Regio- and stereoselective synthesis of fluoroalkenes and fluoroalkadienes

Article abstract of DOI:10.1039/b108796g

(E)-Fluoroalkenes and (E,E)-fluoroalkadienes are synthesized stereoselectively from (E)-2-fluoro-1-iodoalk-1-enes by Pd-catalyzed cross-coupling reaction with organoboranes.

Full text of DOI:10.1039/b108796g

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Regio- and stereoselective synthesis of fluoroalkenes and
fluoroalkadienes
Masanori Yoshida, Daisuke Ota, Tsuyoshi Fukuhara, Norihiko Yoneda and Shoji Hara*
1
Division of Molecular Chemistry, Graduate School of Engineering, Hokkaido University,
Sapporo 060-8628, Japan
Received (in Cambridge, UK) 27th September 2001, Accepted 27th November 2001
First published as an Advance Article on the web 8th January 2002
(E)-Fluoroalkenes and (E,E)-fluoroalkadienes are synthesized stereoselectively from (E)-2-fluoro-1-iodoalk-1-enes
by Pd-catalyzed cross-coupling reaction with organoboranes.
Introduction
Organofluorine compounds often show unique biological
properties originating from the high electronegativity of the
fluorine atom.1 However, organofluorine compounds are scarce
in Nature, and, in order to obtain the desired organofluorine
compound, the building-block methodology using readily
available fluorine-substituted molecules has been employed.2
Recently, we found (E)-(2-fluoroalk-1-enyl)(p-tolyl)iodonium
fluorides 1 could be synthesized stereo- and regioselectively
by the reaction of alk-1-ynes with p-iodotoluene difluoride.3
Scheme 1 Cross-coupling reaction of 1a with phenylboronic acid.
Furthermore, we succeeded in obtaining (E)-2-fluoro-1-
iodoalk-1-enes 2,3 (E,E)-δ-fluoro-α,β,γ,δ-unsaturated carbonyl
the alkyl group at a cis-position to iodine10 or strongly electro-
compounds4 and (E)-β-fluoro-α,β-unsaturated esters5 by using
negative fluorine atom on the double bond retarded the oxi-
1 as a building block. Our next interest was directed to the
dative addition of the palladium catalyst to the iodine–alkenyl
stereoselective synthesis of fluoroalkenes and fluoroalkadienes
bond and the selective formation of 3a was disturbed.11 Con-
by the coupling reaction with organoboranes using a Pd cata-
sequently, we gave up our attempts at the selective synthesis of
lyst.6 Many natural products have double bonds or conjugated
fluoroalkenes using 1, and examined the coupling reaction of
dienes in their structures, and the coupling reactions of
(E)-2-fluoro-1-iodoalk-1-enes 2 which can be prepared from 1.3
organoboranes with aryl or alkenyl halides using a Pd catalyst
are known as the Suzuki–Miyaura reaction,7 which has been
used for the stereoselective synthesis of alkenes and alkadienes.
Therefore, we examined the Pd-catalyzed cross-coupling
reaction of 1 with organoboranes.8
Cross-coupling reaction of (E )-2-fluoro-1-iodoalk-1-enes 2 with
arylboronic acids
The cross-coupling reaction of (E)-2-fluoro-1-iodododec-1-ene
2a with phenylboronic acid was examined to find a suitable
catalyst (Table 1). When Pd(PPh3)4 or Pd(PPh3)2Cl2, a common
catalyst in the Suzuki–Miyaura reaction,7 was used in benzene
and aq. K2CO3 under reflux, it took about 12 h to consume 2a
completely and the desired 3a was obtained in moderate yield
(Entries 1 and 2). As 2a is not stable under the reaction con-
ditions, a more effective catalyst was necessary to obtain 3a
in good yield. Fortunately, the reaction was found to be
accelerated by using Pd(OAc)2 with bidentate ligands and com-
pleted in 5 h (Entries 3–5).12 Finally, we found that 3a could be
obtained in 85% yield by using 2,2Ј-bis(diphenylphosphino)-
1,1Ј-binaphthyl (BINAP) as ligand (Entry 5). Under these
reaction conditions, the cross-coupling reaction between a
variety of (E)-2-fluoro-1-iodoalk-1-enes 2 and arylboronic
acids was carried out, and various types of (E)-fluoroalkenes
were obtained in 74–94% yield and more than 98% stereo-
selectivity (Table 2).
Results and discussion
Cross-coupling reaction using (E )-(2-fluoroalk-1-enyl)( p-tolyl)-
iodonium fluorides 1
The cross-coupling reaction of 1a, prepared from dodec-1-yne,
with phenylboronic acid was carried out in the presence of
Pd(OAc)2, PPh3 and K2CO3 in DMF–water (3 : 1). After
stirring of the mixture for 24 h at room temperature, the desired
(E)-2-fluoro-1-phenyldodec-1-ene 3a was obtained only in
12% isolated yield along with a significant amount of 4-phenyl-
toluene 4 (68% yield) (Scheme 1).9 In order to improve the
result, some bases and solvents were examined, but the forma-
tion of by-product 4 could not be suppressed. It was reported
that stilbene was selectively obtained without formation of a
significant amount of biphenyl in the cross-coupling reaction
of phenylboronic acid with (E)-β-styryl(phenyl)iodonium
salt.8b,c Therefore, in the reaction of 1a with phenylboronic acid,
Cross-coupling reaction of (E )-2-fluoro-1-iodoalk-1-enes 2 with
(E )-alk-1-enyl-boronic acids or -boronates
The coupling reaction of 2 with (E)-alk-1-enylboronic acids
or boronates was also examined to obtain the fluorinated con-
jugated dienes. When the coupling reaction between 2a and
(E)-hex-1-enylboronic acid was carried out under the same
384
J. Chem. Soc., Perkin Trans. 1, 2002, 384–389
This journal is © The Royal Society of Chemistry 2002
DOI: 10.1039/b108796g

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conditions as optimized in Table 1, the desired (5E,7E)-8-
fluorooctadeca-5,7-diene 5a was obtained in 73% yield along
with 9 % of its regioisomer 6 (Table 3). Owing to the low nucleo-
philicity of an alkenylboronic acid compared with aryl deriva-
tive, the transmetallation step on the Pd catalyst slowly pro-
ceeded and a Heck-type side reaction took place competitively
to give the regioisomer 6.13 In order to accelerate the trans-
metallation step and suppress the formation of 6, a stronger
base, KOH, was used instead of K2CO3. As expected, the
reaction went to completion in a shorter reaction time and the
yield of 6 decreased. Finally, we succeeded in synthesizing 5a
in 87% yield without the formation of 6 by using Pd(OAc)2,
BINAP and KOH. Under these reaction conditions, various
types of fluoroalkadienes could be prepared from 2 and (E)-alk-
1-enylborane derivatives with more than 98% stereoselectivity
in 67–87% yield (Table 4). When diisopropyl (E)-but-1-enyl-
boronate was used, the reaction proceeded slowly and the yield
of 5 decreased due to the high solubility of diisopropyl (E)-but-
1-enylboronate in water. This problem was overcome by using
dioxane as solvent instead of benzene (Entries 2 and 5).
Conclusion
(E)-Fluoroalkenes and (E,E)-fluoroalkadienes having various
types of functionalities were synthesized stereoselectively by the
cross-coupling reaction between (E)-2-fluoro-1-iodoalk-1-enes
and organoboranes.
Table 1 Cross-coupling reaction of 2a with phenylboronic acida
Experimental
General
IR spectra were recorded using a JASCO FT/IR-410. 1H NMR
(400 MHz), 19F NMR (376 MHz) and 13C-NMR (100 MHz)
spectra were recorded in CDCl3 on a JEOL JNM-A400II FT
NMR and chemical shifts, δ, are referred to TMS (1H, 13C)
and CFCl3 (19F). EI low- and high-resolution mass spectra
were measured on a JEOL JMS-700TZ, JMS-FABmate or
JMS-HX110. Elemental microanalyses were done using a
Yanagimoto CHN Corder MT-5. For column chromatography,
Merck silica gel 7734 was used, and, for analytical TLC, Merck
silica gel 5715 was used. Et3N–5HF was prepared by the
addition of freshly distilled Et3N to anhydrous HF at 0 ЊC.14
PdCl2, Pd(PPh3)4, Pd(OAc)2, PPh3, phenylboronic acid and
Entry
Catalyst
Time (t/h)
Yield/%b
1
2
3
4
5
Pd(PPh3)4
Pd(PPh3)2Cl2
Pd(OAc)2 ϩ DPPP
Pd(OAc)2 ϩ DPPF
Pd(OAc)2 ϩ BINAP
12
12
5
5
5
65
56
48
70
85
a The reaction was carried out using 2a (0.5 mmol), phenylboronic acid
(1 mmol), Pd cat. (5 mol%), ligand (5 mol%), aq. 2 M K2CO3 (0.5 mL),
and benzene (5 mL). b Isolated yield based on 2a.
Table 2 Cross-coupling reaction of 2 with arylboronic acids
Entry
1
Fluoroiodoalkene 2
Arylboronic acid
Product
Yield/%a
85
2
3
2a
2a
92
94
4
5
6
7
93
77
90
74
a Isolated yield based on 2.
J. Chem. Soc., Perkin Trans. 1, 2002, 384–389
385

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dodec-1-yne were purchased from Tokyo Kasei Co., Ltd.,
and used without further purification. 1,3-Bis(diphenylphos-
phino)propane (DPPP), 1,1Ј-bis(diphenylphosphino)ferrocene
(DPPF) and BINAP were purchased from Kanto Kagaku Co.,
Ltd., and used without further purification. 11-Acetoxyundec-
1-yne15 and 11-chloroundec-1-yne16 were prepared from undec-
10-yn-1-ol which was in turn prepared from undec-10-en-1-ol.16
Methyl dec-9-ynoate17 was prepared form dec-9-enoic acid.
2,2-Dimethyltridec-12-yn-3-one was prepared from undec-10-
mixture of DMF and water (5 mL). To this solution were
added, K2CO3 (346 mg, 2.5 mmol), PPh3 (262 mg, 0.1 mmol),
Pd(OAc)2 (225 mg, 0.1 mmol) and phenylboronic acid (91 mg,
0.75 mmol) sequentially. Then the rection mixture was stirred
for 24 h at room temperature. The resulting solution was
poured into saturated aq. NH4Cl (30 mL) and the separated
aqueous phase was extracted with diethyl ether. The combined
organic phase was washed with water and dried over MgSO4.
After the MgSO4 was removed by filtration, the solvent was
removed by evaporation. The desired product 3a was isolated
in 12% yield by column chromatography (silica gel; hexane–
diethyl ether). 4-Phenyltoluene 4 was obtained as a mixture
with biphenyl, which is the homo-coupled product of phenyl-
boronic acid, and the yield of 4 was determined by gas
chromatography.
t
yn-1-ol by PCC oxidation, reaction with BuMgBr, and PCC
oxidation sequences. o-Tolylboronic acid,18 1-naphthylboronic
acid,18 (E)-hex-1-enylboronic acid,19 diisopropyl (E)-but-1-enyl-
boronate20 and diethyl [(E)-4-ethoxycarbonyl-4-methylpent-1-
enyl]boronate20 were prepared according to the literature. The
procedures for the preparation of 1 and 2 have been already
reported.3,21
General procedure for (E )-fluoroalkenes 3
Cross-coupling reaction of (E )-(2-fluorododec-1-enyl)( p-tolyl)-
To a mixture of benzene (5 mL) and 0.5 mL of 2 M aq. K2CO3
(1.0 mmol) were added Pd(OAc)2 (5.6 mg, 0.025 mmol) and
(S)-(Ϫ)-BINAP (15.6 mg, 0.025 mmol). After the complete
replacement of atomosphere in the flask with N2, an (E)-2-
fluoro-1-iodoalk-1-ene 2 (0.5 mmol) and arylboronic acid
(1.0 mmol) were added. Then the reaction mixture was stirred
under reflux for 5 h and then cooled to room temperature.
The resulting mixture was poured into saturated aq. NaHCO3
(30 mL) and the separated aqueous phase was extracted with
diethyl ether. The combined organic phase was dried over
MgSO4 and concentrated under reduced pressure. The product
3 was isolated by column chromatography (silica gel; hexane–
diethyl ether).
iodonium salt 1a with phenylboronic acid
(E)-(2-Fluorododec-1-enyl)(p-tolyl)iodonium salt 1a, prepared
from dodec-1-yne (83 mg, 0.5 mmol),3 was dissolved in a 3 : 1
Table 3 Cross-coupling reaction of 2a with (E)-hex-1-enylboronic
acid.
Yield/%a
General procedure for (E,E)-fluoroalkadienes 5
To a mixture of benzene (5 mL) and 0.5 mL of 2 M aq. KOH
(1.0 mmol) were added Pd(OAc)2 (5.6 mg, 0.025 mmol) and
(S)-(Ϫ)-BINAP (31.2 mg, 0.05 mmol). After the complete
replacement of atomosphere in the flask with N2, an (E)-
2-fluoro-1-iodoalk-1-ene 2 (0.5 mmol) and alkenylborane
(1.0 mmol) were added. Then the reaction mixture was stirred
under reflux for 2 h and then cooled to room temperature. The
Entry Catalyst
Base
Time (t/h) 5a
6
1
2
3
Pd(OAc)2 ϩ BINAP
Pd(OAc)2 ϩ BINAP
Pd(OAc)2 ϩ 2BINAP
K2CO3 3.5
KOH
KOH
73
89
87
9
1
2
2
trace
a Isolated yield. The ratio of 5a and 6 was determined by 1H-NMR.
Table 4 Stereoselective synthesis of fluoroalkadienes
Entry
1
Fluoroiodoalkene 2
Alkenylboronic acid or ester
Product
Yield/%a
87
2
3
2a
2a
67b
82
4
5
6
85
67b
80
a Isolated yield based on 2. b The reaction was carried out in 1,4-dioxane at 70 ЊC.
386
J. Chem. Soc., Perkin Trans. 1, 2002, 384–389

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resulting solution was poured into saturated aq. NaHCO3 (30
mL) and the separated aqueous phase was extracted with
diethyl ether. The combined organic phase was dried over
MgSO4 and concentrated under reduced pressure. The product
5 was isolated by column chromatography (silica gel; hexane–
diethyl ether). When diisopropyl (E)-but-1-enylboronate was
used as alkenylborane, the coupling reaction was carried out in
1,4-dioxane instead of benzene at 70 ЊC for 2 h.
1077, 1051, 870, 771, 714; m/z 314 (Mϩ, 0.1%), 277 (3), 235 (1),
221 (2), 212 (1), 198 (64), 185 (18), 167 (12), 159 (3), 149 (76),
121 (14), 107 (36), 99 (46), 81 (66), 69 (75), 55 (100), 41 (82)
[Calc. for C11H20FIO (M): 314.0543. Found: Mϩ, 314.0534].
(E )-11-Chloro-2-fluoro-1-iodoundec-1-ene 2f. δH(CDCl3)
1.30–1.44 (10H, m), 1.52–1.59 (2H, m, 4-H2), 1.73–1.81 (2H,
3
m, 10-H2), 2.50 (2H, dt, JH–F 22.4, J 7.3 Hz, 3-H2), 3.53
3
(2H, t, J 6.6 Hz, 11-H2), 5.67 [1H, d, JH–F(olefin) 17.8 Hz,
(E )-2-Fluoro-1-iodododec-1-ene 2a. δH(CDCl3) 0.85 (3H, t,
J 6.5 Hz, 12-H3), 1.20–1.32 (14H, m), 1.44–1.56 (2H, m, 4-H2),
2.46 (2H, dt, 3JH–F 23.0, J 7.6 Hz, 3-H2), 5.63 [1H, d, 3JH–F(olefin)
1-H]; δF(CDCl3) Ϫ82.35 [1F, dt, 3JH–F 22.4, 3JH–F(olefin) 17.8 Hz];
δC(CDCl3) 25.66, 26.83, 28.64, 28.80, 29.12, 29.25, 30.90
(d, 2JC–F 26.4 Hz, 3-C), 32.60, 45.15, 54.73 (d, 2JC–F 40.5 Hz, 1-C),
3
3
1
17.7 Hz, 1-H]; δF(CDCl3) Ϫ82.25 [1F, dt, JH–F 23.0, JH–F(olefin)
17.7 Hz]; δC(CDCl3) 14.11, 22.69, 25.72, 28.75, 29.27, 29.31,
29.47, 29.56, 30.94 (d, 2JC–F 25.6 Hz, 3-C), 31.88, 54.65 (d, 2JC–F
164.13 (d, JC–F 264.4 Hz, 2-C); ν(neat)/cmϪ1 3074, 2929, 2855,
1649, 1463, 1430, 1309, 1131, 1107, 1073, 875, 772, 726; m/z 332
(Mϩ, 33%), 273 (3), 198 (4), 185 (20), 169 (4), 143 (13), 128 (9),
109 (35), 95 (40), 81 (90), 69 (81), 55 (100), 41 (75) [Calc. for
C11H19ClFI (M): 332.0204. Found: Mϩ, 332.0204].
1
39.7 Hz, 1-C), 164.22 (d, JC–F 264.4 Hz, 2-C); ν(neat)/cmϪ1
3080, 2920, 2845, 1645, 1465, 1430, 1380, 1125, 1085, 875, 770,
720; m/z 312 (Mϩ, 18%), 185 (11), 165 (6), 123 (8), 109 (35), 95
(51), 83 (42), 69 (52), 55 (53), 43 (100) [Calc. for C12H22FI (M):
312.0750. Found: Mϩ, 312.0742].
(E )-2-Fluoro-1-phenyldodec-1-ene 3a. δH(CDCl3) 0.88 (3H, t,
J 7.0 Hz, 12-H3), 1.25–1.33 (14H, m), 1.57–1.65 (2H, m, 4-H2),
2.43 (2H, dt, 3JH–F 23.4, J 7.6 Hz, 3-H2), 6.18 [1H, d, 3JH–F(olefin)
21.9 Hz, 1-H], 7.18–7.34 (5H, m, Ph); δF(CDCl3) Ϫ99.03
(1F, m); δC(CDCl3) 14.11, 22.67, 26.37, 28.96 (d, 2JC–F 26.4 Hz,
3-C), 29.14, 29.31 (2C), 29.50, 29.56, 31.88, 108.02 (d, 2JC–F 28.9
Methyl (E )-10-fluoro-11-iodoundec-10-enoate 2b. δH(CDCl3)
1.28–1.39 (8H, br s), 1.51–1.64 (4H, m), 2.31 (2H, t, J 7.3 Hz,
3
2-H2), 2.50 (2H, dt, JH–F 22.5, J 7.3 Hz, 9-H2), 3.67 (3H, s,
OMe), 5.67 [1H, d, 3JH–F(olefin) 17.8 Hz, 11-H]; δF(CDCl3) Ϫ82.36
Hz, 1-C), 126.53 (2C), 128.40 (3C), 134.41 (d, JC–F 14.1 Hz,
3
3
3
1
[1F, dt, JH–F 22.5, JH–F(olefin) 17.8 Hz]; δC(CDCl3) 24.92, 25.68,
ipso-Ph), 162.77 (d, JC–F 252.7 Hz, 2-C); ν(neat)/cmϪ1 3084,
2
28.63, 29.07 (3C), 30.91 (d, JC–F 26.4 Hz, 9-C), 34.09, 51.46,
3059, 3027, 2955, 2926, 2854, 1682, 1601, 1496, 1466, 1377,
1225, 1142, 1095, 913, 885, 844, 747, 697; m/z 262 (Mϩ, 100%),
135 (53), 122 (18), 115 (18), 104 (8), 91 (12), 57 (7), 43 (13)
[Calc. for C18H27F (M): 262.2097. Found: Mϩ, 262.2093] (Calc.
for C18H27F: C, 82.39; H, 10.37. Found: C, 82.58; H, 10.53%).
54.75 (d, 2JC–F 40.5 Hz, 11-C), 164.14 (d, 1JC–F 264.4 Hz, 10-C),
174.28; ν(neat)/cmϪ1 3080, 2930, 2855, 1735, 1645, 1460, 1440,
1365, 1255, 1205, 1175, 1140, 1105, 1075, 880, 775, 720; m/z 311
(Mϩ Ϫ OMe, 20%), 215 (14), 195 (28), 180 (20), 163 (78), 155
(7), 145 (27), 135 (33), 121 (100), 111 (9), 95 (28), 87 (37),
81 (56), 74 (77), 67 (27), 55 (78), 41 (52) [Calc. for C11H17FIO
(M Ϫ OMe): 311.0308. Found: Mϩ Ϫ OMe, 311.0321].
(E )-2-Fluoro-1-(2-methylphenyl)dodec-1-ene 3b. δH(CDCl3)
0.88 (3H, t, J 6.9 Hz, 12-H3), 1.28–1.33 (14H, m), 1.52–1.60
3
(2H, m, 4-H2), 2.25 (3H, s, C6H4Me), 2.30 (2H, dt, JH–F 22.9,
(E )-12-Fluoro-13-iodo-2,2-dimethyltridec-12-en-3-one
2c.
J 7.6 Hz, 3-H2), 6.14 [1H, d, 3JH–F(olefin) 21.2 Hz, 1-H], 7.10–7.18
(4H, m, ArH); δF(CDCl3) Ϫ101.46 (1F, m); δC(CDCl3) 14.11,
δH(CDCl3) 1.13 (9H, s, tBu), 1.23–1.39 (8H, m), 1.51–1.58 (4H,
3
2
m), 2.45–2.54 (4H, m), 5.66 [1H, d, JH–F(olefin) 17.8 Hz, 13-H];
20.07, 22.68, 26.29, 28.56 (d, JC–F 27.2 Hz, 3-C), 29.02, 29.27,
3
3
2
δF(CDCl3) Ϫ82.48 [1F, dt, JH–F 23.3, JH–F(olefin) 17.7 Hz];
δC(CDCl3) 23.88, 25.68, 26.41 (3C), 28.66, 29.12, 29.25, 29.33,
30.90 (d, 2JC–F 26.5 Hz, 11-C), 36.40, 44.08, 54.72 (d, 2JC–F 40.5
29.31, 29.52, 29.57, 31.90, 106.62 (d, JC–F 27.2 Hz, 1-C),
3
125.71, 127.07, 129.03, 129.78, 133.45 (d, JC–F 13.3 Hz, ipso-
Ar), 136.85, 162.36 (d, 1JC–F 252.8 Hz, 2-C); ν(neat)/cmϪ1 3106,
3066, 3021, 2956, 2925, 2854, 1684, 1603, 1484, 1459, 1379,
1233, 1195, 1143, 1095, 885, 845, 788, 746, 721; m/z 276 (Mϩ,
100%), 149 (93), 134 (20), 129 (31), 115 (18), 105 (23), 55 (8), 43
(26) [Calc. for C19H29F (M): 276.2253. Found: Mϩ, 276.2251].
1
Hz, 13-C), 164.15 (d, JC–F 264.4 Hz, 12-C), 216.10; ν(neat)/
cmϪ1 3069, 2963, 2930, 2856, 1707, 1649, 1478, 1462, 1365,
1112, 1066, 771; m/z 368 (Mϩ, 0.2%), 311 (41), 241 (17), 185 (6),
135 (11), 121 (10), 99 (16), 93 (10), 85 (18), 67 (11), 57 (100),
41 (34) [Calc. for C15H26FIO (M): 368.1012. Found: Mϩ,
368.1014].
(E )-2-Fluoro-1-(1-naphthyl)dodec-1-ene 3c. δH(CDCl3) 0.87
(3H, t, J 7.0 Hz, 12-H3), 1.15–1.30 (14H, m), 1.53–1.60 (2H,
m, 4-H2), 2.31 (2H, dt, 3JH–F 22.7, J 7.6 Hz, 3-H2), 6.57 [1H, d,
3JH–F(olefin) 20.5 Hz, 1-H], 7.30–7.53 (4H, m), 7.42–8.00 (3H, m);
δF(CDCl3) Ϫ103.32 (1F, m); δC(CDCl3) 14.12, 22.67, 26.31,
(E )-11-Acetoxy-2-fluoro-1-iodoundec-1-ene 2d. δH(CDCl3)
1.28–1.39 (10H, m), 1.53–1.64 (4H, m), 2.05 (3H, s, MeCO),
3
2.50 (2H, dt, JH–F 22.7, J 7.3 Hz, 3-H2), 4.05 (2H, t, J 6.8 Hz,
11-H2), 5.67 [1H, d, 3JH–F(olefin) 17.8 Hz, 1-H]; δC(CDCl3) 21.03,
25.69, 25.88, 28.59, 28.67, 29.28 (2C), 29.31, 30.92 (d, 2JC–F 26.4
28.74 (d, JC–F 26.4 Hz, 3-C), 28.97, 29.22, 29.28, 29.46, 29.52,
2
2
31.88, 105.56 (d, JC–F 27.3 Hz, 1-C), 124.92, 125.37, 125.93,
2
1
3
Hz, 3-C), 54.73 (d, JC–F 39.7 Hz, 1-C), 64.62, 164.16 (d, JC–F
126.03, 126.67, 127.56, 128.34, 131.54 (d, JC–F 13.2 Hz,
3
1
264.4 Hz, 2-C), 171.22; δF(CDCl3) Ϫ82.48 [1F, dt, JH–F 22.7,
ipso-naphthyl), 132.29, 133.52, 163.29 (d, JC–F 254.4 Hz,
3JH–F(olefin) 17.8 Hz]; ν(neat)/cmϪ1 3077, 2929, 2856, 1740, 1650,
1464, 1430, 1388, 1365, 1240, 1125, 1079, 1038, 871, 772, 714;
m/z 337 (Mϩ Ϫ F, 3%), 324 (3), 311 (2), 254 (10), 229 (14), 221
(7), 209 (4), 198 (79), 185 (14), 169 (3), 149 (66), 121 (10),
107 (25), 93 (31), 69 (44), 55 (67), 43 (100) [Calc. for C13H22IO2
(M Ϫ F): 337.0649. Found: Mϩ Ϫ F, 337.0665].
2-C); ν(neat)/cmϪ1 3062, 3046, 2955, 2925, 2854, 1683, 1596,
1515, 1466, 1174, 1143, 1095, 892, 842, 798, 780, 651, 626;
m/z 312 (Mϩ, 100%), 185 (42), 165 (17), 141 (10), 43 (3) [Calc.
for C22H29F (M): 312.2253. Found: Mϩ, 312.2240] (Calc. for
C22H29F: C, 84.57; H, 9.35. Found: C, 84.84; H, 9.58%).
Methyl (E )-10-fluoro-11-phenylundecenoate 3d. δH(CDCl3)
1.27–1.36 (8H, br s), 1.57–1.65 (4H, m), 2.29 (2H, t, J 7.6 Hz,
(E )-10-Fluoro-11-iodoundec-10-en-1-ol 2e. Mp 30 ЊC;
δH(CDCl3) 1.27–1.40 (11H, m), 1.51–1.61 (4H, m), 2.50 (2H,
dt, 3JH–F 22.4, J 7.6 Hz, 9-H2), 3.64 (2H, t, J 6.6 Hz, 1-H2), 5.67
3
2-H2), 2.43 (2H, dt, JH–F 23.4, J 7.6 Hz, 9-H2), 3.66 (3H, s,
OMe), 6.18 [1H, d, 3JH–F(olefin) 21.9 Hz, 11-H], 7.17–7.34 (5H, m,
Ph); δF(CDCl3) Ϫ99.09 (1F, m); δC(CDCl3) 24.91, 26.32, 28.91
(d, 2JC–F 24.8 Hz, 9-C), 29.07, 29.09 (3C), 34.08, 51.44, 108.09,
3
[1H, d, JH–F(olefin) 17.8 Hz, 11-H]; δF(CDCl3) Ϫ82.50 [1F,
dt, 3JH–F 22.4, 3JH–F(olefin) 17.8 Hz]; δC(CDCl3) 25.66 (2C), 28.65,
2
2
29.14, 29.31, 29.36, 30.88 (d, JC–F 26.4 Hz, 9-C), 32.74, 54.67
(d, JC–F 28.9 Hz, 11-C), 126.56 (2C), 128.42 (3C), 134.34
3
1
(d, 2JC–F 39.7 Hz, 11-C), 63.03, 164.63 (d, 1JC–F 264.4 Hz, 10-C);
ν(neat)/cmϪ1 3330br, 3074, 2927, 2854, 1649, 1463, 1429, 1119,
(d, JC–F 14.1 Hz, ipso-Ph), 162.67 (d, JC–F 251.9 Hz, 10-C),
174.28; ν(neat)/cmϪ1 3085, 3058, 3026, 2930, 2856, 1739, 1682,
J. Chem. Soc., Perkin Trans. 1, 2002, 384–389
387

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1601, 1495, 1436, 1363, 1196, 1171, 1119, 1075, 1029, 915, 885,
749, 698; m/z 292 (Mϩ, 8%), 261 (5), 149 (6), 135 (17), 130 (100),
115 (12), 91 (7), 55 (6), 41 (3) [Calc. for C18H25FO2 (M):
292.1838. Found: Mϩ, 292.1838].
5.97 (1H, m, 4-H); δF(CDCl3) Ϫ104.70 (1F, m); δC(CDCl3)
2
13.69, 14.13, 22.70, 26.01, 26.38, 28.41 (d, JC–F 27.2 Hz, 7-C),
28.97, 29.34, 29.36, 29.55, 29.61, 31.91, 107.96 (d, 2JC–F 26.4 Hz,
3
4
5-C), 121.95 (d, JC–F 10.7 Hz, 4-C), 134.77 (d, JC–F 9.1 Hz,
1
3-C), 161.51 (d, JC–F 251.9 Hz, 6-C); ν(neat)/cmϪ1 3033, 2960,
2926, 2854, 1681, 1631, 1463, 1376, 1319, 1242, 1173, 1141,
1092, 1013, 959, 867, 775, 721; m/z 240 (Mϩ, 100%), 149 (6), 135
(11), 127 (8), 121 (13), 113 (40), 107 (14), 99 (77), 85 (42), 81
(33), 67 (38), 59 (12), 55 (38), 43 (57) [Calc. for C16H29F (M):
240.2253. Found: Mϩ, 240.2253].
(E )-12-Fluoro-2,2-dimethyl-13-phenyltridec-12-en-3-one 3e.
δH(CDCl3) 1.13 (9H, s, tBu), 1.25–1.36 (8H, m), 1.49–1.64 (4H,
m), 2.38–2.48 (4H, m), 6.18 [1H, d, JH–F(olefin) 21.9 Hz, 13-H],
3
7.17–7.34 (5H, m, Ph); δF(CDCl3) Ϫ99.06 (1F, m); δC(CDCl3)
2
23.90, 26.35, 26.42 (3C), 28.95 (d, JC–F 28.2 Hz, 11-C), 29.09,
2
29.18, 29.26, 29.36, 36.41, 44.10, 108.07 (d, JC–F 28.0 Hz,
13-C), 126.55 (2C), 128.42 (3C), 134.39 (d, 3JC–F 14.1 Hz, ipso-
Ph), 162.70 (d, 1JC–F 251.9 Hz, 12-C), 216.11; ν(neat)/cmϪ1 3088,
3059, 3027, 2971, 2930, 2856, 1706, 1684, 1601, 1477, 1465,
1393, 1365, 1223, 1148, 1124, 1070, 987, 914, 885, 842, 749,
698; m/z 318 (Mϩ, 26%), 261 (23), 223 (7), 157 (12), 135 (30),
130 (100), 117 (23), 109 (8), 91 (52), 57 (58), 41 (17) [Calc.
for C21H31FO (M): 318.2359. Found: Mϩ, 318.2347] (Calc. for
C21H31FO: C, 79.20; H, 9.81. Found: C, 79.36, H, 9.96%).
Ethyl (E,E)-7-fluoro-2,2-dimethylheptadeca-4,6-dienoate 5c.
δH(CDCl3) 0.88 (3H, t, J 7.1 Hz, 17-H3), 1.16 (6H, s, Me × 2),
1.22–1.34 (17H, m), 1.48–1.53 (2H, m, 9-H2), 2.26–2.35 (4H,
m), 4.11 (2H, q, J 7.1 Hz, OCH2CH3), 5.46–5.53 (1H, m, 4-H),
3
5.69 [1H, dd, JH–F(olefin) 20.2, J 11.0 Hz, 6-H], 5.90–5.97 (1H,
m, 5-H); δF(CDCl3) Ϫ99.92 (1F, m); δC(CDCl3) 14.13, 14.28,
2
22.69, 24.85 (2C), 26.38, 28.45 (d, JC–F 27.2 Hz, 8-C), 28.96,
29.33, 29.35, 29.54, 29.59, 31.91, 42.59, 43.90, 60.32, 107.83
2
3
(d, JC–F 27.3 Hz, 6-C), 126.12 (d, JC–F 11.5 Hz, 5-C), 128.02
4
1
(d, JC–F 9.9 Hz, 4-C), 162.17 (d, JC–F 253.6 Hz, 7-C), 177.42;
ν(neat)/cmϪ1 3032, 2957, 2927, 2855, 1731, 1679, 1631, 1469,
1386, 1365, 1303, 1242, 1196, 1147, 1095, 1029, 964, 865, 768,
722; m/z 340 (Mϩ, 23%), 266 (18), 225 (100), 205 (6), 149 (5),
135 (12), 121 (21), 107 (14), 93 (23), 79 (22), 67 (32), 55 (22), 43
(27) [Calc. for C21H37FO2 (M): 340.2777. Found: Mϩ, 340.2791]
(Calc. for C21H37FO2: C, 74.07; H, 10.95. Found: C, 74.03; H,
10.98%).
(E )-11-Acetoxy-2-fluoro-1-phenylundec-1-ene 3f. δH(CDCl3)
1.27–1.36 (10H, m), 1.57–1.65 (4H, m), 2.05 (3H, s, MeCO),
2.43 (2H, dt, 3JH–F 23.4, J 7.6 Hz, 3-H2), 4.05 (2H, t, J 6.7 Hz),
3
6.18 [1H, d, JH–F(olefin) 21.9 Hz, 1-H], 7.17–7.34 (5H, m, Ph);
δF(CDCl3) Ϫ99.12 (1F, m); δC(CDCl3) 21.03, 25.87, 26.34,
2
28.59, 28.94 (d, JC–F 28.1 Hz, 3-C), 29.08, 29.21 (2C), 29.35,
64.63, 108.09 (d, 2JC–F 28.9 Hz, 1-C), 126.57 (2C), 128.42 (3C),
3
1
134.40 (d, JC–F 14.1 Hz, ipso-Ph), 162.69 (d, JC–F 252.7 Hz,
2-C), 171.26; ν(neat)/cmϪ1 3085, 3059, 3027, 2930, 2856, 1739,
1683, 1601, 1496, 1447, 1365, 1241, 1135, 1037, 915, 883, 749,
699; m/z 306 (Mϩ, 12%), 246 (6), 148 (51), 130 (100), 122 (8),
115 (17), 91 (9), 69 (6), 55 (7), 43 (18) [Calc. for C19H27FO2 (M):
306.1995. Found: Mϩ, 306.1984] (Calc. for C19H27FO2: C,
74.48; H, 8.88. Found: C, 74.59, H, 8.84%).
Methyl
(E,E)-10-fluoroheptadeca-10,12-dienoate
5d.
δH(CDCl3) 0.90 (3H, t, J 7.1 Hz, 17-H3), 1.27–1.38 (12H, m),
1.48–1.65 (4H, m), 2.05–2.10 (2H, m, 14-H2), 2.26–2.36 (4H,
m), 3.67 (3H, s, OMe), 5.54–5.61 (1H, m, 13-H), 5.69 [1H, dd,
3JH–F(olefin) 20.5, J 11.0 Hz, 11-H], 5.86–5.93 (1H, m, 12-H);
δF(CDCl3) Ϫ104.53 (1F, m); δC(CDCl3) 13.94, 22.24, 24.94,
2
26.35, 28.40 (d, JC–F 27.3 Hz, 9-C), 28.87, 29.11, 29.13 (2C),
(E )-10-Fluoro-11-(2-methylphenyl)undec-10-en-1-ol
3g.
2
31.58, 32.69, 34.09, 51.44, 108.04 (d, JC–F 27.2 Hz, 11-C),
δH(CDCl3) 1.20–1.40 (11H, m), 1.51–1.58 (4H, m), 2.25–2.34
3
4
122.79 (d, JC–F 10.7 Hz, 12-C), 133.38 (d, JC–F 9.8 Hz, 13-C),
3
(5H, m), 3.62 (2H, t, J 6.6 Hz, 1-H2), 6.14 [1H, d, JH–F(olefin)
1
161.36 (d, JC–F 251.9 Hz, 10-C), 174.29; ν(neat)/cmϪ1 3029,
21.2 Hz, 11-H], 7.10–7.16 (4H, m, ArH); δF(CDCl3) Ϫ101.45
(1F, m); δC(CDCl3) 20.07, 25.69, 26.25, 28.54 (d, 2JC–F 27.3 Hz,
9-C), 28.96, 29.17, 29.35, 29.42, 32.79, 63.06, 106.65 (d,
2JC–F 27.2 Hz, 11-C), 125.71, 127.08, 129.03, 129.78, 133.43
2955, 2929, 2857, 1741, 1680, 1631, 1459, 1436, 1364, 1197,
1171, 1119, 1077, 1027, 962, 868, 721; m/z 298 (Mϩ, 76%), 278
(11), 267 (23), 238 (6), 224 (5), 208 (12), 177 (8), 161 (20), 149
(17), 136 (88), 127 (11), 121 (38), 107 (48), 93 (78), 85 (72), 79
(94), 67 (75), 59 (38), 55 (100), 41 (80) [Calc. for C18H31FO2
(M): 298.2308. Found: Mϩ, 298.2308] (Calc. for C18H31FO2:
C, 72.44; H, 10.47. Found: C, 72.35; H, 10.36%).
3
1
(d, JC–F 13.2 Hz, ipso-Ph), 136.85, 162.30 (d, JC–F 252.7 Hz,
10-C); ν(neat)/cmϪ1 3346br, 3061, 3020, 2928, 2855, 1683, 1603,
1484, 1459, 1232, 1194, 1153, 1084, 1056, 883, 846, 788, 747,
724; m/z 278 (Mϩ, 43%), 260 (17), 161 (28), 149 (100), 144 (84),
136 (21), 129 (78), 118 (19), 105 (36), 93 (7), 81 (8), 69 (14), 55
(21), 41 (9) [Calc. for C18H27FO (M): 278.2046. Found:
Mϩ, 278.2046].
(E,E)-10-Fluoropentadeca-10,12-dien-1-ol 5e. δH(CDCl3) 1.01
(3H, t, J 7.6 Hz, 15-H3), 1.22–1.38 (11H, m), 1.51–1.58 (4H, m),
3
2.06–2.13 (2H, m, 14-H2), 2.32 (2H, dt, JH–F 23.4, J 7.3 Hz,
9-H2), 3.64 (2H, t, J 6.6 Hz, 1-H2), 5.59–5.74 (2H, m), 5.87–5.93
(1H, m, 12-H); δF(CDCl3) Ϫ104.73 (1F, m); δC(CDCl3) 13.70,
(E,E)-8-Fluorooctadeca-5,7-diene 5a. δH(CDCl3) 0.86–0.92
(6H, m), 1.25–1.37 (18H, m), 1.49–1.56 (2H, m, 10-H2), 2.05–
2
25.72, 26.00, 26.36, 28.39 (d, JC–F 27.2 Hz, 9-C), 28.92, 29.26,
3
2
2.10 (2H, m, 4-H2), 2.31 (2H, dt, JH–F 23.4, J 7.3 Hz, 9-H2),
29.38, 29.46, 32.79, 63.08, 107.99 (d, JC–F 27.3 Hz, 11-C),
5.57 (1H, dt, J 7.1, 14.9 Hz, 5-H), 5.69 [1H, dd, 3JH–F(olefin) 20.3,
J 11.0 Hz, 7-H], 5.87–5.94 (1H, m, 6-H); δF(CDCl3) Ϫ104.73
(1F, m); δC(CDCl3) 13.94, 14.13, 22.25, 22.71, 26.39, 28.42
3
4
121.90 (d, JC–F 10.7 Hz, 12-C), 134.82 (d, JC–F 9.9 Hz, 13-C),
1
161.45 (d, JC–F 252.0 Hz, 10-C); ν(neat)/cmϪ1 3313br, 3033,
2963, 2929, 2855, 1680, 1631, 1461, 1434, 1371, 1320, 1150,
1128, 1077, 1057, 960, 867, 722; m/z 242 (Mϩ, 45%), 224 (5), 153
(16), 135 (14), 125 (34), 112 (62), 97 (100), 79 (71), 67 (68), 55
(94), 41 (83) [Calc. for C15H27FO (M): 242.2046. Found: Mϩ,
242.2050].
2
(d, JC–F 27.2 Hz, 9-C), 28.97, 29.35 (2C), 29.56, 29.62, 31.59,
31.93, 32.70, 108.01 (d, 2JC–F 26.4 Hz, 7-C), 122.84 (d, 3JC–F 10.7
4
1
Hz, 6-C), 133.31 (d, JC–F 9.9 Hz, 5-C), 161.47 (d, JC–F 251.1
Hz, 8-C); ν(neat)/cmϪ1 3033, 2957, 2926, 2855, 1681, 1632,
1466, 1434, 1377, 1272, 1141, 1094, 960, 867, 722; m/z 268 (Mϩ,
100%), 225 (22), 135 (12), 127 (20), 107 (15), 95 (29), 82 (97), 67
(42), 55 (29), 43 (35) [Calc. for C18H33F (M): 268.2566. Found:
Mϩ, 268.2564].
(E,E)-17-Chloro-8-fluoroheptadeca-5,7-diene 5f. δH(CDCl3)
0.90 (3H, t, J 7.6 Hz, 1-H3), 1.28–1.46 (14H, m), 1.48–1.57
(2H, m), 1.73–1.80 (2H, m, 10-H2), 2.05–2.08 (2H, m, 4-H2),
3
2.34 (2H, dt, JH–F 23.4, J 7.3 Hz, 9-H2), 3.52 (2H, t, J 6.6 Hz,
3
(E,E)-6-Fluorohexadeca-3,5-diene 5b. δH(CDCl3) 0.88 (3H,
t, J 6.8 Hz, 16-H3), 1.01 (3H, t, J 7.5 Hz, 1-H3), 1.23–1.36 (14H,
br s), 1.48–1.56 (2H, m, 8-H2), 2.06–2.13 (2H, m, 2-H2), 2.32
17-H2), 5.54–5.61 (1H, m, 5-H), 5.69 [1H, dd, JH–F(olefin) 20.2,
J 11.0 Hz, 7-H], 5.87–5.93 (1H, m, 6-H); δF(CDCl3) Ϫ104.85
(1F, m); δC(CDCl3) 13.95, 22.23, 26.34, 26.87, 28.39 (d,
2JC–F 27.2 Hz, 9-C), 28.85, 28.88, 29.23, 29.33, 31.58, 32.64,
3
(2H, dt, JH–F 23.7, J 7.3 Hz, 7-H2), 5.58–5.73 (2H, m), 5.87–
388
J. Chem. Soc., Perkin Trans. 1, 2002, 384–389

View Article Online
32.69, 45.17, 108.04 (d, 2JC–F 27.2 Hz, 7-C), 122.78 (d, 3JC–F 10.7
D. P. Matthews, Tetrahedron, 1996, 52, 45; ( f ) F. Tellier, R. Sauvêtre
4
1
and J.-F. Normant, J. Organomet. Chem., 1986, 303, 309.
7 N. Miyaura and A. Suzuki, Chem Rev., 1995, 95, 2457 and references
cited therein.
Hz, 6-C), 133.38 (d, JC–F 9.0 Hz, 5-C), 161.36 (d, JC–F 251.9
Hz, 8-C); ν(neat)/cmϪ1 3029, 2959, 2928, 2856, 1680, 1631,
1465, 1375, 1147, 1075, 962, 868, 726, 653; m/z 288 (Mϩ, 50%),
245 (17), 232 (5), 135 (6), 127 (22), 121 (16), 107 (16), 95 (27), 82
(100), 67 (53), 55 (48), 41 (51) [Calc. for C17H30ClF (M):
288.2020. Found: Mϩ, 288.2027] (Calc. for C17H30ClF: C, 70.68;
H, 10.47. Found: C, 70.48; H, 10.25%).
8 (a) S. Eddarir, C. Francesch, H. Mestdagh and C. Rolando, Bull.
Soc. Chim. Fr., 1997, 134, 741; (b) S. K. Kang, H.-W. Lee, S.-B. Jang
and P.-S. Ho, J. Org. Chem., 1996, 61, 4720; (c) S. K. Kang,
T. Yamaguchi, T.-H. Kim and P.-S. Ho, J. Org. Chem., 1996, 61,
9082; (d ) S. Eddarir, H. Mestdagh and C. Rolando, Tetrahedron
Lett., 1991, 32, 69; (e) J. H. Ryan and P. J. Stang, J. Org. Chem., 1996,
61, 6162; ( f ) P. J. Stang, T. Blume and V. V. Zhdankin, Synthesis,
1993, 35; (g) M. Ochiai, K. Sumi, Y. Takaoka, M. Kunishima,
Y. Nagao, M. Shiro and E. Fujita, Tetrahedron, 1988, 44, 4095.
9 R. J. Hinkle, G. T. Poulter and P. J. Stang, J. Am. Chem. Soc., 1993,
115, 11626.
Acknowledgements
We thank Ms Seiko Oka and Ms Miwa Kiuchi for the
measurements of mass spectra, and Ms Hiroko Matsumoto
and Ms Akiko Maeda for elemental analyses in the Center for
Instrumental Analysis, Hokkaido University.
10 J. Uenishi, R. Kawahama and O. Yonemitsu, J. Org. Chem., 1996,
61, 5716; W. Roush, B. B. Brown and S. E. Drozda, Tetrahedron
Lett., 1988, 29, 3541.
11 Z.-Y. Yang and D. J. Burton, Tetrahedron Lett., 1990, 31, 1369;
J. M. Percy and R. D. Wilkes, Tetrahedron, 1997, 53, 14749.
12 F. Ozawa, K. Kurihara, M. Fujimori, T. Hidaka, T. Toyoshima and
A. Yamamoto, Organometallics, 1989, 8, 180; F. Ozawa, T. Ito and
A. Yamamoto, J. Am. Chem. Soc., 1980, 102, 4933.
13 N. Miyaura and A. Suzuki, J. Organomet. Chem., 1981, 213, C53.
14 S.-Q. Chen, T. Hatakeyama, T. Fukuhara, S. Hara and N. Yoneda,
Electrochim. Acta, 1997, 42, 1951.
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