New methods for the synthesis of fluoroolefins via the palladium catalyzed cross-coupling reaction of 1-fluorovinyl halides with organoboranes and organostannanes

Article abstract of DOI:10.1016/S0022-1139(99)00172-4

The palladium catalyzed cross-coupling reaction of 1-fluorovinyl halides with organoboranes and organostannanes provide two new facile methods to 1-substituted 1-fluoroolefins. The reactions proceed with retention of configuration in good to excellent yields.

Full text of DOI:10.1016/S0022-1139(99)00172-4

Journal of Fluorine Chemistry 101 (2000) 285±290
New methods for the synthesis of ¯uoroole®ns via the palladium
catalyzed cross-coupling reaction of 1-¯uorovinyl
halides with organoboranes and organostannanes
Chen Chen1, Keith Wilcoxen, Charles Q. Huang, Nathalie Strack, James R. McCarthy*
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc. 10555 Science Center Drive, San Diego, CA 92121, USA
Received 9 May 1999; received in revised form 12 July 1999; accepted 12 July 1999
Abstract
The palladium catalyzed cross-coupling reaction of 1-¯uorovinyl halides with organoboranes and organostannanes provide two new
facile methods to 1-substituted 1-¯uoroole®ns. The reactions proceed with retention of con®guration in good to excellent yields. # 2000
Elsevier Science S.A. All rights reserved.
Keywords: Palladium catalyst; Cross-coupling; Fluoroole®n
1. Introduction
The coupling reaction of 1-¯uorovinylstannane with iodo-
benzene proceeded very slowly under standard Stille con-
ditions (without CuI) to give a very poor yield of the desired
product, see [7,28].
New methods to ¯uoroorganic compounds are of con-
siderable interest [1,21±23], in part because of the change in
biological activity often observed by the introduction of
¯uorine into compounds synthesized by medicinal chemists
[2,24]. For this reason ¯uoroole®ns [3,25] have been of
special interest as enzyme inhibitors (see [4,26] and refer-
ences therein.). Recently, we reported the stereospeci®c
Pd(0)/Cu(I) catalyzed cross-coupling of 1-¯uorovinylstan-
nanes with aryl iodides under Stille conditions to afford
substituted ¯uoroole®ns [5,27]. The method requires some-
what forcing conditions since CuI is necessary as a co-
catalyst to obtain good yields of product and to avoid the
formation of large amounts of side products. Herein we
report two new palladium-catalyzed cross-coupling reac-
tions (for the palladium(0) catalyzed coupling reaction of 1-
¯uorovinyl bromides with terminal alkynes, see [6]) of 1-
¯uorovinyl halides with organoboranes or organostannanes
that provide more facile stereospeci®c methods to 1-sub-
stituted 1-¯uoroole®ns. A rationale for the increased facility
of the two new methods to substituted ¯uoroole®ns com-
pared with the Pd(0)/Cu(I)/1-¯uorovinylstannanes method
will be discussed based on the electronic effects of ¯uorine.
A portion of this work was published as a communication
2. Results and discussion
The required 1-¯uorovinyl bromides or chlorides 1±4 are
readily available, as a separable mixture of E, Z isomers, by
the condensation of aldehydes with ¯uorotribromomethane
or ¯uorotrichloromethane in the presence of triphenylpho-
sphine and zinc [8,29±31]. Alternatively, bromination of E-
2-¯uoro-3-phenylacrylic acid [6] followed by debromocar-
boxylation yields pure isomer Z-1. The corresponding E-
isomer [9] E-1 was obtained in 92% isomeric purity by
isomerization of Z-1 with a catalytic amount of bromine in
chloroform.
The coupling of (E)-1-¯uoro-2-phenylvinyl bromide E-1
with phenylboronic acid (5a) proceeded in the presence of
5 mol% of Pd(PPh3)4 under Suzuki conditions (1 M aq.
Na2CO3, benzene±ethanol, re¯ux; cross-coupling of carbon
substituted vinyl halides with arylboronic acids catalyzed by
palladium(0) has been reported [10,32]) to afford b-¯uor-
ostilbene Z-6a2 exclusively in 86% isolated yield (Table 1).
In addition, under these conditions E-1 coupled with aryl-
*Corresponding author. Fax: 1-317-276-5431.
E-mail addresses: cchen@neurocrine.com (C. Chen), jmccarthy@lilly.com
(J.R. McCarthy)
2The E or Z configuration of the product olefins was assigned from the
3JH F coupling constant: 14±18 Hz for a cis H±F coupling. 33±36 Hz for a
trans coupling.
1Fax: 1-619-658-7601.
0022-1139/00/$ ± see front matter # 2000 Elsevier Science S.A. All rights reserved.
PII: S 0 0 2 2 - 1 1 3 9 ( 9 9 ) 0 0 1 7 2 - 4

286
C. Chen et al. / Journal of Fluorine Chemistry 101 (2000) 285±290
Table 1
¯uoro-2-phenylvinyl chloride 2 (mixture of E/Z isomers
with a ratio of E/Z ˆ 44/56) with phenylboronic acid (5a)
under Suzuki conditions gave the ¯uorinated ole®n 6a as a
mixture of E and Z isomers with a 1 : 1 ratio based on GC-
MS and 19F NMR analysis of the crude reaction mixture.
These two isomers were separated by chromatography (Z-
6a, 43% and E-6a, 49%) (Table 3). The coupling reaction of
Cross-coupling of (E)-b-bromo-b-fluorostyrene with organoboranes
(a: Pd(PPh3)4, Na2CO3, benzene±EtOH±H2O, reflux)
Entry
R
Time (h) Product Yield (%)
1-¯uoro-2-(4-methoxyphenyl)vinyl
chloride
3
(E/
Z ˆ 44 : 56) with phenylboronic acid (5a) provided the
products Z-7 and E-7 in 80% isolated yield (Z/
E ˆ 47 : 53). This reaction required approximately 8 h
for complete conversion to 7 vs 4 h for the unsubstituted
phenyl ¯uoroole®n 6a, which can be attributed to the
electron-donating 4-methoxy group. Reaction of 1-¯uoro-
2-phenethylvinyl chloride 4 with phenylboronic acid (3
equiv.) was not complete after 48 h when catalyzed by
tetrakis(triphenylphosphine)palladium(0). However, the
reaction proceed to completion in 24 h when catalyzed
by Pd(PPh3)2Cl2 in re¯uxing dioxane to afford the desired
product in 83% yield as an inseparable mixture of Z-8 and E-
8 in a ratio of 45 : 55.
1
2
3
C6H5
(5a)
(5b)
(5c)
1
1
3
Z-6a
Z-6b
Z-6c
86
89
91
4-ClC6H4
4-MeOC6H4
4
5
(5d)
(5e)
3
3
Z-6d
Z-6e
83
81
E-n-C4H9CH=CH-
Table 2
Cross-coupling of (Z)-b-bromo-b-fluorostyrene with organoboranes
An alternative method to 1-substituted 1-¯uoroole®ns,
that compliments the Sonogashira reaction conditions
reported by Mestdagh and co-workers for the synthesis of
¯uorinated enynes and dienes [6,11], is the palladium
catalyzed coupling of 1-¯uorovinyl bromides E-1 and Z-1
with organostannanes (9). Condensation of phenyltributyl-
stannane (9a) with E-1 using 5 mol% Pd(PPh3)4 as the
catalyst in re¯uxing dioxane provided high yields of the
corresponding Z-6a with retention of double bond geometry.
Several examples of the reaction with E-1 are summarized
in Table 4 showing good to excellent isolated yields. The
reaction of E-1 with (tributylstannyl) phenylacetylene (9g)
to provide Z-6g (75% isolated yield) was carried out for
direct comparison with the Sonogashira conditions reported
with acetylenes and haloole®ns. The yield of Z-6g was
identical by our new route and by the coupling reaction
of b-bromo-b-¯uorostyrene with phenylacetylene under
Sonogashira conditions [11]. It should also be noted that
(a: Pd(PPh3)4, Na2CO3, benzene±EtOH±H2O, reflux)
Entry
R
Time (h) Product Yield (%)
1
2
3
4
5
Ph
(5a)
(5b)
(5c)
(5e)
(5f)
4
4
6
4
5
E-6a
E-6b
E-6c
E-6e
E-6f
92
90
85
82
78
4-ClC6H4
4-MeOC6H4
E-n-C4H9CH=CH-
1-Naphthyl
Table 3
Cross-coupling of (E, Z)-1-chloro-1-fluoroolefins 2±4 with phenylboronic
acid (5a)
(a: Pd(PPh3)4/Na2CO3/benzene±EtOH±H2O/reflux)
Entry R'
Ratio
(E/Z)
Time Product Yield
(%)
Ratio
(Z/E)
Table 4
(h)
Cross-coupling of (E)-b-bromo-b-fluorostyrene with organostannanes
1
2
3
Ph
(2) 44/56
(3) 44/56
4
8
6a
7
92
80
83
50/50
47/53
45/55
4-MeOC6H4
PhCH2CH2
(4) 47/53 24a
8
aPd(PPh3)2Cl2/dioxane/aq.Na2CO3/reflux.
(a: Pd(PPh3)4, dioxane, reflux)
boronic acids 5b±d and vinylboronic acid 5e to give ¯uor-
oole®ns Z-6b±e in 81±91% yields.
Entry
R
Time (h)
Product
Z-6a
Yield (%)
1
2
3
4
Ph
(9a)
(9f)
(9g)
(9h)
16
16
2
86
80
75
78
The coupling reaction of the Z-isomer Z-1 with organo-
boronic acids 5a±c, 5f and vinylboronic acid 5e also pro-
ceeded smoothly to give the corresponding E isomers E-6a±
c and E-6e±f exclusively in 78±92% yields (see Table 2).
It is noteworthy that the coupling reaction also proceeded
with 1-¯uorovinyl chlorides 2±4 (Table 3). Reaction of 1-
Z-6f
PhC=C-
Z-6g
16
Z-6h

C. Chen et al. / Journal of Fluorine Chemistry 101 (2000) 285±290
287
Table 5
Cross-coupling of (Z)-b-bromo-b-fluorostyrene with organostannanes
(a: Pd(PPh3)4, dioxane, reflux)
Entry
R
Time (h)
Product
E-6a
Yield (%)
1
2
3
Ph
(9a)
(9f)
(9g)
16
16
16
94
81
74
E-6f
PhC=C-
E-6g
Fig. 1. Proposed mechanism for the palladium(0) insertion into an 1-
bromo-1-fluoroolefin followed by nucleophilic attack by an arylboronic
acid or an arylstannane.
the reaction proceeds just as ef®ciently with Z-1 to yield E-
6g in 74% (Table 5). This new method provides the pre-
paration of 1-aryl-1-¯uoroole®ns as well as dienes and
enynes and thus compliments the above use of boronic
acids for the cross-coupling reaction.
Pd(0). For a discussion see [13]. For two recent exceptions
to this problem see [33,34].) Consistent with the observation
is the facility of Pd(0) insertions into electron de®cient
heteroaryl chlorides. See, for example, the coupling reaction
of 2,5-dichloropyridine with phenylboronic acid proceeds
under Suzuki conditions to give 5-chloro2-phenylpyridine
in 83% yield [14].
Likewise, the I effect of ¯uorine is consistent with the
``copper effect'' observed for the cross-coupling of ¯uor-
ovinylstannanes with aryl iodides that we recently reported
[7,28]. The ¯uorovinylstannane would presumably be a
poorer nucleophile than the non¯uorinated stannane, thus
requiring CuI to increase the electrophilicity of the palla-
dium(II) ligand±solvent intermediate (see Fig. 2) For key
references on the ``copper-effect'' for Stille coupling, see:
[15,35]. For an example of the reaction of non¯uorinated
vinylstannanes with aryl iodides which does not require CuI
to proceed in good yield, see [16,36].
The cross-coupling reaction proceeds in very good yield
with the more hindered Z-1 as can be seen in Table 5 by
comparing the three entries with entries 1±3 in Table 4. In
addition, it should be noted that the cross-coupling of E-1
with tributylstannyl-1-ethoxyethene (10) is a high yielding
reaction by 19F NMR to form the very labile vinyl ether 11
(Scheme 1). Aqueous work-up of the reaction mixture
resulted in the hydrolysis of the vinyl ether to the a-
¯uoro-a,b-unsaturated ketone 12, that proved dif®cult to
isolate. Percy and Wilkes [12] reported the synthesis of a
series of more stable b-¯uorvinyl ethers by a palladium(0)-
catalyzed coupling of vinyltributylstannane with 1-iodo-1-
¯uoro-2-substituted vinyl MEM ethers.
The facility of these two new methods for the preparation
of 1-substituted 1-¯uoroole®ns can be rationalized by the
I
electron withdrawing effect of ¯uorine, which would
increase the ease of the palladium insertion between the
carbon±bromine and carbon±chlorine bond in the reaction
illustrated in Fig. 1, and is in contrast to the observations
usually made with aryl and vinyl chlorides. (The low
reactivity of aryl chlorides in cross-coupling reactions is
apparently due to their reluctance to oxidatively add to
In summary, the palladium-catalyzed cross-coupling
reactions of 1-¯uorovinyl halides with organoboranes or
organostannanes take advantage of the I effect of ¯uorine
to provide facile and convenient methods for the stereo-
speci®c synthesis of 1-substituted 1-¯uoroole®ns in high
yields.
Scheme 1. Formation of a-fluoro-a,b-unsaturated kenone 12.

288
C. Chen et al. / Journal of Fluorine Chemistry 101 (2000) 285±290
Fig. 2. Proposed mechanism for the palladium(0) insertion into an aryl iodide followed by nucleophilic attack by a fluorovinylstannane.
3. Experimental
ꢀ: 6.52 (d, J ˆ 39.3 Hz, 1H), 6.96 (d, J ˆ 2.1 Hz, 1H), 7.25±
7.42 (m, 5H), 7.49 (d, J ˆ 8.7 Hz, 1H), 7.58 (d, J ˆ 8.1 Hz,
1H), 7.66 (dm, J ˆ 7.2 Hz, 2H); 19F NMR (CDCl3) ꢀ:
125.7 (d, J ˆ 39.5 Hz); 13C NMR (CDCl3) ꢀ: 104.2 (d,
J ˆ 1.1 Hz), 107.1 (d, J ˆ 5.4 Hz), 111.1 (d, J ˆ 1.1 Hz,
121.4 (s), 123.2 (s), 125.3 (s), 127.7 (d, J ˆ 2.3 Hz), 128.6
(S), 129.1 (d, J ˆ 7.8 Hz), 132.7 (d, J ˆ 3.5 Hz), 148.8 (d,
J ˆ 49.0 Hz), 149.1 (d, J ˆ 247.5 Hz), 154.9 (s); GCMS
3.1. General
High-®eld NMR spectra were recorded on a Varian XL-
300 (1H at 300 MHz, 13C at 75.5 MHz) in CDCl3. 19F
chemical shifts are reported in ꢀ (ppm) relative to ¯uorotri-
chloromethane (CFCl3, 0 ppm). GC-MS spectra were
recorded on Hewlett-Packard 5890 Series II with a 5972
mass selective detector. Thin-layer chromatography was
performed on silica gel 60 F254 plates from Whatman.
(Z)-1-Bromo-1-¯uoro-2-phenylethene (Z-1) and (E)-1-
bromo-1-¯uoro-2-phenylethene (E-1) [11], (Z,E)-1-
chloro-1-¯uoro-2-phenylethene (2) [17,37], (Z,E)-1-
chloro-1-¯uoro-2-(4-methoxyphenyl) (3) [18,21] and
(Z,E)-1-chloro-1-¯uoro-2-phenethylethene (4) were synthe-
sized according to literature methods.
‡
(EI): m/e 238 (M ); Anal for C16H11FO (238.26), calcd. C,
80.66; H, 4.65; found C, 80.41; H, 4.78.
(E)-1,2-Diphenyl-1-¯uoroethene (E-6a) Colorless oil
[5,27,19], 92% yield; 1H NMR (CDCl3) ꢀ: 6.45 (d,
J ˆ 21.3 Hz, 1H), 7.20 (m, 4H), 7.32 (m, 3H), 7.41 (m,
2H), 7.60 (m, 1H); 19F NMR (CDCl3) ꢀ: 96.5 (d,
J ˆ 21.5 Hz); 13C NMR (CDCl3) ꢀ: 109.2 (d, J ˆ 30.9 Hz),
127.0 (d, J ˆ 13.7 Hz), 128.1 (s), 128.2 (s), 128.3 (s), 128.7
(d, J ˆ 2.9 Hz), 129.4 (d, J ˆ 1.5 Hz), 131.7 (d,
J ˆ 29.2 Hz), 133.6 (d, J ˆ 12.6 Hz), 157.6 (d,
‡
J ˆ 246.0 Hz); GCMS (EI): m/e 198 (M ).
3.1.1. (Z,E)-1-Chloro-1-fluoro-2-phenethylethene (4)
Mixture of E and Z isomers (47 : 53 ratio); colorless oil;
1H NMR (CDCl3) ꢀ: Z-isomer: 2.43 (m, 2H); 2.70 (m, 2H);
5.29 (dt, J ˆ 10.5, 7.8 Hz, 1H), 7.27 (m, 5H); E-isomer:
2.36 (m, 2H), 2.70 (m, 2H), 4.87 (dt, J ˆ 29.1, 7.6 Hz, 1H),
7.27 (m, 5H); 19F NMR (CDCl3) ꢀ : 78.9 (Z-isomer, d,
J ˆ 9.0 Hz); 81.6 (E-isomer, d, J ˆ 30.0 Hz); GCMS (EI):
(E)-1-(4-Chlorophenyl)-1-¯uoro-2-phenylethene (E-6b)
1
White solid, m.p. 133±7oC, yield: 90%; H NMR (CDCl3)
ꢀ: 6.46 (d, J ˆ 21.6 Hz), 7.13±7.50 (m, 9H); 19F NMR
(CDCl3) ꢀ: 98.0 (d, J ˆ 21.2 Hz); 13C NMR (CDCl3) ꢀ:
106.3 (d, J ˆ 30.6 Hz, 123.6 (d, J ˆ 26.9 Hz), 124.6 (s), 125
(s), 125.2 (d, J ˆ 2.9 Hz), 126.0 (d, J ˆ 5.2 Hz), 126.7 (d,
J ˆ 29.5 Hz), 129.8 (d, J ˆ 12.1 Hz), 134.8 (s), 153.0 (d,
‡
m/e 182 (M ).
‡
J ˆ 245.6 Hz); GCMS (EI): m/e 232 (M ); Anal for
C14H11F (198.24), calcd. C, 84.82; H, 5.59; found C,
84.49; H, 5.67.
(E)-1-Fluoro-1-(4-methoxyphenyl)-2-phenylethene (E-
3.2. Palladium catalyzed cross-coupling reaction of b-
bromo-b-fluorostyrene with organoboronic acid
1
6c) Colorless oil, yield: 85%; H NMR (CDCl3) ꢀ: 3.81
(s, 3H), 6.36 (d, J ˆ 21.6 Hz, 1H), 6.82 (d,J ˆ 8.7 Hz, 2H),
3.2.1. General procedure
7.18 (m, 5H), 7.36 (d, J ˆ 8.7 Hz, 2H); 19F NMR (CDCl3) ꢀ:
A mixture of (Z)- or (E)-1-bromo-1-¯uoro-2-pheny-
lethene (201 mg, 1.0 mmol), organoboronic acid
(1.2 mmol), potassium carbonate (420 mg, 3.0 mmol) in
benzene (15 ml), ethanol (3 ml) and water (3 ml) was
treated with tetrakis(triphenylphosphine)palladium(0)
(60 mg, 0.05 mmol) under nitrogen and then heated at re¯ux
for 1±6 h. This mixture was diluted with ethyl acetate
(100 ml), dried over MgSO4, ®ltrated and concentrated in
vacuo. The residue was chromatographed on silica gel with
hexanes to give the desired product.
‡
95.7 (d, J ˆ 21.4 Hz); GCMS (EI): m/e 228 (M ); HRMS
‡
for C15H13FO (M ): calcd. 228.0950; found 228.0961.
2-Fluoro-1-phenyl-Octa-1E,3E-diene (E-6e) Colorless
1
oil, yield: 82%; H NMR (CDCl3) ꢀ: 0.92 (t, J ˆ 7.2 Hz,
3H), 1.36 (m, 4H), 2.16 (m, 2H), 5.53 (d, J ˆ 38.4 Hz, 1H),
5.90 (ddt, J ˆ 1.2, 15.9, 25.8 Hz, 1H), 6.12 (dt, J ˆ 7.2,
15.9 Hz, 1H), 7.15±7.56 (m, 5H); 19F NMR (CDCl3) ꢀ:
‡
107.4 (dd, J ˆ 27.4, 39.5 Hz); GCMS (EI): m/e 204 (M );
‡
HRMS for C14H17F (M ), calcd. 204.1314; found
204.1323.
For compounds Z-6a, 6b, 6c, and 6e see reference [5,27]
(Z)-1-(Benzofuran-2-yl)-1-¯uoro-2-phenylethene (Z-6d)
White solid, m.p. 101±38C, yield: 83%; H NMR (CDCl3)
(E)-1-Fluoro-1-(1-naphthyl)-2-phenylethene (E-6f) Col-
orless oil, yield: 78%; 1H NMR (CDCl3) ꢀ: 6.73 (d,
1

C. Chen et al. / Journal of Fluorine Chemistry 101 (2000) 285±290
289
1
J ˆ 20.1 Hz, 1H), 6.90 (m, 2H), 7.06 (m, 3H), 7.44 (t,
J ˆ 7.2 Hz, 1H), 7.53 (m, 3H), 7.93 (t, J ˆ 9.0 Hz, 2H),
8.08 (m, 1H); 19F NMR (CDCl3) ꢀ: 84.8 (d, J ˆ 18.3 Hz);
provide (Z)-6f as a colorless oil (75 mg, 80%). H NMR
(CDCl3) ꢀ: 6.25 (d, J ˆ 40.2 Hz, 1H), 6.48 (m, 1H), 6.60±
6.62 (m, 1H), 7.22±7.28 (m, 1H), 7.33±7.39 (m, 2H), 7.44±
7.46 (m, 1H), 7.57±7.61 (m, 2H); 19F NMR (CDCl3) ꢀ:
‡
‡
GCMS (EI): m/e 248 (M ); HRMS for C18H13F (M ),
‡
calcd. 248.1003; found 248.1012.
120.82 (d, J ˆ 39.9 Hz); GCMS (EI): m/e 188 (M ) at
‡
tr ˆ 4.91 min; HRMS: m/e for C12H9FO [M ‡ H ] calcd.
189.0716; found 189.0723.
(Z)-1,4-Diphenyl-2-¯uoro-1-buten-3-yne (Z-6g) Color-
3.3. Palladium catalyzed cross-coupling reaction of 1-
fluorovinyl chloride (E, Z mixture) with arylboronic acids.
1
less oil, 75% yield; H NMR: 6.15 (d, J ˆ 35.1 Hz, 1H),
6.48 (m, 1H), 7.25±7.39 (m, 6H), 7.50±7.57 (m, 4H); 19F
(E)- and (Z)-1-¯uoro-1-(4-methoxyphenyl)-2-pheny-
lethene (7) A mixture of (E, Z)-1-chloro-1-¯uoro-2-(4-
methoxyphenyl)ethene (E/Z ˆ 44 : 56, 93 mg, 0.5 mmol),
phenylboronic acid (74 mg, 0.6 mmol), potassium carbo-
nate (210 mg, 1.5 mmol) in benzene (8 ml), ethanol (1.5 ml)
and water (1.5 ml) was treated with tetrakis(triphenylpho-
sphine)palladium(0) (30 mg, 0.025 mmol) under nitrogen
and heated at re¯ux for 8 h. This mixture was diluted with
ethyl acetate (100 ml), dried over MgSO4, ®ltrated and
concentrated in vacuo. GC-MS analysis of the crude pro-
ducts showed a mixture of (E)- and (Z)-7 with a ratio of
47 : 53 (Z/E). Attempts to separate these two isomers on
silica gel failed, and the product was obtained, after chro-
matography, as a colorless oil (80% yield). 1H NMR
(CDCl3) ꢀ: (Z-7) 3.82 (s, 3H), 6.26 (d, J ˆ 40.2 Hz, 1H),
6.91 (d, J ˆ 9.0 Hz, 2H), 6.30±6.46 (m, 3H), 7.60 (m, 4H);
(E-7) 3.77 (s, 3H), 6.40 (d, J ˆ 21.9 Hz, 1H), 6.76 (d,
J ˆ 8.7 Hz, 2H), 7.08 (d, J ˆ 8.7 Hz, 2H), 6.30±6.46 (m,
NMR (CDCl3) ꢀ: 100.63 (d, J ˆ 35.0 Hz); GCMS: m/e
‡
222 (M ) at tr ˆ 6.31 min; HRMS: m/e for C16H11F
‡
[M ‡ H ] calcd. 223.0923; found 223.0931.
(Z)-1-Fluoro-1-(2-thienyl)-2-phenylethene (Z-6h) Color-
1
less oil, 78% yield; H NMR: 6.15 (d, J ˆ 39.3 Hz, 1H),
7.03±7.07 (m, 1H), 7.22±7.39 (m, 5H), 7.57±7.61 (m, 2H);
‡
19F NMR: 104.19 (d, J ˆ 38.8 Hz); GCMS: m/e 204 (M )
‡
at tr ˆ 5.65 min; HRMS: m/e for C12H9FS [M ‡ H ] calcd.
205.0487; found 205.0494.
(Z)-2-Fluoro-3-ethoxy-1-phenyl-1,3-butadiene (11) Col-
orless oil, 9% yield: 1H NMR: (CDCl3) ꢀ: 1.41 (t,
J ˆ 7.0 Hz, 3H), 3.89 (q, J ˆ 7.0 Hz, 2H), 4.32 (m, 1H),
4.74 (dd, J ˆ 39.5 Hz, 1H), 6.23 (m, 1H), 7.25±7.42 (m,
3H), 7.53±7.59 (m, 2H); 19F NMR (CDCl3) ꢀ: -120.04 (d,
‡
J ˆ 39.2 Hz); GCMS: m/e 192 (M ).
3.5. Palladium catalyzed cross-coupling reaction of (Z)-b-
bromo-b-fluorostyrene with organostannanes.
5H); 19F NMR (CDCl3) ꢀ:
117.7 (Z-isomer, d,
J ˆ 39.8 Hz);
98.6 (E-isomer, d, J ˆ 21.5 Hz); MS
(E)-1-Fluoro-1,2-diphenylethene (E-6a) A solution of
(Z)-1-bromo-1-¯uoro-2-phenylethene (100 mg, 0.5 mmol),
tributylphenyltin (240 mg, 0.65 mmol) in dioxane was trea-
ted with tetrakis(triphenylphosphine)palladium(0) (30 mg,
0.025 mmol) under nitrogen and heated at re¯ux for 16 h.
Chromatography of the reaction mixture on silica gel with
hexanes gave E-6a in 94% isolated yield.
‡ ‡
(EI): m/e 228 (M ); HRMS for C15H13FO (M ), calcd.
228.0950; found 228.0970.
(E)-1-Fluoro-1,4-diphenylbutene and (Z)-1-Fluoro-1,4-
diphenylbutene (8) GC-MS analysis of the crude products
shown a mixture of Z/E ˆ 45 : 55. The two isomers were
1
not separated by silica gel. Colorless oil, 83% yield; H
NMR (CDCl3) ꢀ: (Z-isomer) 2.60 (m, 2H), 2.78 (m, 2H),
5.48 (dt, J ˆ 37.2, 7.5 Hz, 1H), 7.15±7.50 (m,10H); 19F
NMR (CDCl3) ꢀ: 120.5 (Z-isomer, d, J ˆ 36.7 Hz);
(E)-1-Fluoro-1-(2-furfuryl)-2-phenylethene (E-6f) Color-
less oil, 81% yield; 1H NMR (CDCl3) ꢀ: 6.40 (m, 1H), 6.41
(d, J ˆ 24.0 Hz, 1H), 7.23 (m, 1H), 7.51 (m, 5H); GCMS
‡
101.74 (d, J ˆ 23.0 Hz); MS (EI): m/e 226 (M );
‡
(EI): m/e188 (M ).
‡
HRMS for C16H15F (M ): calcd. 226.1258; found
226.1263.
(Z)-3-Fluoro-4-phenyl-3-buten-2-one (12) A mixture of
(E)-b-bromo-b-¯uorostyrene (100 mg, 0.50 mmol), 1-(tri-
butylstannyl)vinyl ethyl ether (10) (200 mg, 0.55 mmol),
tetrakis(triphenylphosphine)palladium(0) (32 mg, 0.025,
5 mol%) in dioxane (5 ml) was re¯uxed under nitrogen
overnight. The 19F NMR was performed on a sample of
the reaction mixture to determine yield (95%, D2O insert for
signal lock-on; C6F6 as external standard). The reaction
mixture was concentrated in vacuo, dissolved in ether,
washed with KF solution and brine. The ether was
concentrated, puri®ed by preparative TLC plates to provide
Z-12 [20] in 14% yield. 1H NMR: 2.42 (d, J ˆ 1.8 Hz, 3H),
6.63 (d, J ˆ 36.6 Hz, 1H), 7.38±7.44 (m, 3H), 7.64±7.72
3.4. Palladium catalyzed cross-coupling reaction of (E)-b-
bromo-b-fluorostyrene with organostannanes.
(Z) 1-Fluoro-1-(2-furanyl)-2-phenylethene (Z-6f) A mix-
ture of (E)-1-¯uoro-1-bromo2-phenylethene (100 mg,
0.50 mmol), 2-(tributylstannyl)furan (195 mg, 0.55 mmol),
tetrakis(triphenylphosphine)palladium(0) (32 mg, 0.025,
5 mol%) in dioxane (5 ml) was re¯uxed under nitrogen
overnight. The 19F NMR was performed on a sample of
the reaction mixture to determine yield (97%, D2O insert for
signal lock-on; C6F6 as external standard). The reaction
mixture was concentrated in vacuo and puri®ed by ¯ash
chromatography on silica gel (eluted with hexane, Rf0.5) to
‡
(m, 2H); GCMS: m/e 164 (M ) at tr ˆ 4.31 min; HRMS:
‡
m/e for C16H11F [M ‡ H ] calcd. 165.0716; found
165.0722.

290
C. Chen et al. / Journal of Fluorine Chemistry 101 (2000) 285±290
[18] H. Yamanaka, T. ando, W. Funasaka, Bull. Chem. Soc. Jpn. 41
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