Chloro-4-¯uoro-1-ꢀtrimethylsilyl)-3-tri-
decen-1-yne ꢀ2f). Pale yellow oil: IR ,neat): 2142 ,CuC),
1739 ,CvO) cm21
.
1H NMR dˆ8.03±8.01,2H, m),
1
1656 ,CvC) cm21. H NMR dˆ5.21,1H, d, Jˆ13.9 Hz),
7.42±7.38 ,3H, m), 5.59 ,1H, dt, Jˆ18.3, 2.4 Hz), 3.66
,3H, s), 2.38±2.42 ,2H, m), 2.29 ,2H, t, Jˆ7.6 Hz), 1.63±
1.54 ,4H, m), 1.42±1.40 ,2H, m), 1.31 ,6H, brs). 19F NMR
3.53 ,2H, t, Jˆ6.6 Hz), 2.48 ,2H, dt, Jˆ21.4, 7.3 Hz), 1.81±
1.74 ,2H, m), 1.61±1.32 ,12H, m), 0.19 ,9H, s). 19F NMR

7148
M. Yoshida et al. / Tetrahedron 57 ,2001) 7143±7148
2. Benayound, F.; Chen, L.; Moniz, G. A.; Zapata, A. J.;
Hammond, G. B. Tetrahedron 1998, 54, 15541±15554.
Zapata, A. J.; Gu, Y.; Hammond, G. B. J. Org. Chem. 2000,
65, 227±234.
dˆ2106.34 ,1F, d, Jˆ18.3 Hz). HRMS ,EI) Calcd for
C20H25FO2 316.1838, Found 316.1824.
4.3.14. ꢀE)-5-Fluoro-1-ꢀ2-tetrahydropyranyloxy)-4-penta-
decen-2-yne ꢀ2n). pale yellow oil: IR ,neat): 2220 ,CuC),
3. ,a) Yang, Z.-Y.; Burton, D. J. Tetrahedron Lett. 1990, 31,
1369±1372. ,b) Yang, Z.-Y.; Burton, D. J. J. Fluorine
Chem. 1991, 53, 307±326. ,c) Ichikawa, J.; Ikeura, C.;
Minamai, T. J. Fluorine Chem. 1993, 63, 281±285.
,d) Eddarir, S.; Francesch, C.; Mestdagh, H.; Rolando, C.
Tetrahedron Lett. 1990, 31, 4449±4452. ,e) Percy, J. M.;
Wilkes, R. D. Tetrahedron 1997, 53, 14749±14762.
4. Eddarir, S.; Francesch, C.; Mestdagh, H.; Rolando, C. Bull.
Soc. Chim. Fr. 1997, 134, 741±755.
1664 ,CvC) cm21
.
1H NMR dˆ5.21,H1 , dt,
Jˆ14.0,
2.4 Hz), 4.82 ,1H, t, Jˆ3.4 Hz), 4.44±4.33 ,2H, m), 3.88±
3.83 ,1H, m), 3.56±3.45 ,1H, m), 2.46 ,2H, dt, Jˆ22.0,
7.3 Hz), 1.88±1.52 ,8H, m), 1.31±1.20 ,14H, m), 0.88
,3H, t, Jˆ6.6 Hz). 19F NMR dˆ293.47 ,1F, dt, Jˆ14.0,
22.0 Hz). HRMS ,EI) Calcd for C20H33FO2 324.2464,
Found 324.2451.
4.3.15. ꢀE)-8-Fluoro-7-octadecen-5-yne ꢀ2o). Pale yellow
5. Quite recently, Yamamoto et al. reported the stereoselective
synthesis of ,Z)-1-¯uoro-1,3-enynes having per¯uoroalkyl
group, see: Saito, S.; Kawasaki, T.; Tsuboya, N.; Yamamoto,
Y. J. Org. Chem. 2001, 66, 796±802.
1
oil: IR ,neat): 2227 ,CuC), 1666 ,CvC) cm21. H NMR
dˆ5.16 ,1H, dt, Jˆ14.6, 2.2 Hz), 2.43 ,2H, dt, Jˆ22.0,
7.3 Hz), 2.29±2.32 ,2H, m), 1.69±1.19 ,20H, m), 0.92
,3H, t, Jˆ7.1Hz), 0.88 ,3H, t, Jˆ7.1Hz). 19F NMR
dˆ297.66 ,1F, dt, Jˆ14.6, 22.0 Hz). HRMS ,EI) Calcd
for C18H31F 266.2410, Found 266.2408.
6. Hara, S.; Yoshida, M.; Fukuhara, T.; Yoneda, N. Chem.
Commun. 1998, 965±966.
7. Hara, S.; Yamamoto, K.; Yoshida, M.; Fukuhara, T.; Yoneda,
N. Tetrahedron Lett. 1999, 40, 7815±7818.
4.3.16. Methyl ꢀE)-9-¯uoro-10-iodo-9-decenoate ꢀ7). Pale
yellow oil: IR ,neat): 1739 ,CvO), 1650 ,CvC) cm21. 1H
NMR dˆ5.69 ,1H, d, Jˆ17.8 Hz), 3.67 ,3H, s), 2.50 ,2H,
dt, Jˆ22.4, 7.3 Hz), 2.31,2H, t, Jˆ7.6 Hz), 1.65±1.51 ,4H,
m), 1.38±1.21 ,6H, brs). 19F NMR dˆ282.53 ,1F, dt,
Jˆ17.8, 22.4 Hz). HRMS ,EI) Calcd for C10H15FIO
,M12OMe) 297.0152, Found 297.0162.
8. Yoshida, M.; Hara, S.; Fukuhara, T.; Yoneda, N. Tetrahedron
Lett. 2000, 41, 3887±3890.
9. Radhakrishnan, U.; Stang, P. J. Org. Lett. 2001, 3, 859±860.
10. Hinkle, R. J.; Poulter, G. T.; Stang, P. J. J. Am. Chem. Soc.
1993, 115, 11626±11627. Stang, P. J.; Blume, T.; Zhdankin,
V. V. Synthesis 1993, 35±36. Ryan, J. H.; Stang, P. J. J. Org.
Chem. 1996, 61, 6162±6165.
11. Sonogashira, K. Comprehensive Organic Synthesis; Trost,
B. M., Fleming, I., Eds.; Pergamon: New York, 1991; Vol.
3, pp. 521±549.
4.3.17. ꢀE)-9-Fluoro-11,12-dehydrocoriolic acid methyl
ester ꢀ6). Pale yellow oil: IR ,neat): 3436 ,C±OH), 2219
1
,CuC), 1731 ,CvO) cm21. H NMR dˆ5.21,H1 , dd,
12. Hay, A. S. J. Org. Chem. 1962, 27, 3320±3321.
13. Kobayashi, Y.; Okamoto, S.; Shimazaki, T.; Ochiai, Y.; Sato,
F. Tetrahedron Lett. 1987, 28, 3959±3962.
Jˆ14.1, 2.0 Hz), 4.49 ,1H, dt, Jˆ1.4, 6.6 Hz), 3.67 ,3H,
s), 2.45 ,2H, dt, Jˆ22.2, 7.1Hz), 2.38 ,1H, brs), 2.31,2H,
t, Jˆ7.6 Hz), 1.73±1.30 ,18H, m), 0.90 ,3H, t, Jˆ6.8 Hz).
19F NMR dˆ294.20 ,1F, dt, Jˆ14.1, 22.2 Hz). HRMS ,EI)
Calcd for C19H31FO3 326.2257, Found 326.2258. Anal. C,
69.91; H, 9.57. Found: C, 69.96; H, 9.52.
14. Chen, S.-Q.; Hatakeyama, T.; Fukuhara, T.; Hara, S.; Yoneda,
N. Electrochim. Acta 1997, 42, 1951±1960.
15. Brandsma, L. Preparative Acetylenic Chemistry; Elsevier:
Amsterdam, 1971.
16. Khan, N. A. Organic Syntheses Collected Volume IV; 1963;
pp. 969±972.
References
17. Cregge, R. J.; Herrmann, J. L.; Lee, C. S.; Richman, J. E.;
Schlessinger, R. H. Tetrahedron Lett. 1973, 14, 2425±2428.
1. Hiyama, T. In Organo¯uorine Compounds; Springer: Berlin,
2000; pp. 137±182. Welch, J. T.; Eswarakrishnan, S. Fluorine
in Bioorganic Chemistry; Wiley: New York, 1991.