A novel approach to 2-chloro-2-fluorostyrenes

Article abstract of DOI:10.1002/ejoc.200390033

A new general catalytic olefination reaction (COR) of aromatic and heteroaromatic aldehydes and ketones was applied to synthesise 2-chloro-2-fluorostyrenes. The two-stage procedure includes the transformation of carbonyl compounds into hydrazones followed by treatment with CFCl₃ mediated by copper catalysis. Trichlorofluoromethane was used as a chlorofluoromethylene transfer reagent. The reaction proceeds stereoselectively and the target alkenes were obtained in high yield. A proposed mechanism for the reaction is discussed. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.

Full text of DOI:10.1002/ejoc.200390033

FULL PAPER
A Novel Approach to 2-Chloro-2-fluorostyrenes
Valentine G. Nenajdenko,*[a] Alexey V. Shastin,[b] Vasily N. Korotchenko,[a]
Georgy N. Varseev,[a] and Elisabeth S. Balenkova[a]
Keywords: Catalysis / Copper / Carbonyl compounds / Alkenes / Olefination
A new general catalytic olefination reaction (COR) of aro- used as a chlorofluoromethylene transfer reagent. The reac-
matic and heteroaromatic aldehydes and ketones was ap-
plied to synthesise 2-chloro-2-fluorostyrenes. The two-stage
tion proceeds stereoselectively and the target alkenes were
obtained in high yield. A proposed mechanism for the reac-
procedure includes the transformation of carbonyl com- tion is discussed.
pounds into hydrazones followed by treatment with CFCl3
mediated by copper catalysis. Trichlorofluoromethane was
( Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2003)
Introduction
(1aϪm) and arylmethylketones (1nϪr) using CFC-11
(CFCl3). We found that CFCl3 can be used as a fluoro-
containing C1-building block for the preparation of 2-
chloro-2-fluorostyrenes from aromatic aldehydes and ke-
tones.
A previously reported preparation of β-chloro-β-fluoro-
alkenes requires a multi-step procedure involving the use of
Grignard reagents.[8] The general methodology for β-
chloro-β-fluoroalkene preparation has been elaborated by
Burton and co-workers and consists of a Wittig-type con-
densation of carbonyl compounds with a chlorofluorome-
thylene phosphorous ylide.[9Ϫ12] Similar β-bromo-β-fluoro-
alkenes and β-chloro-β-fluoroalkenes have been used in pal-
ladium-catalysed cross-coupling reactions.[13]
Fluorine-containing drugs and pesticides have achieved
an increasing interest in modern bioorganic chemistry due
to their remarkable biological activity.[1,2] Extensive studies
have been undertaken in order to develop efficient synthetic
methodologies to selectively introduce fluorine into various
organic compounds.
Earlier we reported a novel catalytic olefination reaction
(COR) of carbonyl compounds.[3] It was found that N-un-
substituted hydrazones of aromatic and heteroaromatic al-
dehydes and ketones are quantitatively converted into ol-
efins and sym-azines by treatment with polyhalogenalkanes,
CHal2XY, in the presence of CuCl as catalyst. This meth-
odology was successfully utilised to synthesise numerous
substituted alkenes.[3Ϫ7] We showed that various polyhalog-
enalkanes such as CCl4,[3,7] CHBr3,[5,7] CBr4 [6,7] and freons
(CF3CCl3 and CF2Cl-CFCl2 [4]) can be used as C1- or C2-
building blocks for the olefination of a wide range of car-
bonyl compounds. The target halogen-containing alkenes
were obtained in good yields. The remarkable features of
this approach are the availability of starting materials, mild
reaction conditions and simplicity of reaction procedure, in-
cluding isolation of the products.
Optimization of the Reaction Conditions
We started our study by optimizing the reaction condi-
tions. The hydrazone of 4-chlorobenzaldehyde (2a) was
used as a model substrate. Recently, we have found the op-
timal conditions for the synthesis of dichlorostyrenes utilis-
ing DMSO as solvent, CuCl (10 mol %) as catalyst and
aqueous ammonia as base.[3] It was found that the nature
of the solvent and the base used are the main factors af-
fecting the yield of the substituted alkenes. However, previ-
ously found conditions for the optimal synthesis of fluorin-
ated alkenes using freons (CF3CCl3 and CF2Cl-CFCl2)
were different — ethanol was used as solvent and 1,2-ethyl-
enediamine as base.[4] This peculiar relationship between
the nature of the halogenated reagents and the reaction
conditions may be linked to a change in catalytic activity
brought about by the complexation of copper with solvent
and base.
Results and Discussion
In the present paper we report the results of our investi-
gation pertaining to olefination of some aromatic aldehydes
[a]
Moscow State University, Department of Chemistry,
Leninskie Gory, Moscow 119899, Russia
Fax: (internat.) ϩ7-095/932-8846
E-mail: nen@acylium.chem.msu.ru
These two types of solvent-base systems were tested in
the reaction between 2a and trichlorofluoroethane. Using
DMSO and aqueous ammonia only trace amounts of the
[b]
Institute of Problems of Chemical Physics,
Chernogolovka, Moscow region, 142432, Russia
E-mail: shastin@icp.ac.ru
302
 2003 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/03/0102Ϫ0302 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2003, 302Ϫ308

A Novel Approach to 2-Chloro-2-fluorostyrenes
FULL PAPER
desired chlorofluoroalkene 3a were obtained. The major fected the ratio of COR products 3 and 4; for instance, the
product from the reaction was the corresponding azine 4a electron-donating group in aldehyde 1e leads to an increase
isolated in 30% yield. However, changing the reaction con- in the yield of azine 4 (increasing to 60%) and a concomit-
ditions (ethanol as solvent and 1,2-ethylenediamine as base) ant decrease in the yield of alkene 3.
resulted in the target alkene 3a being obtained in 58% yield
Table 1. Synthesis of 2-chloro-2-fluorostyrenes 3 from aromatic al-
dehydes 1aϪm
from hydrazone 2a.
Previously we elaborated a one-pot technique for the syn-
thesis of alkenes from aldehydes without isolation of the
Ar
Yield [%]
E/Z ratio[a]
hydrazones.[4,14] This procedure is more convenient for the
preparation of alkenes due to the poor stability of N-unsub-
stituted hydrazones. It was found that the alkene yield was
generally better than that found for the two-stage proced-
ure. This approach was applied to the synthesis of chloro-
fluorostyrene (3a) resulting in an increase in yield to 78%
[from 4-chlorobenzaldehyde (1a)]. The corresponding azine
4a was the only side-product obtained (17%).
Alkene 3
Azine 4
3 ϩ 4
4-ClC6H4, a
4-BrC6H4, b
4-MeC6H4, c
4-MeOC6H4, d
4-Me2NC6H4, e
4-IC6H4, f
78
68
65
50
35
55
62
54
52
68
81
61
57
2.6:1
2.4:1
3.3:1
4:1
4.2:1
2.5:1
2.8:1
3.5:1
2:1
10:1
2.7:1
3.2:1
5:1
17
22
30
43
60
22
12
18
16
8
95
90
95
93
95
77
74
72
68
76
90
72
74
C6H5, g
4-HOC6H4, h
4-O2NC6H4, i
2,6-Cl2C6H3, j
2-BrC6H4, k
2-MeOC6H4, l
1-Napht, m
It should be noted that the olefination reaction proceeds
stereoselectively and the E-isomer of 3a is formed predom-
inantly (E/Z ratio 2.5:1), whereas chlorofluorostyrenes pre-
pared earlier by Burton’s approach have lower E/Z ratios —
usually less than 1.6:1.[8,12]
9
11
17
We tried to improve the stereoselectivity of the reaction.
To this end, various alcohols were investigated as solvents
(MeOH, iPrOH, tBuOH) and various nitrogen-containing
ligands, such as 1,10-phenanthroline and 2,2Ј-bipyridine
were studied. Unfortunately, all our attempts to improve
the stereoselectivity were unsuccessful and so we reverted
back to using EtOH as the solvent.
[a]
1
By H NMR spectroscopy.
In the case of the aryl methyl ketones (1nϪr), the car-
bonyl group was less reactive and the corresponding hy-
drazones could not be prepared and used in situ. We
studied the olefination of ketones by trichlorofluorome-
thane using separately prepared hydrazones. As shown in
Table 2, the hydrazones of aromatic ketones 2nϪr can be
converted into 2-chloro-2-fluoro-1-methylstyrenes (3nϪr)
by treatment with CFCl3 under similar conditions (ethanol
as solvent and ethylenediamine as base).
Substituent Effects on Reaction Selectivity
Having found the optimal reaction conditions, we at-
tempted to study the synthetic scope of the method for the
preparation of 2-chloro-2-fluorostyrenes 3. We found that a
wide variety of aromatic aldehydes (1aϪm) could be con-
verted easily into the corresponding 2-chloro-2-fluorostyr-
enes (3, Scheme 1).
Table 2. Synthesis of 2-chloro-2-fluoro-1-methylstyrenes 3nϪr from
hydrazones 2nϪr
Ar
Yield 3 [%]
E/Z ratio[a]
4-MeOC6H4, n
4-MeC6H4, o
4-ClC6H4, p
4-BrC6H4, q
4-O2NC6H4, r
32
45
61
52
42
3.6:1
4.1:1
3.7:1
3.0:1
3.0:1
[a]
1
By H NMR spectroscopy.
Scheme 1
Examination of Table 1 and 2 reveals that electronic ef-
fects and steric factors are important for the stereocontrol
These results are given in Table 1. Alkene formation gen- of the reaction. Generally, the E/Z isomer ratio is increased
erally proceeds in moderate to high yield. The COR process for aldehydes bearing electron-donating substituents on the
is compatible with many functional groups, including hy- aromatic ring in comparison to the parent benzaldehyde
droxy-, alkoxy- and nitro-containing systems. Substrates (1g, E/Z ratio 2.8:1).[4] Conversely, electron-withdrawing
containing both electron-donating and electron-with- groups decrease the E/Z ratio. Thus, the worst selectivity
drawing substituents on the aromatic ring could be con- (E/Z ratio 2:1) was obtained for 4-nitrobenzaldehyde (1i).
verted into the target alkenes 3. The corresponding sym- Both ortho- and para-substituents affect the isomeric ratio.
azines (4aϪd) were found to be the only side products of In addition, the reaction is very sensitive to steric factors.
the COR process (Scheme 1) and the total isolated yield of For example, shielding of the carbonyl group combined
products 3 and 4 was usually more than 70%. It was found with the electronic effect of two chlorine atoms as in the
that the nature of the substituents on the aromatic ring af- case of 2,6-dichlorobenzaldehyde (1j) leads to an increase
Eur. J. Org. Chem. 2003, 302Ϫ308
303

V. G. Nenajdenko, A. V. Shastin, V. N. Korotchenko, G. N. Varseev, E. S. Balenkova
FULL PAPER
1
1
Table 3. H, 19F NMR chemical shifts and H-19F coupling constants for 2-chloro-2-fluorostyrenes 3aϪm
Ar
1H chemical shifts[a]
E
19F chemical shifts[b]
3JH,F (Hz)[b]
Z
E
Z
E
Z
4-ClC6H4, a
4-BrC6H4, b
4-MeC6H4, c
4-MeOC6H4, d
4-Me2NC6H4, e
4-IC6H4, f
5.73
5.75
5.70
5.76
5.62
5.74
5.83
5.65
5.93
5.83
6.22
6.24
5.98
6.28
6.31
6.27
6.35
6.22
6.30
6.39
6.23
6.47
6.17
6.56
6.63
6.55
Ϫ73.58
Ϫ73.17
Ϫ75.38
Ϫ77.31
Ϫ79.45
Ϫ72.68
Ϫ74.36
Ϫ77.31
Ϫ68.48
Ϫ66.96
Ϫ74.21
Ϫ75.75
Ϫ74.07
Ϫ70.58
Ϫ70.33
Ϫ72.95
Ϫ74.17
Ϫ76.72
Ϫ70.09
Ϫ71.78
Ϫ74.26
Ϫ65.23
Ϫ72.08
Ϫ70.48
Ϫ71.59
Ϫ71.15
30.4
30.2
30.8
31.1
31.3
30.2
30.7
30.7
29.6
29.3
29.6
31.7
30.4
12.3
12.6
12.9
12.9
13.4
12.3
12.9
12.9
12.3
8.0
C6H5, g
4-HOC6H4, h
4-O2NC6H4, i
2,6-Cl2C6H3, j
2-BrC6H4, k
2-MeOC6H4, l
1-Napht, m
11.5
12.6
12.9
[a] 1H NMR (400 MHz, CDCl3/TMS). [b] 19F NMR (376.29 MHz, CDCl3/CFCl3).
in the E/Z ratio to 10:1. However the steric effects don’t the coupling (3JC,F ϭ 3.7Ϫ4.5 Hz) for the cis isomer is
appear to be consistent and are not yet fully understood. greater than that found for the trans isomer (actually no
The striking feature of the reaction with the hydrazones coupling was obtained here). It should also be noted that
of ketones 2nϪr is the unexpectedly high stereoselectivity the signals of the vinyl fluorine in the E-isomer are shifted
in the formation of the tetrasubstituted alkenes 3nϪr. In upfield by 0.6Ϫ1.2 ppm in the 19F NMR spectra (Table 4),
spite of a seemingly small difference between the steric bulk and the signals of the methyl carbon in the E-isomer are
of the methyl group and that of the aromatic moiety the
formation of tetrasubstituted alkenes 3nϪr proceeds with
significant stereoselectivity and the isomer ratio is greater
than 3:1.
Table 4. 19F chemical shifts for 2-chloro-2-fluoro-1-methylstyrenes
3nϪr
Ar
E isomer[a]
Z isomer[a]
Structural Assignment
1
Selected H and 19F NMR chemical shifts and coupling
4-MeOC6H4, n
4-MeC6H4, o
4-ClC6H4, p
4-BrC6H4, q
4-O2NC6H4, r
Ϫ82.64
Ϫ82.12
Ϫ80.68
Ϫ80.60
Ϫ77.68
Ϫ81.50
Ϫ81.50
Ϫ79.88
Ϫ79.81
Ϫ77.08
constants for the chlorofluoroalkenes 3aϪm are reported in
Table 3. Assignment of the hydrogen atoms in the two iso-
mers was established by the magnitude of their 3JH,F coup-
ling constants. Thus, the trans relationship gives rise to a
larger coupling (about 31 Hz), while the cis coupling is
somewhat smaller (about 12 Hz). The signals from the vinyl
hydrogen atom, H-1Ј, in the E-isomer are shifted upfield
(0.5Ϫ0.6 ppm) in comparison with the Z-isomer. Similarly,
the signals of the vinyl fluorine in the E-isomer are shifted
upfield (3Ϫ4 ppm) in the 19F NMR spectra.
The structure of the isomers of the tetrasubstituted al-
kenes 3nϪr were determined by comparison of the JC,F
coupling constants and the chemical shift of the fluorine
and methyl carbon atoms in the 13C and 19F NMR spectra
(Scheme 2), based on literature data for similar compounds
containing a 1-methyl-2-fluorovinyl fragment.[15]
[a] 19F NMR (376.29 MHz, CDCl3/CFCl3).
shifted downfield by 1.3Ϫ1.5 ppm in the 13C NMR spectra.
We analysed the 19F NMR spectra of alkenes 3aϪr and
found that in the para-substituted alkenes, the chemical
3
shifts of the vinyl fluorine and the JH,F coupling constants
show good linear correlations with Hammett substituent
parameters when the σ values[16] were used (Figure 1 and
2). This has been previously observed in the 19F NMR spec-
tra of fluorinated alkenes ArC(H)ϭC(F)CF2Cl.[4]
3
Mechanism of the Reaction
We found that the reaction with CFCl3 is in good agree-
ment with a previously proposed general mechanism for
this new catalytic olefination reaction (COR).[4,6,7] The first
step of the catalytic cycle is oxidation of hydrazone 2 by
CuII to give the corresponding diazoalkane (Scheme 3).
Subsequent copper-catalyzed decomposition of the diazoal-
kane leads to formation of a copper-carbene complex I with
evolution of nitrogen. Complex I is the key intermediate in
Scheme 2
We found that the values of the cis and trans coupling the reaction.[4,7] Two routes for its transformation have been
constants (4JH,F) in this allylic system are similar. However, found to be possible:[4,7] complex I reacts with CFCl3 to
304
Eur. J. Org. Chem. 2003, 302Ϫ308

A Novel Approach to 2-Chloro-2-fluorostyrenes
FULL PAPER
Figure 1. Dependence of chemical shifts of 19F in 3aϪi from Hammett constants
Figure 2. Dependence of chemical shifts of 19F in 3nϪr from Hammett constants
produce the target alkene 3 regenerating the catalyst (inside
It should be noted that two possible types of alkenes
the cycle), or transformation of I proceeds by reaction with could be formed according to the mechanism of the reac-
the diazoalkane to form the sym-azine 4 (outside the cycle). tion (Scheme 4). Recently we found that both chlorine and
The total yield of the products formed by these routes (al- fluorine atoms can be eliminated from a freon molecule as
kene and azine) is greater than 70% (Table 1). Recently we in the case of CFC-113 (CFCl2-CF2Cl) leading to two types
have investigated in detail the transformations of polyhalog- of alkenes.[4] The expected product of olefination with
enalkanes, CHal2XY, and found that these compounds are CFCl3 (chlorofluoroalkene 3) is formed as a result of elim-
partially reduced under COR conditions (outside ination of the two chlorine atoms from CFCl3. The abnor-
cycle).[3Ϫ6] This process proceeds via two single-electron mal product (dichloroalkene) can be formed as a result of
transfer (SET) steps (Scheme 4). The corresponding re- elimination of one chlorine atom and a fluorine atom.
duced compounds, CHalHXY, were detected in the reaction However the abnormal product was not detected in the
media.[3Ϫ6] In the case of CFCl3, the expected CFCl2H was GCMS spectra. The olefination reaction with CFC-11 pro-
not detected, probably due to its high volatility.[2]
ceeds with excellent chemoselectivity and only normal
Eur. J. Org. Chem. 2003, 302Ϫ308
305

V. G. Nenajdenko, A. V. Shastin, V. N. Korotchenko, G. N. Varseev, E. S. Balenkova
FULL PAPER
quenched with hydrochloric acid (5%, 300 mL). The reaction prod-
ucts were extracted with CH2Cl2 (50 mL ϫ3) and dried over so-
dium sulfate. The CH2Cl2 was evaporated and the residue was puri-
fied by column chromatography. The E- and Z-isomers could not
be separated by column chromatography.
Preparation of 2-Chloro-2-fluoro-1-methylstyrenes 3nϪr: Freshly
purified CuCl[21] (50 mg, 0.5 mmol) and 1,2-ethylenediamine
(1.7 mL) were added to a solution of freshly prepared hydrazone
(5 mmol) in ethanol (25 mL). Then, CFCl3 (0.85 mL, 10 mmol) was
added dropwise, maintaining the temperature at 20 °C by means of
a water bath. The reaction mixture was stirred for 24 h and then
quenched with hydrochloric acid (5%, 300 mL). The reaction prod-
ucts were extracted with CH2Cl2 (50 mL ϫ3) and dried over so-
dium sulfate. The CH2Cl2 was evaporated and the residue was puri-
fied by column chromatography.
Scheme 3
Scheme 4
1
All new compounds gave satisfactory 400 MHz H NMR (CDCl3,
Me4Si), 19F NMR (CDCl3, CFCl3) and 100 MHz 13C NMR
(CDCl3) and IR spectroscopic data. 19F NMR spectroscopic data
for alkenes 3aϪr are reported in Table 3 and 4. The known com-
pounds 3a,[8] 3b,[22] 3c,[8] 3d,[8] 3g[9] were identified by comparison
of physical and spectroscopic data with those previously reported
data.
N-[4-(2-Chloro-2-fluorovinyl)phenyl]-N,N-dimethylamine (3e): This
compound was obtained as a mixture of E and Z isomers (4.2:1
products (alkene 3) were formed. This is in agreement with
the C-Hal bond energy.[16]
after purification); colourless oil (340 mg, 35%); Rf (Hexane/
CH2Cl2 1:1) 0.55.%. IR (Nujol): ν˜ ϭ 1610 cmϪ1 (CϭC). E isomer:
3
1H NMR: δ ϭ 2.89 (s, 6 H, Me), 5.62 (d, JH,F ϭ 31.3 Hz, 1 H,
ϪCHϭ), 6.60 (d, 3JH,H ϭ 9.0 Hz, 2 H, Ar), 7.20 (d, 3JH,H ϭ 9.0 Hz,
Conclusion
1
2 H, Ar) ppm. Z isomer: H NMR: δ ϭ 2.89 (s, 6 H, Me), 6.22 (d,
3
3JH,F ϭ 13.4 Hz, 1 H, ϪCHϭ), 6.62 (d, JH,H ϭ 9.1 Hz, 2 H, Ar),
A new general synthesis of 2-chloro-2-fluorostyrenes and
2-chloro-2-fluoro-1-methylstyrenes based on a COR pro-
cess has been developed. Formation of the target alkenes
proceeds with good stereoselectivity (up to 10:1). The pre-
sented synthetic approach permits synthesis of the target
alkenes in high yield from readily available and inexpensive
starting materials using simple experimental procedures.
7.29 (d, 3JH,H ϭ 9.1 Hz, 2 H, Ar) ppm. For mixture of isomers 13
C
NMR: δ ϭ 40.2 (Me), 106.9 (d, 2JC,F ϭ 26.1 Hz, CHϭ, Z isomer),
2
107.5 (d, JC,F ϭ 11.7 Hz, CHϭ, E isomer), 112.1, 120.2, 128.9,
1
1
139.0 (d, JC,F ϭ 293.5 Hz, CFCl, Z isomer), 141.7 (d, JC,F
ϭ
309.1 Hz, CFCl, E isomer), 149.7 (CϪN) ppm. C10H11ClFN
(199.7): calcd. C 60.16, H 5.55; found C 59.88, H 5.39.
1-(2-Chloro-2-fluorovinyl)-4-iodobenzene (3f): This compound was
obtained as a mixture of E and Z isomers (2.5:1 after purification);
colourless crystals (765 mg, 55%); Ϫ IR (Nujol): ν˜ ϭ 1620 cmϪ1
Experimental Section
1
3
(CϭC). Rf (Hexane) 0.6. E isomer: H NMR: δ ϭ 5.74 (d, JH,F
ϭ
3
30.2 Hz, 1 H, ϪCHϭ), 7.11 (d, JH,H ϭ 8.2 Hz, 2 H, Ar), 7.66 (d,
General Remarks: Melting points were determined in sealed capil-
laries and are uncorrected. NMR spectra were recorded on a
Varian VXR-400 spectrometer in CDCl3 with TMS as an internal
standard. IR spectra were obtained with UR-20 spectrometer. Col-
umn and TLC chromatography was performed on silica gel Merck
60 and Merck 60F254 plates, respectively. Mass-spectra were re-
corded on an HP5890 mass spectrometer with the 5989x-G de-
tector.
3JH,H ϭ 8.2 Hz, 2 H, Ar) ppm. Z isomer: H NMR: δ ϭ 6.30 (d,
1
3JH,F ϭ 12.3 Hz, 1 H, ϪCHϭ), 7.19 (d, JH,H ϭ 8.4 Hz, 2 H, Ar),
3
7.67 (d, 3JH,H ϭ 8.4 Hz, 2 H, Ar) ppm. For mixture of isomers 13
C
NMR: δ ϭ 93.2 (CϪI), 106.4 (d, 2JC,F ϭ 29.0 Hz, CHϭ, Z isomer),
2
106.8 (d, JC,F ϭ 9.2 Hz, CHϭ, E isomer), 129.7, 130.0, 130.6,
1
137.8, 142.1 (d, JC,F ϭ 299.1 Hz, ϭCClF, Z isomer), 145.3 (d,
1JC,F ϭ 312.8 Hz, ϭCClF, E isomer) ppm. C8H5ClF (282.5): calcd.
C 34.01, H 1.78; found C 33.86, H 1.73.
Hydrazones 2a,[3] 2n,[17] 2o,[17] 2p,[18] 2q,[19] 2r[20] were prepared by
the literature procedures.
4-(2-Chloro-2-fluorovinyl)phenol (3h): This compound was obtained
as a mixture of E and Z isomers (3.5:1 after purification); colour-
less oil (466 mg, 54%); Rf (CH2Cl2) 0.5. IR (Nujol): ν˜ ϭ 1615 cmϪ1
(CϭC). E isomer: 1H NMR: δ ϭ 5.53 (s, 1 H, OH), 5.65 (d, 3JH,F ϭ
Preparation of 2-Chloro-2-fluorostyrenes 3aϪm: A solution of the
aromatic aldehyde (5 mmol) in EtOH (20 mL) was added dropwise
to a solution of hydrazine hydrate (5 mmol, 0.25 mL) in EtOH
(5 mL) and the mixture was stirred until all the aldehyde had been
consumed (3 hours, TLC monitoring). Then, freshly purified
3
30.7 Hz, 1 H, ϪCHϭ), 6.72 (d, JH,H ϭ 8.8 Hz, 2 H, Ar), 7.19 (d,
1
3JH,H ϭ 8.8 Hz, 2 H, Ar) ppm. Z isomer: H NMR: δ ϭ 5.53 (s, 1
3
3
H, OH), 6.23 (d, JH,F ϭ 12.9 Hz, 1 H, ϪCHϭ), 6.75 (d, JH,H
ϭ
CuCl[21] (50 mg, 0.5 mmol) and 1,2-ethylenediamine (1.7 mL) were 9.0 Hz, 2 H, Ar), 7.27 (d, JH,H ϭ 9.0 Hz, 2 H, Ar) ppm. For mix-
3
added. After 10 minutes CFCl3 (0.85 mL, 10 mmol) was added ture of isomers 13C NMR: δ ϭ 106.6 (d, JC,F ϭ 29.0 Hz, ϭCH,
2
2
dropwise whilst maintaining the temperature at 20 °C by means of
a water bath. The reaction mixture was stirred for 24 h and
Z isomer), 107.0 (d, JC,F ϭ 10.7 Hz, ϭCH, E isomer), 115.3,
124.7, 129.3, 140.4 (d, 1JC,F ϭ 296.0 Hz, CClF, Z isomer), 143.2 (d,
306
Eur. J. Org. Chem. 2003, 302Ϫ308

A Novel Approach to 2-Chloro-2-fluorostyrenes
FULL PAPER
1JC,F ϭ 309.8 Hz, CClF, E isomer), 154.9 (COH) ppm. C8H6ClFO 128.3, 128.6, 129.5, 143.3 (d, JC,F ϭ 297.6 Hz, CFCl, Z isomer),
(172.6): calcd. C 55.67, H 3.50; found C 55.48, H 3.46.
1
1
144.9 (d, JC,F ϭ 303.7 Hz, CFCl, E isomer) ppm. C12H8ClF
(206.6): calcd. C 69.75, H 3.90; found C 69.53, H 3.77.
1-(2-Chloro-2-fluorovinyl)-4-nitrobenzene (3i): This compound was
obtained as a mixture of E and Z isomers (2:1 after purification);
1-(2-Chloro-2-fluoro-1-methylvinyl)-4-methoxybenzene (3n): This
compound was obtained as a mixture of E and Z isomers (3.6:1
colourless crystals (522 mg, 52%); Rf (Hexane/CH2Cl2 1:1) 0.60. IR
(Nujol): ν˜ ϭ 1610 cmϪ1 (CϭC). E isomer: H NMR: δ ϭ 5.93 (d, after purification); colourless oil (328 mg, 32%); Rf (Hexane) 0.3.
1
3
1
3JH,F ϭ 29.6 Hz, 1 H, ϪCHϭ), 7.53 (d, JH,H ϭ 9.0 Hz, 2 H, Ar), IR (Nujol): ν˜ ϭ 1610 cmϪ1 (CϭC). E isomer: H NMR: δ ϭ 1.98
3
1
4
3
8.19 (d, JH,H ϭ 9.0 Hz, 2 H, Ar) ppm. Z isomer: H NMR: δ ϭ
(d, JH,F ϭ 3.4 Hz, 3 H, Me), 3.69 (s, 3 H, OMe), 6.71 (d, JH,H ϭ
6.47 (d, JH,F ϭ 12.3 Hz, 1 H, ϪCHϭ), 7.63 (d, JH,H ϭ 8.8 Hz, 2 9.0 Hz, 2 H, Ar), 7.14 (d, 3JH,H ϭ 9.0 Hz, 2 H, Ar) ppm. Z isomer:
3
3
3
4
H, Ar), 8.21 (d, JH,H ϭ 8.8 Hz, 2 H, Ar) ppm. For mixture of
1H NMR: δ ϭ 1.98 (d, JH,F ϭ 4.2 Hz, 3 H, Me), 3.70 (s, 3 H,
3
3
isomers 13C NMR: δ ϭ 105.9 (d, 2JC,F ϭ 10.4 Hz, CHϭ, Z isomer),
OMe), 6.72 (d, JH,H ϭ 8.8 Hz, 2 H, Ar), 7.09 (d, JH,H ϭ 8.8 Hz,
106.3 (d, JC,F ϭ 10.4 Hz, CHϭ, E isomer), 124.0, 128.6, 128.9, 2 H, Ar) ppm. For mixture of isomers 13C NMR: δ ϭ 15.1 (d,
2
138.3 (CNO2), 147.5 (d, 1JC,F ϭ 315.0 Hz, ϭCFCl, E isomer) ppm. 3JC,F ϭ 3.7 Hz, Me, Z isomer), 16.5 (Me, E isomer), 52.6 (MeO),
2
C8H5ClFNO2 (201.6): calcd. C 47.67, H 2.50; found C 47.81, H 94.1, 110.9 (d, JC,F ϭ 12.7 Hz, ϪCϭ, E isomer), 111.6, 126.7,
1
1
2.63.
138.4 (d, JC,F ϭ 297.0 Hz, CFCl, Z isomer), 138.5 (d, JC,F ϭ
300.0 Hz, CFCl, E isomer) ppm. C10H10ClFO (200.6): calcd. C
59.86, H 5.02; found C 59.68, H 5.14.
1,3-Dichloro-2-(2-chloro-2-fluorovinyl)benzene (3j): This compound
was obtained as a mixture of E and Z isomers (10:1 after purifica-
tion); colourless oil (765 mg, 68%); Rf (Hexane) 0.6. IR (Nujol): 1-(2-Chloro-2-fluoro-1-methylvinyl)-4-methylbenzene (3o): This
1
3
ν˜ ϭ 1610 cmϪ1 (CϭC). E isomer: H NMR: δ ϭ 5.83 (d, JH,F
ϭ
compound was obtained as a mixture of E and Z isomers (4.1:1
3
29.3 Hz, 1 H, ϪCHϭ), 7.19 (t, JH,H ϭ 8.5 Hz, 1 H, Ar), 7.32 (d, after purification); colourless oil (410 mg, 45%); Rf (Hexane) 0.7.
3JH,H ϭ 8.5 Hz, 2 H, Ar) ppm. Z isomer: H NMR: δ ϭ 6.17 (d, IR (Nujol): ν˜ ϭ 1615 cmϪ1 (CϭC). E isomer: H NMR: δ ϭ 1.95
1
1
3JH,F ϭ 8.0 Hz, 1 H, ϪCHϭ), 7.18 (t, JH,H ϭ 8.3 Hz, 1 H, Ar), (d, JH,F ϭ 3.2 Hz, 3 H, ϭC-Me), 2.22 (s, 3 H, Me), 6.97 (d,
3
4
7.27 (d, 3JH,H ϭ 8.3 Hz, 2 H, Ar) ppm. For mixture of isomers 13
C
3JH,H ϭ 8.3 Hz, 2 H, Ar), 7.08 (d, JH,H ϭ 8.3 Hz, 2 H, Ar) ppm.
3
2
1
4
NMR: δ ϭ 102.3 (d, JC,F ϭ 15.3 Hz, CHϭ, E isomer), 127.9, Z isomer: H NMR: δ ϭ 1.92 (d, JH,F ϭ 4.5 Hz, 3 H, ϭC-Me),
1
3
128.0, 129.6, 135.2, 145.8 (d, JC,F ϭ 311.3 Hz, CFCl, E isomer)
2.23 (s, 3 H, Me), 6.97 (d, JH,H ϭ 8.3 Hz, 2 H, Ar), 7.04 (d,
ppm. C8H4Cl3F (225.5): calcd. C 42.61, H 1.79; found C 42.46, 3JH,H ϭ 8.3 Hz, 2 H, Ar) ppm. For mixture of isomers 13C NMR:
3
H 1.76.
δ ϭ 15.1 (d, JC,F ϭ 4.5 Hz, Me-Cϭ, Z isomer) 16.4 (Me-Cϭ, E
isomer), 19.1 (Me-Ar), 110.6 (d, 2JC,F ϭ 12.7 Hz, ϪCϭ, E isomer),
1-Bromo-2-(2-chloro-2-fluorovinyl)benzene (3k): This compound
was obtained as a mixture of E and Z isomers (2.7:1 after purifica-
tion); colourless oil (947 mg, 81%); Rf (Hexane) 0.55. IR (Nujol):
2
112.0 (d, JC,F ϭ 20.2 Hz, ϪCϭ, Z isomer), 125.6, 126.0, 126.8,
1
131.3, 138.4 (d, JC,F ϭ 297.7 Hz, CFCl, Z isomer), 138.9 (d,
1JC,F ϭ 300.0 Hz, CFCl, E isomer) ppm. C10H10ClF (184.6): calcd.
1
3
ν˜ ϭ 1620 cmϪ1 (CϭC). E isomer: H NMR: δ ϭ 6.22 (d, JH,F
ϭ
C 65.05, H 5.46; found C 64.89, H 5.37.
1
29.6 Hz, 1 H, ϪCHϭ), 7.26Ϫ7.34 (m, 4 H, Ar) ppm. Z isomer: H
3
NMR: δ ϭ 6.56 (d, JH,F ϭ 11.5 Hz, 1 H, ϪCHϭ), 7.26Ϫ7.34 (m, 1-Chloro-4-(2-chloro-2-fluoro-1-methylvinyl)benzene (3p): This com-
4 H, Ar) ppm. For mixture of isomers 13C NMR: δ ϭ 106.4 (d,
pound was obtained as a mixture of E and Z isomers (3.7:1 after
2JC,F ϭ 9.1 Hz, CHϭ, E isomer), 122.9, 124.3 (ϭCBr), 127.5, purification); colourless oil (580 mg, 61%); Rf (Hexane) 0.65. IR
129.1, 129.9, 132.9, 145.9 (d, JC,F ϭ 313.0 Hz, CFCl, E isomer), (Nujol): ν˜ ϭ 1610 cmϪ1 (CϭC). E isomer: 1H NMR: δ ϭ 2.00
1
1
143.2 (d, JC,F ϭ 300.0 Hz, CFCl, Z isomer) ppm. C8H5BrClF
(235.5): calcd. C 40.80, H 2.14; found C 40.54, H 2.03.
(4JH,F ϭ 3.2 Hz, 3 H, Me), 7.15Ϫ7.28 (m, 4 H, Ar) ppm. Z isomer:
1H NMR: δ ϭ 1.98 (4JH,F ϭ 4.1 Hz, 3 H, Me), 7.15Ϫ7.28 (m, 4
H, Ar) ppm. For mixture of isomers 13C NMR: δ ϭ 17.0 (d,
3JC,F ϭ 3.9 Hz, Me, Z isomer), 18.4 (Me, E isomer), 112.1 (d,
1-(2-Chloro-2-fluorovinyl)-2-methoxybenzene (3l): This compound
was obtained as a mixture of E and Z isomers (3.2:1 after purifica-
tion); colourless oil (568 mg, 61%); Rf (Hexane) 0.20. IR (Nujol):
ν˜ ϭ 1615 cmϪ1 (CϭC). E isomer: 1H NMR: δ ϭ 3.82 (s, 3 H,
2JC,F ϭ 11.7 Hz, ϪCϭ, E isomer), 113.5 (d, 2JC,F ϭ 20.9 Hz, ϪCϭ
1
, Z isomer), 128.5, 129.1, 129.6 (CCl), 133.4, 140.8 (d, JC,F
ϭ
1
298.7 Hz, CFCl, Z isomer), 141.6 (d, JC,F ϭ 300.0 Hz, CFCl, E
isomer) ppm. C9H7Cl2F (205.1): calcd. C 52.72, H 3.44; found C
52.61, H 3.32.
3
MeO), 6.24 (d, JH,F ϭ 31.7 Hz, 1 H, ϪCHϭ), 6.8Ϫ7.6 (m, 4 H,
Ar) ppm. Z isomer: 1H NMR: δ ϭ 3.82 (s, 3 H, MeO), 6.63 (d,
3JH,F ϭ 12.6 Hz, 1 H, ϪCHϭ), 6.85Ϫ7.53 (m, 4 H, Ar) ppm. For
mixture of isomers 13C NMR: δ ϭ 55.4 (MeO), 101.5 (d, JC,F
ϭ
1-Bromo-4-(2-chloro-2-fluoro-1-methylvinyl)benzene (3q): This com-
pound was obtained as a mixture of E and Z isomers 3.0:1 (after
2
2
11.7 Hz, CHϭ, Z isomer), 101.5 (d, JC,F ϭ 9.1 Hz, CHϭ, E iso-
1
mer), 103.9, 110.4, 110.5, 120.7, 129.0, 141.7 (d, JC,F ϭ 297.4 Hz, purification); colourless oil (643 mg, 52%); Rf (Hexane) 0.65. IR
CFCl, Z isomer), 144.3 (d, JC,F ϭ 311.7 Hz, CFCl, E isomer), (Nujol): ν˜ ϭ 1610 cmϪ1 (CϭC). E isomer: H NMR: δ ϭ 1.99 (d,
1
1
3
155.8 (COMe) ppm. C9H8ClFO (186.6): calcd. C 57.93, H 4.32;
4JH,F ϭ 3.9 Hz, 3 H, Me), 7.11 (d, JH,H ϭ 7.8 Hz, 2 H, Ar), 7.36
3
1
found C 58.20, H 4.17.
(d, JH,H ϭ 7.8 Hz, 2 H, Ar) ppm. Z isomer: H NMR: δ ϭ 1.98
4
3
(d, JH,F ϭ 4.9 Hz, 3 H, Me), 7.07 (d, JH,H ϭ 7.8 Hz, 2 H, Ar),
2-(2-Chloro-2-fluorovinyl)naphthalene (3m): This compound was
obtained as a mixture of E and Z isomers (5:1 after purification);
colourless oil (591 mg, 57%); Rf (Hexane) 0.6. IR (Nujol): ν˜ ϭ 1620
7.37 (d, 3JH,H ϭ 7.8 Hz, 2 H, Ar) ppm. For mixture of isomers 13
C
3
NMR: δ ϭ 14.9 (d, JC,F ϭ 3.7 Hz, Me, Z isomer), 16.3 (Me, E
2
isomer), 109.7 (d, JC,F ϭ 12.7 Hz, ϪCϭ, E isomer), 111.3 (d,
cmϪ1 (CϭC). E isomer: H NMR: δ ϭ 5.98 (d, JH,F ϭ 30.4 Hz, 1
1
3
2JC,F ϭ 30.0 Hz, ϪCϭ, Z isomer), 127.2, 127.6, 129.4, 132.8, 138.8
H, ϪCHϭ), 7.45Ϫ7.58 (m, 3 H, Napht), 7.78Ϫ7.84 (m, 4 H,
(d, 1JC,F ϭ 298.5 Hz, CFCl, Z isomer), 139.6 (d, JC,F ϭ 301.5 Hz,
1
1
3
Napht) ppm. Z isomer: H NMR: δ ϭ 6.55 (d, JH,F ϭ 12.9 Hz, 1
H, ϪCHϭ), 7.45Ϫ7.58 (m, 3 H, Napht), 7.78Ϫ7.84 (m, 4 H,
Napht) ppm. For mixture of isomers 13C NMR: δ ϭ 107.5 (d,
CFCl, E isomer) ppm. C9H7BrClF (249.5): calcd. C 43.32, H 2.83;
found C 43.16, H 2.75.
2JC,F ϭ 12.2 Hz, -CHϭ, Z isomer), 107.8 (d, JC,F ϭ 12.2 Hz, -
1-(2-Chloro-2-fluoro-1-methylvinyl)-4-nitrobenzene (3r): This com-
pound was obtained as a mixture of E-Z isomers 3.0:1 (after puri-
2
CHϭ, E isomer), 125.5, 125.6, 127.0, 127.3, 127.6. 128.0, 128.1,
Eur. J. Org. Chem. 2003, 302Ϫ308
307

V. G. Nenajdenko, A. V. Shastin, V. N. Korotchenko, G. N. Varseev, E. S. Balenkova
FULL PAPER
[6]
A. V. Shastin, V. N. Korotchenko, V. G. Nenajdenko, E. S. Ba-
lenkova, Synthesis 2001, 2081Ϫ2084.
fication); slight yellow oil (447 mg, 42%); Rf (Hexane) 0.15. IR
(Nujol): ν˜ ϭ 1615 cmϪ1 (CϭC). E isomer: 1H NMR: δ ϭ 2.12
[7]
[8]
V. N. Korotchenko, A. V. Shastin, V. G. Nenajdenko, E. S. Ba-
lenkova, J. Chem. Soc., Perkin Trans. 1 2002, 883Ϫ887.
T. Ando, F. Namigata, M. Kataoka, K. Yachida, W. Funasaka,
Bull. Chem. Soc. Japan 1967, 40, 1275Ϫ1278.
D. J. Burton, H. C. Krutzsch, J. Org. Chem. 1970, 35,
2125Ϫ2130.
D. J. Burton, H. C. Krutzsch, J. Org. Chem. 1971, 36,
2351Ϫ2354.
M. J. Van Hamme, D. J. Burton, J. Fluorine Chem. 1977, 10,
131.
(4JH,F ϭ 3.3 Hz, 3 H, Me), 7.51 (d, JH,H ϭ 9.1 Hz, 2 H, Ar), 8.19
3
3
1
(d, JH,H ϭ 9.1 Hz, 2 H, Ar) ppm. Z isomer: H NMR: δ ϭ 2.09
(4JH,F ϭ 4.1 Hz, 3 H, Me), 7.48 (d, 3JH,H ϭ 11.6 Hz, 2 H, Ar), 8.19
(d, JH,H ϭ 11.6 Hz, 2 H, Ar) ppm. For mixture of isomers 13C
3
[9]
NMR: δ ϭ (100 MHz, CDCl3; Me4Si) 17.2 (d, 3JC,F ϭ 3.7 Hz, Me,
2
[10]
[11]
[12]
[13]
[14]
[15]
[16]
Z isomer), 18.5 (Me, Z isomer), 113.1 (d, JC,F ϭ 12.7 Hz, ϪCϭ,
E isomer), 114.3 (d, JC,F ϭ 26.0 Hz, ϪCϭ, Z isomer), 125.5,
131.1, 131.6, 140.8 (d, JC,F ϭ 298.9 Hz, CFCl, Z isomer), 141.6
(d, JC,F ϭ 300.5 Hz, CFCl, E isomer), 147.5 (CϪNO2) ppm.
C9H7ClFNO2 (215.6): calcd. C 50.14, H 3.27; found C 50.01, H
3.14.
2
1
1
M. J. Van Hamme, D. J. Burton, J. Organomet. Chem. 1979,
169, 123Ϫ139.
C. Chen, K. Wilcoxen, N. Strack, J. R. McCarthy, Tetrahedron
Lett. 1999, 40, 827Ϫ830.
V. G. Nenajdenko, V. Shastin, V. N. Korotchenko, E. S. Balen-
kova, Russ. Chem. Bull. 2001, 50, 1047Ϫ1050.
C. Chen, K. Wilcoxen, Y.-F. Zhu, K. Kim, J. R. McCarthy, J.
Org. Chem. 1999, 64, 3476Ϫ3482.
The Chemist’s Companion (Eds.: A. J. Gordon, R. A. Ford),
John Wiley & Sons, New York, 1972.
G. Lock, K. Stach, Chem. Ber. 1944/46, 77/79, 293.
D. E. Pearson, K. N. Carter, C. M. Greer, J. Am. Chem. Soc.
1953, 75, 5905.
H. F. Harnsberger, E. L. Cochran, H. H. Szmant, J. Am. Chem.
Soc. 1955, 77, 5048.
G. R. Newcome, D. L. Fishel, J. Org. Chem. 1966, 31,
677Ϫ679.
D. D. Perrin, W. L. F. Armaredo, Purification of laboratory
chemicals. Pergamon Press, New York, 1988, 322.
D. G. Naae, J. Org. Chem. 1980, 44, 1394Ϫ1401.
Received August 5, 2002
Acknowledgments
Financial support from the Russian Foundation for Basic Research
(Grant nos. 00-03-32760, 00-03-32763 and 02-03-06142) is grate-
fully acknowledged.
[17]
[18]
[1]
Chemistry of Organic Fluorine Compounds II (Eds.: M. Hud-
licky, A. E. Pavlath), American Chemical Society, Washington,
[19]
[20]
[21]
[22]
DC, 1995.
[2]
Fluorine Chemistry: A Comprehensive Treatment (Ed.: M.
Howe-Grant), John Wiley & Sons, New York, 1995.
A. V. Shastin, V. N. Korotchenko, V. G. Nenajdenko, E. S. Ba-
[3]
lenkova, Tetrahedron 2000, 56, 6557Ϫ6563.
[4]
V. N. Korotchenko, A. V. Shastin, V. G. Nenajdenko, E. S. Ba-
lenkova, Tetrahedron 2001, 57, 7519Ϫ7527.
[5]
A. V. Shastin, V. N. Korotchenko, V. G. Nenajdenko, E. S. Ba-
lenkova, Russ. Chem. Bull. 2001, 50, 1401Ϫ1404.
[O02445]
308
Eur. J. Org. Chem. 2003, 302Ϫ308