A general and efficient route for the preparation of phenyl-substituted vinyl fluorides

Article abstract of DOI:10.1002/(SICI)1522-2675(19991215)82:12<2231::AID-HLCA2231>3.0.CO;2-Z

α-fluorobenzyl phosphonate (EtO)₂P(O)CFHPh (2) prepared from diethyl α-hydroxyphosphonate (EtO)₂P(O)CH(OH)Ph (1) and diethylaminosulfur trifluoride (DAST), reacts with bases such as butyllithium, tert- butyllithium, lithium bis(trime

Full text of DOI:10.1002/(SICI)1522-2675(19991215)82:12<2231::AID-HLCA2231>3.0.CO;2-Z

Helvetica Chimica Acta ± Vol. 82 (1999)
2231
A General and Efficient Route for the Preparation of Phenyl-Substituted
Vinyl Fluorides1)
by Hou-Jen Tsaia)*, Keh-Wen Lina), Tzu-hao Tinga), and Donald J. Burtonb)
a) Department of Applied Chemistry, Chung Cheng Institute of Technology, Ta-hsi, Tao-yuan, Taiwan
b) Department of Chemistry, University of Iowa, Iowa City, Iowa 52242, USA
a-Fluorobenzyl phosphonate (EtO)2P(O)CFHPh (2) prepared from diethyl a-hydroxyphosphonate
(EtO)2P(O)CH(OH)Ph (1) and diethylaminosulfur trifluoride (DAST), reacts with bases such as butyllithium,
tert-butyllithium, lithium bis(trimethylsilyl)amide, or lithium diisopropylamide at 788 in THF to give the
‡
phosphonate carbanion [(EtO)2P(O)CFPh] Li (3) which was detected by acylation with propionyl chloride or
by addition of MeOD to the reaction mixture to give (EtO)2P(O)CF(COEt)Ph (4) and (EtO)2P(O)CFDPh
(5), respectively. Addition of aldehydes or ketones to a THF solution of carbanion 3 led to moderate-to-good
yields of phenyl-substituted vinyl fluorides RR'CˆCFPh 6. The stereoselectivity of the products PhCHˆCFPh
(6a) and Ph(Me)CˆCFPh (6i) formed in the reaction was examined. The presence of hexamethylphosphoric
triamide or N,N'-dimethylpropyleneurea as cosolvent in the preparation of 6a and 6i increased the (Z)-
stereoselectivity. However, the presence of LiCl in THF did not alter the (E)/(Z)-ratio of the product.
Introduction. ± Profound changes in the biological activity of an organic compound
are often associated with the replacement of a H-atom in the molecule by an F-atom
[2]. Replacement of the H-atom by the F-atom not only enhances the biological activity
of parent compounds but also increases their thermal and oxidative stabilities [3]. A
variety of monofluoro compounds exhibit remarkable biological activities [4], and
medical and biological sciences exert an increasing demand for fluorinated organic
compounds. Biologically active molecules containing a vinylic F-atom are of special
interest, as this moiety is present in a number of enzyme inhibitors [5]. The main
methods currently afford vinyl fluorides in which the accompanying terminal group is a
halogen [6], ester [7], cyanide [8], or sulfone [9] function. Consequently, the synthesis
of selectively fluorinated building blocks, such as phenyl-substituted fluoro alkenes, has
become an area of interest in recent years [10 ± 12]. Literature methods for the
preparation of phenyl-substituted fluoro alkenes generally lack generality and stereo-
selectivity. Thus, addition of elemental fluorine to prop-1-enylbenzene followed by
subsequent dehydrofluorination gives (Z) and (E)-1-fluoroprop-1-enylbenzenes [10].
Dehydrofluorination of erythro- and threo-difluorides PhCFHCFHPh with t-BuOK
produces a-fluoro cis- and trans-a-fluorostilbene [11]. Dehydroiodination of 1-fluoro-
2-iodo-1-phenylpropane also leads to the preparation of cis- and trans-(1-fluoroprop-1-
enyl)benzenes [12]. Recent research from our laboratory has focused on the use of
fluoroethoxycarbonyl-substituted phosphorus or phosphonate ylides as synthons for
the preparation of a-fluorocarbonyl compounds such as a-fluoro-a,b-unsaturated
esters [13], a-fluoro-b-keto esters [14], a-fluoro-a-alkyl esters [15], and a-fluoro-a,b-
1
)
For a preliminary communication, see [1].

2232
Helvetica Chimica Acta ± Vol. 82 (1999)
unsaturated diesters [16]. Herein, we describe a general, one-pot synthesis of Ph-
substituted vinyl fluorides RR'CˆCFPh, which permits variation of the group in the b-
position from the reaction of diethyl a-fluorobenzylphosphonate carbanion [(EtO)2-
‡
P(O)CFPh] Li (3) with aldehydes and ketones.
Results and Discussion. ± Thermal non-catalyzed addition of diethyl phosphite to
PhCHO [17] at 1108, or MeONa-catalyzed condensation of diethyl phosphite with
PhCHO at room temperature [18] gave the diethyl a-hydroxyphosphonate (EtO)2-
P(O)CH(OH)Ph (1) in 53% yield. The 31P-NMR spectrum of 1 can be observed as a
doublet of quintuplets at 21.6 ppm (J(P,CH) ˆ 10, J(PO,CH) ˆ 7 Hz). J(P,CH) and
J(PO,CH) values were obtained by selective irradiation of H C(a) at 4.1 ppm and
CH2 H-atom at 5.0 ppm. The signal corresponding to the OH H-atom was confirmed by
the 1H-NMR spectrum measured by addition of D2O to the sample in NMR tube. The
signal at 5.2 ppm disappeared after H/D exchange reaction. The conversion of the OH
group into the F-substituent was achieved by the reaction of 1 with diethylaminosulfur
trifluoride (DAST) in CH2Cl2 to obtain diethyl a-fluorobenzylphosphonate (EtO)2-
P(O)CFHPh, 2, in 53% yield (Scheme 1) [19].
Scheme 1
Deprotonation of H C(a) from phosphonate 2 was conveniently carried out at
788 in THF with organolithium reagents such as BuLi, t-BuLi, lithium bis(trimethyl-
silyl)amide, and lithium diisopropylamide (LDA) to give similar results. No reaction
occurred when NaH was used as a base at 788 or 408 in THF. The a-fluorobenzyl-
‡
phosphonate carbanion [(EtO)2P(O)CFPh] Li (3) decomposed at room temper-
ature. Nevertheless, the acid-base reaction between phosphonate 2 and LDA at 788
could be detected by acylation of the product carbanion 3 with propionyl chloride to
give a doublet (J(F,P) ˆ 76 Hz) at 170 ppm in the 19F-NMR spectrum for the acylated
compound (EtO)2P(O)CF(COEt)Ph (4) in 80% yield (19F-NMR). Phosphonate
carbanion 3 could also be detected by addition of MeOD to the reaction mixture to
afford (EtO)2P(O)CFDPh (5), which was not isolated but was identified by a doublet
of triplets at 200 ppm in the 19F-NMR spectrum, with coupling constants of 83 and
7 Hz, respectively (Scheme 2).
Treatment of diethyl a-fluorobenzylphosphonate 2 with LDA in the presence of
aldehydes or ketones in THF at
788 gave phenyl-substituted vinyl fluorides
RR'CˆCFPh, 6, in 47 ± 76% isolated yields (Scheme 3 and Table 1).
The initial step in the synthesis of fluoro alkenes 6 is nucleophilic attack of the
carbanion 3 at the carbonyl C-atom of aldehydes or ketones to form ion 7. Intra-

Helvetica Chimica Acta ± Vol. 82 (1999)
2233
Scheme 2
Scheme 3
Scheme 4
molecular elimination of diethylphosphate anion from 7 affords the phenyl-substituted
vinyl fluorides 6 (Scheme 4).
The results of the preparation of several Ph-substituted vinyl fluorides 6a ± n are
summarized in Table 1.
The (E)/(Z) ratio of 6 was determined by integration of the F-signals in the 19F-
NMR spectra, which appear as doublets between 89.4 and 121.0 ppm upfield from
CFCl3 as an internal standard. The downfield chemical shifts ( 89.4 to 102.7 ppm)
were assigned to the F-atom of the (E)-isomer, whereas the upfield signals ( 105.5 to
121.0 ppm) were assigned to the F-atom of the (Z)-isomer. The assignments of
configuration are based on the reports that 3J(H,F(E)) is larger than 3J(H,F(Z)), and
4
4J(H,F(Z)) is larger than J(H,F(E)) in typical compounds that contain the moieties
1
HCˆCFCO2Et [20] and HCCˆCFCO2Et [7][16], respectively. In the H-NMR
spectrum, the signal for the vinyl H-atom appears in the range of 5.7 to 6.5 ppm
downfield from Me4Si as an internal standard.
The (E)/(Z)-selectivity observed was ca. 1:1 in most of the reactions reported in
Table 1. However, in the preparation of 6h, the (Z)-isomer was obtained preferentially.
This result may possibly be explained by the repulsive interactions between 3,4-
(MeO)2C6H3 and Ph groups [16].

2234
No.
Helvetica Chimica Acta ± Vol. 82 (1999)
Table 1. Preparation of 6 from 2
R
R'
(E)/(Z)a)
Yield [%]b)
6a
6b
6c
6d
6e
6f
6g
6h
6i
6j
6k
6l
6m
6n
Ph
H
H
H
H
H
H
H
H
Me
Ph
Me
CD3
Et
46 : 54
50 : 50
43 : 57
50 : 50
49 : 51
60 : 40
47 : 53
36 : 64
51 : 49
±
71
66
76
65
65c)
74
72
69
4-MeC6H4
4-MeOC6H4
4-ClC6H4
4-NO2C6H4
2-CF3C6H4
Cyclohexyl
3,4-(MeO)2C6H3
Ph
Ph
Me
CD3
Me
50
48
±
±
50c)
52c)
47c)
54c)
50 : 50
±
(CH2)5
a) (E)/(Z)-Ratio was determined by 19F-NMR integration of the vinyl-fluorine signals. b) Isolated yields are
c
based on 2. ) Yield based on 19F-NMR; PhCF3 as internal standard.
The stereoselectivity of 6a and 6i is dependent on the solvent, base, cosolvent, or
metal ion present in the reaction mixture. Different isomer ratios obtained are listed in
Table 2.
The use of LDA in a mixture of THF, and hexamethylphosphoric triamide (HMPT)
or N,N'-dimethylpropyleneurea (DMPU) in the preparation of 6a and 6i increased
(Z)-stereoselectivity. However, the presence of excess LiCl had no influence on the
Table 2. Dependence of Configuration of 6a or 6i on Solvent, Base, Cosolvent, and Metal Ion
Solvent=Base=Cosolvent=Metal ion
ƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒƒ!
(EtO)2P(O)CFHPh ‡ PhC(O)R
Ph(R)CˆCFPh
((E),(Z))
788 to r:t:
2
6a R ˆ H
6i R ˆ Me
Entry
R
Solvent/Base/Cosolvent/Metal ion
(E)/(Z)
Yield [%]a)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
H
H
H
H
THF/LDA/±/±
46 : 54
24 : 76
38 : 62
45 : 55
51 : 49
38 : 62
40 : 60
50 : 50
49 : 51
65 : 35
48 : 52
66 : 34
46 : 54
60 : 40
57: 43
87
84
82
86
80
74
72
75
78
62
72
63
73
52
71
THF/LDA/HMPT/±
THF/LDA/DMPU/±
THF/LDA/±/2 LiCl
THF/LDA/±/±
THF/LDA/HMPT/±
THF/LDA/DMPU/±
THF/LDA/±/2 LiCl
THF/BuLi/±/±
THF/t-BuOK/±/±
CH2Cl2/BuLi/±/±
CH2Cl2/t-BuOK/±/±
Et2O/BuLi/±/±
Et2O/t-BuOK/±/±
Hexane/LDA/±/±
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
a) Yields based on 19F-NMR; PhCF3 as internal standard.

Helvetica Chimica Acta ± Vol. 82 (1999)
2235
configuration of 6a and 6i [16]. In the preparation of 6i, the (E)/(Z)-ratio changed
from 48 :52 to 66 :34 when the base was changed from BuLi to t-BuOK in CH2Cl2 as
solvent. However, the stereoselectivity of 6i was unaffected when the solvent was
changed from THF to Et2O or CH2Cl2 with the BuLi base. A higher yield (80%; 19F-
NMR) was observed with LDA as the base in THF. However, only a 52% yield (19F-
NMR) was observed with t-BuOK as base in Et2O.
The formation of Ph-substituted fluoro alkenes is analogous to the Wittig reaction
[21] and is illustrated in Scheme 5. The formation of the intermediate 9 from 3 and
carbonyl compounds is reversible [22], and that intermediate can exist in two
diastereoisomeric forms, 9a and 9b [13][16]. Complexation of soluble Li salts [23] with
the intermediate 9 retards the reversibility between the isomers 9a and 9b.
Consequently, each of these intermediates undergoes cyclization to 10a and 10b,
respectively, and decomposition via a syn elimination to stereospecifically give the Ph-
substituted fluoro alkenes (E)-6 and (Z)-6. Thus, the erythro-form 9a should lead to the
(E)-isomer, while the threo-form should lead to the (Z)-isomer. Steric hindrance
between the Ph and 3,4-(MeO)2C6H3 groups should be greater in 9a than 9b, and
irreversible decomposition of the isomers 9a and 9b should give specific Ph-substituted
vinyl fluorides 6. The relative rates of formation and decomposition of the intermediate
should determine the (E)/(Z)-ratio. Slow decomposition of alkoxy anions should lead
to increased reversibility of the initial step to form the (Z)-isomer as the major product
[16]. The decisive influence of dissolved Li salts on the isomer ratio in Wittig and
related reactions is well-documented [24]. Different isomer ratios are possible for (E)-
and (Z)-PhCHˆCFPh (6a), or (E)- and (Z)-Ph(Me)CˆCFPh (6i), when the alkoxide
Scheme 5

2236
Helvetica Chimica Acta ± Vol. 82 (1999)
ion 9a or 9b is associated with the Li cation, or if the cation is coordinated by HMPTor
DMPU, and removed from the reaction site.
Conclusion. ± We have demonstrated that treatment of phosphonate carbanion
‡
[(EtO)2P(O)CFPh] Li , 3, derived from diethyl a-fluorobenzylphosphonate and LDA
with aldehydes or ketones provides a viable synthesis of Ph-substituted vinyl fluorides.
Since the mild reaction conditions employed in this synthesis permit the presence of
sensitive functionalities, this method allows for variation of groups in the b-position and
affors the convenience of carrying out all the transformations in one pot from readily
available starting materials.
We thank the National Science Council of the Republic of China, the National Science Foundation, and the
Chung Cheng Institute of Technology for supports of this work.
Experimental Part
General. THF was purified by distillation from sodium benzophenone ketyl. (EtO)2P(OH)H, PhCHO,
MeC(O)Me, cyclohexanone, CH2Cl2, and HMPT were distilled prior to use. LDA, (Me3Si)2NLi, t-BuLi, t-
BuOK, LiCl, MeOD, and DAST were used without further purification. Aromatic aldehydes (4-MeC6H4CHO,
4-MeOC6H4CHO, 4-ClC6H4CHO, 4-NO2C6H4CHO, 3,4-(MeO)2C6H3CHO), cyclohexanecarbaldehyde, Et-
C(O)Cl, PhC(O)Ph, and DMPU were used without further purification. Normality of BuLi was determined via
procedures of Duhamel and Plaquevent [25] and Bergbreiter and Pendergrass [26]. NaH (80% dispersion in
mineral oil) was washed with hexane prior to use. GLPC Analyses were performed on a 5% OV-101 column with
a thermal conductivity detector. FT-IR Spectra were recorded as CCl4 solns. with a soln. cell of 0.1-cm path
1
length. 19F- (against internal CFCl3), {1H}31P-NMR (against external 85% H3PO4), H- and 13C-NMR spectra
(against internal TMS) were recorded on a Bruker WM360X spectrometer. All chemical shifts are reported in
ppm downfield (positive) of the standard. MS Analyses were performed at 70 eV in the electron-impact (EI)
mode on a single quadrapole instrument interfaced to a gas chromatograph fitted with an OV-101 column. HR-
MS Analyses were performed at 70 eV in the EI mode.
Preparation of Diethyl a-Hydroxybenzylphosphonate ((EtO)2P(O)CH(OH)Ph). A 250-ml two-necked
flask equipped with the septum port, a Teflon-coated magnetic stirbar, and a water condenser topped with a T
tube leading to a source of N2, and a mineral-oil bubbler was charged sequentially with 0.2 mol (27.6 g, 26 ml) of
diethyl phosphite and 0.25 mol (26.6 g, 26 ml) of freshly distilled PhCHO. The contents of the flask were heated
at 100 ± 1108 for 10 h, then filtered through a funnel to give 16g (52%) of (EtO)2P(O)CH(OH)Ph. M.p. 82 ± 848.
IR: 3300 (br.), 3033m, 2983m, 2930m, 1392s, 1235m, 1034m. 1H-NMR: 7.49 (m, 2 H); 7.35 (m, 3 H); 5.23 (1 H);
5.03 (d, J ˆ 10, 1 H); 4.16 (q, J ˆ 7, 4 H); 1.32 (t, J ˆ 7, 6 H). 13C-NMR: 128.2 ± 127.0; 70.7 (d, J(C,P) ˆ 158);
‡
63.4; 63.1; 16.3; 16.2. 31P-NMR: 21.6 (dquint., J(P,CH) ˆ 10, J(PO,CH) ˆ 7). GC-MS: 245 (0.17, [M ‡ 1] ), 244
‡
‡
‡
‡
(1.83, M ), 215 (0.81, [M Et] ), 199 (0.64, [M OEt] ), 138 (23.33, [M PhCOH] or [(EtO)2P(O) ‡ H]),
‡
111 (41.43), 106 (29.52), 105 (34.72), 82 (24.64), 79 (13.93), 77 (Ph ).
Preparation of Diethyl a-Fluorobenzylphosphonate ((EtO)2P(O)CFHPh). A 250-ml two-necked flask
equipped with a septum port, a magnetic stirbar, and a water condenser topped with a T-tube leading to a source
of N2 and a mineral oil bubbler was charged with 20 ml CH2Cl2 and 19.2 mmol (3.12 g, 2.4 ml) of
diethylaminosulfur trifluoride (DAST). The contents of the flask were cooled to 788 via a dry ice/i-PrOH
slush bath. To the cooled soln., 16.4 mmol (4.0 g) of (EtO)2P(O)CH(OH)Ph in 40 ml of CH2Cl2 was added
dropwise via syringe during 1 h. The mixture was allowed to warm to r.t. and stirred further for 2 h, then it was
carefully quenched by pouring into a soln. of EtOH (120 ml) and pyridine (5 ml). After 1 h, this mixture was
poured into ice-H2O (400 ml) and extracted with CH2Cl2 (3 Â 150 ml). The combined extracts were washed with
dil. HCl (2 Â 80 ml) and H2O (2 Â 60 ml), dried (anh. MgSO4), filtered, and concentrated in vacuo. The residue
was distilled at 100 ± 1028/0.3 mmHg ([19]: 1108/0.4 mmHg) to obtain 2.1 g (52%) of the title compound (GLPC
purity 99%). IR: 3067m, 2931m, 2910m, 2868m, 1392s, 1264m, 1029m. 1H-NMR: 7.48 (m, 2 H); 7.36 (m, 3 H);
5.68 (dd, 2J(H,F) ˆ 45, 2J(H,P) ˆ 8, 1 H); 4.07 (m, 4 H); 1.25 (t, 3J(H,H) ˆ 7, 3 H); 1.24 (t, 3J(H,H) ˆ 7, 3 H).
13C-NMR: 133.1 ± 126.8; 89.4 (dd, 1J(C,F) ˆ 183, 1J(C,F) ˆ 169); 63.7 (s); 63.6 (s); 16.4 (s); 16.3 (s). 19F-NMR:
200.4 (dd, 2J(F,P) ˆ 84, 2J(F,H) ˆ 45). 31P-NMR: 16.4 (ddquint., 2J(P,F) ˆ 84, 2J(P,H) ˆ 8, 3J(P,H) ˆ 7). GC-
‡
‡
‡
‡
MS: 246 (0.86, M ), 218 (3.35, [M CH2ˆCH2] ), 217 (5.19, [M Et] ), 109 (100.00, [M (EtO)2P(O)] ).

Helvetica Chimica Acta ± Vol. 82 (1999)
2237
General Procedure for Preparation of 6 as Described for (E)- and (Z)-(1-Fluoro-2-phenylethenyl)benzene
(6a). A 100 ml two-necked flask equipped with a septum port, a magnetic stirring bar, and a reflux water
condenser topped with a T-tube leading to a source of N2, and mineral-oil bubbler was charged sequentially with
16 ml of dry THFand 8.0 mmol (1.97 g) of (EtO)2P(O)CFHPh. The contents of the flask were cooled to 788 in
a dry ice/i-PrOH slush bath. To the cooled soln., 10.5 mmol (7.0 ml) of a 1.5m cyclohexane soln. of LDA
mono(tetrahydrofuran) was added dropwise via syringe. The resulting bright yellow soln. was stirred at 788 for
30 min, then 10 mmol (1.06 g) of freshly distilled PhCHO were added dropwise via syringe. The resulting soln.
was stirred at 788 for 30 min. and then allowed to warm to r.t. over 4 h, and stirred at that temp. overnight. 19F-
NMR Analysis of the mixture indicated the absence of 2 and the formation of 6a. The mixture was poured into
H2O (40 ml), and the aq. layer was extracted with Et2O (3 Â 40 ml). The combined org. layers were washed with
dil. HCl until the washings were neutral. The resulting soln. was washed successively with brine (30 ml) and H2O
(30 ml), dried (MgSO4), filtered, and concentrated in vacuo. The residue was purified by FC (120 g of silica gel,
200 ± 425 mesh) eluting with hexane/AcOEt (24 : 1) to give 1.13 g (71%) of (E/Z)-6a. The (E)/(Z) ratio of 6a,
determined by the integration of the 19F signals in the 19F-NMR spectrum, was 46 to 54. (E)-6a: 1H-NMR:
7.67 ± 7.35 (m, 10 H); 6.45 (d, 3J(H,F(Z)) ˆ 22, 1 H). 19F-NMR:
95.2 (d, 3J(F,H(Z)) ˆ 22). (Z)-6a:
1H-NMR: 7.67 ± 7.35 (m, 10 H); 6.32 (d, 3J(H,F(E)) ˆ 39, 1 H). 19F-NMR:
113.5 (d, 3J(F,H(E)) ˆ 39).
(E/Z)-6a: IR: 3061s, 1657s, 1501s, 1333s. 13C-NMR: 133.7 ± 127.1; 124.3 (d, 2J(C ˆ CF(E)) ˆ 8); 105.8 (d, 2J(C ˆ
‡
CF(Z)) ˆ 11). GC-MS: 198 (92.94, M ), 197 (75.69), 196 (49.41), 40 (100.00).
(E)- and (Z)-1-(2-Fluoro-2-phenylethenyl)-4-methylbenzene (6b). Yield: 1.18 g (66%). (E)-6b: 1H-NMR:
7.64 ± 7.04 (m, 9 H); 6.42 (d, 3J(H,F(Z)) ˆ 22, 1 H); 2.29 (s, 3 H). 19F-NMR: 97.9 (d, 3J(F,H(Z)) ˆ 22). GC-
‡
MS: 212 (31.96, M ), 105 (45.66), 95 (42.47), 91 (42.47), 63 (84.47), 51 (100.00), 50 (50.23). (Z)-6b: 1H-NMR
7.64 ± 7.04 (m, 9 H); 6.28 (d, 3J(H,F(E) ˆ 42), 1 H); 2.36 (s, 3 H). 19F-NMR: 117.1 (d, 3J(F,H(E) ˆ 42)). GC-
‡
MS: 212 (100.00, M ), 197 (72.94), 196 (85.10), 183 (14.71). (E/Z)-6b: IR: 3060s, 1657s, 1514s, 1333s.
13C-NMR: 159.1 (s); 156.7 (d, 1J(C,F) ˆ 257); 137.2 ± 128.1, 124.2 (d, 2J(CˆCF(E)) ˆ 8); 105.8
(d, 2J(CˆCF(Z)) ˆ 10); 21.3 (s), 21.1 (s).
(E)- and (Z)-1-(2-Fluoro-2-phenylethenyl)-4-methoxybenzene (6c). Yield: 1.38 g (76%). (E)-6c: 1H-NMR:
7.61 ± 6.88 (m, 9 H); 6.40 (d, 3J(H,F(7)) ˆ 22, 1 H); 3.74 (s, 3 H). 19F-NMR: 99.2 (d, 3J(F,H(Z)) ˆ 22). (Z)-
6c: 1H-NMR: 7.61 ± 6.88 (m, 9 H); 6.25 (d, 3J(H,F(E)) ˆ 42, 1 H); 3.79 (s, 3 H). 19F-NMR:
119.2 (d,
3J(F,H(E)) ˆ 42). (E/Z)-6c: IR: 3061m, 1684m, 1512s, 1300s. 13C-NMR: 158.8 (s), 155.9 (d, 1J(C,F) ˆ 255);
133.2 ± 124.2; 123.8 (d, 2J(CˆCF(E)) ˆ 8); 105.4 (d, 2J(CˆCF(Z)) ˆ 11); 55.2 (s). GC-MS: 228 (100.00, M ),
‡
213 (40.31), 183 (23.44), 165 (37.19).
(E)- and (Z)-1-Chloro-4-(2-fluoro-2-phenylethenyl)benzene (6d). Yield: 1.21 g (65%). (E)-6d: 1H-NMR:
7.60 ± 7.28 (m, 9 H); 6.30 (d, 3J(H,F(Z)) ˆ 22, 1 H). 19F-NMR: 95.1 (d, 3J(F,H(Z)) ˆ 22). (Z)-6d: 1H-NMR:
7.60 ± 7.28 (m, 9 H); 6.20 (d, 3J(H,F(E)) ˆ 39, 1 H). 19F-NMR: 115.3 (d, 3J(F,H(E)) ˆ 39). (E/Z)-6d: IR:
3072m, 1653s, 1496s, 1334m. 13C-NMR: 157.5 (d, 1J(C,F) ˆ 259); 132.9 ± 128.2; 124.3 (d, 2J(CˆCF(E)) ˆ 8);
‡
104.7 (d, 2J(CˆCF(Z)) ˆ 10). GC-MS: 232 (16.79, M ), 229 (15.63), 228 (100.00), 213 (36.34), 165 (39.53).
(E)- and (Z)-1-(2-Fluoro-2-phenylethenyl)-4-nitroethene (6e). Yield: 65% (19F-NMR). (E)-6e: 19F-NMR:
89.4 (d, 3J(F,H(Z)) ˆ 22). (Z)-6e: 19F-NMR: 110.9 (d, 3J(F,H(trans)) ˆ 39). (E/Z)-6e: IR: 3085m, 1654s,
‡
1598s, 1344s. GC-MS: 243 (2.31, M ), 105 (22.76), 44 (48.13).
(E)- and (Z)-1-(2-Fluoro-2-phenylethenyl)-2-(trifluoromethyl)benzene (6f). Yield: 1.59 g (74%). (E)-6f:
1H-NMR: 8.00 ± 7.13 (m, 9 H); 6.35 (d, 3J(H,F(Z)) ˆ 20, 1 H). 19F-NMR: 96.3 (d, 3J(F,H(Z)) ˆ 20); 60.9
‡
(s). GC-MS: 266 (81.44, M ), 245 (22.29), 197 (71.13), 196 (100.00). (Z)-6f: 1H-NMR: 8.00 ± 7.13 (m, 9 H);
6.65 (d, 3J(H,F(E)) ˆ 37, 1 H). 19F-NMR: 114.2 (d, 3J(F,H(E)) ˆ 37); 59.4 (s). (E/Z)-6f: IR: 3089m, 1654s,
1498s, 1316s. 13C-NMR: 158.3 (d, 1J(C,F) ˆ 261); 157.3 (s); 133.1 ± 125.9; 124.8 (d, 2J(CˆCF(E)) ˆ 8); 101.1
‡
(d, 2J(CˆCF(Z)) ˆ 10). GC-MS: 266 (80.86, M ), 245 (21.89), 197 (71.77), 196 (100.00). HR-MS: Calc.
266.0719; found: (E)-6f: 266.0699; (Z)-6f: 266.0692.
(E)- and (Z)-(2-Cyclohexyl-1-fluoroethenyl)benzene (6g). Yield: 1.18 g (72%). (E)-6g: 1H-NMR: 7.50 ±
7.26 (m, 5 H); 5.25 (dd, 3J(H,F(Z)) ˆ 22, 3J(H,H) ˆ 11, 1 H); 2.30 ± 2.23 (m, 1 H); 1.76 ± 1.11 (m, 10 H). 19F-
‡
NMR: 102.4 (d, 3J(F,H(Z)) ˆ 22). GC-MS: 204 (32.16, M ), 147 (33.73), 146 (38.43), 122 (100.00). (Z)-6g:
1H-NMR: 7.50 ± 7.26 (m, 5 H); 5.27 (dd, 3J(H,F(E)) ˆ 39, 3J(H,H) ˆ 9, 1 H); 2.70 ± 2.60 (m, 1 H); 1.76 ± 1.11
(m, 10 H). 19F-NMR: 121.0 (d, 3J(F,H(E)) ˆ 39). (E/Z)-6g: IR: 3062m, 1653s, 1448s. 13C-NMR: 157.1 (s),
‡
155.8 (d, 1J(C,F) ˆ 240); 133.2 ± 127.5; 123.9 (d, 2J(C,F(E)) ˆ 7); 35.3 ± 25.7. GC-MS: 204 (6.22, M ), 123
(26.78), 122 (100.00), 67 (23.43). HR-MS: Calc.: 204.1314; found: (E/Z)-6g: 204.1334/204.1342.
(E)- and (Z)-1-(2-Fluoro-2-phenylethenyl)-3,4-dimethoxybenzene. Yield: 1.43 g (69%). (E)-6h: 1H-NMR:
7.65 ± 7.15 (m, 5 H); 6.90 ± 6.60 (m, 3 H); 6.40 (d, 3J(H,F(Z)) ˆ 22, 1 H); 3.93 (s, 3 H); 3.90 (s, 3 H). 19F-NMR:
99.3 (d, 3J(F,H(Z)) ˆ 22). (Z)-6h: 1H-NMR: 7.65 ± 7.15 (m, 5 H); 6.90 ± 6.60 (m, 3 H); 6.25 (d, 3J(H,F(E)) ˆ

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Helvetica Chimica Acta ± Vol. 82 (1999)
40); 3.85 (s, 3 H); 3.60 (s, 3 H). 19F-NMR: 118.7 (d, 3J(F,H(E)) ˆ 40). (E/Z)-6h: IR: 3060m, 1650m, 1590s,
1450s. 13C-NMR: 160.3 ± 157.2; 150.1 (d, 1J(C,F) ˆ 269); 133.6 ± 123.9; 115.4 ± 98.2; 55.5 (s); 55.4 (s); 55.3 (s);
‡
55.2 (s); GC-MS: 258 (100.00, M ), 243 (18.0), 195 (38.0).
(E)- and (Z)-(1-Fluoro-2-methyl-2-phenylethenyl)benzene (6i). Yield: 0.84 g (50%). (E)-6i: 1H-NMR:
7.49 ± 7.18 (m, 5 H); 2.11 (d, 4J(H,F(Z)) ˆ 4, 3 H). 19F-NMR: 102.7 (q). (Z)-6i: 1H-NMR: 7.49 ± 7.18 (m,
5 H); 2.07 (d, 4J(H,F(E)) ˆ 2, 3 H). 19F-NMR: 105.5. (E/Z)-6i: IR: 3065m, 1664m, 1558m, 1257m. 13C-NMR:
‡
158.0 (d, 1J(C,F) ˆ 269); 128.8 ± 127.1; 18.5 (s). GC-MS: 212 (100.00, M ), 197 (42.4), 133 (14.4).
(1-Fluoro-2,2-diphenylethenyl)benzene (6j). Yield: 1.05 g (48%). 1H-NMR: 7.73 ± 7.71 (m, 5 H); 7.51 ± 7.47
‡
(m, 5 H); 7.40 ± 7.37 (m, 5 H). 13C-NMR: 137.5 ± 127.8. 19F-NMR: 103.5 (s). GC-MS: 274 (100.00, M ), 182
(22.6), 105 (44.8), 77 (22.4); IR: 3086m, 1599m, 1261m.
(1-Fluoro-2,2-dimethylethenyl)benzene (6k). Yield: 50% (19F-NMR). 19F-NMR: 106.3.
[1-Fluoro-2,2-bis(trideuteromethyl)ethenyl]benzene (6l). Yield: 52% (19F-NMR). 19F-NMR: 107.5.
(E)- and (Z)-1-Fluoro-(2-ethyl-2-methylethenyl)benzene (6m). Yield: 47% (19F-NMR). 19F-NMR:
107.8; 104.3.
(Cyclohexylidene)fluoromethylbenzene. Yield: 54% (19F-NMR). 19F-NMR: 109.4.
Dependence of the Configuration of (E/Z)-6a and (E/Z)-6i on Metal Ion and/or Cosolvent as Described by
Reaction of the Anion Derived from 2 with LDA in THF/HMPT and PhCHO. A soln. of 2.0 mmol (0.49 g) of 2,
2.0 mmol (0.39 ml) of hexamethylphosphoric triamide (HMPT), and 6 ml of dry THF was cooled and stirred at
788, as 3.3 mmol (2.2 ml) of a 1.5m cyclohexane soln. of LDA mono(tetrahydrofuran) was added dropwise via
syringe. The resulting bright yellow soln. was stirred at 788 for 20 min, and then 3.0 mmol (0.32 g) of freshly
distilled PhCHO was added dropwise via syringe. The resulting mixture was stirred at 788 for 1 h and then
allowed to warm to r.t. during 4 h and stirred at that temp. overnight to obtain 84% yield (19F-NMR) of (E)- and
(Z)-6a. The (E/Z)-ratio of 6a, determined by the integration of the F signals in the 19F-NMR spectrum, was
24 : 76.
Dependence of the Configuration of (E/Z)-6i on Solvent and Base as Described by Reaction of the Anion
Derived from 2 with t-BuOK in CH2Cl2 and PhC(O)Me. A soln. of 6 ml of dry THF and 2.0 mmol (0.22 g) of t-
BuOK was cooled and stirred at 788, as 2.0 mmol (0.49 g) of 2 was added dropwise via syringe. The resulting
bright yellow soln. was stirred at 788 for 20 min, and then 2.0 mmol (0.24 g) of freshly distilled PhC(O)Me was
added dropwise via syringe. The resulting mixture was stirred at 788 for 1 h and then allowed to warm to r.t.
over 4 h and stirred at that temp. overnight to obtain 63% yield (19F-NMR) of (E)- and (Z)-6i. The (E/Z)-ratio
of 6i, determined by the integration of the F signals in the 19F-NMR spectrum, was 66 : 34.
Detection of 3 as Described for Quenching the Reaction of 3 with EtC(O)Cl at 788. A soln. of 4.0 mmol
(0.99 g) of 2 and 8 ml of dry THF was cooled and stirred at 788, as 6.0 mmol (4.0 ml) of a 1.5m cyclohexane
soln. of LDA mono(tetrahydrofuran) was added dropwise via syringe. The resulting bright yellow soln. was
stirred at 788 for 20 min, and then 6.0 mmol (0.55 g) of freshly distilled EtC(O)Cl was added dropwise via
syringe. The resulting mixture was stirred at 788 for 1 h and then allowed to warm to r.t. over 4 h and stirred at
that temp. overnight. 19F-NMR Analysis of the reaction mixture is consistent with the formation of
(EtO)2P(O)CF{C(O)Et}Ph at 170.2 ppm (d, J(F,C,P) ˆ 76).
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Received August 2, 1999