New synthetic approach to α-fluoro-β-arylvinyl sulfones and their application in Diels-Alder reactions

Article abstract of DOI:10.1016/j.tet.2008.07.097

A new pathway towards α-fluoro-β-arylvinyl sulfones was elaborated. The reaction of β-bromo-β-fluorostyrenes with sodium 4-methylphenylsulfinate proceeds with maximum 94:6 stereoselectivity and 72-90% yields. The formed α-fluoro-β-arylvinyl sulfones were

Full text of DOI:10.1016/j.tet.2008.07.097

Tetrahedron 64 (2008) 9725–9732
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
New synthetic approach to
a
-fluoro-
b-arylvinyl sulfones and their
application in Diels–Alder reactions
,
b
b
Aleksey V. Shastin a, Valentine G. Nenajdenko b , Vasiliy M. Muzalevskiy , Elizabeth S. Balenkova ,
**
,
Roland Fro¨hlich c, Gu¨nter Haufe c
*
a Institute of Problems of Chemical Physics, Chernogolovka, Moscow Region 142432, Russia
b Moscow State University, Department of Chemistry, Leninskie Gory, Moscow 119992, Russia
c Organisch-Chemisches Institut, Westfa¨lische Wilhelms-Universita¨t Mu¨nster, D-48149 Mu¨nster, Germany
a r t i c l e i n f o
a b s t r a c t
Article history:
A new pathway towards a-fluoro-b-arylvinyl sulfones was elaborated. The reaction of b-bromo-b-fluo-
Received 19 July 2008
Accepted 22 July 2008
Available online 26 July 2008
rostyrenes with sodium 4-methylphenylsulfinate proceeds with maximum 94:6 stereoselectivity and
72–90% yields. The formed -fluoro- -arylvinyl sulfones were found to be good dienophiles for Diels–
a
b
Alder reactions with simple 1,3-dienes. From corresponding (E)-configured dienophiles and cyclo-
pentadiene, cycloadducts bearing the fluorine substituent in exo-position were formed predominantly,
while with diphenylisobenzofuran the products with endo-orientation of the fluorine were obtained as
the major products. From these cycloadducts, as a proof of principle, p-toluenesulfinic acid was elimi-
nated to give 2-fluoro-3-(4-nitrophenyl)norbornadiene, the formal [4þ2]-cycloadduct of cyclo-
pentadiene and 1-fluoro-2-(4-nitrophenyl)acetylene, or the corresponding diphenylisobenzofuran
Keywords:
Diels–Alder reaction
Fluoroalkynes
a
-Fluoro-b-arylvinyl sulfones
Fluoronorbornadienes
Stereoselectivity
Vinyl fluorides
cycloadducts, respectively. This reaction was not successful when other
for elimination.
b-hydrogen atoms are accessible
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
reaction, we elaborated new methods for the synthesis of various
fluorinated alkenes.10 Among them
b
-chloro-
b-(trifluoromethyl)-
Fluorine-containing organic compounds were intently in-
vestigated in recent years.1 One reason for the particular interest in
such compounds is their manifold physiological activity.2 Numer-
ous publications were dedicated to elaboration of new methods for
their synthesis.3 Molecules containing a vinylic fluorine atom are of
special interest, both as starting materials for various syntheses4
and as biologically active compounds. For instance, fluoroolefins
are potential enzyme inhibitors5 and can be used as a bioisosteric
replacement of an amido group in peptides6 or amino acid amides.7
A couple of years ago, a new catalytic olefination reaction
starting from aldehydes or ketones was discovered.8 We found that
N-unsubstituted hydrazones of these carbonyl compounds can be
smoothly transformed into various substituted alkenes by treat-
ment with polyhalogenoalkanes in the presence of catalytic
amounts of copper salts and a base (Scheme 1). Advantages over
other methods9 are inexpensive starting materials and simplicity of
chemical transformation and isolation of products. Applying this
styrenes, ArC(H)]C(Cl)CF3,
b
-bromo- -(trifluoromethyl)styrenes,
b
ArC(H)]C(Br)CF3 are of particular interest, because one of the
halogen atoms can be easily substituted by different nucleophiles.
By way of example, the reactions with copper cyanide, alkyl-
thiolates and arylthiolates are new approaches to
a
-fluoro- and
a
-trifluoromethylacrylonitriles11 or to trifluoromethyl(vinylsulfides),
respectively.12
O
S
.
1) N2H4, H2O
ArCHO
2) CBr3F,
cat. CuCl
TosNa 2H2O
Br
Ar
Ar
N-methylpyrrolidinone
O
F
180-185 °C
72-90%
F
1
2
Scheme 1. Synthesis of b-bromo-b-fluorostyrenes 1 and its reactions with sodium 4-
methylphenylsulfinate.
Substitution of bromine in
4-methylphenylsulfinate would open a new pathway to
-arylvinyl sulfones, which are useful building blocks in organic
b
-bromo-
b
-fluorostyrenes with
a
-fluoro-
b
synthesis.
a-Fluoro-b-arylvinyl sulfones are widely used in
* Corresponding author. Tel.: þ49 251 8333281; fax: þ49 251 8339772.
** Corresponding author. Tel.: þ7 495 9392276; fax: þ7 495 9328846.
E-mail addresses: shastin@icp.ac.ru (A.V. Shastin), nen@acylium.chem.msu.ru
(V.G. Nenajdenko), haufe@uni-muenster.de (G. Haufe).
synthesis of 1-fluorovinylstannanes,13 fluorostyrenes,14 3-fluo-
ropyrrole derivatives15 and fluorotriazoles.16 Due to the electron-
deficient double bond and the possibility to eliminate the sulfonic
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.07.097

9726
A.V. Shastin et al. / Tetrahedron 64 (2008) 9725–9732
group, this class of compounds might be useful for both Michael
additions17 and Diels–Alder reactions.18 Most general methods for
substituent into various carbo- and heterocyclic compounds. To the
best of our knowledge only two examples of Diels–Alder reactions
the synthesis of
a
-fluorovinyl sulfones are the Wittig19 and the
with
far.19,32
Initially, the thermal Diels–Alder reactions of the sulfone 2a
a-fluorovinyl sulfones have been described in the literature so
Peterson olefination reactions,20 as well as condensations of fluo-
romethylvinylsulfones with carbonyl compounds.14 However, ab-
solute solvents, inert atmosphere, application of toxic phosphorous
or excess of organometallic compounds are required for the men-
tioned methods. Thus, the development of new, more convenient
with 2,3-dimethylbutadiene and Danishefsky’s diene were in-
vestigated. While the first reaction gave the desired cyclohexene 3
in 89% yield, the reaction mixture decomposed and no pure product
could be isolated in case of Danishefsky’s diene (Scheme 2).
methods towards
issue.
a-fluoro-b-arylvinyl sulfones is an important
NO2
2. Results and discussion
2.1. Synthesis of -fluorovinyl sulfones
Tos
toluene
150 °C
F
a
O2N
Tos
F
2a
89 %
3
Initially we found that
b-bromo-b-fluorostyrenes 1 gave a-flu-
oro- -arylvinyl sulfones 2 in high yields upon heating with sodium
b
Scheme 2. Reaction of sulfone 2a with 2,3-dimethylbutadiene.
4-methylphenylsulfinate in N-methylpyrrolidinone at 180–185 ꢀC
(Table 1). The reactions proceeded regioselectively providing only
one regioisomer in all cases. Furthermore, the method was shown
to be quite general and a variety of aromatic sulfones 2 containing
both electron donating and electron withdrawing substituents at
the aromatic ring were accessible. The reaction occurred stereo-
selectively. In most cases a slight increase of the E/Z ratio comparing
to the starting 1 was observed, probably due to the better acces-
The structure of compound 3 was determined by spectroscopic
methods. Most characteristic for the trans-orientation of fluorine
and the vicinal proton is the big 3JH,F coupling constant of 32.2 Hz,
found both in the 1H and in the 19F NMR spectra.
Subsequently, we investigated reactions of a-fluoro-b-arylvinyl
sulfones 2 with cyclopentadiene. The reactions were carried out
without solvent using excess of the diene in a sealed tube at 150 ꢀC
leading to mixtures of the corresponding Diels–Alder adducts 4 and
5 in about 3:2 ratio and 53–87% yields (Scheme 3). About 7–8 h of
reaction time were needed for complete consumption of the
starting material in case of the sulfones 2a and 2e with electron
withdrawing substituents at the aromatic ring. As expected, the
reaction time increased dramatically for the electron donor
substituted compound 2d (Table 2).
sibility for the nucleophile of one side of the
was not further investigated.
b-carbon atom. This
The structure of the isomeric a-fluoro-b-arylvinyl sulfones 2 was
mainly determined by 1H NMR spectroscopy. Most characteristi-
cally, the 3JH,F coupling constants between fluorine and the vinylic
proton were found to be 32–35 Hz, which is typical for the trans-
3
position of the coupling nuclei. For the minor cis-isomers JH,F of
15–20 Hz were found (see Section 4).
Ar
Tos
neat
150 °C
Tos
Ar
F
Ar
2.2. Diels–Alder reactions of a-fluorovinyl sulfones
F
F
5
Tos
4
Though a very innovative alternative pathway was described
recently,21 the two Diels–Alder strategies combining either a fluo-
rinated diene or a fluorinated dienophile with the corresponding
non-fluorinated counterpart, remains the most convenient ap-
proach towards selectively fluorinated mono- or polycyclic cyclo-
hexene derivatives.4,22 Many reactions of this type have been used
for syntheses of fluorinated model compounds in order to study the
selectivity of such reactions,23,24 but also for the preparation of
analogues of biologically active compounds such as cantharidin,
2
53-87%
3 : 2
Scheme 3. Reaction of the a-fluoro-b-arylvinyl sulfones 2 with cyclopentadiene.
In addition to spectroscopic investigations, the structure of the
diastereomers 4 and 5 was confirmed by X-ray analysis of the pure
diastereomers 4a and 5a containing a 4-nitrophenyl group. For the
major diastereomer 4a unexpectedly the exo-F-endo-Tos-exo-Ar
configuration was determined. The minor diastereomer 5a was
found to have the endo-F-exo-Tos-endo-Ar configuration (Figs.1 and
2). The preferred formation of the cycloadduct with exo-orientation
of the fluorine substituent was also found in the reaction of
cyclopentadiene with 3-fluorofuran-2(5H)-one.33
In contrast, for the Diels–Alder reaction of diphenylisobenzo-
furan with the dienophiles 2a and 2b the reverse stereoselection
was found (Scheme 4). The 4-chloro substituted dienophile 2b gave
an 89:11 mixture of diastereomers 6b and 7b in favour of the endo-
fluoro diastereomer.
endothall25 and -homosteroids.26
D
Alsovinylsulfones are known as active dienophiles,27 which were
used as synthetic equivalents of ethylenes28 in [4þ2]-cycloaddition
reactions followed by reductive elimination of the sulfonic group
(mercury amalgam in most cases29) or as synthetic equivalents of
acetylenes30 in case of subsequent
b-elimination of sulfinic acid from
the corresponding Diels–Alder adduct using a strong base (e.g.,
t-BuOK31). Thus, a similar synthetic sequence might be a very con-
venient method for selective introduction of a vinylic fluorine
The structure of diastereomer 6a was confirmed by X-ray anal-
ysis (Fig. 3).
Table 1
Synthesis of
a
-fluoro-
b
-arylvinyl sulfones 2
E/Z ratio 1a
Ar
E/Z ratio 2a
Yield of 2 (%)
Table 2
a
b
c
d
e
f
4-O2NC6H4–
4-ClC6H4–
Ph
78:22
86:14
85:15
83:17
78:22
83:17
85:15
89:11
94:6
88:12
89:11
91:9
90
86
89
88
79
72
75
Synthesis of the Diels–Alder adducts 4 and 5
Ar
Reaction time (h)
Yield of 4þ5 (%)
4-MeOC6H4–
a
b
c
d
e
4-O2NC6H4-
4-ClC6H4–
Ph
4-MeOC6H4–
4-MeO2CC6H4–
7
12
23
54
8
87
65
53
81
67
4-MeO2CC6H4–
2-MeOC6H4–
4-MeC6H4–
80:20
92:8
g
a
determined by 1H NMR spectroscopy.

A.V. Shastin et al. / Tetrahedron 64 (2008) 9725–9732
9727
O1
N1
C10
O28
C11
C12
C4
C5
C3
C9
N27
O29
C31-C36
O2
C21-C26
C2
C2
C8
C7
C13
C3
C9
O12
O11
C6
F1
C4
O1
C1
S1
C5
C6
S1
C1
C10
O3
O4
F1
C19
C17
C14
C15
C13-C18
C19
C7
C101-C106
C18
C8
C16
C20
Figure 1. X-ray structure of 4a.
Figure 3. X-ray structure of 6a.
the [4þ2]-cycloadducts of 1,3-dienes and 1-aryl-2-fluo-
roacetylenes. The chemistry of fluoroacetylenes is almost not in-
vestigated. This might be due to the instability and explosive
behaviour of some fluoroacetylenes. Only perfluoro-3-methylbut-
1-yne and perfluoropropyne have been used in cycloadditions so
far.34 2-Fluoro-1-phenylacetylene itself was formed as one of the
products of thermal decomposition of the lithium derivative of
C4
C3
C7
C1
C8
C13
C6
C12
N1
C5
C9
O3
C1
F1
C10
C11
O1
trans-a,b-difluorostyrene. However, the compound was not iso-
O2
S1
lated and the spectroscopic properties and reactivity were not
C19
investigated.35
O4
C14
In order to prove the above-mentioned hypothetic pathway
towards 2-fluoronorbornadienes and corresponding 7-oxa-de-
rivatives, we treated the mixture of the cycloadducts 4a and 5a and
pure diastereomers 6a and 6b, which all have the proton and the
arylsulfonyl group in cis-position, with potassium tert-butoxide in
THF. In all cases, the elimination was complete at room temperature
in few minutes and the target compounds 8, 9a and 9b were iso-
lated in 60–65% yields. The 2-fluoronorbornadiene 8 is a thermo-
labile compound, which decomposed at room temperature in a few
hours. The corresponding 7-oxa analogues 9a and 9b were found to
be more stable at room temperature, but complete decomposition
was observed after several days (Scheme 5).
C18
C17
C15
C16
C20
Figure 2. X-ray structure of 5a.
It should be noted, that in neither of the mentioned reactions
any product derived from the minor Z-alkenes was isolated. We
consider that the most probable explanation of this fact could be
the loss of corresponding products during purification due to their
low amount (less than 10%) in reaction mixture.
We also tried p-toluenesulfinic acid elimination from the Diels–
Alder adduct 3. In this case the formation of the non-fluorinated
product 10 occurred by HF elimination. Subsequent spontaneous
oxidation of the intermediary cyclohexadiene leads to the biphenyl
Ph
Ph
Ph
F
O
O
Ar
Ar
F
150 °C
toluene
Tos
Ar
O
NO2
NO2
F
Tos
Ph
Ph
6
t-BuOK
Tos
Ph
F
2
7
THF, RT
F
a Ar = 4-O2N-C6H4
b Ar = 4-Cl-C6H4
94 %
82 %
75
89
:
:
25
11
Tos
4a, 5a
60%
8
Scheme 4. Reaction of the
a
-fluoro-b-arylvinyl sulfones
2
with diphenyl-
isobenzofuran.
Ph
O
Ph
O
Ar
Tos
t-BuOK
THF, RT
Ar
Ph
Ph
F
2.3. Elimination reactions of 4-methylphenylsulfonyl group
F
6
9
a Ar = 4-O2N-C6H4
b Ar = 4-Cl-C6H4
62%
65%
We have seen above that the arylsulfonyl group and the vicinal
proton are in a cis-configuration. Thus,
b-elimination of arylsulfinic
acid from the Diels–Alder adducts should provide a formal access to
Scheme 5. Elimination of p-toluenesulfinic acid from Diels–Alder adducts.

9728
A.V. Shastin et al. / Tetrahedron 64 (2008) 9725–9732
10. Its structure was established by ESI-MS and 1H NMR spectra
(Scheme 6).
4.3. General procedure for the synthesis of the
arylvinyl sulfones 2
a-fluoro-b-
A one-neck 50 ml round bottom flask was charged with the
corresponding -bromo- -fluorostyrene 1 (5 mmol), TosNa$2H2O
NO2
NO2
b
b
t-BuOK
THF, RT
(0.60 g, 6 mmol), dry N-methylpyrolidinone (5 ml) and flushed
with argon. The reaction mixture was heated under reflux at
180–185 ꢀC for 8–10 h (TLC control). After cooling down to room
temperature, the reaction mixture was quenched with water
(100 ml). The organic phase was separated and the aqueous phase
was extracted with CH2Cl2 (3ꢁ20 ml). The combined extract was
washed with brine and dried over sodium sulfate. After evaporation
of the solvent, the residue was purified by column chromatography
on silica gel (hexane/CH2Cl2, 2:1) to afford the corresponding sul-
fones 2. The (E)- and (Z)-isomers of 2 could not be separated by
column chromatography.
Tos
Tos
F
3
10
Scheme 6. Elimination of HF from Diels–Alder adduct 3.
3. Conclusions
We discovered a new synthetic pathway towards
vinyl sulfones 2 by direct nucleophilic substitution of bromine in
bromo- -fluorostyrenes 1 with 4-methylphenylsulfinate. The reactions
a-fluoro-b-aryl-
b-
b
proceeded stereoselectively with 72–90% yields. The isomers with (E)-
configuration of the double bond were formed preferentially with
retention of the configuration. The presence of the strong electron-
withdrawing 4-methylphenylsulfonyl group at the double bond enables
compounds 2 to react as dienophiles in Diels–Alder reactions with
active dienes, like 2,3-dimethylbutadiene and cyclopentadiene giving
diastereomeric cycloadducts in the latter case. In the major product the
fluorine substituent is attached in exo-position. In contrast, the corre-
sponding reactions of 2a and 2b with diphenylisobenzofuran gave
preferentially the Diels–Alder adducts with fluorine in the endo-posi-
tion. As a proof of principle, the elimination of the 4-methyl-
phenylsulfonyl group from the Diels–Alder adducts 4a,5a and 6a,6b
gave a 2-fluoronorbornadiene 8 and the 7-oxa analogues 9, respectively,
which are the formal Diels–Alder products of cyclopentadiene or
diphenylisobenzofuran with the 1-aryl-2-fluoroacetylenes.
4.3.1. 1-Fluoro-2-(4-nitrophenyl)vinyl-4-methylphenyl sulfone (2a)
Mixture of E/Z isomers (89:11 after purification); yellowish
solid (1.44 g, 90%). IR (Nujol):
n
¼1350, 1520, 1600 (C]C) cmꢂ1
.
(E)-Isomer: 1H NMR (400 MHz, CDCl3):
d 2.49 (s, 3H, Me), 7.12 (d,
1H, CH]CF, J¼33.5 Hz), 7.43 (d, 2H, Tos, J¼8.0 Hz), 7.74 (d, 2H, 4-
NO2C6H4–, J¼8.1 Hz), 7.91 (d, 2H, Tos, J¼8.0 Hz), 8.25 (d, 2H, 4-
NO2C6H4–, J¼8.1 Hz); 13C NMR (100 MHz, CDCl3):
d 21.8 (Me),
112.4 (CH), 124.1 (CH), 129.0 (CH), 130.3 (CH), 130.8 (d, CH,
J¼7.3 Hz), 133.6, 135.7 (d, J¼3.7 Hz), 146.4, 148.2, 156.3 (d,
CH]CF, J¼311.0 Hz). (Z)-Isomer: 1H NMR (400 MHz, CDCl3):
d
2.49 (s, 3H, Me), 6.90 (d, 1H, CH]CF, J¼20.2 Hz), 7.40 (d, 2H,
Tos, J¼8.0 Hz), 7.62 (d, 2H, 4-NO2C6H4–, J¼8.3 Hz), 7.78 (d, 2H,
Tos, J¼8.0 Hz), the other signals are identical to those of the (E)-
isomer; ESI-MS (m/z): calcd for C15H12FNO4SNa [M]þ 344.0369,
found 344.0363.
4.3.2. 1-Fluoro-2-(4-chlorophenyl)vinyl-4-methylphenyl
sulfone (2b)
4. Experimental
4.1. General
Mixture of E/Z isomers (94:6 after purification); yellowish solid
(1.33 g, 86%). IR (Nujol):
(400 MHz, CDCl3):
n
¼1600 (C]C) cmꢂ1. (E)-Isomer: 1H NMR
d
2.48 (s, 3H, Me), 7.01 (d, 1H, CH]CF,
1H, 13C and 19F NMR spectra were recorded on Bruker ARX 300
and Bruker AMX 400 spectrometers in CDCl3 with TMS, CDCl3 and
CCl3F as internal standards. IR spectra were obtained with an UR-20
spectrometer. Mass spectra (ESI-MS) were measured on a MicroTof
Bruker Daltonics. Column and TLC chromatographies were per-
formed on silica gel Merck 60 and Merck 60F254 plates, respectively.
J¼34.4 Hz), 7.38 (d, 2H, 4-ClC6H4–, J¼8.6 Hz), 7.41 (d, 2H, Tos,
J¼8.4 Hz), 7.51 (d, 2H, 4-ClC6H4–, J¼8.6 Hz), 7.91 (d, 2H, Tos,
J¼8.4 Hz); 13C NMR (100 MHz, CDCl3):
d 21.7 (Me), 113.8 (CH), 128.1
(d, J¼4.4 Hz), 128.8 (CH), 129.3 (CH), 130.2 (CH), 131.4 (d, CH,
J¼2.2 Hz), 134.3, 136.3 (d, J¼2.9 Hz), 145.9, 154.3 (d, CH]CF,
J¼305.9 Hz). (Z)-Isomer: 1H NMR (400 MHz, CDCl3):
d 6.82 (d, 1H,
b
-Bromo-b-fluorostyrenes 1 were synthesized according to our
CH]CF, J¼21.5 Hz), 7.78 (d, 2H, Tos, J¼8.3 Hz), the other signals are
previously reported procedure.10d 2,3-Dimethylbutadiene and
cyclopentadiene were distilled prior to use.
identical to those of the (E)-isomer; ESI-MS (m/z): calcd for
C
15H12ClFO2SNa [Mþ] 333.0123, found 333.0128.
4.3.3. 1-Fluoro-2-phenylvinyl-4-methylphenyl sulfone (2c)
4.2. General procedure for the synthesis of the
fluorostyrenes 1
b
-bromo-b-
Mixture of E/Z isomers (88:12 after purification); white solid
(1.12 g, 86%). IR (Nujol):
(400 MHz, CDCl3):
n
¼1620 (C]C) cmꢂ1. (E)-Isomer: 1H NMR
d
2.48 (s, 3H, Me), 7.05 (d, 1H, CH]CF,
A solution of the corresponding aldehyde (2 mmol) in ethanol
(8 ml) was added dropwise to a solution of hydrazine hydrate
(0.11 ml, 2.1 mmol) in ethanol (4 ml) with intensive stirring. After
completion of hydrazone formation (TLC monitoring), ethylenedi-
amine (0.2 ml, 1.5 equiv) and CuCl (0.002 g, 1 mol %) were added.
The reaction mixture was cooled to 0 ꢀC and CBr3F (0.3 ml,1.5 equiv)
was added dropwise with stirring. The reaction mixture was stirred
for 4–48 h at room temperature to the completion (TLC monitoring)
and 5% aq HCl (50 ml) was added. The reaction products were
extracted with CH2Cl2 (3ꢁ30 ml) and the combined extract was
dried with Na2SO4. The solvent was evaporated and the residue was
purified by column chromatography on silica gel (hexane/CH2Cl2,
J¼34.6 Hz), 7.38–7.44 (m, 5H, Ph, Tos), 7.56–7.62 (m, 2H, Ph), 7.91 (d,
2H, Tos, J¼8.1 Hz); 13C NMR (100 MHz, CDCl3):
d 21.7 (Me), 115.1,
128.7, 129.0, 130.1, 130.2, 130.3, 130.3 (d, J¼2.2 Hz), 134.5, 145.7,
153.9 (d, CH]CF, J¼305.2 Hz). (Z)-Isomer: 1H NMR (400 MHz,
CDCl3):
d
6.90 (d, 1H, CH]CF, J¼21.7 Hz), 7.78 (d, 2H, Tos, J¼8.6 Hz);
13C NMR (100 MHz, CDCl3):
d
128.1, 129.6 (d, J¼3.7 Hz), the other
signals are identical to those of the (E)-isomer; ESI-MS (m/z): calcd
for C15H13FO2SNa [Mþ] 299.0518, found 299.0512.
4.3.4. 1-Fluoro-2-(4-methoxyphenyl)vinyl-4-methylphenyl
sulfone (2d)
Mixture of E/Z isomers (88:11 after purification); white solid
gradient). The (E)- and (Z)-isomers of
b
-bromo-
b-fluorostyrenes
(1.35 g, 88%). IR (Nujol):
(400 MHz, CDCl3):
n
¼1610 (C]C) cmꢂ1. (E)-Isomer: 1H NMR
110d could not be separated by column chromatography.
d
2.47 (s, 3H, Me), 3.85 (s, 3H, MeO), 6.92 (d, 2H,

A.V. Shastin et al. / Tetrahedron 64 (2008) 9725–9732
9729
4-MeOC6H4–, J¼8.8 Hz), 7.01 (d, 1H, CH]CF, J¼35.1 Hz), 7.39 (d, 2H,
4.4. General procedure for cycloaddition reactions of the
-fluoro- -arylvinyl sulfones 2 with 2,3-dimethylbutadiene
and cyclopentadiene
Tos, J¼8.2 Hz), 7.54 (d, 2H, 4-MeOC6H4–, J¼8.8 Hz), 7.90 (d, 2H, Tos,
a
b
J¼8.3 Hz); 13C NMR (100 MHz, CDCl3):
d
21.7 (Me), 55.6 (MeO),
114.4, 115.0 (CH), 122.2 (d, C–CH]CF, J¼3.7 Hz), 128.6 (CH), 130.1
(CH), 131.9 (d, CH, J¼7.3 Hz), 134.9, 145.5, 149.7 (CH]CF,
J¼300.1 Hz), 161.5 (d, J¼2.9 Hz). (Z)-Isomer: 1H NMR (400 MHz,
The corresponding
a-fluoro-b-arylvinyl sulfone 2 (1 mmol) and
the diene (1.0 ml) were heated in a sealed glass tube with a Young-
tap. The excess of the diene was evaporated at reduced pressure
and the residue was purified by column chromatography on silica
gel (cyclohexane/ethyl acetate, 20:1).
CDCl3):
d
3.86 (s, 3H, MeO), 6.83 (d, 1H, CH]CF, J¼23.0 Hz), 7.36 (d,
2H, Tos, J¼8.3 Hz), 7.48 (d, 2H, 4-MeOC6H4–, J¼8.6 Hz), 7.81 (d, 2H,
Tos, J¼8.3 Hz); 13C NMR (100 MHz, CDCl3):
d 55.3 (MeO), 113.6 (CH),
118.7 (CH), 128.6 (CH), 129.9 (CH), the other signals are identical to
those of the (E)-isomer; ESI-MS (m/z): calcd for C16H15FO3SNa [Mþ]
329.0624, found 329.0618.
4.4.1. 1-(6-Fluoro-3,4-dimethyl-6-[(4-methylphenyl)-
sulfonyl]cyclohex-3-en-1-yl)-4-nitrobenzene (3)
Obtained from 2a by heating with 2,3-dimethylbutadiene at
4.3.5. Methyl 4-(2-fluoro-2-[(4-methylphenyl)-
sulfonyl]vinyl)benzoate (2e)
150 ꢀC for 7 h. Pale brown solid (0.36 g, 89%). Mp 155–157 ꢀC. 1H
NMR (300 MHz, CDCl3):
d 1.68 (s, 6H, Me), 2.28 (dd, 1H, –CH2–,
Mixture of E/Z isomers (91:9 after purification); white solid
J¼17.3, 5.7 Hz), 2.36 (s, 3H, CH3), 2.38–2.53 (m, 2H, –CH2–), 2.85–
3.05 (m, 1H, –CH2–), 3.65 (dq, 1H, –CH–Ar, J¼32.3, 5.9 Hz), 7.07 (d,
2H, Ar, J¼8.1 Hz), 7.32 (d, 2H, Ar, J¼8.1 Hz), 7.37 (d, 2H, Tos,
J¼8.5 Hz), 7.90 (d, 2H, Tos, J¼8.5 Hz); 19F NMR (282 MHz, CDCl3):
(1.32 g, 79%). IR (Nujol):
NMR (400 MHz, CDCl3):
n
¼1610, 1720 (C]C) cmꢂ1. (E)-Isomer: 1H
d
2.49 (s, 3H, Me), 3.94 (s, 3H, CO2CH3), 7.08
(d, 1H, CH]CF, J¼34.4 Hz), 7.42 (d, 2H, Tos, J¼8.2 Hz), 7.64 (d, 2H, 4-
MeO2CC6H4–, J¼8.2 Hz), 7.92 (d, 2H, Tos, J¼8.2 Hz), 8.06 (d, 2H, 4-
d
ꢂ160.5; 13C NMR (75 MHz, CDCl3):
d 21.6 (Me, Tos), 18.2 (Me), 18.5
MeO2CC6H4–, J¼8.2 Hz); 13C NMR (100 MHz, CDCl3):
d
21.8 (Me),
(Me), 36.8 (d, –CH2–, J¼22.3 Hz), 38.2 (d, –CH2–, J¼4.7 Hz), 44.0
(–CH–, J¼18.6 Hz), 109.4 (d, –CF–, J¼225.8 Hz), 120.6, 123.0 (CH),
125.1, 129.2 (CH), 129.7 (d, CH, J¼1.8 Hz), 130.2 (d, CH, J¼2.7 Hz),
132.4, 145.2 (Ar), 146.2, 147.0 (–CH]CH–); ESI-MS (m/z): calcd for
52.4 (CO2CH3), 113.8 (CH), 128.9 (CH), 129.9 (CH), 130.0 (CH), 130.3
(CH), 131.3 (d, J¼2.2 Hz), 133.8 (d, J¼3.7 Hz), 134.0, 146.1, 155.2 (d,
CH]CF, J¼308.1 Hz), 166.2 (CO2CH3). (Z)-Isomer: 1H NMR
(400 MHz, CDCl3):
d
6.90 (d, 1H, CH]CF, J¼20.1 Hz), 7.52 (d, 2H, 4-
C
21H21FNO4SNa [Mþ] 426.1151, found 426.1141.
MeO2CC6H4–, J¼8.2 Hz), 7.76 (d, 2H, Tos, J¼8.2 Hz); 13C NMR
(100 MHz, CDCl3):
d
52.0 (CO2CH3), 129.6 (CH), 129.8 (CH), 134.5,
4.4.2. 5-Fluoro-5-[(4-methylphenyl)sulfony]-6-(4-nitrophenyl)-
bicyclo[2.2.1]hept-2-ene (4a,5a)
167.2 (CO2CH3), the other signals are identical to those of the (E)-
isomer; ESI-MS (m/z): calcd for C17H15FO4SNa [M]þ 357.0567, found
357.0573.
Obtained from 2a by heating with cyclopentadiene at 150 ꢀC for
7 h. White solid (0.34 g, 87%). Major diastereomer 4a: 1H NMR
(300 MHz, CDCl3):
d 1.73–1.82 (m, 1H, –CH2–), 2.35–2.48 (m, 1H,
4.3.6. 1-Fluoro-2-(2-methoxyphenyl)vinyl-4-methylphenyl
sulfone (2f)
–CH2–), 2.43 (s, 3H, CH3), 3.29 (br s,1H, –CH–), 3.44 (br s,1H, –CH–),
4.15 (dd, 1H, –CH–Ar, J¼13.7, 2.9 Hz), 6.23 (dd, 1H, –CH], J¼5.5,
3.3 Hz), 6.62 (dd, 1H, –CH], J¼5.5, 2.9 Hz), 7.29–7.39 (m, 4H, Tos,
Ar), 7.80 (d, 2H, Tos, J¼8.1 Hz), 8.04 (d, 2H, Ar, J¼8.8 Hz); 19F NMR
Mixture of E/Z isomers (80:20 after purification); white solid
(1.10 g, 72%). IR (Nujol):
(400 MHz, CDCl3):
n
¼1610 (C]C) cmꢂ1. (E)-Isomer: 1H NMR
d
2.47 (s, 3H, Me), 3.89 (s, 3H, MeO), 6.94 (t, 1H,
(282 MHz, CDCl3):
d
ꢂ155.9 (d, J¼15.3 Hz); 13C NMR (75 MHz,
2-MeOC6H4–, J¼8.0 Hz), 7.33–7.37 (m, 2H, 2-MeOC6H4–), 7.39 (d,
2H, Tos, J¼8.0 Hz), 7.59 (d, 1H, CH]CF, J¼36.4 Hz), 7.73 (dd, 1H, 2-
MeOC6H4–, J¼8.0, 1.3 Hz), 7.92 (d, 2H, Tos, J¼8.0 Hz); 13C NMR
CDCl3): d 21.7 (Me), 48.5 (–CH2–), 48.6 (–CH–), 50.4 (d, –CH–,
J¼20.4 Hz), 51.4 (d, –CH–, J¼16.5 Hz), 114.9 (d, –CF–, J¼236.5 Hz),
122.9 (CH), 129.8 (CH), 130.1 (CH), 130.6 (CH), 131.9, 143.9 (d,
J¼3.8 Hz), 145.9, 146.9 (Ar), 134.1 (d, J¼6.4 Hz), 140.0 (–CH]CH–).
(100 MHz, CDCl3):
d 21.7 (Me), 55.6 (MeO), 114.1, 109.2 (CH), 110.9
(CH), 118.5 (d, C–CH]CF, J¼4.4 Hz), 120.8 (CH), 128.7 (CH), 130.1
(CH), 130.4 (d, CH, J¼13.2 Hz), 131.8 (CH), 134.8, 145.5, 153.6
(CH]CF, J¼303.0 Hz), 157.6. (Z)-Isomer: 1H NMR (400 MHz,
Minor diastereomer 5a: 1H NMR (300 MHz, CDCl3):
d 1.96 (d, 1H,
–CH2–, J¼9.5 Hz), 2.30 (d, 1H, –CH2–, J¼9.5 Hz), 2.47 (s, 3H, CH3),
2.78 (br s, 1H, –CH–), 3.28 (br s, 1H, –CH–), 3.78 (dd, 1H, –CH–Ar,
J¼15.5, 2.4 Hz), 6.36 (br s, 1H, –CH]), 6.62 (br s, 1H, –CH]), 7.37 (d,
2H, Tos, J¼8.0 Hz), 7.58 (d, 2H, Ar, J¼8.8 Hz), 7.77 (d, 2H, Tos,
J¼8.0 Hz), 8.17 (d, 2H, Ar, J¼8.8 Hz); 19F NMR (282 MHz, CDCl3):
CDCl3):
d 2.46 (s, 3H, MeO), 3.82 (s, 3H, MeO), 7.79 (d, 2H, Tos,
J¼8.3 Hz); 13C NMR (100 MHz, CDCl3):
d 55.4 (MeO), 110.1 (CH),
120.0 (CH), 128.8 (CH), 129.8 (CH), 132.2 (CH), 135.1, 145.4, 157.1.
Anal. Calcd for C16H15FO3S: C, 62.73; H, 4.94. Found: C, 62.60; H
4.75.
d
ꢂ149.3 (d, J¼15.3 Hz); 13C NMR (75 MHz, CDCl3):
d 22.3 (Me), 48.1
(–CH–), 48.4 (–CH2–), 50.6 (d, –CH–, J¼6.4 Hz), 50.9 (d, –CH–,
J¼16.5 Hz), 113.4 (d, –CF–, J¼239.1 Hz), 123.7 (CH), 130.2 (CH), 130.3
(CH), 130.8 (CH), 132.4, 133.5, 147.1 (Ar), 133.9 (d, J¼6.4 Hz), 141.2
4.3.7. 1-Fluoro-2-(4-methylphenyl)vinyl-4-methylphenyl
sulfone (2g)
(–CH]CH–); ESI-MS (m/z): calcd for
C
20H18FNO4SNa [Mþ]
Mixture of E/Z isomers (92:8 after purification); white solid
410.0838, found 410.0831. Anal. Calcd for C20H18FNO4S: C, 62.00; H,
4.68; N, 3.62. Found: C, 61.99; H, 4.45; N, 3.54.
(1.09 g, 75%). IR (Nujol):
(400 MHz, CDCl3):
n
¼1610 (C]C) cmꢂ1. (E)-Isomer: 1H NMR
d
2.36 (s, 3H, Me), 2.45 (s, 3H, Me), 7.04 (d, 1H,
CH]CF, J¼35.4 Hz), 7.19 (d, 2H, 4-MeC6H4–, J¼8.1 Hz), 7.38 (d, 2H,
4.4.3. 5-Fluoro-5-[(4-methylphenyl)sulfonyl]-6-(4-chlorophenyl)-
bicyclo[2.2.1]hept-2-ene (4b,5b)
Tos, J¼8.3 Hz), 7.46 (d, 2H, 4-MeC6H4–, J¼8.1 Hz), 7.91 (d, 2H, Tos,
J¼8.3 Hz); 13C NMR (100 MHz, CDCl3):
d
21.3 (Me), 21.5 (Me), 115.1,
Obtained from 2b by heating with cyclopentadiene at 150 ꢀC for
128.5, 128.7, 129.6, 130.0, 130.1, 134.5, 140.7 (d, J¼2.2 Hz), 145.5,
12 h. White solid (0.24 g, 65%). Major diastereomer 4b: 1H NMR
153.1 (CH]CF, J¼303.0 Hz). (Z)-Isomer: 1H NMR (400 MHz,
(300 MHz, CDCl3):
d 1.67–1.76 (m, 1H, –CH2–), 2.33 (d, 1H, –CH2–,
CDCl3):
d
2.36 (s, 3H, Me), 2.45 (s, 3H, Me), 6.85 (d, 1H, CH]CF,
J¼9.8 Hz), 2.42 (s, 3H, CH3), 3.20 (br s, 1H, –CH–), 3.43 (br s, 1H,
–CH–), 3.99 (dd, 1H, –CH–Ar, J¼14.1, 3.0 Hz), 6.18 (dd, 1H, –CH],
J¼5.2, 3.4 Hz), 6.60 (dd, 1H, –CH], J¼5.2, 2.9 Hz), 7.04–7.38 (m, 6H,
Tos, Ar), 7.78 (d, 2H, Tos, J¼7.9 Hz); 19F NMR (282 MHz, CDCl3):
J¼22.5 Hz), 7.33 (d, 2H, J¼8.3 Hz), 7.79 (d, 2H, 4-, J¼8.3 Hz); 13C
NMR (100 MHz, CDCl3):
d
21.2 (Me), 126.6 (d, J¼3.7 Hz), 128.6,
129.8, 129.9 (d, J¼2.9 Hz), 134.9, 139.2, 145.6, 152.7 (CH]CF,
J¼288.3 Hz), the other signals are identical to those of the (E)-
isomer. Anal. Calcd for C16H15FO2S: C, 66.19; H, 5.21. Found: C,
66.02; H 5.04.
d
ꢂ156.1 (d, J¼15.3 Hz); 13C NMR (75 MHz, CDCl3):
d 22.2 (Me), 48.9
(–CH2–), 49.0 (–CH–), 50.7 (d, –CH–, J¼20.3 Hz), 51.7 (d, –CH–,
J¼17.8 Hz), 115.1 (d, –CF–, J¼236.5 Hz), 128.3 (CH), 131.5 (CH), 130.2

9730
A.V. Shastin et al. / Tetrahedron 64 (2008) 9725–9732
(CH), 132.7, 135.1, 136.7, 146.0 (Ar), 134.0 (d, J¼5.1 Hz), 140.8
(–CH]CH–). Minor diastereomer 5b: 1H NMR (300 MHz, CDCl3):
2.40 (s, 3H, CH3), 3.25 (br s, 1H, –CH–), 3.47 (br s, 1H, –CH–), 3.88 (s,
3H, CO2CH3), 4.06 (dd, 1H, –CH–Ar, J¼14.1, 3.1 Hz), 6.21 (dd, 1H,
–CH], J¼5.5, 3.5 Hz), 6.62 (dd, 1H, –CH], J¼5.5, 2.9 Hz), 7.25–7.41
(m, 4H, Tos, Ar), 7.78 (d, 2H, Tos, J¼8.1 Hz), 7.83 (d, 2H, Ar, J¼8.3 Hz);
d
1.90 (d, 1H, –CH2–, J¼9.3 Hz), 2.45 (s, 3H, CH3), 2.76 (br s,1H, –CH–
), 3.64 (dd, 1H, –CH–Ar, J¼15.6, 2.1 Hz), 6.32 (br s, 1H, –CH]); 19F
NMR (282 MHz, CDCl3):
d
ꢂ149.4 (d, J¼15.3 Hz); 13C NMR (75 MHz,
19F NMR (282 MHz, CDCl3):
d
ꢂ156.0 (d, J¼15.3 Hz); 13C NMR
CDCl3):
d
22.2 (Me), 48.3 (–CH–), 48.5 (–CH2–), 50.3 (d, –CH–,
(75 MHz, CDCl3): d 21.7 (Me), 48.5 (–CH2–), 48.7 (–CH–), 50.4 (d,
J¼6.4 Hz), 114.0 (d, –CF–, J¼236.5 Hz), 128.7 (CH), 131.1 (CH), 130.2
(CH), 130.5 (CH), 133.2, 135.2, 137.0, 146.0 (Ar); 133.6 (d, J¼5.1 Hz),
141.5 (–CH]CH–); ESI-MS (m/z): calcd for C20H18ClFO2SNa [Mþ]
399.0598, found 399.0595. Anal. Calcd for C20H18ClFO2S: C, 63.74;
H, 4.81. Found: C, 63.42; H 4.58.
–CH–, J¼20.4 Hz), 51.7 (d, –CH–, J¼15.3 Hz), 52.1 (CO2Me), 114.9 (d,
–CF–, J¼236.5 Hz), 129.7 (CH), 128.9 (CH), 130.0 (CH), 132.2, 136.4,
145.6 (Ar), 133.6 (d, J¼7.6 Hz), 140.5 (–CH]CH–), 167.0 (CO2Me).
Minor diastereomer 5e: 1H NMR (300 MHz, CDCl3):
d 1.92 (d, 1H,
–CH2–, J¼9.5 Hz), 2.41 (s, 3H, CH3), 2.77 (br s, 1H, –CH–), 3.25 (br s,
1H, –CH–), 3.72 (dd, 1H, –CH–Ar, J¼15.4, 2.4 Hz), 3.90 (s, 3H,
CO2CH3), 6.31–6.36 (m, 1H, –CH]), 6.58–6.60 (m, 1H, –CH¼); 19F
4.4.4. 5-Fluoro-5-((4-methylphenyl)sulfonyl)-6-phenyl-
bicyclo[2.2.1]hept-2-ene (4c,5c)
NMR (282 MHz, CDCl3):
CDCl3): d 21.7 (Me), 48.2 (–CH2–), 48.4 (–CH2–), 50.5 (d, –CH–,
d
ꢂ149.4 (d, J¼15.3 Hz); 13C NMR (75 MHz,
Obtained from 2c by heating with cyclopentadiene at 150 ꢀC for
23 h. White solid (0.18 g, 53%). Major diastereomer 4c: 1H NMR
J¼17.8 Hz), 51.8 (d, –CH–, J¼15.3 Hz), 113.9 (d, –CF–, J¼239.1 Hz),
129.4 (CH), 129.1 (CH), 130.3 (CH), 132.7, 136.6, 145.5 (Ar), 133.3 (d,
J¼5.1 Hz), 141.1 (–CH]CH–), 166.0 (CO2Me); ESI-MS (m/z): calcd for
(300 MHz, CDCl3):
d 1.66–1.74 (m, 1H, –CH2–), 2.35 (d, 1H, –CH2–,
J¼9.4 Hz), 2.40 (s, 3H, CH3), 3.23 (br s, 1H, –CH–), 3.46 (br s, 1H,
–CH–), 4.00 (dd, 1H, –CH–Ar, J¼14.3, 3.1 Hz), 6.18 (dd, 1H, –CH],
J¼5.5, 3.5 Hz), 6.64 (dd, 1H, –CH], J¼5.5, 2.9 Hz), 7.08–7.38 (m, 7H,
Tos, Ar), 7.79 (d, 2H, Tos, J¼7.5 Hz); 19F NMR (282 MHz, CDCl3):
C
22H21FO4SNa [Mþ] 423.1042, found 423.1037.
4.5. General procedure for cycloaddition reactions of the
a-
d
ꢂ156.0 (d, J¼15.3 Hz); 13C NMR (75 MHz, CDCl3):
d
22.1 (Me), 48.9
fluoro- -arylvinyl sulfones 2 with 1,3-diphenylisobenzofuran
b
(–CH2–), 49.1 (–CH–), 50.7 (d, –CH–, J¼17.8 Hz), 52.2 (d, –CH–,
J¼17.8 Hz), 115.3 (d, –CF–, J¼236.5 Hz), 127.6, 128.1 (CH), 127.4 (CH),
130.1 (CH), 130.2 (CH), 130.5 (CH), 136.6, 145.8 (Ar), 133.6 (d,
J¼5.1 Hz), 141.2 (–CH]CH–). Minor diastereomer 5c: 1H NMR
The corresponding a-fluoro-b-arylvinyl sulfone 2 (1 mmol), 1,3-
diphenylisobenzofuran (270 mg, 1 mmol) and toluene (1.0 ml)
were heated in a sealed glass tube with a Young-tap. Toluene was
evaporated at reduced pressure and the residue was purified by
column chromatography on silica gel (cyclohexane/ethyl acetate,
10:1).
(300 MHz, CDCl3):
d
1.90 (d, 1H, –CH2–, J¼9.3 Hz), 2.44 (s, 3H, CH3),
2.78 (br s, 1H, –CH–), 3.23 (br s, 1H, –CH–), 3.67 (dd, 1H, –CH–Ar,
J¼15.7, 2.3 Hz), 6.29–6.35 (m,1H, –CH]), 6.57–6.62 (m,1H, –CH]);
19F NMR (282 MHz, CDCl3):
d
ꢂ149.5 (d, J¼15.3 Hz); 13C NMR
(75 MHz, CDCl3):
d
22.1 (Me), 48.5 (–CH–), 48.6 (–CH2–), 51.0 (d,
4.5.1. 2-Fluoro-2-[(4-methylphenyl)sulfonyl]-3-(4-nitrophenyl)-
1,4-diphenyl-1,2,3,4-tetrahydro-1,4-epoxynaphthalene (6a,7a)
Obtained from 2a by heating with 1,3-diphenylisobenzofuran at
150 ꢀC for 17 h. Major diastereomer 6a: white crystals (0.416 g,
–CH–, J¼17.8 Hz), 114.0 (d, –CF–, J¼239.1 Hz),127.6 (CH), 128.6 (CH),
129.8 (CH), 130.7 (CH), 136.7 (Ar); 141.7 (–CH]CH–); ESI-MS (m/z):
calcd for C20H19FO2SNa [Mþ] 365.0987, found 365.0971. Anal. Calcd
for C20H19FO2S: C, 70.15; H, 5.59. Found: C, 70.62; H, 5.57.
70%), mp 224–226 ꢀC. 1H NMR (300 MHz, CDCl3):
d 2.35 (s, 3H,
CH3), 4.69 (d, 1H, –CH–Ar, J¼14.0 Hz), 6.37 (dd, 2H, J¼8.9, 2.1 Hz),
6.99 (d, 2H, J¼7.9 Hz), 7.04 (d, 1H, J¼7.2 Hz), 7.16 (dd, 2H, J¼8.3,
1.5 Hz), 7.26–7.43 (m, 10H), 7.53 (d, 1H, J¼7.4 Hz), 7.61 (d, 2H,
J¼7.4 Hz), 7.94 (d, 2H, J¼8.9 Hz); 19F NMR (282 MHz, CDCl3):
4.4.5. 5-Fluoro-5-[(4-methylphenyl)sulfonyl]-6-(4-
methoxyphenyl)-bicyclo[2.2.1]hept-2-ene (4d,5d)
Obtained from 2d by heating with cyclopentadiene at 150 ꢀC for
54 h. White solid (0.30 g, 81%). Major diastereomer 4d: 1H NMR
d
ꢂ148.53 (d, J¼14.0 Hz); 13C NMR (75 MHz, CDCl3):
d 21.7 (Me),
(300 MHz, CDCl3):
d
1.61–1.72 (m, 1H, –CH2–), 2.32 (d, 1H, –CH2–,
59.5 (d, J¼16.0 Hz), 90.3 (d, J¼22.8 Hz), 90.9, 112.3 (d, J¼250.4 Hz),
122.5, 122.6, 123.3, 125.6, 126.3, 128.0, 128.1, 128.4, 128.7, 129.4,
129.6 (d, J¼1.0 Hz), 131.8, 132.3 (d, J¼2.9 Hz), 133.1, 135.7, 139.8,
143.4, 145.0, 147.5; ESI-MS (m/z): calcd for C35H26FNO5SNa [Mþ]
614.1395, found 614.1408.
J¼9.4 Hz), 2.41 (s, 3H, CH3), 3.18 (br s, 1H, –CH–), 3.42 (br s, 1H,
–CH–), 3.74 (s, 3H, CH3O), 3.96 (dd, 1H, –CH–Ar, J¼14.3, 3.1 Hz), 6.16
(dd, 1H, –CH], J¼5.3, 3.3 Hz), 6.63 (dd, 1H, –CH], J¼5.3, 3.0 Hz),
6.69 (d, 2H, Ar, J¼8.7 Hz), 7.03 (d, 2H, Ar, J¼8.7 Hz), 7.28 (d, 2H, Tos,
J¼8.0 Hz), 7.78 (d, 2H, Tos, J¼8.0 Hz); 19F NMR (282 MHz, CDCl3):
Minor diastereomer 7a: white crystals (0.138 g, 24%), mp 131–
d
ꢂ156.1 (d, J¼15.3 Hz); 13C NMR (75 MHz, CDCl3):
d
22.1 (Me), 48.9
133 ꢀC. 1H NMR (300 MHz, CDCl3):
d 2.37 (s, 3H, CH3), 4.47 (d, 1H,
(–CH2–), 49.2 (–CH–), 50.8 (d, –CH–, J¼20.4 Hz), 51.4 (d, –CH–,
J¼17.8 Hz), 55.6 (MeO), 113.5 (CH), 127.9, 130.1 (CH), 130.5 (CH),
131.2 (CH), 136.1, 145.1, 158.3 (Ar), 133.6 (d, J¼5.1 Hz), 141.2
(–CH]CH–). Minor diastereomer 5d: 1H NMR (300 MHz, CDCl3):
–CH–Ar, J¼11.0 Hz), 7.10–7.27 (m, 8H), 7.31–7.41 (m, 4H), 7.47–7.56
(m, 3H), 7.62 (dd, 2H, J¼8.3, 1.5 Hz), 7.68–7.76 (m, 3H), 8.14 (dd, 2H,
J¼7.7, 1.5 Hz); 19F NMR (282 MHz, CDCl3):
d
ꢂ151.08 (d, J¼11.0 Hz);
13C NMR (75 MHz, CDCl3):
d
21.7 (Me), 59.0 (d, J¼16.7 Hz), 91.8, 93.2
d
1.87 (d,1H, –CH2–, J¼9.3 Hz), 2.44 (s, 3H, CH3), 2.75 (br s,1H, –CH–
(d, J¼23.4 Hz), 113.4 (d, J¼253.6 Hz), 119.5, 122.2, 123.8, 126.0, 127.8,
128.0, 128.2, 128.4, 129.0, 129.7, 130.0 (d, J¼2.0 Hz), 131.6, 132.4,
133.3, 134.9, 146.1, 146.7, 148.6. ESI-MS (m/z): calcd for
), 3.18 (br s, 1H, –CH–), 3.65 (dd, 1H, –CH–Ar, J¼15.5, 2.1 Hz), 3.78 (s,
3H, CH3O), 6.27–6.33 (m, 1H, –CH]), 6.55–6.60 (m, 1H, –CH]),
6.82 (d, 2H, Ar, J¼8.8 Hz); 19F NMR (282 MHz, CDCl3):
d
ꢂ149.4 (d,
C
35H26FNO5SNa [Mþ] 614.1395, found 614.1408.
J¼15.3 Hz); 13C NMR (75 MHz, CDCl3):
d 22.1 (Me), 48.5 (–CH2–),
48.6 (–CH–), 50.3 (d, –CH–, J¼17.8 Hz), 50.7 (d, –CH–, J¼20.4 Hz),
113.9 (CH), 127.8, 130.2 (CH), 130.8 (CH), 136.3, 145.0, 157.9 (Ar),
133.4 (d, J¼5.1 Hz), 141.8 (–CH]CH–); ESI-MS (m/z): calcd for
4.5.2. 2-Fluoro-2-[(4-methylphenyl)sulfonyl]-3-(4-chlorophenyl)-
1,4-diphenyl-1,2,3,4-tetrahydro-1,4-epoxynaphthalene (6b,7b)
Obtained from 2b by heating with 1,3-diphenylisobenzofurane
at 150 ꢀC for 67 h. Major diastereomer 6b: white crystals (0.424 g,
C
21H21FO3SNa [Mþ] 395.1093, found 395.1089.
73%), mp 103–105 ꢀC. 1H NMR (300 MHz, CDCl3):
d 2.33 (s, 3H, CH3),
4.4.6. Methyl 4-(3-Fluoro-3-[(4-methylphenyl)sulfonyl]-
bicyclo[2.2.1]hept-5-en-2-yl)benzoate (4e,5e)
4.50 (d, 1H, –CH–Ar, J¼14.4 Hz), 6.08 (dd, 2H, J¼8.6, 2.0 Hz), 6.95–
7.05 (m, 5H), 7.16–7.41 (m, 12H), 7.50 (d, 1H, J¼7.5 Hz), 7.64 (d, 2H,
Obtained from 2e by heating with cyclopentadiene at 150 ꢀC for
J¼6.9 Hz); 19F NMR (282 MHz, CDCl3):
d
ꢂ148.43 (d, J¼14.3 Hz); 13
C
8 h. White solid (0.27 g, 67%). Major diastereomer 4e: 1H NMR
NMR (75 MHz, CDCl3):
d
21.6 (Me), 59.4 (d, J¼16.4 Hz), 90.2 (d,
(300 MHz, CDCl3):
d
1.69–1.78 (m,1H, –CH2–), 2.33–2.38 (m,1H, –CH2–),
J¼22.8 Hz), 90.7, 112.0 (d, J¼249.7 Hz), 122.6, 123.1, 125.7, 126.4,

A.V. Shastin et al. / Tetrahedron 64 (2008) 9725–9732
9731
127.7, 127.8, 128.3, 128.4, 128.5, 129.3, 129.5 (d, J¼1.3 Hz), 130.8 (d,
4.6.4. 4,5-Dimethyl-40-nitro-1,10-biphenyl-2-yl 4-methylphenyl
sulfone (10)
Obtained from 3. Yellow oil (not purified). 1H NMR (300 MHz,
CDCl3): 2.26 (s, 3H, Me), 2.28 (s, 3H, Me), 2.35 (s, 3H, Tos), 6.87 (s,
J¼1.9 Hz), 132.1, 132.7 (d, J¼2.6 Hz), 133.5, 134.0, 136.1, 143.5, 144.8,
145.5; ESI-MS (m/z): calcd for C35H26ClFNO3SNa [Mþ] 603.1173,
found 603.1153.
d
Minor diastereomer 7b: white crystals (0.052 g, 9%), mp 91–
1H, Ar), 6.96 (d, 2H, J¼8.3 Hz, 4-NO2C6H4), 7.09 (d, 2H, J¼8.7 Hz,
Tos), 7.11 (d, 2H, J¼8.3 Hz, 4-NO2C6H4), 7.99 (d, 2H, J¼8.7 Hz, Tos),
8.07 (s, 1H, Ar); ESI-MS (m/z): calcd for C21H19NNaO4S [Mþ]
404.0932, found 404.0930.
92 ꢀC. 1H NMR (300 MHz, CDCl3):
d 2.36 (s, 3H, CH3), 4.33 (d, 1H,
–CH–Ar, J¼11.0 Hz), 6.81 (d, 2H, J¼8.1 Hz), 7.06–7.26 (m, 6H), 7.29–
7.40 (m, 6H), 7.45–7.55 (m, 3H), 7.61 (dd, 2H, J¼8.3, 1.3 Hz), 7.72 (dd,
1H, J¼6.0,1.5 Hz), 8.17 (d, 2H, J¼6.8 Hz); 19F NMR (282 MHz, CDCl3):
d
ꢂ151.11 (d, J¼11.0 Hz); 13C NMR (75 MHz, CDCl3):
d
21.7 (Me), 58.6
4.7. X-ray crystal structure analyses
(d, J¼17.3 Hz), 91.8, 93.0 (d, J¼24.1 Hz), 113.2 (d, J¼252.9 Hz), 119.4,
123.7, 126.2, 127.5, 127.7, 128.2, 128.5, 128.8, 129.6, 130.0 (d,
J¼1.9 Hz), 132.1, 133.5, 135.5, 141.0 (d, J¼5.5 Hz), 145.8, 149.2; ESI-
4.7.1. exo-5-Fluoro-5-[(4-methylphenyl)sulfonyl]-exo-6-(4-
nitrophenyl)-bicyclo[2.2.1]hept-2-ene (4a)
MS (m/z): calcd for
C
35H26ClFNO3SNa [Mþ] 603.1173, found
C
20H18FNO4S, M¼387.41, colourless crystal 0.35ꢁ0.15ꢁ0.15 mm,
603.1167.
a¼11.258(1),
b¼8.839(1),
c¼18.517(1) Å,
b
¼103.14(1)ꢀ,
V¼1794.4(3) Å3, rcalcd¼1.434 g cmꢂ3
,
m
¼1.932 mmꢂ1, empirical ab-
4.6. General procedure for the reactions of cycloadducts 3, 4,
5 and 6 with t-BuOK
sorption correction (0.551ꢃTꢃ0.760), Z¼4, monoclinic, space group
P21/c (No. 14),
l
¼1.54178 Å, T¼223(2) K,
u and 4 scans, 11,830 re-
flections collected (ꢄh,ꢄk,ꢄl), [(sin
q
)/
l
]¼0.60 Åꢂ1
,
3153 in-
(I)],
A 10 ml round bottom flask was charged with a mixture of ad-
ducts 4,5 (1 mmol) or pure adducts 3 and 6 (0.2 mmol) and dry THF
(2 ml) and a solution of t-BuOK (120 mg, 1.05 mmol) (or 27 mg,
0.24 mmol) in dry THF (2 ml) was added dropwise. After comple-
tion of the reaction (TLC control), THF was evaporated in vacuum.
The residue was dissolved in cyclohexane and passed through
a short filter with silica gel in case of 8 and 10 or was purified by
column chromatography on silica gel (cyclohexane/ethyl acetate,
10:1) in case of 9.
dependent (Rint¼0.039) and 2870 observed reflections [Iꢅ2
s
245 refined parameters, R¼0.042, wR2¼0.116, max. residual elec-
tron density 0.34(ꢂ0.33) e Åꢂ3, hydrogen atoms calculated and
refined as riding atoms.
4.7.2. endo-5-Fluoro-5-[(4-methylphenyl)sulfonyl]-endo-6-(4-
nitrophenyl)-bicyclo[2.2.1]hept-2-ene (5a)
C
20H18FNO4S, M¼387.41, colourless crystal 0.50ꢁ0.30ꢁ0.10 mm,
a¼8.237(1),
b¼20.207(1),
c¼11.746(1) Å,
b
¼110.41(1)ꢀ,
V¼1832.3(3) Å3, rcalcd¼1.404 g cmꢂ3
,
m
¼1.892 mmꢂ1, empirical ab-
4.6.1. 2-Fluoro-3-(4-nitrophenyl)bicyclo[2.2.1]hepta-2,5-diene (8)
Obtained from the mixture of 4a and 5a. Colourless, unstable
sorption correction (0.451ꢃTꢃ0.833), Z¼4, monoclinic, space group
P21/n (No. 14),
l
¼1.54178 Å, T¼223(2) K,
u and 4 scans, 8736 re-
solid (0.14 g, 60%). 1H NMR (300 MHz, CDCl3):
d
2.25–2.30 (m,
flections collected (ꢄh,ꢄk,ꢄl), [(sin
q
)/l
]¼0.60 Åꢂ1
,
3072 in-
(I)],
1H, –CH2–), 2.43 (dt, 1H, –CH2–, J¼6.4, 1.4 Hz), 3.48–3.52 (m, 1H,
–CH–), 3.88–3.92 (m, 1H, –CH–), 7.07 (d, 2H, Ar, J¼8.1 Hz), 6.95
(ddd, 1H, –CH], J¼5.0, 3.1, 0.5 Hz), 7.05 (pent, 1H, –CH],
J¼2.4 Hz), 7.51 (d, 2H, Ar, J¼8.8 Hz), 8.18 (d, 2H, Ar, J¼8.8 Hz); 19F
dependent (Rint¼0.040) and 2848 observed reflections [Iꢅ2
s
245 refined parameters, R¼0.056, wR2¼0.145, max. residual elec-
tron density 0.54(ꢂ0.26) e Åꢂ3, hydrogen atoms calculated and
refined as riding atoms.
NMR (282 MHz, CDCl3):
d
ꢂ110.5; 13C NMR (75 MHz, CDCl3):
d
47.1 (d, –CH2–, J¼4.5 Hz), 48.8 (d, –CH2–, J¼19.7 Hz), 67.3
4.7.3. endo-2-Fluoro-2-[(4-methylphenyl)sulfonyl]-endo-3-
(4-nitrophenyl)-1,4-diphenyl-1,2,3,4-tetrahydro-1,4-epoxy-
naphthalene (6a)
(–CH–, J¼5.6 Hz), 121.7 (CH), 123.4 (d, CH, J¼6.7 Hz), 126.7, 132.0
(Ar); 137.4 (d, C]C–Ar, J¼5.1 Hz), 139.1 (d, –CH]CH–, J¼4.2 Hz),
141.0 (d, –CH]CH–, J¼5.9 Hz), 176.1 (d, –CF–, J¼311.3 Hz); ESI-
C
35H26FNO5S,
M¼591.63,
colourless
crystal
MS (m/z): calcd for
C
13H10FNO2Na [Mþ] 254.0593, found
0.35ꢁ0.25ꢁ0.12 mm, a¼13.2017(5), b¼19.1893(7), c¼11.3914(4) Å,
254.0588.
b
¼91.410(2)ꢀ, V¼2884.9(2) Å3, rcalcd¼1.362 g cmꢂ3
,
m
¼1.432 mmꢂ1
,
empirical absorption correction (0.634ꢃTꢃ0.847), Z¼4, monoclinic,
4.6.2. 2-Fluoro-3-(4-nitrophenyl)-1,4-diphenyl-1,4-dihydro-1,4-
epoxynaphthalene (9a)
space group P21/c (No. 14),
l¼1.54178 Å, T¼223 K,
u and 4 scans,
22,073 reflections collected (ꢄh,ꢄk,ꢄl), [(sin
q)/l
]¼0.60 Åꢂ1, 5079
Obtained from 6a. Yellow solid (54 mg, 62%), mp 80–81 ꢀC. 1H
independent (Rint¼0.051) and 4528 observed reflections [Iꢅ2
s(I)],
NMR (300 MHz, CDCl3):
d
7.09–7.77 (m,16H), 8.09 (d, 2H, J¼8.8 Hz);
389 refined parameters, R¼0.046, wR2¼0.121, max. (min.) residual
electron density 0.33(ꢂ0.34) e Åꢂ3, hydrogen atoms calculated and
refined as riding atoms.
19F NMR (282 MHz, CDCl3):
d
ꢂ118.42; 13C NMR (75 MHz, CDCl3):
d
88.7 (d, J¼25.7 Hz), 93.2 (d, J¼7.7 Hz), 121.3, 121.4, 125.9, 126.4,
126.7 (d, J¼4.2 Hz), 127.1, 127.6, 128.7, 128.9, 129.0, 129.2, 129.5,
129.8, 130.2, 132.7, 137.7, 146.3, 149.5 (d, J¼3.2 Hz), 150.4 (d,
J¼2.4 Hz), 171.8 (d, J¼321.4 Hz); ESI-MS (m/z): calcd for
The data sets were collected with a Nonius KappaCCD diffrac-
tometer. Programs used: data collection COLLECT (Nonius B.V.,
1998), data reduction Denzo-SMN,36 absorption correction
Denzo,37 structure solution SHELXS-97,38 structure refinement
SHELXL-97,39 graphics SCHAKAL.40
C
28H18FNO3Na [Mþ] 458.1168, found 458.1188.
4.6.3. 2-Fluoro-3-(4-chlorophenyl)-1,4-diphenyl-1,4-dihydro-1,4-
epoxynaphthalene (9b)
CCDC 675468, 675469 and 688574 contain the supplementary
crystallographic data for this paper. These data can be obtained free
of charge at www.ccdc.cam.ac.uk/conts/retrieving.html [or from
the Cambridge Crystallographic Data Centre, 12 Union Road, Cam-
bridge CB2 1EZ, UK; fax: þ44(1223)336 033, e-mail:
deposit@ccdc.cam.ac.uk].
Obtained from 6b. Yellow solid (56 mg, 65%), mp 84–85 ꢀC. 1H
NMR (300 MHz, CDCl3): d 7.04–7.28 (m, 7H), 7.39–7.51 (m, 6H), 7.58
(d, 1H, J¼6.8 Hz), 7.63–7.68 (m, 2H), 7.74 (d, 2H, J¼8.1 Hz); 19F NMR
(282 MHz, CDCl3):
d
ꢂ124.27; 13C NMR (75 MHz, CDCl3):
d 88.7 (d,
J¼21.5 Hz), 93.2 (d, J¼7.7 Hz), 120.9, 121.2, 125.6, 126.0, 127.2 (d,
J¼1.3 Hz), 127.5, 127.6, 128.6, 128.7, 128.8, 129.0, 129.5, 130.3, 131.9
(d, J¼3.2 Hz), 132.9, 133.1, 133.3, 150.1 (d, J¼2.9 Hz), 150.9 (d,
J¼2.6 Hz), 173.5 (d, J¼315.1 Hz); ESI-MS (m/z): calcd for
Acknowledgements
This project was supported by the Deutsche For-
schungsgemeinschaft (DFG) through grant Gz: 436 RUS 113/858/
C
28H18FNO3Na [Mþ] 447.0928, found 447.0922.

9732
A.V. Shastin et al. / Tetrahedron 64 (2008) 9725–9732
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A. V.; Balenkova, E. S. Russ. Chem. Rev. 2004, 73, 957–989; (c) Takeda, T. Modern
Carbonyl Olefination; Wiley-VCH: Weinheim, 2004.