Synthesis and Diels-Alder reactions of α-fluoro- and α-trifluoromethylacrylonitriles

Article abstract of DOI:10.1016/j.jfluchem.2007.02.014

A novel synthetic method for the preparation of α-fluoro- and the still unknown α-trifluoromethylacrylonitriles is elaborated. The reaction of α-fluorovinylbromides and α-trifluoromethylvinylbromides with CuCN leads to the title compounds in good to high yields. While the α-fluoroacrylonitriles were isolated as mixture of Z/E-isomers, the α-trifluoromethylacrylonitriles were obtained as pure Z-isomers. The α-trifluoromethylacrylonitriles are shown to be excellent dienophiles for Diels-Alder reactions.

Full text of DOI:10.1016/j.jfluchem.2007.02.014

Journal of Fluorine Chemistry 128 (2007) 818–826
www.elsevier.com/locate/fluor
Synthesis and Diels–Alder reactions of a-fluoro- and
a-trifluoromethylacrylonitriles
a
b
Valentine G. Nenajdenko a, , Vasiliy M. Muzalevskiy , Aleksey V. Shastin ,
*
Elizabeth S. Balenkova a, Gu¨nter Haufe c,
*
a Moscow State University, Department of Chemistry, Leninskie Gory, Moscow 119992, Russia
b Institute of Problems of Chemical Physics, Chernogolovka, Moscow Region 142432, Russia
¨ ¨ ¨ ¨
Organisch-Chemisches Institut, Westfalische Wilhelms-Universitat Munster, D-48149 Munster, Germany
c
Received 14 February 2007; received in revised form 21 February 2007; accepted 21 February 2007
Available online 25 February 2007
Abstract
A novel synthetic method for the preparation of a-fluoro- and the still unknown a-trifluoromethylacrylonitriles is elaborated. The reaction of a-
fluorovinylbromides and a-trifluoromethylvinylbromides with CuCN leads to the title compounds in good to high yields. While the a-
fluoroacrylonitriles were isolated as mixture of Z/E-isomers, the a-trifluoromethylacrylonitriles were obtained as pure Z-isomers. The a-
trifluoromethylacrylonitriles are shown to be excellent dienophiles for Diels–Alder reactions.
# 2007 Elsevier B.V. All rights reserved.
Keywords: Catalytic olefination reaction; Substitution with CuCN; a-Fluoroacrylonitriles; a-Trifluoromethylacrylonitriles; Diels–Alder reaction
1. Introduction
alkenes. Based on COR we elaborated a novel approach
to synthesis of b,b-chlorofluorostyrenes ArC(H) C(Cl)F [20],
b,b-chloro(trifluoromethyl)styrenes ArC(H) C(Cl)CF3, b,b-
fluoro(chlorodifluoromethyl)styrenes ArC(H) C(F)CF2Cl [21],
gem-difluoroalkenes [22], b,b-fluoro(bromodifluoromethyl)-
styrenes ArC(H) C(F)CF2Br [23], b,b-bromo(trifluoromethyl)-
styrenes ArC(H) C(Br)CF3 [24] and b,b-bromofluorostyrenes
ArC(H) C(Br)F [25].
Fluorine-containing drugs and pesticides are an object of
increasing interest in modern bioorganic chemistry due to their
remarkable biological activity [1–5]. Extensive studies have
been made to develop a cheap and efficient synthetic
methodology for the synthesis of various organofluorine
compounds [6–9]. Biologically active molecules containing a
vinylic fluorine atom are of special interest, in part, because
fluoroolefins are potential enzyme inhibitors [10] and can be
used as an isosteric replacement for an amido group in peptides
[11–13] or aminoacids [14].
The advantages of the proposed method over existent
methods like Burton’s Wittig-type conversion of benzaldehydes
[26,27] are the inexpensive starting materials, convenient
reaction conditions and smooth handling of the products. Also
utilizing of excess of metalloorganic or organophosphorous
compounds is not required. b,b-Bromo(trifluoromethyl)styr-
enes and b,b-bromofluorostyrenes are of special interest
because of rather labile bromine–carbon bond, which opens
a pathway for direct substitution reactions with different
nucleophiles. As result various alkenes can be prepared.
It should be very interesting to replace bromine by a cyano
group, because it could open a new route to a-fluoroacryloni-
triles and the still unknown a-trifluoromethylacrylonitriles. The
electron-deficient double bond of this class of compounds
might be useful for both the Michael addition [28], and the
Diels–Alder reaction [29]. Also the nitrile function might be
Recently, we reported a novel catalytic olefination reaction
(COR) of aldehydes and ketones [15–23]. It was found that N-
unsubstituted hydrazones of carbonyl compounds can be
smoothly transformed into various substituted alkenes by
treatment with polyhalogenoalkanes in the presence of catalytic
amounts of CuCl. It was also shown that COR can be
successfully used for synthesis of different fluorocontaining
* Corresponding author.
E-mail addresses: nen@acylium.chem.msu.ru (V.G. Nenajdenko),
shastin@icp.ac.ru (A.V. Shastin), haufe@uni-muenster.de (G. Haufe).
0022-1139/$ – see front matter # 2007 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2007.02.014

V.G. Nenajdenko et al. / Journal of Fluorine Chemistry 128 (2007) 818–826
819
reaction conditions, we studied the synthetic scope of the
method for the preparation of a-fluoroacrylonitriles and
a-(trifluoromethyl)acrylonitriles. It was shown, that a wide
variety of aromatic vinyl bromides containing both electron
donating and electron-withdrawing substituents at the aromatic
ring 1, 2a–1, 2i can be converted to the corresponding a-fluoro-
3 and a-trifluoromethylacrylonitriles 4 (Scheme 1, Table 1).
Aliphatic a-fluoroacrylonitriles also could be obtained by
this method (see 3k). Unfortunately in case of the heptyl
substituted aliphatic a-(trifluoromethyl)acrylonitrile only
traces of the desired product 4k were obtained. The
stereoselectivity of the reaction of bromofluoroalkenes with
CuCN was quite good and alkenes 3 were obtained as mixtures
of Z/E-isomers in which the Z-isomers dominate. The ratio of Z/
E-isomers of a-fluoroacrylonitriles 3 was almost the same like
in the initial vinylbromides. In case of the 2-bromo-2-
(trifluoromethyl)styrenes 2 the reaction proceeds 100 %
stereoselectively and the E-isomers of the a-(trifluoromethy-
l)acrylonitriles were obtained as the sole products, although the
initial styrenes 2 were used as a mixture of Z/E-isomers
(Table 1).
Scheme 1. Reaction of a-fluoro- and a-trifluoromethyl vinylbromides with
copper(I) cyanide.
converted into an ester through the Pinner reaction [30], or into
an aldehyde by reduction with diisobutylaluminum hydride
(DIBALH) and hydrolysis [31,32].
Different synthetic approaches have been proposed for
synthesis of 2-fluoroacrylonitriles [28,31,32–36]. The most
general route is based on the Horner–Wadsworth–Emmons
(HWE) reaction of a cyanofluoromethyl-substituted phospho-
nate with carbonyl compounds [31,32,36,37]. But usually, these
reactions proceed with low stereoselectivity and require
utilization of absolute solvents, organometallic and toxic
organophosphorous compounds.
The structure of isomers was determined by NMR spectro-
scopy. It is well known, that coupling constants between atoms
at double bond in cis-position are smaller than in trans-position.
The configuration of isomers was doubtlessly determined by
2. Results and discussion
2.1. Synthesis of 2-fluoro- and 2-
trifluoromethylacrylonitriles
3
comparison of coupling constants JH,F between fluorine and
1
the vinylic proton in H NMR spectra of fluoroalkenes 3 (for
3
values of JH,F constants see Section 4).
The reaction of bromoarenes with CuCN is well known and
it is one of most powerful methods for preparation of aromatic
nitriles [38]. It was also reported, that substitution of the
bromine atom in vinylbromides is possible under the conditions
of this reaction. [39]. At the beginning, we investigated the
reaction of 1-(2-bromo-2-fluorovinyl)-4-chlorobenzene with
CuCN in DMF at 90 to 120 8C. But at these temperatures
reaction proceeded very slow. On the other hand, strong sudden
tarring was observed after 5–6 h at this temperature. However,
heating at 150–155 8C led to complete conversion of
bromofluorostyrene giving the target nitrile in 82% yield
during 3 h. It should be noted, that in the case of longer reaction
times the yield dropped down because of decomposition. We
also found, that these conditions are suitable for the conversion
of 1-(2-bromo-2-trifluoromethylvinyl)-4-chlorobenzene to the
corresponding nitrile in good yield. Using these optimized
To determine the configuration of the a-(trifluoromethyl)a-
crylonitriles, the 13C NMR spectrum for compound 4b was
recorded without proton decoupling and the spin–spin coupling
constants between the nitrile C atom and the trifluoromethyl C
atom with the proton at the double bond were measured. We
3
found that the JH,C constant of nitrile group is 13.8 Hz and
3JH,C constant of trifluromethyl group is 7.4 Hz. Consequently,
proton and nitrile group are in trans-position and compounds 4
have E-configuration.
2.2. Diels–Alder reactions of 2-fluoro- and 2-
trifluoromethylacrylonitriles
The Diels–Alder reaction is the most attractive approach for
the synthesis of selectively fluorinated mono- or polycyclic
Table 1
Synthesis of nitriles 3 and 4
R
E/Z ratio, 1 [25]
Z/E ratio, 2 [24]
Z/E ratio, 3 (%)
Yield of 3
Yield of 4 (%)
a
a
b
c
d
e
f
g
h
i
4-NO2C6H4–
4-ClC6H4–
3.5
6
3.4
4.3
4
83
82
70
89
70
81
79
47
64
54
–
7.5
7.0
8.4
8.2
4.8
7.9
8.2
8.7
–
75
Ph
6.2
5
72
4-MeOC6H4–
3,4-MeOC6H3–
4-CO2MeC6H4–
2-MeOC6H4–
2-NO2C6H4–
4-MeC6H4–
5.4
6.3
3.2
3.9
3.5
2.4
0.8
85
4.5
3.5
3.6
3.3
5.5
0.9
70
58
82
62
67
k
n-C7H15
–
Traces
a
Reaction was not carried out.

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V.G. Nenajdenko et al. / Journal of Fluorine Chemistry 128 (2007) 818–826
Scheme 2. Reactions of cyclopentadiene with a-trifluoromethylacrylonitriles.
Fig. 1. Coupling constants of compounds 7c and 8c.
Scheme 3. Reaction of nitrile 4b with 2,3-dimethylbutadiene.
cyclohexene derivatives [40,41]. This type of reactions has been
shown to be of particular interest in syntheses of fluorinated
analogues of biologically active compounds such as canthar-
idin, endothall [42] and D-homosteroids [43]. Previously, we
found that simple vinyl fluorides such as a- or b-fluorostyrenes
are weak dienophiles which only react with very active dienes
like diphenylisobenzofuran [44,45] or some fluorinated
cyclohexa-2,4-dienones [46]. Electron-withdrawing substitu-
ents such as carbonyl functions, sulfoxide or sulfonyl groups
attached to the fluorovinyl moiety increase the reactivity of the
dienophiles. Therefore, 2-fluoroacroleins [47,48], a,b-unsatu-
rated a-fluorocarboxylic acid derivatives [49–54], and unsa-
turated a,b-difluoroketones [55,56], b-fluoroalkylated enones
[57], fluorinated furan-2(5H)-ones [58], fluorinated vinylsul-
fones [59,60] or an electron-poor fluorinated vinyl sulfoxide
[61] were shown to be moderate or good dienophiles.
group we observed almost complete consumption of starting
material after heating to 150 8C for 5 h, but not any of the
products could be isolated because of decomposition. Even at
lower temperature the product mixture decomposed. In case of
the less reactive nitrile 3b reaction proceeded very slow
yielding inseparable mixture of target compound with several
products.
Furane, 1,3-cyclohexadiene, 2,3-dimethylbutadiene and
Danishefsky’s diene were also tested in Diels–Alder reaction
under similar conditions. While the nitrile 4b did not react with
the less reactive furane and 1,3-cyclohexadiene, the reaction
with 2,3-dimethylbutadiene gave the desired cyclohexene 6b in
moderate yield (Scheme 3).
Danishefsky’s diene, which is well-known as a strong
diene, reacted smoothly with the CF3-nitriles, giving
only one regioisomer of the corresponding ketones as
mixtures of diasteremers 7 and 8 in approximately 2:1 ratio
(Scheme 4).
So, we decided to use prepared nitriles for Diels–Alder
reactions. First, we investigated reactions of a-trifluoromethy-
lacrylonitriles 4 with cyclopentadiene and found, that rather
high temperature is needed for this reaction. The nitrile 4b was
completely converted to Diels–Alder adduct 5b with excellent
yield by heating to 130 8C without solvent for 16 h (Scheme 2).
In case of the less electron-deficient nitriles 4c and 4d
150 8C, 24 or 72 h, respectively, were required for full
consumption of the starting material. Unfortunately, the
increased reaction temperature and time lead to low yields
of target products. So, the adduct 5c was obtained only in 32%
yield and the adduct of nitrile 4d with cyclopentadiene could
not be isolated in pure form because of the complex mixture of
unknown byproducts. Reaction proceeded non-stereoselec-
tively with 4b,c giving an 1:1 the mixture of endo/exo adducts
in both cases.
The regio and stereochemistry of the products 7 and 8 was
assigned 1H NMR spectroscopically, particularly by the
multiplicity of the protons neighboring the methoxy group
or the phenyl group, respectively. For compound 7c we
observed the latter signal at 3.31 ppm as a doublet of doublets
3
with JHH = 14.2 Hz and 3.4 Hz. The signal for 8c is not
resolved. Also the H atom neighboring the methoxy group is
indicative. These signals appear for compound 7c as doublet of
3
doublets with JHH = 8.5 and 4.9 Hz at 3.97 ppm and for the
minor isomer 8c as a triplet with 3JHH = 2.9 Hz at 4.33 ppm (see
Fig. 1). The alternative regioisomers would have more complex
signals. It should be also noted, that the 1H NMR spectrum of
diastereomer 7c is in good agreement with the spectrum of
diastereomer with the same configuration of close analogous
adduct of Danishefsky’s diene with methyl (E)-2-cyanocinna-
mate [62].
Next, we tried to react a-fluoroacrylonitriles 3 with
cyclopentadiene. For the most reactive nitrile 3a with nitro
Scheme 4. Reactions of Danishefsky’s diene with a-trifluoromethylacrylonitriles.

V.G. Nenajdenko et al. / Journal of Fluorine Chemistry 128 (2007) 818–826
821
3. Conclusions
DMSO (2 mmol, 2 ml) and the mixture was stirred until
aldehyde disappeared (3 h, TLC monitoring). Then freshly
purified CuCl 20 mg (0.2 mmol) and aqueous ammonia
(0.7 ml) were added. After 10 min a solution of CBr3CF3
(1.93 g, 6 mmol) in DMSO (2 ml) was added dropwise,
maintaining the temperature at 20 8C (water bath). The reaction
mixture was stirred for 24 h and quenched with hydrochloric
acid (5%) (100 ml). Reaction products were extracted with
CH2Cl2 (3 Â 20 ml). Extracts were dried over sodium sulfate,
CH2Cl2 was evaporated and the residue was purified by column
chromatography. E- and Z-isomers mixture of alkenes could not
be separated by column chromatography.
We discovered a novel approach to the synthesis of a-fluoro-
and a-trifluoromethylacrylonitriles by direct nucleophilic
substitution of bromine with copper(I) cyanide of fluorinated
bromostyrenes. These reactions proceed stereoselectively in
good to high yields. In case of the a-trifluoromethylacryloni-
triles the reaction proceeds 100% stereoselectively and only the
isomers with E-configuration were obtained. It should be noted,
that a-trifluoromethylacrylonitriles were synthesized for the
first time. The presence of strong electron-withdrawing groups
at the double bond of these molecules opens the possibility for
both Michael additions, and Diels–Alder reactions. It was
shown, that 2-trifluoromethylacrylonitriles do react with active
dienes, like cyclopentadiene, 2,3-dimethylbutadien and
Danishefsky’s diene as dienophiles giving the desired
cycloadducts in high yields as a mixture of diastereomers.
The b-fluoroacrylonitriles 3 were shown to be not useful as
dienophiles in Diels–Alder reaction with the mentioned dienes.
4.3. General procedure for the synthesis of the nitriles 3
and 4
One-neck round bottom 25 ml flask was charged with
5 mmol of corresponding bromostyrene, 0.54 g (6 mmol)
CuCN, 3 ml dry DMF and flushed with argon. Reaction
mixture was heated with reflux condenser at 150–155 8C for 3–
4 h (TLC control). After cooling down to room temperature
20 ml of dichloromethane and 100 ml of water were added.
Formed precipitate of copper salts was filtered off and washed
twice with 20 ml of dichloromethane. Organic phase was
separated; water phase was extracted with 2 Â 20 ml of
dichloromethane. Joint extract was washed with water, brine
and dried over sodium sulfate. After evaporation of the solvent,
the residue was chromatographed on a column with silica gel
(using appropriate mixture of hexane/dichloromethane 2-1 as
the eluent) to afford the corresponding nitriles. E- and Z-
isomers mixture of alkenes could not be separated by column
chromatography.
4. Experimental
NMR spectra were recorded on Bruker ARX 300, Bruker
AMX 400 and Varian Inova 500 MHz spectrometers in CDCl3
with TMS and CCl3F as an internal standards. IR spectra were
obtained with UR-20 spectrometer. Mass spectra (ESI-MS)
were measured on a MicroTof Bruker Daltinics. Column and
TLC chromatography was performed on silica gel Merck 60
and Merck 60F254 plates, respectively. Bromofluorostyrenes
and bromotrifluorostyrenes were synthesized according to
previously reported procedures [24,25]. All dienes were
distillated before using.
1H NMR and 13C NMR spectra of compounds (3b, 3c, 3i)
are in agreement with published data [36].
4.1. General procedure for the synthesis of the b-bromo-b-
fluorostyrenes 1
4.3.1. 2-Fluoro-3-(4-nitrophenyl)acrylonitrile (3a)
A solution of 2 mmol of the corresponding aldehyde in 8 ml
ethanolwasaddeddropwisetothesolutionof0.11 ml(2.1 mmol)
hydrazine hydrate in 4 ml of ethanol with intensive stirring. After
completion of hydrazone formation (TLC monitoring) 0.2 ml
(1.5 eq.) of ethylenediamine and 0.002 g (1 mol%) of CuCl were
added. The reaction mixture was cooled to 0 8C and 0.3 ml (1.5
eq.) CBr3F was added dropwise with stirring. The reaction
mixture was stirred for 4–48 h at room temperature to the
completion (TLC monitoring) and 50 ml 5% aq. HCl was added
(in the cases of pyridine-2-carbaldehyde only water was added).
The reaction products were extracted with CH2Cl2 (3 Â 30 ml)
and extract was dried with Na2SO4. The solvent was evaporated
and the residue was purified by column chromatography on SiO2
(hexane-CH2Cl2 mixture as eluent). The E- and Z-isomers could
not be separated by column chromatography.
A mixture of Z/E-isomers 3.5/1 (after purification); pale
brown solid (800 mg, 83%), IR (Nujol): n = 1480 (NO2), 1600
(C C), 2230 (CN) cmÀ1. Z-isomer: 1H NMR (400 MHz,
CDCl3): d 6.61 (d, 1H, CH CF, J = 33.4 Hz), 7.76 (d, 2H, 4-
NO2C6H4–, J = 9.0 Hz) 8.28 (d, 2H, 4-NO2C6H4–, J = 9.0 Hz);
13C NMR (100 MHz, CDCl3): d 112.3 (d, CN, J = 46.8 Hz),
121.3 (d, CH CF, J = 6.5 Hz), 124.2, 131.0 (d, J = 8.7 Hz),
133.1 (d, CH CF, J = 259.8 Hz), 135.8 (d, J = 5.9 Hz), 148.3 (d,
J = 2.9 Hz). E-isomer: 1H NMR (400 MHz, CDCl3): d 7.18 (d,
1H, CH CF, J = 15.4 Hz), 7.78 (d, 2H, 4-NO2C6H4–,
J = 8.7 Hz), 8.27 (d, 2H, 4-NO2C6H4–, J = 8.7 Hz); 13C NMR
(100 MHz, CDCl3): d 111.7 (d, CN, J = 45.9 Hz), 124.0 (d,
CH CF, J = 27.1 Hz), 124.4, 129.4 (d, J = 3.7 Hz), 132.9 (d,
CH CF, J = 267.9 Hz), 134.6(d, J = 7.3 Hz), 148.6. Anal. calcd.
for C9H5FN2O2: C, 56.26; H, 2.62. Found: C, 56.40; H 2.70.
4.2. General procedure for the synthesis of the b-bromo-b-
trifluoromethyl styrenes 2
4.3.2. 2-Fluoro-3-(4-chlorophenyl)acrylonitrile (3b)
A mixture of Z/E-isomers 4.3/1 (after purification); pale
green solid (750 mg, 82%), IR (Nujol): n = 1480 (NO2), 1610
(C C), 2230 (CN) cmÀ1. Z-isomer: 1H NMR (400 MHz,
CDCl3): d 6.45 (d, 1H, CH CF, J = 34.1 Hz) 7.42 (d, 2H,
A solution of aromatic aldehyde (2 mmol) in DMSO (5 ml)
was added dropwise to a solution of 1 M hydrazine hydrate in

822
V.G. Nenajdenko et al. / Journal of Fluorine Chemistry 128 (2007) 818–826
4-ClC6H4–, J = 8.6 Hz) 7.51 (d, 2H, 4-ClC6H4–, J = 8.6 Hz);
13C NMR (100 MHz, CDCl3): d 113.0 (d, CN, J = 46.1 Hz),
122.4 (d, CH CF, J = 6.6 Hz), 128.4 (d, J = 5.9 Hz), 129.4
(CH), 131.4 (d, CH, 4-ClC6H4–, J = 8.1 Hz), 131.5 (d, CH CF,
J = 255.4 Hz), 136.8 (d, J = 3.7 Hz). E-isomer: 1H NMR
(400 MHz, CDCl3): d 7.05 (d, 1H, CH CF, J = 16.2 Hz), other
signals are identical to Z-isomer; 13C NMR (100 MHz, CDCl3):
d 112.3 (d, CN, J = 46.8 Hz), 124.9 (d, CH CF, J = 24.9 Hz),
126.6 (d, J = 6.6 Hz), 129.5 (CH), 129.7 (d, CH, 4-ClC6H4–,
J = 2.9 Hz), 131.0 (d, CH CF, J = 274.5 Hz), 136.6. Anal.
calcd. for C9H5ClFN: C, 59.53; H, 2.78. Found: C, 59.73; H
2.60.
4.3.7. 2-Fluoro-3-(2-methoxyphenyl)acrylonitrile (3g)
A mixture of Z/E-isomers 3.9/1 (after purification); white
solid (700 mg, 79%), IR (Nujol): n = 1610 (C C), 2240
(CN) cmÀ1. Z-isomer: 1H NMR (400 MHz, CDCl3): d 3.89 (s,
3H, MeO), 6.94 (d, 1H, 2-MeOC6H4–, J = 8.3 Hz), 7.02 (t, 1H,
2-MeOC6H4–, J = 7.6 Hz), 7.04 (d, 1H, CH CF, J = 36.6 Hz),
7.40 (dd, 1H, 2-MeOC6H4–, J = 1.5 Hz, J = 7.8 Hz), 7.78 (dd,
1H, 2-MeOC6H4–, J = 1.5 Hz, J = 7.8 Hz); 13C NMR
(100 MHz, CDCl3): d 55.7 (MeO), 110.8 (CH), 113.6 (d,
CN, J = 46.1 Hz), 117.4, 121.0, 128.0, 130.8 (d, CH CF,
J = 237.1 Hz), 131.2 (d, J = 13.9 Hz), 132.2, 156.9. E-isomer:
1H NMR (400 MHz, CDCl3): d 7.42 (d, 1H, CH CF,
J = 17.4 Hz), 7.65 (d, 1H, 2-MeOC6H4–, J = 7.6 Hz), other
signals are identical to Z-isomer; 13C NMR (100 MHz, CDCl3):
d 55.5 (MeO), 110.9, 119.0 (d, J = 5.9 Hz), 156.3, other signals
are identical to Z-isomer. Anal. calcd. for C10H8FNO: C, 67.79;
H, 4.55. Found: C, 67.59; H 4.45.
4.3.3. 2-Fluoro-3-phenylacrylonitrile (3c)
A mixture of Z/E-isomers 0.8/1 (after purification); colour-
less liquid (520 mg, 70%); IR (Nujol): n = 1620 (C C), 2230
(CN) cmÀ1
.
4.3.8. 2-Fluoro-3-(2-nitrophenyl)acrylonitrile (3h)
A mixture of Z/E-isomers 3.5/1 (after purification); yellow
solid (460 mg, 47%), IR (Nujol): n = 1480 (NO2), 1600 (C C),
4.3.4. 2-Fluoro-3-(4-methoxyphenyl)acrylonitrile (3d)
A mixture of Z/E-isomers 5.4/1 (after purification); white
solid (790 mg, 89%), IR (Nujol): n = 1610 (C C), 2240
1
2230 (CN) cmÀ1. Z-isomer: H NMR (400 MHz, CDCl3): d
(CN) cmÀ1
.
7.16 (d, 1H, CH CF, J = 31.5 Hz), 7.61–7.82 (m, 3H, 2-
NO2C6H4–), 8.18 (d, 1H, 2-NO2C6H4–, J = 8.2 Hz); 13C NMR
(100 MHz, CDCl3): d 112.1 (d, CN, J = 46.1 Hz), 118.9 (d,
CH CF, J = 5.9 Hz), 123.9 (d, J = 4.4 Hz), 125.3, 130.9, 131.8
(d, J = 8.8 Hz), 132.8 (d, CH CF, J = 246.6 Hz), 133.7, 148.2.
E-isomer: 1H NMR (400 MHz, CDCl3): d 7.71 (d, 1H, CH CF,
J = 15.7 Hz), 8.29 (d, 1H, 2-NO2C6H4–, J = 8.6 Hz); 13C NMR
(100 MHz, CDCl3): d 111.1 (d, CN, J = 46.8 Hz), 123.5 (d,
CH CF, J = 27.8 Hz), 124.3 (d, J = 8.1 Hz), 125.6, 131.2,
134.4, other signals are identical to Z-isomer. Anal. calcd. for
C9H5FN2O2: C, 56.26; H, 2.62. Found: C, 56.06; H 2.70.
4.3.5. 2-Fluoro-3-(3,4-dimethoxyhenyl)acrylonitrile (3e)
A mixture of Z/E-isomers 6.3/1 (after purification); white
solid (730 mg, 70%), IR (Nujol): n = 1610 (C C), 2240
(CN) cmÀ1. Z-isomer: 1H NMR (400 MHz, CDCl3): d 3.92 (s,
3H, MeO), 3.95 (s, 3H, MeO), 6.41 (d, 1H, CH CF,
J = 34.8 Hz) 6.91 (d, 1H, 3,4-diMeOC6H3–, J = 9.0 Hz)
7.12–7.16 (m, 2H, 3,4-diMeOC6H3–); 13C NMR (100 MHz,
CDCl3): d 55.8 (MeO), 55.9 (MeO), 111.0 (CH), 112.4 (d,
J = 9.5 Hz), 113.6 (d, CN, J = 46.1 Hz), 122.9 (d, J = 5.1 Hz),
123.6 (d, J = 5.9 Hz), 124.4 (d, J = 8.1 Hz), 129.9 (d, CH CF,
J = 250.3 Hz), 149.0, 151.1 (d, J = 2.9 Hz). E-isomer: 1H NMR
(400 MHz, CDCl3): d 7.03 (d, 1H, CH CF, J = 17.0 Hz) other
signals are identical to Z-isomer; 13C NMR (100 MHz, CDCl3):
d 111.2, 122.9 (d, J = 3.7 Hz), 126.2 (d, CH CF, J = 24.9 Hz),
other signals are identical to Z-isomer. Anal. calcd. for
C11H10FNO2: C, 63.76; H, 4.86. Found: C, 64.00; H 4.50.
4.3.9. 2-Fluoro-3-(4-methylphenyl)acrylonitrile (3i)
A mixture of Z–E-isomers 2.4/1 (after purification); white
solid (510 mg, 64%), IR (Nujol): n = 1610 (C C), 2230
(CN) cmÀ1
.
4.3.10. 2-Bromodec-2-enenitrile (3k)
A mixture of Z/E-isomers 0.9/1 (after purification); colourless
1
liquid (620 mg, 54%). H NMR (300 MHz, CDCl3) for the
4.3.6. Methyl 4-(2-cyano-2-fluorovinyl)benzoate (3f)
A mixture of Z/E-isomers 3.2/1 (after purification); white
solid (810 mg, 81%), IR (Nujol): n = 1610 (C C), 1720
mixture of isomers: d 0.89 (t, 3H, J = 6.6), 1.20–1.53 (m, 10H),
2.18–2.33 (m, 2H), 5.76 (dt, 1H, CH CF, J = 32.9 Hz,
J = 7.9 Hz), 6.12 (dt, 1H, CH CF, J = 14.2 Hz, J = 8.5 Hz);
19F NMR (282 MHz, CDCl3) for the mixture of isomers: d
À123.5 (d, J = 14.2), À125.4 (d, J = 32.9); 13C NMR (75 MHz,
CDCl3) for the mixture of isomers: d 14.1, 22.7, 24.7, 26.4, 26.5,
28.0, 28.1, 28.6, 28.7, 28.8, 28.9, 29.0, 29.1, 31.8, 111.2 (d, CN,
J = 48.1 Hz,), 112.5 (d, CN, J = 47.5 Hz,), 126.9 (d, CH CF,
J = 14.8 Hz), 127.3 (d, CH CF, J = 14.8 Hz), 132.3 (d, CH CF,
J = 243.0 Hz), 132.7 (d, CH CF, J = 239.8 Hz); ESI-MS (m/z):
calcd. for C10H16FNNa [M]+ 192.1162, found 192.1159.
1
(CO2Me), 2240 (CN) cmÀ1. Z-isomer: H NMR (400 MHz,
CDCl3): d 3.96 (s, 3H, CO2Me), 6.52 (d, 1H, CH CF,
J = 33.9 Hz) 7.64 (d, 2H, 4-CO2MeC6H4–, J = 8.3 Hz), 8.10 (d,
2H, 4-CO2MeC6H4–, J = 8.3 Hz); 13C NMR (100 MHz,
CDCl3): d 52.5 (CO2Me), 112.7 (d, CN, J = 46.1 Hz), 122.5
(d, CH CF, J = 6.6 Hz), 130.1 (d, J = 8.1 Hz), 130.2, 131.6 (d,
J = 2.9 Hz), 132.3 (d, CH CF, J = 257.6 Hz), 133.9 (d,
1
J = 5.6 Hz), 166.1 (CO2Me). E-isomer: H NMR (400 MHz,
CDCl3): d 7.11 (d, 1H, CH CF, J = 16.2 Hz), 7.67 (d, 2H, 4-
CO2MeC6H4–, J = 8.3 Hz), 8.12 (d, 2H, 4-CO2MeC6H4–,
J = 8.3 Hz); 13C NMR (100 MHz, CDCl3): d 112.1 (d, CN,
J = 46.8 Hz), 125.0 (d, CH CF, J = 24.9 Hz), 128.4 (d,
J = 2.9 Hz), 130.3, 132.5 (d, J = 7.3 Hz). Anal. calcd. for
C11H8FNO2: C, 64.39; H, 3.93. Found: C, 64.21; H 3.81.
4.3.11. (2E)-3-(4-chlorophenyl)-2-
(trifluoromethyl)acrylonitrile (4b)
White solid (870 mg, 75%), mp 40–41 8C; IR (Nujol):
n = 1610 (C C), 2230 (CN) cmÀ1 1H NMR (400 MHz,
;

V.G. Nenajdenko et al. / Journal of Fluorine Chemistry 128 (2007) 818–826
823
CDCl3): d 7.50 (d, 2H, 4-ClC6H4–, J = 8.6 Hz), 7.65 (s, 1H,
CH CCF3), 7.85 (d, 2H, 4-ClC6H4–, J = 8.6 Hz); 19F NMR
(282 MHz, CDCl3): d À64.23; 13C NMR (100 MHz, CDCl3): d
102.1 (q, CH CCF3, J = 37.3), 112.8 (CN), 120.9 (q, CF3,
J = 273.7), 128.7, 129.8 (CH-arom), 131.5 (CH-arom), 139.6,
147.5 (q, CH CCF3, J = 4.4). Anal. calcd. for C10H5ClF3N: C,
51.86; H, 2.18. Found: C, 52.02.; H 2.30; ESI-MS (m/z): calcd.
for C10H5ClF3NNa [M]+ 253.9960, found 253.9955.
J = 36.6), 112.6 (CN), 120.8 (q, CF3, J = 273.7), 130.1 (CH-
arom), 130.3 (CH-arom), 132.1, 134.0, 147.7 (q, CH CCF3,
J = 4.4), 165.7 (CO2Me). Anal. calcd. for C12H8F3NO2: C,
56.48; H, 3.16. Found: C, 56.62; H 3.29.
4.3.16. (2E)-3-(2-methoxyphenyl)-2-
(trifluoromethyl)acrylonitrile (4g)
Colourless oil (930 mg, 82%); IR (Nujol): n = 1610 (C C),
2230 (CN) cmÀ1; 1H NMR (400 MHz, CDCl3): d 3.93 (s, 3H,
MeO), 7.00 (d, 1H, arom, J = 7.9 Hz), 7.08 (t, 1H, arom,
J = 7.9 Hz), 7.55 (t, 1H, arom, J = 7.9 Hz), 8.18 (d, 1H, arom,
J = 7.9 Hz), 8.21 (s, 1H, CH CCF3); 13C NMR (100 MHz,
CDCl3): d 55.8 (MeO), 100.7 (q, CH CCF3, J = 36.6), 111.3
(CH-arom), 113.5 (CN), 119.4, 121.0 (CH-arom), 121.5 (q,
CF3, J = 275.2), 128.8 (CH-arom), 135.0 (CH-arom), 143.9 (q,
CH CCF3, J = 4.4), 158.8. Anal. calcd. for C11H8ClF3NO: C,
58.15; H, 3.55. Found: C, 58.26; H 3.47.
4.3.12. (2E)-3-phenyl-2-(trifluoromethyl)acrylonitrile (4c)
White solid (710 mg, 72%), mp 43–44 8C; IR (Nujol):
n = 1620 (C C), 2230 (CN) cmÀ1 1H NMR (400 MHz,
;
CDCl3): d 7.53 (t, 2H, Ph, J = 7.4 Hz), 7.60 (t, 1H, Ph,
J = 7.4 Hz), 7.70 (s, 1H, CH CCF3), 7.91 (d, 2H, Ph,
J = 7.4 Hz); 19F NMR (282 MHz, CDCl3): d À64.17; 13C
NMR (100 MHz, CDCl3): d 101.5 (q, CH CCF3, J = 36.6),
113.1 (CN), 121.2 (q, CF3, J = 273.0), 129.4 (2CH-arom),
130.3 (2CH-arom), 133.3 (CH-arom), 149.0 (CH CCF3,
J = 4.4); ESI-MS (m/z): calcd. for C10H6ClF3NNa [M]+
220.0350, found 220.0345. Anal. calcd. for C10H6ClF3N: C,
60.92; H, 3.07. Found: C, 60.82; H 3.10.
4.3.17. (2E)-3-(2-nitrophenyl)-2-
(trifluoromethyl)acrylonitrile (4h)
Yellow solid (750 mg, 62%), mp 88–89 8C; IR (Nujol):
n = 1600 (C C), 2225 (CN) cmÀ1 1H NMR (400 MHz,
;
4.3.13. (2E)-3-(4-methoxyphenyl)-2-
(trifluoromethyl)acrylonitrile (4d)
CDCl3): d 7.74–7.91 (m, 3H, arom), 8.30–8.37 (m, 1H, arom),
8.33 (s, 1H, CH CCF3); 13C NMR (100 MHz, CDCl3): d 106.7
(q, CH CCF3, J = 36.6), 111.6 (CN), 120.3 (q, CF3, J = 275.2),
125.7 (CH-arom), 126.9, 130.6 (CH-arom), 132.6 (CH-arom),
134.9 (CH-arom), 147.0, 148.3 (q, CH CCF3, J = 4.4). Anal.
calcd. for C10H5F3N2O2: C, 49.60; H, 2.08. Found: C, 49.72; H
2.19.
Colourless liquid (970 mg, 85%); IR (Nujol): n = 1600
(C C), 2220 (CN) cmÀ1. 1H NMR (400 MHz, CDCl3): d 3.90
(s, 3H, MeO), 7.01 (d, 2H, 4-MeOC6H4–, J = 9.0 Hz), 7.57 (s,
1H, CH CCF3), 7.90 (d, 2H, 4-MeOC6H4–, J = 9.0 Hz); 19F
NMR (282 MHz, CDCl3): d À63.61; 13C NMR (100 MHz,
CDCl3): d 55.6 (MeO), 97.7 (q, CH CCF3, J = 36.6), 113.8
(CN), 114.8 (CH-arom), 121.6 (q, CF3, J = 273.0), 123.0, 132.8
(CH-arom), 148.2 (CH CCF3, J = 4.4), 163.7; ESI-MS (m/z):
calcd. for C11H8ClF3NONa [M]+ 250.0456, found 250.0439.
Anal. calcd. for H, C11H8ClF3NO: C, 58.15; H, 3.55. Found: C,
58.20; H 3.40.
4.3.18. (2E)-3-(4-methylphenyl)-2-
(trifluoromethyl)acrylonitrile (4i)
White solid (710 mg, 67%), mp 32–33 8C; IR (Nujol):
n = 1620 (C C), 2230 (CN) cmÀ1 1H NMR (400 MHz,
;
CDCl3): d 2.45 (s, 3H, Me), 7.32 (d, 2H, 4-MeC6H4–,
J = 8.2 Hz), 7.63 (s, 1H, CH CCF3), 7.81 (d, 2H, 4-MeC6H4–,
J = 8.2 Hz); 13C NMR (100 MHz, CDCl3): d 21.8 (Me), 102.2
(q, CH CCF3, J = 36.6), 113.4 (CN), 121.3 (q, CF3, J = 272.2),
127.7, 130.1 (CH-arom), 130.5 (CH-arom), 144.5, 148.8 (q,
CH CCF3, J = 3.0). Anal. calcd. for C11H8F3N: C, 62.56; H,
3.82. Found: C, 62.61; H 3.94.
4.3.14. (2E)-3-(3,4-dimethoxyphenyl)-2-
(trifluoromethyl)acrylonitrile (4e)
White solid (900 mg, 70%), mp 37–38 8C; IR (Nujol):
n = 1600 (C C), 2220 (CN) cmÀ1 1H NMR (400 MHz,
;
CDCl3): d 3.95 (s, 3H, MeO), 3.97 (s, 3H, MeO), 6.95 (d,
1H, 3,4-diMeOC6H3–, J = 8.5 Hz), 7.38 (dd, 1H, 3,4-
diMeOC6H3–, J = 8.5 Hz, J = 2.0 Hz), 7.56 (s, 1H, CH CCF3),
CCF3), 7.68 (d, 1H, 3,4-diMeOC6H3–, J = 2.0 Hz); 13C NMR
(100 MHz, CDCl3): d 56.0 (MeO), 56.1 (MeO), 97.9 (q,
CH CCF3, J = 36.6), 111.0 (2CH-arom), 113.9 (CN), 121.7 (q,
CF3, J = 273.0), 123.3, 126.8 (CH-arom), 148.5 (CH CCF3,
J = 4.4), 149.4, 153.5. Anal. calcd. for C12H10F3NO2: C, 56.04;
H, 3.92. Found: C, 56.20; H 3.80.
4.4. General procedure for cycloaddition reactions of the
nitriles 3 and 4 with dienes
One millimole of the corresponding a-trifluoromethylacry-
lonitrile and 1.5 ml of diene were heated in sealed glass tube
with a Young-tap. The excess of dienes was evaporated at
reduced pressure and the residue was purified by column
chromatography with silica gel (using mixture of cyclohexane/
ethyl acetate 20-1 as the eluent).
4.3.15. Methyl 4-((1E)-2-cyano-3,3,3-trifluoroprop-1-
enyl)benzoate (4f)
White solid (740 mg, 58%), mp 56–57 8C; IR (Nujol):
4.4.1. 3-(4-Chlorophenyl)-2-
(trifluoromethyl)bicyclo[2.2.1]hept-5-ene-2-carbonitrile
(5b)
3-(4-Chlorophenyl)-2-(trifluoromethyl)bicyclo[2.2.1]hept-
5-ene-2-carbonitrile (5b) was obtained from 4b by heating with
n = 1610 (C C), 2230 (CN) cmÀ1
;
1H NMR (400 MHz,
CDCl3): d 3.93 (s, 3H, Me), 7.70 (s, 1H, CH CCF3), 7.91
(d, 2H, arom, J = 8.2 Hz), 8.12 (d, 2H, arom, J = 8.2 Hz); 13C
NMR (100 MHz, CDCl3): d 52.5 (Me), 103.9 (q, CH CCF3,

824
V.G. Nenajdenko et al. / Journal of Fluorine Chemistry 128 (2007) 818–826
cyclopentadiene at 130 8C during 16 h. Colourles solid
(253 mg, 87%); H NMR (300 MHz, CDCl3) for the mixture
(CH-arom), 133.9 (arom), 137.0 (arom); ESI-MS (m/z): calcd.
for C16H15ClF3NNa [M]+ 336.0743, found 336.0737. Anal.
calcd. for C16H15ClF3N: C, 61.25; H, 4.82; N, 4.46. Found: C,
61.20; H 4.75; N, 4.46.
1
of diastereomers: d 1.73 (bd, 1H, –CH2–, J = 9.8 Hz), 1.96 (bd,
2H, –CH2–, J = 9.8 Hz), 2.33 (bd, 1H, –CH2–, J = 9.8 Hz), 3.13
(d, 1H, –CH-Ar, J = 1.9 Hz), 3.24 (bs, 1H, –CH–), 3.30 (bs, 1H,
–CH–), 3.49 (bs, 1H, –CH–), 3.56 (bs, 1H, –CH–), 3.70 (d, 1H,
–CH-Ar, J = 2.9 Hz), 6.16 (pent, 1H, –CH , J = 2.7 Hz), 6.53–
6.60 (m, 2H, –CH ), 6.71 (dd, 1H, –CH , J = 5.7 Hz,
J = 3.0 Hz), 7.20–7.39 (m, 8H, arom); 19F NMR (282 MHz,
CDCl3) for the mixture of diastereomers: d À66.74, À68.61;
13C NMR (75 MHz, CDCl3) for the mixture of diastereomers: d
48.4, 48.5, 49.6, 49.1, 50.3, 51.1, 51.8, 52.3, 56.1 (d,
J = 25.4 Hz), 56.6 (d, J = 28.0 Hz); 116.4 (CN), 117.4 (CN),
124.8 (q, CF3, J = 282.3 Hz), 125.2 (q, CF3, J = 282.3 Hz);
129.1 (CH), 129.5 (CH), 130.1 (CH), 130.9 (CH), 132.0, 134.4,
134.5, 135.6 (arom); 133.2, 136.9, 139.5, 141.2 (–CH CH–);
ESI-MS (m/z): calcd. for C15H11ClF3NNa [M]+ 320.0430,
found 320.0424.
4.5. General procedure for reactions of the nitriles 3 and 4
with Danishefsky’s diene
One millimole of a-trifluoromethylacrylonitrile and
1.2 mmol of Danishefsky’s diene in 1 ml of dry toluene were
heated in sealed glass tube with a Young-tap at 1208. Toluene
was evaporated at reduced pressure and the residue was purified
by column chromatography with silica gel (using mixture of
cyclohexane/ethyl acetate 1-1 as the eluent).
4.5.1. 2-Methoxy-6-(4-chlorophenyl)-4-oxo-1-
(trifluoromethyl)cyclohexanecarbonitrile (7 + 8b)
2-Methoxy-6-(4-chlorophenyl)-4-oxo-1-(trifluoromethyl)-
cyclohexanecarbonitrile (7 + 8b) was obtained from 4b by
heating with Danishefsky’s diene at 120 8C during 48 h.
Colourles oil (250 mg, 76%); major diastereomer 7b: 1H NMR
(300 MHz, CDCl3): d 2.52 (dd, 1H, J = 15.9 Hz, J = 3.0 Hz,
CH2), 2.86–3.17 (m, 3H, CH2), 3.33 (dd, 1H, J = 14.2 Hz,
J = 3.4 Hz, CH-Ar), 3.50 (s, 3H, MeO), 3.98 (dd, 1H,
J = 8.1 Hz, J = 4.9 Hz, CH-MeO), 7.30–7.40 (m, 4H, arom);
19F NMR (282 MHz, CDCl3): d À67.3; 13C NMR (75 MHz,
CDCl3): d 41.4 (CH-Ar), 42.6 (CH2), 44.1 (CH2), 54.8 (q,
J = 24.4 Hz, C-CF3), 58.5 (MeO), 77.1 (CH-MeO), 113.1 (CN),
123.5 (q, J = 287.2 Hz, CF3,); 129.2, 129.6, 134.7, 135.0
(arom); 202.3 (C O); minor diastereomer 8b: 1H NMR
(300 MHz, CDCl3): d 2.60 (bd, 1H, J = 15.4 Hz, CH2), 3.45 (s,
3H, MeO), 4.34 (t, 1H, 2.9 Hz, CH-MeO), other signals are
identical to major diastereomer; 19F NMR (282 MHz, CDCl3):
d À64.4; 13C NMR (75 MHz, CDCl3): d 39.9 (CH-Ar), 41.4
(CH2), 44.5 (CH2), 53.3 (q, J = 25.6 Hz, C-CF3), 57.9 (MeO),
78.6 (CH-MeO), 114.6 (CN), 123.0 (q, J = 286.0 Hz, CF3,),
202.9 (C O), other signals are identical to major diastereomer;
ESI-MS (m/z): calcd. for C15H13ClF3NO2Na [M]+ 354.0483,
found 354.0485.
4.4.2. 3-Phenyl-2-(trifluoromethyl)bicyclo[2.2.1]hept-5-
ene-2-carbonitrile (5c)
3-Phenyl-2-(trifluoromethyl)bicyclo[2.2.1]hept-5-ene-2-
carbonitrile (5c) was obtained from 4c by heating with
cyclopentadiene at 150 8C during 24 h. Colourles solid (85 mg,
32%); 1H NMR (500 MHz, CDCl3) for the mixture of
diastereomers: d 1.71 (bd, 1H, –CH2–, J = 9.7 Hz), 1.94 (bd,
2H, –CH2–, J = 9.7 Hz), 2.39 (bd, 1H, –CH2–, J = 9.7 Hz), 3.16
(d, 1H, –CH-Ar, J = 2.1 Hz), 3.27 (bs, 1H, –CH–), 3.31 (bs, 1H,
–CH–), 3.47 (bs, 1H, –CH–), 3.54 (bs, 1H, –CH–), 3.74 (d, 1H,
–CH-Ar, J = 2.8 Hz), 6.14 (pent, 1H, –CH , J = 2.7 Hz), 6.52–
6.56 (m, 2H, –CH ), 6.73 (dd, 1H, –CH , J = 5.5 Hz,
J = 3.2 Hz), 7.25–7.45 (m, 10H, arom); 19F NMR (470 MHz,
CDCl3) for the mixture of diastereomers: d À66.98, À68.88;
13C NMR (125 MHz, CDCl3) for the mixture of diastereomers:
d 47.9, 48.0, 48.1, 48.7, 49.9, 51.1, 51.3, 52.5, 55.6 (d,
J = 26.4 Hz), 56.1 (d, J = 27.0 Hz); 116.0 (CN), 117.1 (CN),
124.4 (q, CF3, J = 282.2 Hz), 124.8 (q, CF3, J = 282.2 Hz);
127.9 (CH), 127.8 (CH), 128.2 (CH), 128.4 (CH), 128.8 (CH),
129.0 (CH), 136.6, 137.8 (arom); 132.6, 136.0, 139.4, 140.9 (–
CH CH–); ESI-MS (m/z): calcd. for C15H12F3NNa [M]+
286.0820, found 286.0814.
4.5.2. 2-Methoxy-6-phenyl-4-oxo-1-
(trifluoromethyl)cyclohexanecarbonitrile (7 + 8c)
Methoxy-6-phenyl-4-oxo-1-(trifluoromethyl)cyclohexane-
carbonitrile (7 + 8c) was obtained from 4c by heating with
Danishefsky’s diene at 120 8C during 72 h. Colourles oil
4.4.3. 6-(4-Chlorophenyl)-3,4-dimethyl-1-
(trifluoromethyl)cyclohex-3-ene-1-carbonitrile (5b)
6-(4-Chlorophenyl)-3,4-dimethyl-1-(trifluoromethyl)cyclo-
hex-3-ene-1-carbonitrile (5b) was obtained from 4b by heating
with 2,3-dimethylbutadiene at 150 8C during 24 h. Colourles
solid (105 mg, 50%), mp 50–52 8C; 1H NMR (500 MHz,
CDCl3): d 1.71 (bs, 3H, Me), 1.73 (bs, 3H, Me), 2.25 (dd, 1H, –
CH2–, J = 17.4 Hz, J = 5.0 Hz), 2.54 (bd, 1H, –CH2–,
J = 16.7 Hz), 2.63–2.76 (m, 2H, –CH2–), 3.11 (dd, 1H, –
1
(252 mg, 88%); major diastereomer 7c: H NMR (300 MHz,
CDCl3): d 2.56 (dd, 1H, J = 15.9 Hz, J = 3.0 Hz, CH2), 2.82–
3.21 (m, 3H, CH2), 3.31 (dd, 1H, J = 14.2 Hz, J = 3.4 Hz, CH-
Ar), 3.51 (s, 3H, MeO), 3.97 (dd, 1H, J = 8.5 Hz, J = 4.9 Hz,
CH-MeO), 7.35–7.41 (bs, 5H, arom); 19F NMR (282 MHz,
CDCl3): d À66.6; 13C NMR (75 MHz, CDCl3): d 40.7 (CH-Ar),
41.5 (CH2), 43.1 (CH2), 53.6 (q, J = 24.4 Hz, C-CF3), 57.2
(MeO), 76.3 (CH-MeO), 112.0 (CN), 122.3 (q, J = 286.6 Hz,
CF3,); 126.9, 127.5, 127.6, 135.2 (arom); 201.4 (C O); minor
diastereomer 8c: 1H NMR (300 MHz, CDCl3): d 2.59–2.68 (bd,
1H, J = 15.4 Hz, CH2), 3.46 (s, 3H, MeO), 4.33 (t, 1H, 2.9 Hz,
CH-MeO), other signals are identical to major diastereomer;
CHAr, J = 12.0 Hz, J = 5.0 Hz), 7.28–7.35 (m, 4H, arom); 19
F
NMR (470 MHz, CDCl3): d and 70.51; 13C NMR (125 MHz,
CDCl3): d 18.3 (Me), 18.4 (Me), 37.3 (q, –CH–, J = 1.5 Hz),
37.5 (–CH2–), 42.7 (–CH2–), 48.2 (q, CF3, J = 26.4 Hz), 116.1
(q, CN, J = 1.5 Hz), 120.1 (–C(Me) ), 123.9 (q, CF3,
J = 284.2 Hz), 126.6 (–C(Me) ), 128.8 (CH-arom), 129.9

V.G. Nenajdenko et al. / Journal of Fluorine Chemistry 128 (2007) 818–826
825
19F NMR (282 MHz, CDCl3): d À64.4; 13C NMR (75 MHz,
CDCl3): d 39.3 (CH-Ar), 40.1 (CH2), 43.4 (CH2), 52.2 (q,
J = 25.6 Hz, C-CF3), 56.5 (MeO), 77.4 (CH-MeO), 113.5 (CN),
121.8 (q, J = 286.0 Hz, CF3,); 134.8 (arom); 202.1 (C O),
other signals are identical to major diastereomer; ESI-MS (m/
z): calcd. for C15H14F3NO2Na [M]+ 320.0868, found 320.0874.
Anal. calcd. for C15H14F3NO2: C, 60.60; H, 4.75; N, 4.71.
Found: C, 60.28; H 4.65; N, 4.53.
[9] I. Ojima, J.R. McCarthy, J.T. Welch (Eds.), Fluorine-Containing Synthons,
ACS Symposium Series 911, American Chemical Society, Washington,
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[10] K. Uneyama, Organofluorine Chemistry, Blackwell, Oxford, 2006.
[11] Y. Allmendinger, E. Felder, E. Hungerbuehler, in: J.T. Welch (Ed.),
Selective Fluorination in Organic and Bioorganic Chemistry, American
Chemical Society, Washington, DC, 1991.
[12] T. Allmendinger, P. Furet, E. Hungerbuehler, Tetrahedron Lett. 31 (1990)
7279.
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4.5.3. 2-Methoxy-6-(4-methoxyphenyl)-4-oxo-1-
(trifluoromethyl)cyclohexanecarbonitrile (7 + 8d)
2-Methoxy-6-(4-methoxyphenyl)-4-oxo-1-(trifluoro-
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methyl)cyclohexanecarbonitrile (7 + 8d) was obtained from 4d
by heating with Danishefsky’s diene at 120 8C during 136 h.
Colourles oil (280 mg, 86%); major diastereomer 7d: 1H NMR
(300 MHz, CDCl3): d 2.53 (dd, 1H, J = 15.9 Hz, J = 3.0 Hz,
CH2), 2.82–3.17 (m, 3H, CH2), 3.29 (dd, 1H, J = 14.1 Hz,
J = 3.3 Hz, CH-Ar), 3.50 (s, 3H, MeO), 3.81 (s, 3H, MeO-Ar),
3.96 (dd, 1H, J = 8.3 Hz, J = 4.9 Hz, CH-MeO), 6.90 (d, 2H,
J = 8.8 Hz, Ar), 7.29 (d, 2H, J = 8.8 Hz, Ar); 19F NMR
(282 MHz, CDCl3): d À66.6; 13C NMR (75 MHz, CDCl3): d
41.4 (CH-Ar), 44.5 (2CH2), 53.6 (q, J = 25.0 Hz, C-CF3), 55.3
(MeO-Ar), 58.5 (MeO), 77.5 (CH-MeO), 113.3 (CN), 124.3 (q,
J = 286.6 Hz, CF3,); 114.3, 128.4, 129.3, 159.7 (arom); 203.0
(C O); minor diastereomer 8d: 1H NMR (300 MHz, CDCl3): d
2.60 (bd, 1H, J = 15.6 Hz, CH2), 3.45 (s, 3H, MeO), 4.33 (t, 1H,
3.0 Hz, CH-MeO), 7.01 (d, 2H, J = 8.9 Hz, Ar), other signals
are identical to major diastereomer; 19F NMR (282 MHz,
CDCl3): d À64.4; 13C NMR (75 MHz, CDCl3): d 40.0 (CH-Ar),
42.7 (CH2), 45.0 (CH2), 57.8 (MeO), 78.7 (CH-MeO), 114.6
(CN), 123.4 (q, J = 286.0 Hz, CF3,), 203.6 (C O), other signals
are identical to major diastereomer; ESI-MS (m/z): calcd. for
C16H16F3NO3Na [M]+ 350.0974, found 350.0980.
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This research was supported by the Deutsche Forschungs-
gemeinschaft (DFG) through grant GZ: 436 RUS 113/
858/0-1.
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