Efficient synthesis of fluoroalkenes via diethylzinc-promoted wittig reaction

Article abstract of DOI:10.1055/s-2006-950208

The synthesis of α-fluoroacrylates and α-bromo-α- fluoroalkenes was achieved in very good yields using aldehydes and ketones, triphenylphosphine, diethylzinc as promoter, and ethyl dibromofluoroacetate or dibromofluoromethane, respectively. A change in th

Full text of DOI:10.1055/s-2006-950208

PAPER
3409
Efficient Synthesis of Fluoroalkenes via Diethylzinc-Promoted Wittig Reaction
Efficient
S
ynthe
u
sis of Fluoro
d
alkenes via
i
D
iethy
v
lzinc-Promot
i
edWit
n
tigreaction e Zoute, Guillaume Dutheuil, Jean-Charles Quirion, Philippe Jubault,* Xavier Pannecoucke*
IRCOF, LHO, UMR CNRS 6014, Université et INSA de Rouen, Rue Lucien Tesnière, 76131 Mont-Saint-Aignan, France
E-mail: philippe.jubault@insa-rouen.fr; E-mail: xavier.pannecoucke@insa-rouen.fr
Received 2 June 2006
conditions used tetrahydrofuran as solvent at room tem-
Abstract: The synthesis of a-fluoroacrylates and a-bromo-a-fluo-
perature with a ratio of aldehyde/diethylzinc/tribromo-
fluoromethane/triphenylphosphine of 1.0:1.2:1.2:1.2.
This is the highest yield obtained for this particular alde-
roalkenes was achieved in very good yields using aldehydes and ke-
tones, triphenylphosphine, diethylzinc as promoter, and ethyl
dibromofluoroacetate or dibromofluoromethane, respectively. A
change in the addition sequence was critical in order to obtain ex- hyde using this route.
clusively a-fluoroacrylates in good yields.
Various aldehydes were subjected to these optimized re-
Key words: Wittig reaction, fluoroalkene, ketone, aldehyde, dieth-
ylzinc
action conditions, giving the corresponding a-bromo-a-
fluoroalkenes in high yields (Table 1). Under the above
conditions, even unactivated aldehydes could be convert-
ed into the corresponding a-bromo-a-fluoroalkenes
(Table 1, entries 1–3). The reaction is general and can tol-
erate various functional groups, such as ester, nitro, pro-
tected alcohol, and others, with yields always around 80–
90%.
Organofluorine compounds have received considerable
interest in recent years due to their increasing importance
in the life sciences, especially for drug development and
crop protection.1 Modification of the physiological activ-
ity of bioactive compounds by introducing fluorine into
molecules frequently leads to the discovery of novel and
potent biochemical tools and medicinal agents.
R1
H
F
R1
H
THF, r.t., 1 h
+ CBr3F + PPh3 + Et2Zn
O
Br
a-Bromo-a-fluoroalkenes and a-fluoro-a,b-unsaturated
esters (a-fluoroacrylates) have broad application as inter-
mediates in the preparation of biologically active fluori-
nated compounds. Though other methods have been
developed,2 the main synthetic approaches to a-bromo-a-
fluoroalkenes and a-fluoroacrylates and related com-
pounds use the Wittig2c and the Horner–Wadsworth–
Emmons reactions. Several efficient syntheses of a-
fluoroacrylates have been recently reported using the lat-
ter approach, for example, an efficient one-pot version3
and an efficient Z-selective Horner–Wadsworth–Emmons
reaction.4 Concerning the Wittig synthesis of a-fluoro-
acrylates, a one-pot sequence from (alkoxycarbonylmeth-
yl)triphenylphosphonium bromides has been recently
reported using Selectfluor as an electrophilic fluorinating
agent.5 For the synthesis of a-bromo-a-fluoroalkenes, the
classical Wittig reaction using triphenylphosphine or zinc
as a promoter usually gives low yields with unactivated
ketones or aliphatic aldehydes.
Scheme 1 Synthesis of a-bromo-a-fluoroalkenes.
Table 1 Reaction with Aldehydes
Entry Product R1
Yielda (%) Ratiob Z/E
1
2
1a
1b
1c
1d
1e
1f
CH2CH2Ph
88
49:51
53:47
42:58
55:45
58:42
49:51
70:30
58:42
52:48
55:45
52:48
56:44
56:44
CH2CH2OTBDPS
CHMeCH2OTBDPS
4-BrC6H4
90 (99c)
83
3
4
74
6
4-O2NC6H4
85
7
4-MeOC6H4
2-O2NC6H4
94c
87
8
1g
1h
1i
9
2-MeOC6H4
3,4-(OCH2O)C6H3
4-MeO2CC6H4
2-naphthyl
91
10
11
12
13
14
91
Recently, our group has reported the synthesis of a-bro-
mo-a-fluoroalkenes via the diethylzinc-promoted Wittig
reaction.6 It was, to our knowledge, the first report that di-
ethylzinc can promote the Wittig reaction (Scheme 1).7
1j
81
1k
1l
78
4-NCC6H4
84
By optimizing the reaction conditions, that is, changing
the solvent, the temperature, the nature of the phosphine,
and the number of equivalents of reagents, the yield of 3-
phenylpropanal could be increased to 88%. The optimized
1m
4-F3CC6H4
70
a Isolated yield; ratio aldehyde/Et2Zn/CBr3F/PPh3 = 1.0:1.2:1.2:1.2.
b Ratio determined by 19F NMR or 1H NMR.
c Ratio aldehyde/Et2Zn/CBr3F/PPh3 = 1.0:1.5:1.5:1.5.
SYNTHESIS 2006, No. 20, pp 3409–3418
x
x.
x
x
.
2
0
0
6
Advanced online publication: 21.08.2006
DOI: 10.1055/s-2006-950208; Art ID: P06506SS
© Georg Thieme Verlag Stuttgart · New York

3410
L. Zoute et al.
PAPER
Unfortunately, regardless of the conditions or the alde- Table 2 Reaction with Ketones
hyde, the stereoselectivity was never better than 70:30.
Pure Z- or E-isomer could be obtained via chemoselective
Entry Starting ketone
Product Yielda (%) Ratiob Z/E
transformation of one of the two isomers (Scheme 2).
1
2
3
1n
1o
1p
66
69
83
–
O
R1
F
+ side products
LiHMDS or DBU
E
–c
H
Br
O
R1
H
F
55–98% yield
Br
R1
Br
R1
H
F
BuLi, ZnCl2
Pd(0)
+
46:54
O
Z
H
F
Bu
up to 95% yield
Bn
Scheme 2 Access to pure (Z)- or (E)-a-bromo-a-fluoroalkenes.
O
4
5
1q
1r
78
53
41:59
70:30
O
O
To broaden the scope of the reaction, we then subjected
unactivated ketones to Wittig conditions with diethylzinc
activation (Table 2). The yields of isolated a-bromo-a-
fluoroalkenes from aromatic or aliphatic ketones were of-
ten moderate to good and the ketone could contain various
functional groups such as amine, protected alcohol, etc.
However, the reaction was not suitable for readily enoliz-
able substrates such as N,N-diallyl-2-oxocyclopentane-
carboxamide (Table 2, entry 10) or 3,4-dihydronaph-
thalen-2(1H)-one. In these particular cases, the a-hydro-
gen is probably too acidic and the ylide reacts first with it,
instead of adding to the carbonyl group.
Me
Si
Me
Me
6
7
1s
1t
66
39
–
O
Ph
Ph
45:55
O
In a second step, we decided to investigate the generality
of diethylzinc as a Wittig promoter and applied our pro-
cess to the synthesis of a-fluoroacrylates.
8
9
1u
1v
76
–
N
O
Using standard conditions, as described for the synthesis
of terminal a-bromo-a-fluoroalkenes, we studied the reac-
tion between p-anisaldehyde (1 equiv), triphenylphos-
phine (1.2 equiv), and ethyl dibromofluoroacetate (1.2
equiv) in the presence of diethylzinc (added via syringe
pump over 30 min) in dry tetrahydrofuran under argon. At
the end of the reaction, the 19F NMR spectra showed the
presence of starting material (35%) and of four products
identified as the two diastereomeric alcohols 3a (60%)
and two isomeric a-fluoroacrylates 2a (less than 5%)
(Scheme 3). No further reaction was then observed, even
after 24 hours.
51d
44:56
O
O
OTBDPS
10
1w
0
–
O
N
a Isolated yield; ratio ketone/Et2Zn/CBr3F/PPh3 = 1.0:1.5:1.5:1.5.
b Ratio determined by 19F NMR or 1H NMR.
c Not determined.
d Ratio ketone/Et2Zn/CBr3F/PPh3 = 1.0:3:3:3.
O
PPh3 + Br2FCCO2Et + Et2Zn +
OMe
H
This disappointing result prompted us to fully reexamine
the parameters of this reaction, especially the order of ad-
dition and the number of equivalents of each reaction part-
ner used in this process.
THF, 10 min
F
H
In a first assay, p-anisaldehyde (1 equiv) was added drop-
wise to a tetrahydrofuran solution of triphenylphosphine,
diethylzinc, and ethyl dibromofluoroacetate (1 equiv
each), which had been introduced successively in this or-
der at room temperature and stirred for 30 minutes. Under
these conditions, after one hour, the 19F NMR spectrum
showed the presence of the starting aldehyde and of two
F
OH
H
EtO2C
+
EtO2C
Br
OMe
OMe
2a
3a
Scheme 3 Synthesis of fluoroacrylates.
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York

PAPER
Efficient Synthesis of Fluoroalkenes via Diethylzinc-Promoted Wittig reaction
3411
products identified as the two isomeric a-fluoroacrylates even unactivated aldehydes could be converted into the
2a. No trace of alcohol was observed. Moreover the GC corresponding a-fluoroacrylates 2a–j. With yields always
analysis of the reaction mixture showed a 67:33 ratio be- around 75–95%, the reaction is general and tolerates var-
tween p-anisaldehyde and 2a. No further reaction was ob- ious functional groups such as ester or protected alcohol.
served even after 24 hours.
Table 4 Reaction with Aldehydes R1CHOa
A change in the addition sequence was critical in order to
THF, r.t.
CO2Et
obtain exclusively a-fluoroacrylates. If diethylzinc, tri-
phenylphosphine, and ethyl dibromofluoroacetate are
added prior to p-anisaldehyde, the expected compounds
2a were obtained; otherwise bromofluoro alcohols 3a are
the major products. We next changed the number of
equivalents of each partner (except p-anisaldehyde) in or-
der to improve the conversion. The results obtained dur-
ing this study are collected in Table 3.
R1
R1CHO + Br2FCCO2Et + PPh3 + Et2Zn
F
2a–j
Entry R1
Product Yieldb (%) Ratioc Z/E
1
2
4-MeOC6H4
(CH2)4Me
2a
2b
2c
2d
2e
2f
91
85:15
70:30
65:35
80:20
68:32
75:25
80:20
85:15
70:30
70:30
98
When two equivalents of triphenylphosphine were used
(Table 3, entry 2), a slight improvement in the conversion
of aldehyde into 2a was observed. Moreover, no trace of
dibromofluoroacetate was detected in the 19F NMR spec-
trum of the reaction mixture. However, when two equiva-
lents of diethylzinc were used (Table 3, entry 3), the
conversion did not improve. Addition of two equivalents
of each component (relative to the aldehyde) led to a very
interesting 85% conversion (Table 3, entry 4) into 2a.
3
CH2CH2OTBDPS
Ph
83
4
98
5
CH2CH2Ph
4-F3CC6H4
4-BrC6H4
94
6
98
7
2g
2h
2i
77
8
4-pyridyl
30 (96d)
90
9
CH2CHMe2
4-MeO2CC6H4
Table 3 Optimization of the Parameters
10
2j
88
Entry Number of equivalentsa
GC Ratiob
a Ratio aldehyde/Et2Zn/Br2FCCO2Et/PPh3 = 1.0:4.0:2.0:4.0.
b Isolated yield.
PPh3
Et2Zn
Br2FCCO2Et 2a
4-MeC6H4CHO
c Ratio determined by 19F NMR.
1
2
3
4
5
6
7
1
2
1
2
3
3
4
1
1
2
2
2
3
4
1
1
1
2
2
3
2
33
50
67
50
77
15
30
15
0
d Conversion determined by GC analysis in the reaction mixture, rapid
degradation occurred during purification on silica gel.
22
To broaden the scope of the reaction, we then subjected
ketones to Wittig conditions as described above. We first
tested an activated ketone, 2,2,2-trifluoroacetophenone
and obtained the expected a-fluoroacrylate 2n in 92%
yield (ratio Z/E = 35:65). Others unactivated ketones were
then engaged in this reaction and the obtained results are
collected in Table 5.
85
70
85
100
a 1 equiv of p-anisaldehyde was introduced.
b Determined on a DB1 column.
Table 5 Reaction with Ketones R1COR2 a
R2
THF, r.t.
CO2Et
Finally the optimal conditions, resulting in complete con-
version of the aldehyde into fluoroacrylate 2a (Table 3,
entry 7), were obtained when four equivalents of triphe-
nylphosphine, four equivalents of diethylzinc and two
equivalents of ethyl dibromofluoroacetate were used.
R1
R1COR2 + Br2FCCO2Et + PPh3 + Et2Zn
F
2k–n
Entry R1
R2
Product Yieldb (%) Ratioc Z/E
It should be noticed that when triphenylphosphine, dieth-
ylzinc, and ethyl dibromofluoroacetate were introduced in
this order to a tetrahydrofuran solution, a slight exother-
micity was observed (the internal temperature rose to
35 °C). The aldehyde was added when the temperature
had gone down to 20 °C (ca. 10 min). The reaction was
complete within ten minutes after addition of the aldehyde
as indicated by GC analysis.
1
2
3
4
Ph
Me
Me
2k
2l
77
98
80
92
60:40
60:40
–
CH2CH2Ph
(CH2)5
Ph
2m
2n
CF3
35:65
a Ratio ketone/Et2Zn/Br2FCCO2Et/PPh3 = 1.0:4.0:2.0:4.0.
b Isolated yield.
Various aldehydes were subjected to these optimized re-
action conditions, giving the corresponding a-fluoroacry-
lates in high yields (Table 4). Under these conditions,
c Ratio determined by 19F NMR.
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York

3412
L. Zoute et al.
PAPER
and concentrated under reduced pressure. The residue was then
chromatographed (silica gel, cyclohexane–EtOAc), affording the
desired a-bromo-a-fluoroalkene.
Concerning the mechanism of such a process (Scheme 4),
we suggest that the first step is the reaction between dieth-
ylzinc and ethyl dibromofluoroacetate to generate the cor-
responding zinc carbenoid. The latter reacts with
triphenylphosphine to form the key ylide intermediate,
which reacts with the aldehyde or ketone leading to the
expected a-fluoroacrylate 2. Indeed, if diethylzinc was
added to a solution containing ethyl dibromofluoroace-
tate, aldehyde, and triphenylphosphine, we obtained a
mixture of alkene 2 and alcohol 3, meaning that the reac-
tion between zinc carbenoid and aldehyde is much more
rapid than its reaction with triphenylphosphine.
(Z)- and (E)-(4-Bromo-4-fluorobut-3-enyl)benzene (1a)
Ratio Z/E = 49:51; Rf = 0.7 (cyclohexane–EtOAc, 98:2).
IR (neat): 3028, 2927, 1807, 1718, 1667, 1603, 1495, 1454, 1178,
1111, 1088, 1022, 1000, 747, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.3–7.1 (m, 5 H, H6, H7, H8), 5.5
(dt, 3JH–H = 7.6 Hz, 3JH–F = 12.8 Hz, 0.5 H, H2Z), 5.0 (dt, 3JH–H = 7.6
Hz, 3JH–F = 31.0 Hz, 0.5 H, H2E), 2.7–2.6 (m, 2 H, H4), 2.4–2.2 (m,
2 H, H3).
13C NMR (75.5 MHz, CDCl3): d = 139.5, 134.5 (d, J = 314 Hz),
130.6 (d, J = 320 Hz), 127.2, 127.3, 125, 110.5 (d, J = 13 Hz), 107.9
(d, J = 16 Hz), 33.8 (d, J = 2 Hz), 33.5 (d, J = 2 Hz), 28.2, 28.1.
19F NMR (282.5 MHz, CDCl3): d = –71.7 (d, J = 13.1 Hz, 0.5 F),
–75.4 (dt, J = 31.2 Hz, J = 2.6 Hz, 0.5 F).
In the case of the synthesis of a-bromo-a-fluoroalkenes
(Scheme 4), the aldehyde can be added at the beginning of
the reaction. Indeed, in this particular case, the tribromo-
fluoromethane deriving zinc carbenoid is less nucleo-
philic (carbene character is more pronounced) than that
prepared from ethyl dibromofluoroacetate, allowing the
phosphine to react first.
+
MS (EI): m/z = 228–230 (M+), 149 (M+ – Br), 91 (PhCH2 ).
Anal. Calcd for C10H10BrF: C, 52.43; H, 4.40. Found: C, 52.22; H,
4.51.
In conclusion, we found that diethylzinc could act very ef-
ficiently as a Wittig promoter. Applied to the synthesis of
a-bromo-a-fluoroalkenes and to a-fluoroacrylates, this
procedure appears to be rapid, convenient, and high-yield-
ing for aldehydes and ketones. Moreover, the reaction tol-
erates various functional groups. On-going studies
include the determination of the exact mechanism (by
NMR and IR spectroscopy), the use of supported triphe-
nylphosphine-type reagents, and the replacement of tri-
phenylphosphine by other nucleophiles.
(Z)- and (E)-(4-Bromo-4-fluorobut-3-enyloxy)tert-butyldiphe-
nylsilane (1b)
Ratio Z/E = 53:47; Rf = 0.7 (cyclohexane–EtOAc, 98:2).
IR (neat): 3448, 3072, 2958, 2859, 1792, 1742, 1671, 1590, 1473,
1428, 1113, 1024, 822, 701, 613, 509 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.7–7.6 (m, 4 H, H8), 7.5–7.3 (m,
6 H, H9, H10), 5.6 (dt, 3JH–F = 13.3 Hz, 3JH–H = 7.8 Hz, 0.5 H, H2Z),
5.1 (dt, 3JH–F = 31.2 Hz, 3JH–H = 7.8 Hz, 0.5 H, H2E), 3.7–3.6 (m, 2
H, H4), 2.4–2.2 (m, 2 H, H3), 1.1 (s, 9 H, H6).
13C NMR (75.5 MHz, CDCl3): d = 136.7 (d, J = 277 Hz), 132.5 (d,
J = 255 Hz), 136.0, 134.0, 130.0, 128.1, 110.0 (d, J = 13 Hz), 107.0
(d, J = 10 Hz), 62.0 (dd, J = 2 Hz, J = 2 Hz), 31.5 (d, J = 4 Hz), 30.0
(d, J = 2 Hz), 27.0, 19.6.
19F NMR (282.5 MHz, CDCl3): d = –70.6 (d, J = 13.2 Hz, 0.5 F),
–75.0 (dt, J = 31.2 Hz, J = 2.1 Hz, 0.5 F).
F
R1
R2
+
Ph3P
R1
R2
O
R
R = Br or CO2Et
O
MS (EI): m/z = 349–351 (M+ – C4H9).
ZnEt
Ph3P CFR
Anal. Calcd for C20H24BrFOSi: C, 58.96; H, 5.94. Found: C, 58.73;
H, 6.08.
Ph3P CFR
Br2FCR + Et2Zn
RCFBrZnEt
(Z)- and (E)-(4-Bromo-4-fluoro-2-methylbut-3-enyloxy)tert-bu-
tyldiphenylsilane (1c)
Ph3P
Ratio Z/E = 42:58; Rf = 0.7 (cyclohexane).
Scheme 4 Proposed mechanism.
IR (neat): 3399, 3071, 2960, 2858, 1667, 1472, 1427, 1126, 1028,
824, 740, 702, 613, 505 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.8–7.6 (m, 4 H, H9), 7.6–7.4 (m,
6 H, H10, H11), 5.5 (dd, 3JH–H = 9.7 Hz, 3JH–F = 13.3 Hz, 0.4 H, H2Z),
5.0 (dd, 3JH–H = 9.7 Hz, 3JH–F = 31.7 Hz, 0.6 H, H2E), 3.7–3.5 (m, 2
H, H4), 3.0–2.8 (m, 0.6 H, H3E), 2.7–2.5 (m, 0.4 H, H3Z), 1.2 (s, 9 H,
H6), 1.2–1.1 (m, 3 H, H7).
13C NMR (75.5 MHz, CDCl3): d = 135.6 (d, J = 315 Hz), 136.1,
134.0, 133.5, 132.2 (d, J = 316 Hz), 128.1, 116.0 (d, J = 12 Hz),
113.3 (d, J = 14 Hz), 68.0 (d, J = 2 Hz), 67.8 (d, J = 3 Hz), 36.7 (d,
J = 4 Hz), 34.8, 27.4, 27.3, 19.73, 19.71, 10.8.
All commercial solvents were distilled before using. THF was dis-
tilled from sodium benzophenone ketyl under N2. TLC was per-
formed on Merck 60F-250 silica gel plates. Flash column
chromatography purifications were carried out using silica gel (70–
230 mesh). 1H NMR, 13C NMR, and 19F NMR (CFCl3 as external
reference) were recorded at 300.13 MHz, 75.47 MHz, and 282.40
MHz respectively.
a-Bromo-a-fluoroalkenes from Aldehydes; General Procedure
To a soln of PPh3 (1.2 mmol, 1.2 equiv), tribromofluoromethane
(1.2 mmol, 1.2 equiv), and an appropriate aldehyde (1.0 mmol, 1.0
equiv) in anhyd THF (40 mL), was added a soln of 1 M Et2Zn in
hexanes (1.2 mmol, 1.2 equiv) dropwise via a syringe pump over 20
min at r.t. under argon. The mixture was stirred for 1 h. The result-
ing soln was then quenched with MeOH (10 mL), stirred for 15 min,
19F NMR (282.5 MHz, CDCl3): d = –71.7 (d, J = 13.3 Hz, 0.6 F),
–74.7 (d, J = 31.7 Hz, 0.4 F).
MS (EI): m/z = 363–365 (M+ – C4H9).
Anal. Calcd for C21H26BrFOSi: C, 59.85; H, 6.22. Found: C, 59.97;
H, 6.24.
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York

PAPER
Efficient Synthesis of Fluoroalkenes via Diethylzinc-Promoted Wittig reaction
3413
(Z)- and (E)-1-Bromo-4-(2-bromo-2-fluorovinyl)benzene (1d)
Ratio Z/E = 55:45; Rf = 0.8 (cyclohexane).
1H NMR (300 MHz, CDCl3): d = 8.0 (m, 1 H, H5), 7.5 (m, 3 H, H6,
H7, H8), 7.0 (d, 3JH–F = 11.8 Hz, 0.7 H, H2Z), 6.5 (d, 3JH–F = 30.1 Hz,
0.3 H, H2E).
IR (neat): 3064, 3026, 2924, 1650, 1487, 1400, 1107, 1085, 1046,
1010, 866, 853, 808, 794 cm–1.
13C NMR (75.5 MHz, CDCl3): d = 147.3, 146.6, 134.9 (d, J = 319
Hz), 133.7, 133.3 (d, J = 332 Hz), 133.8, 132.4 (d, J = 2 Hz), 131.5
(d, J = 9 Hz), 128.8, 128.3, 127.1 (d, J = 9 Hz), 126.0 (d, J = 4 Hz),
124.0, 107.7 (d, J = 5 Hz), 108.8 (d, J = 28 Hz).
19F NMR (282.5 MHz, CDCl3): d = –64.3 (d, J = 11.8 Hz, 0.7 F),
–67.6 (d, J = 30.1 Hz, 0.3 F).
1H NMR (300 MHz, CDCl3): d = 7.5–7.4 (m, 2 H, H5), 7.3 (2 d,
3
J = 8.5 Hz, J¢ = 8.7 Hz, 2 H, H4), 6.6 (d, JH–F = 17.0 Hz, 0.5 H,
H2Z), 5.9 (d, 3JH–F = 32.0 Hz, 0.5 H, H2E).
13C NMR (75.5 MHz, CDCl3): d = 133.8 (d, J = 317 Hz), 132.8 (d,
J = 331 Hz), 132.2, 131.7 (d, J = 7 Hz), 130.8 (d, J = 8 Hz), 130.1
(d, J = 3 Hz), 130.1 (d, J = 4 Hz), 122.0, 112.1 (d, J = 6 Hz), 111.0
(d, J = 25 Hz).
19F NMR (282.5 MHz, CDCl3): d = –64.0 (d, J = 17.0 Hz, 0.5 F),
–67.2 (d, J = 32.0 Hz, 0.5 F).
MS (EI): m/z = 245–247 (M+), 166 (M+ – Br).
Anal. Calcd for C8H5BrFNO2: C, 39.05; H, 2.05; N, 5.69. Found: C,
39.27; H, 2.13; N, 5.75.
(Z)- and (E)-1-(2-Bromo-2-fluorovinyl)-2-methoxybenzene (1h)
Ratio Z/E = 58:42; Rf = 0.6 (cyclohexane).
MS (EI): m/z = 278–282 (M+), 199–201 (M+ – Br).
Anal. Calcd for C8H5Br2F: C, 34.33; H, 1.80. Found: C, 34.41; H,
1.86.
IR (neat): 3079, 2936, 2837, 1651, 1600, 1486, 1464, 1437, 1273,
1251, 1123, 1080, 1029, 820, 750, 632 cm–1.
(Z)- and (E)-1-(2-Bromo-2-fluorovinyl)-4-nitrobenzene (1e)
Ratio Z/E = 58:42; mp 47–49 °C; Rf = 0.3 (cyclohexane–EtOAc,
98:2).
1H NMR (300 MHz, CDCl3): d = 7.6 (d, J = 8.0 Hz, 1 H, H6), 7.3–
7.1 (m, 1 H, H4), 6.9–6.8 (m, 1 H, H5), 6.8 (d, J = 8.1 Hz, 1 H, H7),
6.7 (d, 3JH–F = 15.1 Hz, 0.6 H, H2Z), 6.3 (d, 3JH–F = 34.3 Hz, 0.4 H,
H2E), 3.7 (s, 3 H, H9).
13C NMR (75.5 MHz, CDCl3): d = 157.2 (d, J = 4 Hz), 156.1, 133.4
(d, J = 315 Hz), 131.5 (d, J = 331 Hz), 129.8, 129.7, 129.5 (d, J = 2
Hz), 129.3 (d, J = 2 Hz), 121.7 (d, J = 5 Hz), 121.1, 120.8 (d, J = 8
Hz), 120.7, 111.0, 110.8, 107.6 (d, J = 25 Hz), 107.3 (d, J = 5 Hz),
55.9.
IR (KBr): 3069, 3022, 2833, 1642, 1594, 1510, 1341, 1286, 1108,
1081, 875, 841, 748, 689, 489 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.2 (2 d, J = 8.7 Hz, J¢ = 8.7 Hz,
2 H, H5), 7.5 (2 d, J = 8.7 Hz, J¢ = 8.7 Hz, 2 H, H4), 6.7 (d,
3JH–F = 14.4 Hz, 0.6 H, H2Z), 6.0 (d, 3JH–F = 31.9 Hz, 0.4 H, H2E).
13C NMR (75.5 MHz, CDCl3): d = 145.9, 145.6, 134.3 (d, J = 320
Hz), 137.6 (d, J = 5 Hz), 137.2 (d, J = 9 Hz), 134.0 (d, J = 334 Hz),
127.9 (d, J = 3 Hz), 127.5 (d, J = 8 Hz), 122.9, 122.4 (d, J = 24 Hz),
110.5 (d, J = 6 Hz), 109.4 (d, J = 26 Hz).
19F NMR (282.5 MHz, CDCl3): d = –65.6 (d, J = 15.1 Hz, 0.6 F),
–69.5 (d, J = 34.3 Hz, 0.4 F).
MS (EI): m/z = 230–232 (M+), 151 (M+ – Br).
19F NMR (282.5 MHz, CDCl3): d = –59.3 (d, J = 14.4 Hz, 0.6 F),
–62.3 (d, J = 31.9 Hz, 0.4 F).
Anal. Calcd for C9H8BrFO: C, 46.78; H, 3.49. Found: C, 46.98; H,
3.48.
MS (EI): m/z = 245–247 (M+), 215–217 (M+ – NO), 199–201 (M+ –
NO2).
(Z)- and (E)-1-(2-Bromo-2-fluorovinyl)-3,4-(methylene-
dioxy)benzene (1i)
Ratio Z/E = 52:48; Rf = 0.5 (cyclohexane).
Anal. Calcd for C8H5BrFNO2: C, 39.05; H, 2.05; N, 5.69. Found: C,
39.09; H, 2.07; N, 5.87.
IR (neat): 3480, 3046, 2897, 1651, 1504, 1488, 1257, 1041, 930,
866 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.1 (d, J = 1.5 Hz, 0.5 H, H4Z), 7.0
(d, J = 1.0 Hz, 0.5 H, H4E), 6.9–6.7 (m, 2 H, H7, H8), 6.6 (d,
3JH–F = 15.4 Hz, 0.5 H, H2Z), 6.0 (2 s, 2 H, H9), 5.9 (d, 3JH–F = 32.5
Hz, 0.5 H, H2E).
13C NMR (75.5 MHz, CDCl3): d = 148.3, 148.1, 147.8, 147.6 (d,
J = 3 Hz), 134.4 (d, J = 314 Hz), 133.0 (d, J = 329 Hz), 127.1 (d,
J = 5 Hz), 125.5 (d, J = 9 Hz), 123.3 (d, J = 4 Hz), 122.8 (d, J = 6
Hz), 108.8, 113.1 (d, J = 6 Hz), 111.8 (d, J = 24 Hz), 108.5 (2 d),
101.0.
19F NMR (282.5 MHz, CDCl3): d = –67.6 (d, J = 15.4 Hz, 0.5 F),
–70.6 (d, J = 32.5 Hz, 0.5 F).
(Z)- and (E)-1-(2-Bromo-2-fluorovinyl)-4-methoxybenzene (1f)
Ratio Z/E = 49:51; Rf = 0.6 (5% EtOAc–cyclohexane).
IR (neat): 3060, 3004, 2934, 2837, 1651, 1608, 1513, 1463, 1253,
1180, 1083, 1037, 853, 808, 590 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.3 (2 d, J = 8.7 Hz, J¢ = 8.4 Hz,
2 H, H4), 6.8 (2 d, J = 8.7 Hz, J¢ = 8.4 Hz, 2 H, H5), 6.5 (d,
3JH–F = 15.0 Hz, 0.5 H, H2Z), 5.8 (d, 3JH–F = 33.3 Hz, 0.5 H, H2E), 3.7
(2 s, 3 H, H7).
13C NMR (75.5 MHz, CDCl3): d = 159.0 (d, J = 3 Hz), 133.9 (d,
J = 314 Hz), 133.4 (d, J = 329 Hz), 129.0 (d, J = 7 Hz), 128.5 (d,
J = 23 Hz), 125.0 (d, J = 8 Hz), 123.0 (d, J = 4 Hz), 115.2 (d, J = 3
Hz), 114.4 (d, J = 5 Hz), 113.1 (d, J = 7 Hz), 111.1 (d, J = 24 Hz),
56.0.
MS (EI): m/z = 244–246 (M+), 165 (M+ – Br).
19F NMR (282.5 MHz, CDCl3): d = –68.2 (d, J = 15.0 Hz, 0.5 F),
–71.4 (d, J = 33.3 Hz, 0.5 F).
Anal. Calcd for C9H6BrFO2: C, 44.11; H, 2.47. Found: C, 44.38; H,
2.65.
MS (EI): m/z = 230–232 (M+), 215–217 (M+ – CH3).
Methyl (Z)- and (E)-4-(2-Bromo-2-fluorovinyl)benzoate (1j)
Ratio Z/E = 55:45; mp 48–50 °C; Rf = 0.6 (cyclohexane–EtOAc,
9:1).
Anal. Calcd for C9H8BrFO: C, 46.78; H, 3.49. Found: C, 46.58; H,
3.67.
IR (KBr): 3026, 2954, 1943, 1714, 1641, 1609, 1439, 1278, 1114,
870, 765, 698, 589 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.1–7.9 (br s, 2 H, H5), 7.6 (d,
J = 8.4 Hz, 1.1 H, H4Z), 7.5 (d, J = 8.5 Hz, 0.9 H, H4E), 6.7 (d,
(Z)- and (E)-1-(2-Bromo-2-fluorovinyl)-2-nitrobenzene (1g)
Ratio Z/E = 70:30; mp 44–46 °C; Rf = 0.3 (cyclohexane).
IR (KBr): 3052, 2922, 2853, 1651, 1524, 1344, 1105, 785, 742, 682
cm–1.
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York

3414
L. Zoute et al.
PAPER
3JH–F = 14.9 Hz, 0.55 H, H2Z), 6.0 (d, 3JH–F = 32.3 Hz, 0.45 H, H2E),
4.0 (s, 1.35 H, H8E), 3.8 (s, 1.65 H, H8Z).
J = 3.45 Hz), 125.7 (q, J = 3.45 Hz), 112.5 (d, J = 6 Hz), 111.2 (d,
J = 25 Hz).
13C NMR (75.5 MHz, CDCl3): d = 167.9, 167.9, 138.1 (d, J = 5 Hz),
135.5 (d, J = 318 Hz), 137.4 (d, J = 9 Hz), 134.9 (d, J = 334 Hz),
131.3, 131.0, 130.7, 130.5 (d, J = 3 Hz), 129.6 (d, J = 3 Hz), 129.2
(d, J = 8 Hz), 113.8 (d, J = 6 Hz), 112.4 (d, J = 25 Hz), 53.5.
19F NMR (282.5 MHz, CDCl3): d = –62.2 (d, J = 14.9 Hz, 0.6 F),
–64.5 (d, J = 32.3 Hz, 0.4 F).
19F NMR (282.5 MHz, CDCl3): d = –62.2 (d, J = 15.1 Hz, 0.6 F),
–63.2 (3 F), –65.1 (d, J = 32.2 Hz, 0.4 F).
MS (EI): m/z = 268–270 (M+), 249–251 (M+ – F), 189 (M+ – Br),
169, 120.
a,a-Bromofluoroalkenes from Ketones; General Procedure
To a soln of PPh3 (1.5 mmol, 1.5 equiv), tribromofluoromethane
(1.5 mmol, 1.5 equiv), and an appropriate ketone (1.0 mmol, 1.0
equiv) in anhyd THF (40 mL), was added a soln of 1 M Et2Zn in
hexanes (1.5 mmol, 1.5 equiv) dropwise via a syringe pump over 20
min at r.t. under argon. The mixture was stirred for 1 h. The result-
ing soln was then quenched with MeOH (10 mL), stirred for 15 min,
and concentrated under reduced pressure. The residue was then
chromatographed (silica gel, cyclohexane–EtOAc), affording the
desired a-bromo-a-fluoroalkene.
MS (EI): m/z = 258–260 (M+), 227–229 (M+ – OMe), 199–201 (M+
– CO2Me), 120.
Anal. Calcd for C10H8BrFO2: C, 46.36; H, 3.11. Found: C, 46.57; H,
3.34.
(Z)- and (E)-2-(2-Bromo-2-fluorovinyl)naphthalene (1k)
Ratio Z/E = 52:48; mp 83–85 °C; Rf = 0.6 (cyclohexane–EtOAc,
98:2).
IR (KBr): 3102, 2879, 1645, 1505, 1281, 1252, 1082, 908, 868, 825,
744, 481 cm–1.
1H NMR (300 MHz, CDCl3): d = 8.0–7.7 (m, 4 H), 7.7–7.3 (m, 3
H), 6.8 (d, 3JH–F = 15.1 Hz, 0.5 H, H2Z), 6.1 (d, 3JH–F = 32.8 Hz, 0.5
H, H2E).
(Bromofluoromethylene)cyclohexane (1n)
Rf = 0.8 (cyclohexane–EtOAc, 95:5).
1H NMR (300 MHz, CDCl3): d = 2.2 (m, 2 H, H3 or H7), 2.1 (m, 2
H, H3 or H7), 1.5 (m, 6 H, H4, H5).
13C NMR (75.5 MHz, CDCl3): d = 126.9 (d, J = 302 Hz), 120.7 (d,
J = 10 Hz), 31.1, 27.5 (d, J = 6 Hz), 27.0 (d, J = 6 Hz), 26.9.
19F NMR (282.5 MHz, CDCl3, decoupled): d = –82.8.
13C NMR (75.5 MHz, CDCl3): d = 133.5 (d, J = 316 Hz), 132.3 (d,
J = 332 Hz), 133.7, 133.6, 133.2, 133.1 (d, J = 2 Hz), 130.4 (d, J = 5
Hz), 129.3 (d, J = 9 Hz), 128.8, 128.6, 128.5, 128.4, 128.3 (d, J = 4
Hz), 128.1, 128.0, 127.8 (d, J = 7 Hz), 126.9, 126.8, 126.3 (d, J = 3
Hz), 126.0 (d, J = 8 Hz), 113.7 (d, J = 6 Hz), 112.3 (d, J = 24 Hz).
19F NMR (282.5 MHz, CDCl3): d = –65.1 (d, J = 15.1 Hz, 0.5 F),
–67.9 (d, J = 32.8 Hz, 0.5 F).
(Z)- and (E)-2-(2-Bromo-2-fluoro-1-methylvinyl)naphthalene
(1o)
Rf = 0.7 (cyclohexane–EtOAc, 98:2).
IR (neat): 3056, 1651, 1589, 1505, 1121, 1013, 857, 817, 747 cm–1.
MS (EI): m/z = 250–252 (M+), 170 (M+ – Br).
1H NMR (300 MHz, CDCl3): d = 7.9–7.6 (m, 4 H, H7, H8, H9, H10),
7.5–7.3 (m, 3 H, H4, H5, H12), 2.2–2.0 (m, 3 H, H13).
Anal. Calcd for C12H8BrF: C, 57.40; H, 3.21. Found: C, 57.69; H,
3.35.
13C NMR (75.5 MHz, CDCl3): d = 136.7, 133.6, 134.3, 133.6,
133.1, 133.0, 130.9 (d, J = 317 Hz), 129.3 (d, J = 322 Hz), 128.6,
128.5, 128.4, 128.2, 128.1, 128.0 (d, J = 3 Hz), 127.4 (d, J = 4 Hz),
126.8, 126.7, 126.6 (d, J = 3 Hz), 126.2 (d, J = 5 Hz), 120.0 (d, J = 7
Hz), 118.2 (d, J = 4 Hz), 21.1 (d, J = 3 Hz), 18.3 (d, J = 4 Hz).
19F NMR (282.5 MHz, CDCl3): d = –74.4 (could not be resolved).
MS (EI): m/z = 264–266 (M+), 183 (M+ – Br).
(Z)- and (E)-4-(2-Bromo-2-fluorovinyl)benzonitrile (1l)
Ratio Z/E = 56:44; mp 79–81 °C; Rf = 0.4 (cyclohexane–EtOAc,
95:5).
IR (KBr): 3466, 2298, 1645, 1605, 1503, 1412, 1281, 1068, 866,
550 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.7–7.4 (m, 4 H, H4, H5), 6.6 (d,
3JH–F = 14.6 Hz, 0.6 H, H2Z), 6.0 (d, 3JH–F = 32.0 Hz, 0.4 H, H2E).
Anal. Calcd for C13H10BrF: C, 58.89; H, 3.80. Found: C, 58.78; H,
3.71.
13C NMR (75.5 MHz, CDCl3): d = 137.6 (d, J = 320 Hz), 137.2 (d,
J = 334 Hz), 137.2, 136.7 (d, J = 9 Hz), 132.9, 132.6, 129.3 (d, J = 4
Hz), 128.9 (d, J = 8 Hz), 119.0, 112.4 (d, J = 6 Hz), 111.9, 111.5,
111.1 (d, J = 26 Hz).
19F NMR (282.5 MHz, CDCl3): d = –60.3 (d, J = 14.6 Hz, 0.6 F),
–63.1 (d, J = 32.0 Hz, 0.4 F).
(Z)- and (E)-1-Benzyloxy-4-[1-(Bromofluoromethylene)pro-
pyl]benzene (1p)
Ratio Z/E = 46:54; mp 65–67 °C; Rf = 0.5 (cyclohexane).
IR (KBr): 3035, 2968, 2874, 1660, 1607, 1511, 1454, 1386, 1239,
1177, 1133, 1013, 835, 815, 744, 696, 550 cm–1.
MS (EI): m/z = 225–227 (M+), 146 (M+ – Br).
1H NMR (300 MHz, CDCl3): d = 7.4–7.2 (m, 5 H, H11, H12, H13),
7.2–7.0 (m, 2 H, H6), 7.0–6.8 (m, 2 H, H5), 5.0 (s, 2 H, H9), 2.5–2.3
(m, 2 H, H2), 0.9 (q, J = 7.8 Hz, 3 H, H1).
Anal. Calcd for C9H5BrFN: C, 47.82; H, 2.23; N, 6.20. Found: C,
47.98; H, 2.25; N, 6.19.
13C NMR (75.5 MHz, CDCl3): d = 158.7, 137.2, 129.3 (d, J = 316
Hz), 130.4 (d, J = 3 Hz), 129.8 (d, J = 3 Hz), 128.1 (d, J = 195 Hz),
129.0, 128.7, 128.4, 128.0, 127.9, 125.6, 123.5 (d, J = 6 Hz), 115.0,
114.9, 70.9, 28.2, 25.5 (d, J = 4 Hz), 12.9 (d, J = 2 Hz,), 12.5 (d,
J = 4 Hz).
(Z)- and (E)-1-(2-Bromo-2-fluorovinyl)-4-(trifluoromethyl)ben-
zene (1m)
Ratio Z/E = 56:44; Rf = 0.6 (5% EtOAc–cyclohexane).
IR (KBr): 3070, 1651, 1619, 1415, 1325, 1170, 1130, 1069, 1018,
842, 598 cm–1.
19F NMR (282.5 MHz, CDCl3): d = –76.5 (s, 0.5 F), –76.7 (t, J = 3.6
1H NMR (300 MHz, CDCl3): d = 7.7–7.5 (m, 4 H, H4, H5), 6.8 (d,
3JH–F = 14.5 Hz, 0.6 H, H2Z), 6.1 (d, 3JH–F = 32.3 Hz, 0.4 H, H2E).
Hz, 0.5 F).
MS (EI): m/z = 334–336 (M+), 240 (M+ – Br).
13C NMR (75.5 MHz, CDCl3): d = 136.9 (d, J = 318 Hz), 136.7 (d,
J = 335 Hz), 137.8 (d, J = 11 Hz), 135.7 (d, J = 9 Hz), 134.4, 134.1,
130.4 (d, J = 4 Hz), 130.3 (d, J = 3 Hz), 128.7, 128.6, 126.0 (q,
Anal. Calcd for C17H16BrFO: C, 60.91; H, 4.81. Found: C, 61.07; H,
4.88.
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York

PAPER
Efficient Synthesis of Fluoroalkenes via Diethylzinc-Promoted Wittig reaction
3415
(Z)- and (E)-1-(Bromofluoromethylene)-1,2,3,4-tetrahydro-
naphthalene (1q)
129.1, 128.3, 127.0, 126.9 (d, J = 1 Hz), 126.1 (d, J = 1 Hz), 121.8
(d, J = 6 Hz), 117.4–117.0, 15.5, 12.0.
Ratio Z/E = 41:59; Rf = 0.8 (cyclohexane–EtOAc, 98:2).
19F NMR (282.5 MHz, CDCl3): d = –72.5 (d, J = 3.8 Hz, 0.5 F),
–74.4 (d, J = 4.3 Hz, 0.5 F).
MS (EI): m/z = 240–242 (M+), 161 (M+ – Br).
IR (neat): 3429, 3061, 2934, 1686, 1451, 1253, 1199, 783, 745, 660
cm–1.
1H NMR (300 MHz, CDCl3): d = 7.9–7.7 (m, 1 H, H8), 7.4–7.1 (m,
3 H, H9, H10, H11), 2.9–2.7 (m, 3 H, 1 H3 and 2 H5), 2.6–2.5 (m, 1 H,
1 H3), 2.0–1.8 (m, 2 H, H4).
1-Benzyl-4-(bromofluoromethylene)piperidine (1u)
Rf = 0.5 (cyclohexane).
13C NMR (75.5 MHz, CDCl3): d = 140.3 (d, J = 5 Hz), 133.4 (d,
J = 3 Hz), 131.4 (d, J = 7 Hz), 131.6 (d, J = 10 Hz), 123.8 (d,
J = 221 Hz), 127.6 (d, J = 326 Hz), 129.2, 129.1, 129.0, 128.5,
128.1, 127.9 (d, J = 1 Hz), 126.6, 125.8, 119.0 (d, J = 17 Hz), 116.0
(d, J = 14 Hz), 31.1, 30.6, 30.6, 26.0 (d, J = 6 Hz), 23.2 (d, J = 1
Hz), 22.7 (d, J = 2 Hz).
19F NMR (282.5 MHz, CDCl3): d = –69.0 (t, J = 3.6 Hz, 0.4 F),
–72.6 (s, 0.6 F).
MS (EI): m/z = 240–242 (M+).
IR (neat): 3341, 3028, 2964, 2906, 2803, 2761, 1681, 1494, 1455,
1439, 1364, 1338, 1298, 1231, 1103, 1079, 985, 862, 738, 698, 586,
465 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.3–7.1 (m, 5 H, H9, H10, H11), 3.4
(s, 2 H, H7), 2.5–2.3 (m, 6 H, H4, H5, H3 or H6), 2.3–2.1 (m, 2 H, H3
or H6).
13C NMR (75.5 MHz, CDCl3): d = 138.5, 129.5, 128.7, 127.5, 128.1
(d, J = 310 Hz), 117.7 (d, J = 12 Hz), 63.2, 53.6 (dd, J = 2 Hz, J = 2
Hz), 30.5, 27.2 (d, J = 5 Hz).
Anal. Calcd for C11H10BrF: C, 54.80; H, 4.18. Found: C, 54.62; H,
4.31.
19F NMR (282.5 MHz, CDCl3, decoupled): d = –82.1.
MS (EI): m/z = 283–285 (M+), 204 (M+ – Br).
Anal. Calcd for C13H15BrFN: C, 54.95; H, 5.32; N, 4.93. Found: C,
54.98; H, 5.36; N, 4.90.
(Z)- and (E)-(2-Bromo-2-fluoro-1-phenylvinyl)trimethylsilane
(1r)
Ratio Z/E = 70:30; Rf = 0.5 (cyclohexane).
1H NMR (300 MHz, CDCl3): d = 7.3–7.0 (m, 3 H, H4, H6), 7.0–6.8
(m, 2 H, H5), 0.1–0 (m, 9 H, H7).
13C NMR (75.5 MHz, CDCl3): d = 139.8 (d, J = 11 Hz), 138.6,
136.1 (d, J = 315 Hz), 134.1 (d, J = 332 Hz), 129.3, 129.1, 128.9 (d,
J = 3 Hz), 128.5 (d, J = 1 Hz), 127.4, 127.3, 124.6 (d, J = 28 Hz),
122.4 (d, J = 9 Hz), 0.0 (d, J = 3 Hz), –0.1 (d, J = 2 Hz).
19F NMR (282.5 MHz, CDCl3): d = –39.61 (0.7 F), –39.64 (0.3 F).
MS (EI): m/z = 272–274 (M+), 257–259 (M+ – CH3).
(Z)- and (E)-{[(2-(Bromofluoromethylene)cyclopentyl]meth-
oxy}tert-butyldiphenylsilane (1v)
Ratio Z/E = 44:56; Rf = 0.7 (cyclohexane–EtOAc, 98:2).
IR (neat): 3394, 3071, 2958, 2857, 1682, 1471, 1428, 1111, 1092,
823, 701, 504 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.6 (m, 4 H, H11), 7.3 (m, 6 H, H12,
H13), 3.6 (m, 1 H, H7), 3.5–3.4 (m, 1 H, H7), 3.0–2.9 (m, 0.4 H, H6Z),
2.7–2.6 (m, 0.6 H, H6E), 2.4–2.2 (m, 1.1 H, H3E), 2.2–2.1 (m, 0.9 H,
H3Z), 2.0–1.5 (br m, 4 H, H4, H5), 1.0 (s, 9 H, H9).
Anal. Calcd for C11H14BrFSi: C, 48.36; H, 5.16. Found: C, 48.97;
H, 5.37; large error due to rapid decomposition.
13C NMR (75.5 MHz, CDCl3): d = 142.9 (d, J = 249 Hz), 136.4,
135.2, 134.4, 131.0, 130.4, 128.7, 128.4, 125.3 (2 d, J = 10 Hz),
64.9, 64.2, 46.3, 45.3, 32.8, 31.3, 30.2, 29.8, 27.6, 26.7, 25.3, 24.7,
20.0.
3-(Bromofluoromethylene)-1,5-diphenylpentane (1s)
Rf = 0.5 (cyclohexane).
19F NMR (282.5 MHz, CDCl3): d = –74.0 (m, 0.4 F), –77.3 (m, 0.6
IR (neat): 3085, 3026, 2928, 2861, 1663, 1496, 1454, 1182, 1099,
1073, 748, 698 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.4–7.0 (m, 10 H, H6, H7, H8, H12,
H13, H14), 2.8–2.6 (m, 4 H, H4, H10), 2.6–2.4 (m, 2 H, H3 or H9), 2.4–
2.2 (m, 2 H, H3 or H9).
F).
MS (EI): m/z = 447 (M+), 201, 181, 135, 109, 91, 81, 57 (t-Bu+).
Anal. Calcd for C23H28BrFOSi: C, 61.74; H, 6.31. Found: C, 61.57;
H, 6.42.
13C NMR (75.5 MHz, CDCl3): d = 141.5, 141.4, 129.6 (d, J = 313
Hz), 129.0, 128.9, 128.8, 128.7, 126.6, 126.5, 120.5 (d, J = 10 Hz),
34.7, 34.5 (d, J = 7 Hz), 33.9 (d, J = 4 Hz), 31.3 (d, J = 5 Hz).
a-Fluoroacrylates from Aldehydes or Ketones; General Proce-
dure
To an anhyd THF soln (10 mL) of PPh3 (4 mmol, 4 equiv) and ethyl
bromodifluoroacetate (2 mmol, 2 equiv) was rapidly added 1 M
Et2Zn in hexane (4 mmol, 4 equiv) under argon. The mixture was
stirred for 10 min (until the internal temperature returned to r.t.),
then the appropriate carbonyl compound was rapidly added. The
mixture was stirred for 10 min. The resulting soln was then
quenched with EtOH (15 mL), stirred for 15 min, and concentrated
under reduced pressure. The residue was taken up in Et2O (5 mL)
and filtered through Celite and then it was chromatographed (silica
gel, cyclohexane–EtOAc) to afford the expected a-fluoroacrylate.
19F NMR (282.5 MHz, CDCl3, decoupled): d = –77.6.
MS (EI): m/z = 332–334 (M+), 253 (M+ – Br), 105 (PhCH2CH2 ).
+
Anal. Calcd for C18H18BrF: C, 64.88; H, 5.44. Found: C, 64.83; H,
5.37.
(Z)- and (E)-1-[(1E)-4-Bromo-4-fluoro-3-methylbuta-1,3-di-
enyl]benzene (1t)
Ratio Z/E = 45:55; Rf = 0.8 (cyclohexane–EtOAc, 95:5).
IR (neat): 3048, 3024, 2926, 1802, 1763, 1701, 1633, 1616, 1495,
1447, 1281, 1116, 1030, 958, 749, 691 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.5–7.2 (m, 5 H, H6, H7, H8), 7.2
(d, J = 16.0 Hz, 1 H, H3), 6.9 (d, J = 16.0 Hz, 1 H, H4), 2.0–1.8 (m,
3 H, H9).
13C NMR (75.5 MHz, CDCl3): d = 137.4, 132.8 (d, J = 349 Hz),
132.7 (d, J = 351 Hz), 131.4 (d, J = 12 Hz), 129.8 (d, J = 5 Hz),
Ethyl (Z)- and (E)-2-Fluoro-3-(4-methoxyphenyl)acrylate (2a)
Ratio Z/E = 85:15; Rf = 0.3 (cyclohexane–EtOAc, 9:1).
IR (neat): 2983, 1726, 1660, 1607, 1514, 1371, 1256, 1179, 1098,
1030, 830 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.5 (d, 2 H, H6), 6.8–6.7 (m, 3 H,
H3, H5), 4.2 (2 q, J = 7.2 Hz, 2 H, H9), 3.7 (2 s, 3 H, H8), 1.3 (t,
J = 7.0 Hz, 2.55 H, H10Z), 1.2 (t, J = 7.0 Hz, 0.45 H, H10E).
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York

3416
L. Zoute et al.
PAPER
13C NMR (75.5 MHz, CDCl3): d = 161.5 (d, J = 34 Hz), 160.7 (d,
J = 36 Hz), 160.5 (d, J = 3 Hz), 160.1 (d, J = 1 Hz), 145.0 (d,
J = 263 Hz), 132.4 (d, J = 9 Hz), 132.1 (d, J = 3 Hz), 123.7 (d, J = 5
Hz), 123.0 (d, J = 10 Hz), 121.9 (d, J = 27 Hz), 117.3 (d, J = 5 Hz),
114.2, 113.4, 61.6, 61.4, 55.6, 55.5, 14.2, 14.0.
19F NMR (282.5 MHz, CDCl3): d = –119.5 (d, J = 23.6 Hz, 0.1 F),
–129.2 (d, J = 35.5 Hz, 0.9 F).
J = 20 Hz), 131.3 (d, J = 5 Hz), 130.4 (d, J = 8 Hz), 129.8 (d, J = 3
Hz), 129.7 (d, J = 3 Hz), 128.9, 128.2, 121.6 (d, J = 26 Hz), 117.6
(d, J = 5 Hz), 62.0, 61.8, 14.4, 14.0.
19F NMR (282.5 MHz, CDCl3): d = –117.6 (d, J = 22.5 Hz, 0.2 F),
–125.7 (d, J = 35.5 Hz, 0.8 F).
MS (EI): m/z = 194 (M+), 165 (M+ – Et), 101.
HRMS (EI): m/z [M]+ calcd for C11H11FO2: 194.2075; found:
MS (EI): m/z = 224 (M+), 195 (M+ – Et).
194.2067 and 194.2080.
Anal. Calcd for C12H13FO3: C, 64.28; H, 5.84. Found: C, 63.71; H,
6.02.
Ethyl (Z)- and (E)-2-Fluoro-5-phenylpent-2-enoate (2e)
Ratio Z/E = 68:32; Rf = 0.3 (cyclohexane–EtOAc, 9:1).
Ethyl (Z)- and (E)-2-Fluorooct-2-enoate (2b)
Ratio Z/E = 70:30; Rf = 0.5 (cyclohexane–EtOAc, 9:1).
IR (neat): 2984, 2935, 1732, 1678, 1455, 1373, 1314, 1270, 1241,
1184, 1105, 746, 698, 502 cm–1.
IR (neat): 2960, 2932, 1732, 1678, 1467, 1373, 1309, 1261, 1201,
1148, 1089, 765 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.4–7.3 (m, 5 H, Harom), 6.2 (dt,
3JH–F = 33.1 Hz, 3JH–F = 7.9 Hz, 0.7 H, H3Z), 6.0 (dt, 3JH–F = 21.0 Hz,
3JH–F = 7.9 Hz, 0.3 H, H3E), 4.4–4.3 (m, 2 H, H10), 2.9–2.6 (m, 4 H,
H4–5), 1.4–1.3 (m, 3 H, H11).
13C NMR (75.5 MHz, CDCl3): d = 160.7 (d, J = 36 Hz), 160.5 (d,
J = 35.0 Hz), 148.1 (d, J = 256 Hz), 147.2 (d, J = 252 Hz), 140.5 (d,
J = 12 Hz), 137.1 (d, J = 12 Hz), 133.5 (d, J = 19 Hz), 129.2, 126.7,
122.8 (d, J = 18 Hz), 120.0 (d, J = 12 Hz), 61.9, 61.7, 35.7, 34.9,
27.7, 26.4, 14.6, 14.5.
3
1H NMR (300 MHz, CDCl3): d = 6.0 (dt, JH–H = 8.0 Hz,
3JH–F = 33.3 Hz, 0.7 H, H3Z), 5.8 (dt, 3JH–H = 8.3 Hz, 3JH–F = 21.6 Hz,
0.3 H, H3E), 4.2–4.1 (m, 2 H, H9), 2.4 (dq, J = 1.7 Hz, J = 8.6 Hz,
0.6 H, H4E), 2.1 (dq, J = 2.2 Hz, J = 7.2 Hz, 1.4 H, H4Z), 1.4–1.2 (m,
9 H, H5, H6, H7, H8), 0.8 (t, J = 6.8 Hz, 3 H, H10).
13C NMR (75.5 MHz, CDCl3): d = 161.1 (d, J = 36 Hz), 161.0 (d,
J = 26 Hz), 148.0 (d, J = 255 Hz), 147.0 (d, J = 250 Hz), 123.8 (d,
J = 18 Hz), 121.0 (d, J = 12 Hz), 61.5, 61.3, 31.4, 29.0 (d, J = 2 Hz),
29.0 (d, J = 2 Hz), 25.5 (d, J = 5 Hz), 24.2 (d, J = 2 Hz), 22.5, 22.4,
14.1, 14.0.
19F NMR (282.5 MHz, CDCl3): d = –123.2 (d, J = 21.5 Hz, 0.3 F),
–131.6 (d, J = 33.3 Hz, 0.7 F).
19F NMR (282.5 MHz, CDCl3): d = –122.1 (d, J = 21.5 Hz, 0.3 F),
–130.1 (d, J = 33.3 Hz, 0.7 F).
+
MS (EI): m/z = 222 (M+), 202, 91 (PhCH2 ).
HRMS-EI: m/z [M]+ calcd for C13H15FO2: 222.1056; found:
222.1058 and 222.1032.
MS (EI): m/z = 188 (M+), 91, 41.
Ethyl (Z)- and (E)-2-Fluoro-3-[4-(trifluoromethyl)phenyl]acry-
late (2f)
Ratio Z/E = 75:25; Rf = 0.5 (cyclohexane–EtOAc, 9:1).
IR (neat): 2987, 1736, 1325, 1126, 1068, 1018, 829 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.6–7.1 (m, 4 H, H5, H6), 6.8 (d,
J = 34.6 Hz, 0.8 H, H3Z), 6.8 (d, J = 17.0 Hz, 0.2 H, H3E), 4.2 (q,
J = 7.0 Hz, 1.5 H, H9Z), 4.1 (q, J = 7.4 Hz, 0.5 H, H9E), 1.3 (t, J = 7
Hz, 2.3 H, H10Z), 1.1 (t, J = 7.0 Hz, 0.7 H, H10E).
13C NMR (75.5 MHz, CDCl3): d = 161.4 (d, J = 35 Hz), 160.5 (d,
J = 36 Hz), 148.6 (d, J = 272 Hz), 148.3 (d, J = 260 Hz), 132.1,
131.6 (d, J = 11 Hz), 131.3 (d, J = 4 Hz), 131.3, 130.6 (d, J = 8 Hz),
130.2 (d, J = 3 Hz), 126.1 (q, J = 4 Hz), 120.2 (d, J = 27 Hz), 116.1
(d, J = 5 Hz), 62.6, 62.3, 14.5, 14.1.
Ethyl (Z)- and (E)-5-(tert-Butyldiphenylsilyloxy)-2-fluoropent-
2-enoate (2c)
Ratio Z/E = 65:35; Rf = 0.4 (cyclohexane–EtOAc, 9:1).
IR (neat): 3071, 2932, 2958, 1738, 1681, 1473, 1428, 1314, 1215,
1112, 1027, 939, 824, 741, 703, 614, 505 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.7–7.3 (m, 10 H, Harom), 6.2 (dt,
3JH–H = 7.8 Hz, 3JH–F = 21.4 Hz, 0.7 H, H3Z), 6.0 (dt, 3JH–H = 7.9 Hz,
3JH–F = 21.4 Hz, 0.3 H, H3E), 4.3 (q, J = 7.2 Hz, 1.3 H, H12Z), 4.3 (q,
J = 7.2 Hz, 0.7 H, H12E), 3.7 (t, J = 6.4 Hz, 2 H, H5), 2.8–2.7 (m, 0.7
H, H4E), 2.5–2.4 (m, 1.3 H, H4Z), 1.3 (t, J = 7.2 Hz, 3 H, H13), 1.0 (s,
9 H, H7).
13C NMR (75.5 MHz, CDCl3): d = 161.1 (d, J = 36 Hz), 160.5 (d,
J = 36.0 Hz), 149.1 (d, J = 256 Hz), 148.1 (d, J = 252 Hz), 137.5 (d,
J = 10 Hz), 136.0, 134.1, 130.1, 120.4 (d, J = 19 Hz), 117.9 (d,
J = 12 Hz), 61.5, 61.3, 31.4, 29.0 (d, J = 2 Hz), 29.0 (d, J = 1.7 Hz),
25.5 (d, J = 5.2 Hz), 24.2 (d, J = 2.3 Hz), 22.5, 22.4, 14.1, 14.0.
19F NMR (282.5 MHz, CDCl3): d = –63.3 (0.7 F), –63.4 (2.3 F),
–115.1 (d, J = 21.5 Hz, 0.2 F), –122.5 (d, J = 34.4 Hz, 0.8 F).
MS (EI): m/z = 262 (M+).
19F NMR (282.5 MHz, CDCl3): d = –121.4 (d, J = 21.5 Hz, 0.3 F),
–129.7 (d, J = 33.3 Hz, 0.7 F).
MS (EI): m/z = 343 (M+ – t-Bu).
Anal. Calcd for C12H10F4O2: C, 54.97; H, 3.84. Found: C, 54.76; H:
3.90.
Ethyl (Z)- and (E)-3-(4-Bromophenyl)-2-fluoroacrylate (2g)
Ratio Z/E = 80:20; Rf = 0.3 (cyclohexane–EtOAc, 9:1).
Anal. Calcd for C23H29FO3Si: C, 68.97; H, 7.30. Found: C, 68.93;
H, 7.16.
IR (neat): 2981, 1732, 1670, 1489, 1373, 1286, 1234, 1204, 1095,
1070, 1010, 828, 762, 472 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.5–7.3 (m, 4 H, H5, H6), 6.8 (d,
J = 34.7 Hz, 0.8 H, H3Z), 6.8 (d, J = 21.9 Hz, 0.2 H, H3E), 4.3 (q,
J = 7.2 Hz, 1.6 H, H8Z), 4.2 (q, J = 7.0 Hz, 0.4 H, H8E), 1.4 (t, J = 7.2
Hz, 2.4 H, H9Z), 1.2 (t, J = 7.2 Hz, 0.6 H, H9E).
13C NMR (75.5 MHz, CDCl3): d = 160.2 (d, J = 34 Hz), 160.3 (d,
J = 35 Hz), 147.4 (d, J = 265 Hz), 147.2 (d, J = 254 Hz), 132.1,
131.6 (d, J = 11 Hz), 131.3 (d, J = 4 Hz), 131.3, 130.0 (d, J = 5 Hz),
129.9 (d, J = 10 Hz), 124.0, 122.9, 120.5 (d, J = 27 Hz), 116.3 (d,
J = 5 Hz), 62.1, 61.8, 14.2, 14.0.
Ethyl (Z)- and (E)-2-Fluoro-3-phenylacylate (2d)
Ratio Z/E = 80:20; Rf = 0.6 (cyclohexane–EtOAc, 9:1).
IR (neat): 2984, 1732, 1660, 1450, 1372, 1283, 1202, 1100, 1020,
768, 692 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.4–7.3 (m, 5 H, H5, H6, H7), 6.9
(d, J = 35.2 Hz, 0.8 H, H3Z), 6.9 (d, J = 22.2 Hz, 0.2 H, H3E), 4.3 (q,
J = 7.2 Hz, 1.6 H, H8Z), 4.2 (q, J = 7.2 Hz, 0.2 H, H8E), 1.4 (t, J = 7.2
Hz, 2.4 H, H9Z), 1.2 (t, J = 7.2 Hz, 0.6 H, H9E).
13C NMR (75.5 MHz, CDCl3): d = 161.6 (d, J = 35 Hz), 160.6 (d,
J = 36 Hz), 147.2 (d, J = 267 Hz), 142.0 (d, J = 258 Hz), 133.9 (d,
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York

PAPER
Efficient Synthesis of Fluoroalkenes via Diethylzinc-Promoted Wittig reaction
3417
19F NMR (282.5 MHz, CDCl3): d = –116.3 (d, J = 22.5 Hz, 0.2 F),
–124.4 (d, J = 35.5 Hz, 0.8 F).
MS (EI): m/z = 272–274 (M+), 148, 120.
J = 30 Hz), 129.6, 129.5, 128.7, 128.4, 138.9, 138.0, 131.8, 131.1,
128.6, 128.5, 128.4, 128.3, 128.1, 127.8, 127.8, 61.7, 61.4, 19.7,
19.6, 14.6, 14.0.
19F NMR (282.5 MHz, CDCl3): d = –124.4 (q, J = 4.3 Hz, 0.4 F),
–126.3 (q, J = 3.2 Hz, 0.6 F).
MS (EI): m/z = 208 (M+), 162.
Anal. Calcd for C11H10BrFO2: C, 48.38; H, 3.69. Found: C, 48.59;
H, 3.78.
Ethyl (Z)- and (E)-2-Fluoro-3-(4-pyridyl)acrylate (2h)
Ratio Z/E = 85:15; Rf = 0.4 (cyclohexane–EtOAc, 9:1).
1H NMR (300 MHz, CDCl3): d = 7.6–7.3 (m, 4 H, H5, H6), 6.9 (d,
J = 35.2 Hz, 0.9 H, H3Z), 6.9 (d, J = 22.1 Hz, 0.1 H, H3E), 4.3 (q,
J = 7.2 Hz, 1.7 H, H7Z), 4.2 (q, J = 7.2 Hz, 0.3 H, H7E), 1.4 (t, J = 7.2
Hz, 2.55 H, H8Z), 1.2 (t, J = 7.2 Hz, 0.45 H, H8E).
Anal. Calcd for C12H13FO2: C, 69.22; H 6.29. Found: C, 69.24; H:
6.09.
Ethyl 2-Fluoro-3-methyl-5-phenylpent-2-enoate (2l)
Ratio Z/E = 60:40; Rf = 0.5 (cyclohexane–EtOAc, 9:1).
IR (neat): 2983, 1722, 1664, 1455, 1299, 1127, 699, 543 cm–1.
19F NMR (282.5 MHz, CDCl3): d = –117.7 (d, J = 22.5 Hz, 0.15 F),
–125.8 (d, J = 35.5 Hz, 0.85 F).
1H NMR (300 MHz, CDCl3): d = 7.4–7.2 (m, 5 H, H7, H8, H9), 4.3
(m, 2 H, H11), 2.8 (m, 3 H, H4, H5), 2.5–2.4 (m, 1 H, H4), 2.0 (d,
J = 3.2 Hz, 1.2 H, H10E), 1.8 (d, J = 4.3 Hz, 1.8 H, H10Z), 1.2 (m, 3
H, H12).
13C NMR (75.5 MHz, CDCl3): d = 161.8 (d, J = 35 Hz), 161.4 (d,
J = 35 Hz), 144.7 (d, J = 249 Hz), 144.3 (d, J = 246.9 Hz), 133.1 (d,
J = 13 Hz), 133.0 (d, J = 14 Hz), 141.6, 141.4, 134.3, 134.0, 128.8,
128.5, 61.4, 34.9, 34.8, 34.7, 33.9, 17.4 (d, J = 2 Hz), 17.2 (d, J = 9
Hz), 14.6.
Ethyl (Z)- and (E)-2-Fluoro-5-methylhex-2-enoate (2i)
Ratio Z/E = 70:30; Rf = 0.5 (cyclohexane–EtOAc, 9:1).
IR (neat): 2961, 2873, 1732, 1678, 1467, 1373, 1324, 1293, 1227,
1152, 1085, 1050, 764 cm–1.
3
3
1H NMR (300 MHz, CDCl3): d = 6.1 (dt, JH–H = 8.0 Hz, JH–F
=
33.3 Hz, 0.7 H, H3Z), 5.9 (dt, 3JH–H = 8.2 Hz, 3JH–F = 22.1 Hz, 0.3 H,
H3E), 4.3–4.2 (m, 2 H, H7), 2.4 (t, J = 7.3 Hz, 0.6 H, H4E), 2.1 (dt,
J = 1.6 Hz, J = 7.2 Hz, 1.4 H, H4Z), 1.8–1.3 (m, 1 H, H5), 1.3 (m, 3
H, H8), 0.9 (d, J = 6.6 Hz, 6 H, H6, H6¢).
19F NMR (282.5 MHz, CDCl3): d = –126.9 (q, J = 11 Hz, 0.6 F),
–128.6 (q, J = 11 Hz, 0.4 F).
+
MS (EI): m/z = 236 (M+), 216, 91 (PhCH2 ).
13C NMR (75.5 MHz, CDCl3): d = 161.3 (d, J = 36 Hz), 161.2 (d,
J = 36 Hz), 148.4 (d, J = 255 Hz), 147.4 (d, J = 251 Hz), 122.6 (d,
J = 18 Hz), 119.6 (d, J = 12 Hz), 61.6, 61.3, 34.2 (d, J = 5 Hz), 33.2
(d, J = 2 Hz), 28.7 (d, J = 2 Hz), 28.0 (d, J = 2 Hz), 22.3, 14.5.
19F NMR (282.5 MHz, CDCl3): d = –122.2 (d, J = 21.5 Hz, 0.3 F),
–131.1 (d, J = 33.3 Hz, 0.7 F).
HRMS-EI: m/z [M+] calcd for C14H17FO2: 236.1213; found:
236.1227 and 236.1220.
Ethyl (Z)- and (E)-Cyclohexylidenefluoroacetate (2m)
Rf = 0.6 (cyclohexane–EtOAc, 9:1).
IR (neat): 2922, 1722, 1661, 1437, 1264, 1183, 1119, 722, 541 cm–1.
1H NMR (300 MHz, CDCl3): d = 4.2 (q, J = 7.1 Hz, 2 H, H7), 2.7
(m, 2 H, H4, H4¢), 2.3 (dd, J = 2.0 Hz, J = 4.1 Hz, 2 H, H4, H4¢), 1.5
(m, 6 H, H5, H6), 1.3 (t, J = 7.1 Hz, 3 H, H8).
MS (EI): m/z = 174 (M+), 104.
Ethyl (Z)- and (E)-3-[4-(Methoxycarbonyl)phenyl]-2-fluoro-
acrylate (2j)
13C NMR (75.5 MHz, CDCl3): d = 160.64 (d, J = 35 Hz), 139.95 (d,
J = 245 Hz), 135.48 (d, J = 12 Hz), 59.9, 26.8, 26.6, 26.5, 26.4,
26.1, 13.2.
Ratio Z/E = 70:30; Rf = 0.3 (cyclohexane–EtOAc, 9:1).
IR (neat): 2955, 1731, 1667, 1609, 1436, 1372, 1279, 1204, 1111,
1019, 861, 816, 769 cm–1.
19F NMR (282.5 MHz, CDCl3): d = –131.8.
MS (EI): m/z = 186 (M+), 158.
HRMS-EI: m/z [M+] calcd for C10H15FO2: 186.1056; found:
1H NMR (300 MHz, CDCl3): d = 7.2–7.9 (m, 4 H, H5, H6), 6.9 (d,
3JH–F = 34.4 Hz, 0.7 H, H3Z), 6.8 (d, J = 21.4 Hz, 0.3 H, H3E), 4.3 (q,
J = 7.2 Hz, 1.4 H, H10Z), 4.2 (q, J = 7.2 Hz, 0.6 H, H10E), 3.8 (s, 2.1
H, H9Z), 3.8 (s, 0.9 H, H9E), 1.3 (t, J = 7.2 Hz, 2.1 H, H11), 1.1 (t,
J = 7.2 Hz, 0.9 H, H11).
186.1054.
13C NMR (75.5 MHz, CDCl3): d = 166.9, 166.7, 161.3 (d, J = 36
Hz), 160.5 (d, J = 36 Hz), 148.4 (d, J = 256 Hz), 147.5 (d, J = 252
Hz), 137.3 (d, J = 9 Hz), 136.1 (d, J = 8 Hz), 131.0 (d, J = 3 Hz),
130.5, 130.4, 130.3, 129.9 (d, J = 3 Hz), 129.6, 120.6 (d, J = 26 Hz),
116.6 (d, J = 5 Hz), 62.5, 62.2, 52.5, 14.5, 14.2.
19F NMR (282.5 MHz, CDCl3): d = –115.0 (d, J = 21.4 Hz, 0.3 F),
–122.3 (d, J = 34.8 Hz, 0.7 F).
Ethyl (Z)- and (E)-2,4,4,4-Tetrafluoro-3-phenylbut-2-enoate
(2n)
Ratio Z/E = 35:65; Rf = 0.5 (cyclohexane–EtOAc, 9:1).
IR (neat): 2988, 1746, 1656, 1446, 1373, 1306, 1265, 1231, 1185,
1137, 1017, 952, 700 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.3–7.2 (m, 5 H, H5, H6, H7), 4.3
(q, J = 7.2 Hz, 1.3 H, H9E), 3.9 (q, J = 7.2 Hz, 0.7 H, H9Z), 1.3 (t,
J = 7.2 Hz, 2.0 H, H10E), 0.9 (t, J = 7.2 Hz, 1.0 H, H10Z).
MS (EI): m/z = 252 (M+), 221, 193.
13C NMR (75.5 MHz, CDCl3): d = 159.6 (d, J = 35 Hz), 159.3 (d,
J = 34 Hz), 152.0 (d, J = 284 Hz), 149.6 (d, J = 284 Hz), 137.8 (d,
J = 30 Hz), 133.8 (d, J = 74 Hz), 129.6–128.4 (m), 125–117 (m),
63.5, 62.8, 14.1, 13.7.
19F NMR (282.5 MHz, CDCl3): d = –58.8 (d, J = 9.7 Hz, 1.95 F),
–60.9 (d, J = 24.7 Hz, 1.05 F), –107.2 (q, J = 9.7 Hz, 0.35 F), –108.9
(q, J = 24.7 Hz, 0.65 F).
Ethyl (Z)- and (E)-2-Fluoro-3-phenylbut-2-enoate (2k)
Ratio Z/E = 60:40; Rf = 0.6 (cyclohexane–EtOAc, 9:1).
IR (neat): 2988, 1746, 1666, 1306, 1265, 1231, 1185, 1137, 1017,
952, 699 cm–1.
1H NMR (300 MHz, CDCl3): d = 7.3–7.1 (m, 5 H, H5, H6, H7), 4.2
(q, J = 7.2 Hz, 0.8 H, H9E), 3.9 (q, J = 7.2 Hz, 1.2 H, H9Z), 2.3 (d,
J = 3.6 Hz, 1.2 H, H8E), 2.0 (d, J = 4.4 Hz, 1.8 H, H8Z), 1.3 (t, J = 7.2
Hz, 1.2 H, H10E), 1.3 (t, J = 7.2 Hz, 1.8 H, H10Z).
MS (EI): m/z = 262 (M+), 233 (M+ – Et).
HRMS-EI: m/z [M+] calcd for C12H10F4O2: 262.0617; found:
13C NMR (75.5 MHz, CDCl3): d = 161.6 (d, J = 35 Hz), 161.0 (d,
J = 36 Hz), 145.6 (d, J = 252 Hz), 143.5 (d, J = 254 Hz), 129.5 (d,
262.0643 and 262.0608.
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York

3418
L. Zoute et al.
PAPER
(2) For access to a-fluoroacrylates, see: (a) Burton, D. J.; Yang,
Z.; Qiu, W. Chem. Rev. 1996, 96, 1641; and references cited
therein. (b) Ishihara, T.; Kuroboshi, M. Chem. Lett. 1987,
1145. (c) Barma, D. K.; Kundu, A.; Zhang, H.; Mioskowski,
C.; Falck, J. R. J. Am. Chem. Soc. 2003, 125, 3218.
(d) Ishihara, T.; Shintani, A.; Yamanaka, H. Tetrahedron
Lett. 1998, 39, 4865.
(3) Xu, Z.; Desmarteau, D. D. J. Chem. Soc., Perkin Trans. 1
1992, 313.
(4) (a) Sano, S.; Yokoyama, K.; Terashini, R.; Shiro, M.; Nagao,
Y. Tetrahedron Lett. 2002, 43, 281. (b) Sano, S.; Saito, K.;
Nagao, Y. Tetrahedron Lett. 2003, 44, 3987.
(5) Suzuki, Y.; Sato, M. Tetrahedron Lett. 2004, 45, 1679.
(6) Lei, X.; Dutheuil, G.; Pannecoucke, X.; Quirion, J.-C. Org.
Lett. 2004, 6, 2101.
(7) For others applications of diethylzinc, see: (a) Hata, T.;
Kitagawa, H.; Shimizu, M.; Hiyama, T. Bull. Chem. Soc.
Jpn. 2000, 73, 1691. (b) Aggarwal, V. K.; Ali, A.; Coogan,
M. P. J. Org. Chem. 1997, 62, 8628.
References
(1) For reviews on fluoro-containing compounds, see:
(a) Hiyama, T. Organofluorine Compounds: Chemistry
Applications; Springer: Berlin, 2000. (b) Iseki, K.
Tetrahedron 1998, 54, 13887. For other related
publications, see: (c) Kirsch, P. Modern Fluoroorganic
Chemistry; Wiley-VCH: Weinheim, 2004. (d) Adejare, A.;
Ojima, I.; McCarthy, J. R.; Welch, J. T. J. Med. Chem. 1997,
40, 2967. (e) Hudlicky, M.; Ojima, I.; McCarthy, J. R.;
Welch, J. T. J. Nat. Prod. 1997, 60, 866. (f) Ojima, I.;
McCarthy, J. R.; Welch, J. T. Biomedical Frontiers of
Fluorine Chemistry; ACS Symposium Series 639:
Washington USA, 1996. For access to bromofluoroalkenes,
see: (g) Eddarir, S.; Francesch, C.; Mestdagh, H.; Rolando,
C. Bull. Soc. Chim. Fr. 1997, 134, 741. (h) Kuroboshi, M.;
Yamada, N.; Takebe, Y.; Hiyama, T. Tetrahedron Lett.
1995, 36, 6271.
Synthesis 2006, No. 20, 3409–3418 © Thieme Stuttgart · New York