Synthesis of 2-mono- and 2,3-disubstituted polycyclic alkenes

Article abstract of DOI:10.1002/1099-0690(200212)2002:23<4024::AID-EJOC4024>3.0.CO;2-N

A range of mono- and disubstituted (-Br, -Cl, -SPh, -SO₂Ph) polycyclic alkenes has been prepared starting from alkenes by inexpensive and high-yielding synthetic routes. ( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002).

Full text of DOI:10.1002/1099-0690(200212)2002:23<4024::AID-EJOC4024>3.0.CO;2-N

FULL PAPER
Synthesis of 2-Mono- and 2,3-Disubstituted Polycyclic Alkenes
Paola Peluso,[a] Carla Greco,[a] Ottorino De Lucchi,[a] and Sergio Cossu*[a]
Keywords: Bromine / Chiral resolution / Halogenation / Oxidation / Sulfones
A range of mono- and disubstituted (−Br, −Cl, −SPh, −SO2Ph)
polycyclic alkenes has been prepared starting from alkenes
by inexpensive and high-yielding synthetic routes.
( Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany,
2002)
Introduction
fonyl) derivative 6. Alternatively (path D), compound 5 can
be obtained through the formation of 7Ϫ9, by a double
The synthesis of innumerable biologically active targets PhSCl addition and dehydrochlorination sequence. Some
entails the use of a wide variety of usefully functionalised common intermediates also offer synthetic alternative me-
polycyclic intermediates.[1] Among several examples, some ans to reach the final bis(phenylsulfonyl) derivatives 6, such
substituents, such as halogen and arylsulfonyl moieties, as, for example (paths E, F), the conversion of vinyl brom-
make polycyclic alkenes of interest because these groups ide 2 into the corresponding phenylsulfone 10, which is in
can be transformed into other functions and, if necessary, turn transformed, through 11, into the desired bis(phenyl-
eventually removed.[2] Prior to this work, the preparation of sulfonyl)alkene 6.
polycyclic 1,2-bis(phenylsulfonyl)alkenes had generally been
achieved essentially through cycloaddition reactions be-
tween appropriately functionalised dienophiles and di-
enes.[3] The DielsϪAlder reaction is undoubtedly of excep-
tional utility for the construction of certain six-membered
rings, but the applicability of the method is sometimes lim-
ited by unavailability of the reagents. For the development
of synthetic strategies suitable for the preparation of meso-
1,2-bis(phenylsulfonyl) polycyclic alkenes not directly ac-
cessible by cycloaddition reactions, alternative synthetic
routes via halogen- or phenylthio-substituted cycloalkenes
were considered attractive. Here we report on the synthesis
of a series of mono- and bis(phenylsulfonyl)-substituted po-
lycyclic alkenes produced through simple and inexpensive
transformations of readily accessible alkenes.
Scheme 1
By path A, 2-bromonorbornadiene 2b and 2,3-dibro-
monorbornadiene 4b were prepared through a synthetic
procedure modified from that originally reported by
Szeimis.[5] The first bromination step for norbornene,
benzonorbornadiene, naphthonorbornadiene and 5,8-(di-
methoxy)benzonorbornadiene[4] was more conveniently
(Scheme 2) performed under radical conditions, with 1,2-
dibromotetrachloroethane serving as the source of bromine
in CCl4 solution.[6] Under these reaction conditions, the
WagnerϪMeerwein rearrangement of the polycyclic skel-
eton of the intermediate carbocation was totally sup-
pressed,[7] and compounds 1a and 1cϪe were obtained pre-
dominantly as their anti-dibrominated isomers. In any case,
the mixtures of isomers were directly treated with base
(tBuOK in refluxing THF) to afford the 2-bromoalkenes 2a
and 2cϪe.[7c] Treatment of 2a and 2cϪe with bromine in
Results and Discussion
The envisaged direct synthetic routes to functionalised
norbornene, norbornadiene, benzonorbornadiene and
naphthonorbornadiene, starting from commercial or simply
achievable compounds, are represented in Scheme 1.[4] They
involve (path A) the preparation of the vinyl-brominated
key intermediates 1Ϫ4, the subsequent transformation
(path B) of 4 into the corresponding bis(phenylthio) deriv-
ative 5 and the oxidation (path C) of 5 to bis(phenylsul-
[a]
`
Dipartimento di Chimica, Universita Ca’ Foscari di Venezia,
Dorsoduro 2137, 30123 Venezia, Italy
Fax: (internat.) ϩ 39-041/234-8517
E-mail: cossu@unive.it
4024
 2002 WILEY-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim 1434Ϫ193X/02/1223Ϫ4024 $ 20.00ϩ.50/0 Eur. J. Org. Chem. 2002, 4024Ϫ4031

Synthesis of 2-Mono- and 2,3-Disubstituted Polycyclic Alkenes
CCl4 at reflux temperature furnished tribromo derivatives
FULL PAPER
(Phenylsulfonyl)-substituted polycyclic alkenes 6aϪe
3a and 3cϪe, which were dehydrobrominated to afford the were prepared from (phenylthio)-substituted precursors
2,3-dibromo derivatives 4a and 4cϪe under the reaction through sulfur oxidation processes. The oxidation of 2,3-
conditions described above.
bis(phenylthio)norbornene 5a (Scheme 5) with mCPBA in
CH2Cl2 at 0 °C furnished 2,3-bis(phenylsulfonyl)norbor-
nene 6a.
Scheme 5
Scheme 2
Under the same reaction conditions, however, compound
5b, containing an additional CϪC double bond, produced
a complex mixture of compounds (Scheme 6) consisting of
partially oxidised products 6ba,b, overoxidised epoxide 6bc
and the desired 6b, the latter in 50% yield.[3d] Similar yields
of 6b were also obtained in experiments performed at lower
temperature or with other classic oxidising agents such as
H2O2 under acidic catalysis conditions or dimethyldioxir-
ane.[9]
These last compounds were fruitfully employed for the
preparation of bis(phenylthio)-substituted alkenes 5aϪe
(path B) under suitably optimised reaction conditions. 2,3-
Dibromonorbornene 4a proved to be inert towards the
freshly prepared thiophenol sodium salt in THF, even after
prolonged reaction times at reflux temperatures. However,
the synthesis of 2,3-bis(phenylthio)norbornene 5a was ac-
complished in 80% isolated yield (Scheme 3) by treatment
of 4a with equivalent amounts of PhSH in KOH/DMF at
80 °C.
Scheme 3
Scheme 6
Under these reaction conditions, the dibrominated nor-
bornadiene 4b, the benzonorbornadienes 4c and 4e and the
naphthonorbornadiene 4d (Figure 1) also furnished the cor-
responding bis(phenylthio) derivatives 5bϪe in comparable
yields.
It was found that the oxidation of 5b could be carried out
successfully by use of TBA-OXONE in CH2Cl2, a sulfur-
selective oxidising system,[9b] which provided 6b in almost
quantitative yield.
Oxidation of compounds 5cϪe was performed without
inconvenience with mCPBA, affording bis(phenylsulfonyl)
derivatives 6cϪe (Figure 2).
Figure 1. 2,3-Bis(phenylthio)norbornadiene derivatives
Compounds 5a and 5b were also prepared from 2,3-
dichloronorbornene 4aa and 2,3-dichloronorbornadiene
4ba, used in place of 2,3-dibromonorbornene 4a and 2,3-
dibromonorbornadiene 4b as starting reagents. Compounds
4aa and 4ba are inexpensive reagents, readily obtained by
cycloaddition reaction between trichloroethylene and cyclo-
pentadiene.[8] In particular, 4ba was obtained by dehydroch-
lorination of the primary cycloadduct 3ba, while 4aa was
obtained from 3ba by catalytic hydrogenation and dehy-
drochlorination (Scheme 4).
Figure 2. 2,3-Bis(phenylsulfonyl)benzonorbornadienes
The second synthetic route (Path D, Scheme 1) to mono-
and bis(phenylsulfonyl)alkenes 6 requires a double PhSCl
addition/dehydrochlorination sequence, followed by a final
oxidation. Although the addition of this reagent to a double
bond is a widely applied methodology,[10] this reaction pre-
sents some difficulty in some instances when applied to po-
lycyclic hydrocarbons, because of rearrangement of the hy-
drocarbon skeleton.[10b] The addition of freshly prepared
PhSCl to the double bond of a norbornene and benzonor-
bornadiene occurs instantaneously in refluxing dichlorome-
Scheme 4
Eur. J. Org. Chem. 2002, 4024Ϫ4031
4025

P. Peluso, C. Greco, O. De Lucchi, S. Cossu
FULL PAPER
der identical reaction conditions, through the formation of
intermediates 8, 10 and 11c.
Taking the reactivity of polycyclic alkenes into account,
we considered a conceptually new role for these 2,3-
bis(phenylsulfonyl)alkenes: the meso stereochemistry makes
them key intermediates in a new stereoselective process. In
fact, racemic mixtures of polycyclic ketones could be ‘‘sym-
metrised’’ to the corresponding symmetric meso-2,3-bis-
(phenylsulfonyl) derivative,[11] and then asymmetrically de-
symmetrised. The overall process comprises a total resolu-
tion process with some peculiar aspects (Figure 3): a) a ra-
cemic mixture of compounds could be totally converted
into only one enantiomer of a desired configuration, thus
avoiding the formation of waste products, and b) the syn-
thesis of otherwise unavailable antipodes from available en-
antiomers could be achieved through the total switch of
configuration of the reagents.
Scheme 7
thane (Scheme 7) affording exo-(phenylthio), endo-chloro
derivatives 7a and 7c as the products of a totally anti-select-
ive addition, as confirmed by NMR (COSY, NOESY) ex-
periments. On dehydrochlorination of 7a and 7c (tBuOK/
THF), phenyl vinyl sulfides 8a and 8c were obtained, and
these were again treated with PhSCl as described above. In
this case an inseparable mixture of isomers of 9a and 9c
was isolated, and this partially decomposed under silica gel
chromatographic conditions. Consequently, 9a and 9c were
used as obtained in the successive dehydrochlorination step
(tBuOK/THF at reflux), giving 2,3-bis(phenylthio)alkenes
5a and 5c.
However, the electronic features of the benzo-fused ring
influence the behaviour of the reagents. For example, the
methoxy group has an activating effect on the aromatic ring
of 5,8-dimethoxybenzonorbornadiene, and in the case of
naphthonorbornadiene the external aromatic ring also ac-
tivates the internal α-naphthalenic position towards elec-
trophilic reagents. Surprisingly, treatment of these alkenes
with PhSCl, of more weakly electrophilic character than
bromine,[10b] resulted in the formation of a complex mixture
of products. In this regard, the PhSCl and the bromine ad-
dition/elimination processes represent complementary
methods, the former appearing to be more appropriate for
the functionalisation of norbornene and benzonorbornadi-
ene systems and the latter more suitable for other substrates.
Figure 3. Double role of ‘‘symmetrisation’’/‘‘desymmetrisation’’
strategy
This approach constitutes an alternative synthetic
method for the preparation of enantiopure polycyclic ke-
tones, always of interest even for simple structures.[12] With
the goal of confirming this hypotheses, some very simple
preliminary experiments starting from racemic norcamphor,
chosen as the model, were performed (Figure 4).
Figure 4. Total resolution of norcamphor
Commercial (Ϯ)-norcamphor was quantitatively trans-
formed into tosylhydrazone 12, which was in turn converted
into (Ϯ)-2-bromonorbornene 1a (15Ϫ35% unoptimised av-
Scheme 8
In addition (Scheme 8), an alternative synthetic route to erage yields) through a Shapiro reaction.[13] Racemic 1a was
bis(phenylsulfonyl)alkenes 6 starting from vinyl bromide 2 transformed (this work) into 2,3-bis(phenylsulfonyl)norbor-
(path E) was explored, as demonstrated in the cases of 6a nene 6a, which was desymmetrised by use of the hydroben-
and 6c. Treatment of 2a with PhSH in DMF/KOH indeed zoin[2a] or hydrobenzoin monomethyl ether[2b,2e] methodo-
resulted in the formation of 8a. After oxidation (mCPBA or logy. The synthetic procedure affords either (ϩ)-nor-
TBA-OXONE), (phenylsulfonyl)alkene 10a (path F) was camphor [(R,R)-hydrobenzoin or (S,S)-hydrobenzoin mon-
recovered. This compound, when treated with lithium diiso- omethyl ether method] or alternatively (Ϫ)-norcamphor as
propylamide (LDA) and subsequent quenching of the de- the final products. The absolute configuration was estab-
rived anions with diphenyl disulfide (PhSSPh), gave lished by correlation of the data for ketal 13 with the data
phenylthio derivative 11a in excellent yields. The bis(phenyl- obtained by catalytic hydrogenation of ketal 14. This com-
sulfonyl)alkene 6a was obtained by subsequent oxidation pound was also obtained by an independent pathway, while
(mCPBA). The synthesis of 6c from 2c was carried out un- the absolute configurations both of endo- and exo-(phenyl-
4026
Eur. J. Org. Chem. 2002, 4024Ϫ4031

Synthesis of 2-Mono- and 2,3-Disubstituted Polycyclic Alkenes
FULL PAPER
apparatus, afforded a colourless oil (24.6 g, 54% yield). The com-
pound exhibits spectroscopic data identical to those reported.[5]
sulfonyl) derivatives had been established previously
(Scheme 9).[2a,2b,2f]
2,3-Dibromobicyclo[2.2.1]hepta-2,5-diene (4b): A solution of bi-
cyclo[2.2.1]hepta-2,5-diene (8.91 g, 97 mmol, 10 mL) in dry THF
(40 mL), stirred under argon at Ϫ35 °C, was treated with a solution
of tBuOK (10.9 g, 97 mmol) in the same solvent (50 mL). After
5 min, the resulting mixture was cooled to Ϫ80 °C. nBuLi (40 mL
of a 2.5  solution in hexanes) was cautiously added dropwise over
1 h. The temperature was adjusted to Ϫ65 °C and 2-bromobicy-
clo[2.2.1]hepta-2,5-diene (2b) (16.6 g, 97 mmol) was added by syr-
inge over 15 min. The reaction mixture was stirred for 1 h at Ϫ35
°C, treated with 1,2-dibromoethane (10 mL, excess, added by syr-
inge over 15 min), and finally allowed to come to room temper-
ature. H2O (15 mL) was added and the organics were extracted with
Et2O (4 ϫ 30 mL). The combined organic phases were washed
with H2O (3 ϫ 40 mL) and brine (2 ϫ 20 mL), dried (Na2SO4)
and concentrated under reduced pressure. The residue was distilled
(3 Torr, 70 °C), giving a colourless oil (12 g, 50% yield). The com-
pound exhibits spectroscopic data identical to those reported.[5]
Scheme 9
Conclusion
Several routes for the preparation of both mono- and dis-
ubstituted polycyclic alkenes, much of these latter hitherto
unknown, from symmetric alkenes have been reported. The
concepts of total resolution of racemic ketones and of chiral
interconversion between enantiomers are intrinsically impli-
cit in the proposed transformations. In order to develop
new approaches to biologically active compounds by asym-
metric discrimination processes (ADPs) with meso com-
pounds, and in view of the fact that different functionalities,
of associated different properties, may play important roles
in synthetic organic chemistry, numerous experiments con-
cerning the behaviour of the structurally related molecules
of Cs symmetry presented here, or their oxa and aza ana-
logues, also in chiral versions, towards different classes of
reagents are in progress.
2,2,3-Tribromo-1,4-dihydro-1,4-methanonaphthalene (3c) and 2,3-
Dibromo-1,4-dihydro-1,4-methanonaphthalene (4c): A solution of
Br2 (3.6 g, 22.6 mmol, 1.16 mL) in CCl4 (5 mL) was added rapidly
to
a solution of 2-bromo-1,4-dihydro-1,4-methanonaphthalene
(2c)[7c] (5.0 g, 22.6 mmol) in CCl4 (25 mL), stirred under argon at
reflux temperature. After a few minutes, the solvent was removed
under reduced pressure, giving 3c as a red oil consisting of a mix-
ture of isomers (8.6 g, quantitative yield). 2-endo,2-exo,3-endo Iso-
mer: 1H NMR (200 MHz, CDCl3): δ ϭ 2.30 (dt, J ϭ 10.2, 1.8 Hz, 1
H, 1/2 AB system), 2.63 (dt, J ϭ 10.2, 1.5 Hz, 1 H, 1/2 AB system),
3.49Ϫ4.04 (m, 2 H, 1-H, 4-H), 5.22 (d, J ϭ 3.8 Hz, 1 H, 3-H),
7.08Ϫ7.29 (m, 4 H, Ar). 2-endo,2-exo,3-exo Isomer: 1H NMR
(200 MHz, CDCl3): δ ϭ 2.19 (dq, J ϭ 10.0, 2.0 Hz, 1 H, 1/2 AB
system), 2.73 (dt, J ϭ 10.0, 1.3 Hz, 1 H, 1/2 AB system), 3.49Ϫ4.04
(m, 2 H, 1-H, 4-H), 4.35 (d, J ϭ 2.5 Hz, 1 H, 3-H), 7.08Ϫ7.29 (m,
4 H, Ar). A solution of 3c (mixture of isomers, 5.0 g, 13.1 mmol)
in THF (15 mL), stirred under argon at room temperature, was
treated with a solution of tBuOK (4.5 g, 39.3 mmol) in the same
solvent (20 mL). The resulting brown mixture was then stirred at
reflux temperature for an additional 3 h. After the mixture had
cooled to room temperature, the solvent was removed under re-
duced pressure and the residue was diluted with Et2O (60 mL). The
organic phase was washed with H2O (3 ϫ 50 mL) and brine (2 ϫ
30 mL), dried (MgSO4) and concentrated under reduced pressure
(3.8 g, 96% yield). The compound, after recrystallisation from n-
hexane, shows spectroscopic data identical to those reported.[7b]
Experimental Section
General Remarks: Melting points are not corrected and were deter-
mined with a Büchi 535 apparatus. NMR spectra were recorded
with a Bruker AC 200 spectrometer operating at 200 (1H) and 50
(13C) MHz. IR spectra were recorded with a Nicolet Magna IR-
750 spectrophotometer. Commercial high purity reagents were em-
ployed without further purification. High purity solvents were pre-
pared by standard procedures. Known compounds were prepared
according to literature procedures or purchased from standard
chemical suppliers and purified to match the reported physical and
2,2,3-Tribromo-1,4-dihydro-1,4-methanoanthracene (3d) and 2,3-Di-
bromo-1,4-dihydro-1,4-methanoanthracene (4d): The procedure pre-
viously described for the preparation of 3c and 4c was employed.
By use of a solution of 2-bromo-1,4-dihydro-1,4-methanoanthra-
cene (2d)[7c] (0.92 g, 3.39 mmol) in CCl4 (20 mL) and a solution of
Br2 (0.54 g, 3.39 mmol, 0.17 mL) in the same solvent, the reaction
furnished 3d as a pale yellow oil (1.5 g, quantitative yield). 1H
NMR (200 MHz, CDCl3, mixture of isomers): δ ϭ 2.22Ϫ2.48 (m,
2 H), 2.74Ϫ2.94 (m, 2 H), 3.67Ϫ3.74 (m, 2 H), 4.04 (t, J ϭ 1.6 Hz,
1 H), 4.23Ϫ4.29 (m, 1 H), 4.56 (d, J ϭ 2.7 Hz, 1 H), 5.42 (d, J ϭ
spectroscopic data. Microanalyses were performed with
PerkinϪElmer 2400 CHN Elemental Analyser.
a
2-Bromobicyclo[2.2.1]hepta-2,5-diene (2b): A solution of bicyclo-
[2.2.1]hepta-2,5-diene (25.02 g, 271.6 mmol, 27.6 mL) in THF
(250 mL) was stirred under argon at Ϫ35 °C and cautiously treated
(exothermic reaction) with portions of tBuOK (30.57 g, 272 mmol).
The resulting mixture was cooled to Ϫ78 °C, and nBuLi (108.6 mL
of a 2.5  solution in hexanes, 271 mmol) was added by syringe
over 30 min. After 10 min at Ϫ78 °C, the temperature was adjusted
to Ϫ60 °C and, after a further 30 min, 1,2-dibromoethane (61.0 g, 3.6 Hz, 1 H), 7.38Ϫ7.95 (m, 12 H, Ar). A solution of 3d (1.46 g,
28 mL, 324 mmol) was added by syringe over 15 min. The reaction
mixture was allowed to come to room temperature (6 h), treated
with H2O (1 mL) and diluted with Et2O (50 mL). The organic
phase was washed with brine (2 ϫ 20 mL) and with H2O (2 ϫ
20 mL), dried (Na2SO4) and concentrated under reduced pressure.
The residue, purified by distillation (3 Torr, 50 °C) in a Kugelrohr
3.39 mmol) in THF (20 mL) treated with a solution of tBuOK
(0.57 g, 5.1 mmol) in the same solvent (20 mL) for 6 h at reflux,
and recrystallisation from Et2O/n-hexane gave red crystals. 0.9 g;
80% yield; m.p. 161 °C. IR (KBr disk): ν˜ ϭ 3063, 3040, 3002, 2948,
1
2871, 1574, 1513, 1275, 891, 753, 737 cmϪ1. H NMR (200 MHz,
CDCl3): δ ϭ 2.40 (dt, J ϭ 7.9, 2.4 Hz, 1 H, 1/2 AB system), 2.80
Eur. J. Org. Chem. 2002, 4024Ϫ4031
4027

P. Peluso, C. Greco, O. De Lucchi, S. Cossu
FULL PAPER
(dt, J ϭ 7.9, 1.7 Hz, 1 H, 1/2 AB system), 4.04 (t, J ϭ 1.7 Hz, 2
2,3-Bis(phenylthio)bicyclo[2.2.1]hepta-2,5-diene (5b). Method A: A
H), 7.50Ϫ7.40 (m, 2 H, Ar), 7.70 (s, 2 H, Ar), 7.72Ϫ7.79 (m, 2 H, solution of 2,3-dibromobicyclo[2.2.1]hepta-2,5-diene (4b) (1.0 g,
Ar) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 57.93, 63.68, 120.40,
4.0 mmol), PhSH (0.9 g, 8.0 mmol, 0.84 mL) and KOH (0.7 g,
125.85, 127.86, 132.24, 133.00, 144.11, 206.97 ppm. C15H10Br2 12 mmol) in dry DMF (15 mL) was stirred under argon at 80 °C
(350): calcd. C 51.47, H 2.88; found C 51.61, H 2.60.
for 20 h. After cooling to room temperature, the reaction mixture
was diluted with Et2O (40 mL), washed with H2O (3 ϫ 20 mL),
dried (Na2SO4) and concentrated under reduced pressure. The res-
idue was purified by flash chromatography (eluent: n-hexane/acet-
one, 9:1) affording a pale yellow oil (1.0 g, 80% yield). Method B:
Under the same reaction conditions, starting from 2,3-dichlorob-
icyclo[2.2.1]hepta-2,5-diene (4ba) (1.5 g, 14.1 mmol), 3.0 g (70%
yield) of product was obtained. IR (neat, NaCl): ν˜ ϭ 3072, 2979,
2,2,3-Tribromo-5,8-dimethoxy-1,4-dihydro-1,4-methanonaphthalene
(3e) and 2,3-Dibromo-5,8-dimethoxy-1,4-dihydro-1,4-methanonaph-
thalene (4e): The procedure described above for the preparation of
3c and 4c was employed. Through the use of a solution of 2-bromo-
1,4-dihydro-1,4-methano-5,8-dimethoxynaphthalene (2e)[7c] (1.0 g,
3.56 mmol) in CCl4 (20 mL) and a solution of Br2 (0.57 g,
3.56 mmol, 0.17 mL) in the same solvent (2 mL), a yellow oil
2940, 2868, 1591, 1486, 1446, 1301, 748, 696 cmϪ1 1H NMR
.
1
(1.57 g, quantitative yield) was obtained. 3e: H NMR (200 MHz,
(200 MHz, CDCl3): δ ϭ 2.04 (dt, J ϭ 6.4, 1.6 Hz, 1 H, 1/2 AB
system), 2.22 (dt, J ϭ 6.4, 1.6 Hz, 1 H, 1/2 AB system), 3.43Ϫ3.50
(m, 2 H), 6.67 (t, J ϭ 1.8 Hz, 2 H), 7.12Ϫ7.40 (m, 10 H, Ar) ppm.
13C NMR (50 MHz, CDCl3): δ ϭ 55.86, 69.14, 126.66, 128.94,
130.22, 134.75, 141.10, 146.78 ppm. C19H16S2 (308): calcd. C 73.98,
H 5.23; found C 73.73, H 5.41.
CDCl3, mixture of isomers in 2:1 ratio): δ ϭ 2.10Ϫ3.11 (series of
m, 4 H, both isom.), 3.62Ϫ3.66 (m, 1 H, maj. isom), 3.78 (s, 3 H,
OMe, maj. isom.), 3.80 (s, 3 H, OMe, min. isom.), 3.82 (s, 3 H,
OMe, maj. isom.), 3.85 (s, 3 H, OMe, min. isom.), 4.01Ϫ4.10 (m,
1 H, maj. isom.), 4.25Ϫ4.29 (m, 1 H, maj. isom), 4.37Ϫ4.43 (m, 1
H, min. isom.), 4.47 (d, J ϭ 2.9 Hz, 1 H, min. isom.), 5.25 (d, J ϭ
3.4 Hz, 1 H, min. isom.), 6.70 (s, 2 H, Ar, min. isom.), 6.73 (s, 2 2,3-Bis(phenylthio)-1,4-dihydro-1,4-methanonaphthalene (5c): The
H, Ar, maj. isom.) ppm. Subsequent treatment of a solution of 3e
(1.57 g, 3.56 mmol) in THF (20 mL) with a solution of tBuOK
(1.2 g, 10.68 mmol) in the same solvent (15 mL, 6 h at reflux tem-
procedures reported above for the preparation of 5a were em-
ployed. Method A: Through the use of a mixture of 2,3-dibromo-
1,4-dihydro-1,4-methanonaphthalene (4c) (1.0 g, 3.33 mmol) in
perature) afforded colourless crystals (0.64 g, 50% yield) after flash DMF (15 mL), PhSH (1.1 g, 9.99 mmol, 1.0 mL) and KOH (0.56 g,
chromatography (eluent: n-hexane/CH2Cl2, 9:1); m.p. 87Ϫ88 °C. 9.99 mmol) (80 °C for 20 h), a solid residue was obtained. This was
IR (KBr disk): ν˜ ϭ 3009, 2964, 2940, 2833, 1590, 1505, 1443, 1282, recrystallised from n-hexane/Et2O as a colourless solid (0.95 g, 80%
1244, 1159, 791, 722, 638 cmϪ1. 1H NMR (200 MHz, CDCl3): δ ϭ yield). Method B: A solution of PhSCl (1.15 g, 8.0 mmol) in n-
2.33 (dt, J ϭ 6.0, 4.0 Hz, 1 H, 1/2 AB system), 2.67 (dt, J ϭ 6.0, hexane (20 mL) was added under argon, at reflux temperature, to
4.0 Hz, 1 H, 1/2 AB system), 3.83 (s, 6 H, OMe), 4.22 (t, J ϭ
a stirred solution of 2-(phenylthio)-1,4-dihydro-1,4-methanonaph-
4.0 Hz, 2 H), 6.63 (s, 2 H, Ar) ppm. 13C NMR (50 MHz, CDCl3): thalene (8c) (2.0 g, 8.0 mmol) in CH2Cl2 (15 mL). After a few mi-
δ ϭ 55.54, 56.93, 67.37, 111.78, 133.44, 136.73, 149.27 ppm. nutes, the solvent was removed under reduced pressure to give 2-
C13H12Br2O2 (360): calcd. C 43.37, H 3.36, found C 43.12, H 3.21.
chloro-2,3-bis(phenylthio)-1,4-dihydro-1,4-methanonaphthalene
(9c) (2.2 g, 70% yield) as an oil, which was purified by flash chro-
matography (eluent: n-hexane/CH2Cl2, 9:1). 1H NMR (200 MHz,
CDCl3, mixture of isomers): δ ϭ 2.30Ϫ2.76 (series of m, 4 H),
3.13Ϫ3.15 (m, bs, 1 H), 3.17Ϫ3.21 (m, bs, 1 H), 3.49 (d, J ϭ 4.0 Hz,
1 H), 3.61Ϫ3.69 (m, 1 H), 3.70Ϫ3.80 (m, 1 H), 3.89 (d, J ϭ 4.0 Hz,
1 H), 7.12Ϫ7.64 (m, 14 H, Ar) ppm. 13C NMR (50 MHz, CDCl3,
mixture of isomers): δ ϭ 47.05, 47.53, 48.17, 48.58, 52.65, 52.96,
54.14, 54.81, 56.85, 57.19, 66.92, 121.90, 122.84, 123.21, 123.65,
124.12, 124.34, 126.94, 127.08, 127.26, 127.47, 127.58, 127.75,
128.01, 128.30, 128.71, 128.92, 129.03, 129.24, 129.33, 130.60,
130.87, 130.99, 131.31, 132.81, 133.55, 134.11, 135.45, 135.64,
136.47, 138.70, 144.96 ppm. A solution of 9c (4.0 g, 10 mmol) in
THF (15 mL) was treated with a solution of tBuOK (1.7 g,
15 mmol) in the same solvent (30 mL), and heated at reflux temper-
ature for 1 h. The compound was purified by flash chromatography
(eluent: n-hexane/CH2Cl2, 97:3) to give colourless crystals (2.5 g,
70% yield); m.p. 116 °C. IR (KBr disk): ν˜ ϭ 3072, 2979, 2947,
2,3-Bis(phenylthio)bicyclo[2.2.1]heptene (5a). Method A: A mixture
of 2,3-dibromobicyclo[2.2.1]heptene (4a) (1.0 g, 4.0 mmol), PhSH
(0.9 g, 8.0 mmol, 0.84 mL), KOH (0.7 g, 12 mmol) and DMF
(15 mL) was stirred under argon at 80 °C for 20 h. After cooling
to room temperature, the reaction mixture was diluted with Et2O
(40 mL), washed with H2O (3 ϫ 20 mL), dried (Na2SO4) and con-
centrated under reduced pressure. The residue was purified by flash
chromatography (eluent: n-hexane). Method B: A solution of PhSCl
(0.28 g, 1.94 mmol) in CH2Cl2 (5 mL) was added to a solution of
2-(phenylthio)bicyclo[2.2.1]heptene (8a) (0.4 g, 1.98 mmol) in
15 mL of the same solvent, stirred under argon at reflux temper-
ature. After a few minutes, the solvent was removed under reduced
pressure, giving 9a as a pale yellow oil [0.68 g, 1H NMR (200 MHz,
CDCl3): δ ϭ 1.13Ϫ1.85 (series of m, 7 H), 2.93Ϫ3.06 (m, 2 H),
7.06Ϫ7.52 (series of m, 12 H, Ar)], which was diluted with THF
(8 mL) and treated with a solution of tBuOK (0.442 g, 3.94 mmol)
in THF (40 mL) at room temperature for 30 min, and then at reflux
temperature for an additional 3 h. After the mixture had cooled to
room temperature, the solvent was removed under reduced pressure
and the mixture was diluted with Et2O (60 mL). The organic phase
was washed with H2O (3 ϫ 30 mL) and brine (3 ϫ 30 mL), dried
(MgSO4) and concentrated under reduced pressure. The residue
was purified by flash chromatography (eluent n-hexane) to give a
colourless solid (0.39 g, 71% yield); m.p. 77 °C. IR (KBr disk): ν˜ ϭ
1
2868, 1755, 1591, 1479, 1446, 1268, 755, 748, 696 cmϪ1. H NMR
(200 MHz, CDCl3): δ ϭ 2.35 (dt, J ϭ 8.0, 1.6 Hz, 1 H, 1/2 AB
system), 2.53 (dt, J ϭ 8.0, 1.2 Hz, 1 H, 1/2 AB system), 3.80Ϫ3.85
(m, 2 H), 6.93Ϫ7.45 (m, 14 H, Ar) ppm. 13C NMR (50 MHz,
CDCl3): δ ϭ 55.60, 63.85, 121.57, 124.96, 126.97, 129.06, 130.52,
134.35, 147.50, 149.28 ppm. C23H18S2 (358): calcd. C 77.05, H 5.06;
found C 76.90, H 5.24.
1
3072, 2967, 2947, 2868, 1591, 1485, 1446, 1288, 762, 696 cmϪ1. H
2,3-Bis(phenylthio)-1,4-dihydro-1,4-methanoanthracene (5d): The
NMR (200 MHz, CDCl3): δ ϭ 1.20Ϫ1.35, 1.54Ϫ1.74 (series of m, procedure previously described (Method A) for the preparation of
6 H), 2.97 (br. s, 2 H), 7.19Ϫ7.43 (m, 10 H, Ar) ppm. 13C NMR
5a was employed, with a mixture of 2,3-dibromo-1,4-dihydro-1,4-
(50 MHz, CDCl3): δ ϭ 27.24, 44.22, 48.15, 126.57, 128.57, 128.98, methanoanthracene (4d) (0.1 g, 0.28 mmol), DMF (20 mL), PhSH
129.92, 131.87 ppm. C19H18S2 (310): calcd. C 73.50, H 5.84; found (0.092 g, 0.84 mmol, 0.086 mL) and KOH (0.047 g, 0.84 mmol).
C 73.72, H 5.62.
4028
Workup after 30 h at 80 °C gave a residue that, when treated with
Eur. J. Org. Chem. 2002, 4024Ϫ4031

Synthesis of 2-Mono- and 2,3-Disubstituted Polycyclic Alkenes
FULL PAPER
n-hexane, furnished a colourless solid (0.09 g, 79% yield); m.p.
180Ϫ181 °C. IR (KBr disk): ν˜ ϭ 3065, 3012, 1986, 2947, 1755,
(25 mL), under the conditions described above, to afford the com-
pound (0.4 g, 80% yield); m.p. 163 °C. IR (KBr disk): ν˜ ϭ 3092,
1591, 1479, 1446, 755, 696 cmϪ1. 1H NMR (200 MHz, CDCl3): δ ϭ 3057, 3015, 2998, 2947, 2878, 1583, 1564, 1460, 1321, 1159, 1086,
2.37 (dt, 1 H, J ϭ 8.12, 1.5 Hz, 1/2 AB system), 2.57 (dt, J ϭ 8.1, 1018, 771, 754, 689, 638, 602 cmϪ1. H NMR (200 MHz, CDCl3):
1
1.5 Hz, 1 H, 1/2 AB system), 3.93 (br. s, 2 H), 7.31Ϫ7.46 (m, 10
δ ϭ 2.26 (dt, J ϭ 6.8, 1.2 Hz, 1 H, 1/2 AB system), 2.62 (dt, J ϭ
H, Ar), 7.50 (s, 2 H, Ar), 7.65Ϫ7.76 (m, 4 H, Ar) ppm. 13C NMR 8.0, 1.7 Hz, 1 H, 1/2 AB system), 4.45 (m, 2 H), 7.42Ϫ7.90,
(50 MHz, CDCl3): δ ϭ 54.76, 60.25, 119.65, 125.44, 127.07, 127.76,
129.13, 130.58, 132.23, 134.30, 145.95, 146.86 ppm. C27H20S2 (408):
calcd. C 79.37, H 4.93; found C 79.02, H 4.78.
6.85Ϫ7.09 (series of m,14 H, Ar) ppm. 13C NMR (50 MHz,
CDCl3): δ ϭ 56.02, 68.40, 122.87, 127.87, 128.50, 129.17, 134.15,
139.15, 145.87, 159.96 ppm. C23H18O4S2 (422): calcd. C 65.38, H
4.01; found C 65.27, H 4.01.
5,8-Dimethoxy-2,3-bis(phenylthio)-1,4-dihydro-1,4-methano-
naphthalene (5e): The procedure described above (Method A) for
the preparation of 5a was employed, with a mixture of 4e (0.1 g,
2,3-Bis(phenylsulfonyl)-1,4-dihydro-1,4-methanoanthracene
(6d):
The reaction conditions described for the preparation of compound
0.28 mmol), DMF (20 mL), PhSH (0.092 g, 0.84 mmol, 0.086 mL) 6c (Method A) were employed. Starting from a solution of 5d
and KOH (0.047 g, 0.84 mmol). Workup after 24 h at 80 °C gave (0.08 g, 0.196 mmol) in CH2Cl2 (5 mL), and a solution of mCPBA
a solid that, after recrystallisation from Et2O/n-hexane, provided
colourless crystals (0.08 g, 68% yield); m.p. 134Ϫ135 °C. IR (KBr
disk): ν˜ ϭ 3066, 3013, 2973, 2933, 2913, 2840, 1593, 1500, 1446,
(0.26 g, 50% mixture in H2O, 0.98 mmol) in CH2Cl2 (10 mL), the
reaction was complete after 5 h. The residue was purified by recrys-
tallisation from Et2O, giving colourless crystals (0.09 g, quantitat-
ive yield); m.p. 165 °C. IR (KBr disk): ν˜ ϭ 3061, 2993, 2951, 1446,
1
1280, 1253, 1173, 1080, 746, 700, 653 cmϪ1. H NMR (200 MHz,
CDCl3): δ ϭ 2.28 (dt, J ϭ 8.0, 2.0 Hz, 1 H, 1/2 AB system), 2.42 1319, 1161, 1086, 879, 758, 730, 689, 647, 601 cmϪ1 1H NMR
.
(dt, J ϭ 8.0, 2.0 Hz, 1 H, 1/2 AB system), 3.75 (s, 6 H, OMe), 4.13 (200 MHz, CDCl3): δ ϭ 2.26 (dt, J ϭ 4.0, 2.0 Hz, 1 H, 1/2 AB
(t, J ϭ 2.0 Hz, 2 H), 6.56 (s, 2 H, Ar), 7.23Ϫ7.44 (m, 12 H, Ar)
system), 2.68 (dt, J ϭ 4.0, 2.0 Hz, 1 H, 1/2 AB system), 4.56 (t,
ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 52.57, 57.02, 63.92, 111.79,
J ϭ 2.0 Hz, 2 H), 7.40Ϫ7.89 (m, 16 H, Ar) ppm. 13C NMR
126.95, 128.98, 130.80, 134.42, 138.27 ppm. C25H22O2S2 (418): (50 MHz, CDCl3): δ ϭ 55.18, 65.16, 121.68, 126.20, 127.94, 128.56,
calcd. C 71.74, H 5.30; found C 71.53, H 5.52.
129.13, 131.91, 134.19, 139.33, 141.73, 158.67 ppm. C27H20O4S2
(472): calcd. C 68.62, H 4.27; found C 68.73, H 4.05.
2,3-Bis(phenylsulfonyl)bicyclo[2.2.1]heptene (6a): A stirred solution
of 2,3-bis(phenylthio)bicyclo[2.2.1]heptene (5a, 0.1 g, 0.32 mmol)
5,8-Dimethoxy-2,3-bis(phenylsulfonyl)-1,4-dihydro-1,4-methano-
in CH2Cl2 (10 mL) was treated at 0 °C with a solution of mCPBA naphthalene (6e): The reaction conditions described for the pre-
(0.3 g of a 70% mixture in H2O, 1.28 mmol) in CH2Cl2 (15 mL) paration of compound 6c (Method A) were employed, starting
with monitoring by TLC. After 1 h, the crude reaction mixture was
washed with Na2CO3 (3 ϫ 40 mL of a 10% aqueous solution),
H2O (3 ϫ 30 mL) and brine (3 ϫ 20 mL), dried (MgSO4) and
concentrated under reduced pressure. The residue was purified by
recrystallisation from Et2O to afford a colourless solid (0.09 g, 80%
yield); m.p. 153 °C. IR (KBr disk): ν˜ ϭ 3068, 3003, 2941, 2879,
1583, 1564, 1479, 1448, 1336, 1311, 1180, 1147, 1085, 866, 796,
from a solution of 5e (0.07 g, 0.167 mmol) in CH2Cl2 (5 mL) and
a solution of mCPBA (0.182 g, 70% mixture in H2O, 0.83 mmol)
in CH2Cl2 (10 mL). Workup after 6 h at 0 °C furnished a solid that
was purified by crystallisation from Et2O, giving yellow crystals
(0.05 g, 66% yield); m.p. 161 °C. IR (KBr disk): ν˜ ϭ 3101, 3072,
3016, 2992, 2953, 2938, 2837, 1661, 1568, 1500, 1456, 1338, 1319,
1269, 1257, 1155, 1084, 1059, 798, 762, 729, 687 cmϪ1 1H NMR
.
752, 688, 636, 617, 603 cmϪ1
1.07Ϫ1.94 (series of m, 6 H), 3.48Ϫ3.58 (br. s, 2 H), 8.04Ϫ8.15,
7.52Ϫ7.74 (m, 10 H, Ar) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ H, OMe), 4.73 (t, J ϭ 1.0 Hz, 2 H), 6.44 (s, 2 H, Ar), 7.40Ϫ8.03
.
1H NMR (200 MHz, CDCl3): δ ϭ (200 MHz, CDCl3): δ ϭ 2.20 (dt, J ϭ 7.9, 1.5 Hz, 1 H, 1/2 AB
system), 2.52 (dt, J ϭ 7.9, 1.6 Hz, 1 H, 1/2 AB system), 3.72 (s, 6
25.47, 48.90, 128.63, 129.27, 134.12, 140.17, 152.90 ppm.
C19H18O4S2 (374): calcd. C 60.94, H 4.85 found C 61.12, H 5.02.
(m, 10 H, Ar) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 53.05, 55.76,
69.48, 110.43, 128.71, 128.87, 133.86, 134.37, 139.48, 148.93, 160.64
ppm. C25H22O4S2 (450): calcd. C 66.64, H 4.92; found C 66.91,
H 4.74.
2,3-Bis(phenylsulfonyl)bicyclo[2.2.1]hepta-2,5-diene (6b): A mixture
of 2,3-bis(phenylthio)bicyclo[2.2.1]hepta-2,5-diene (5b) (1.0 g,
3.2 mmol), dry CH2Cl2 (25 mL) and TBA-OXONE (8.3 g,
9.7 mmol) was stirred under argon at room temperature for 1 h.
The solvent was removed under reduced pressure and the residue
was percolated through a short silica gel column and recrystallised
from CH2Cl2/Et2O to afford colourless needles (1.16 g, 98% yield).
The recorded spectroscopic data are identical to those reported in
literature.[3]
2-endo-Chloro-3-exo-(phenylthio)bicyclo[2.2.1]heptane (7a):[10] A so-
lution of PhSCl (15 g, 106 mmol) in CH2Cl2 (100 mL) was added
at reflux temperature under argon to an efficiently stirred solution
of norbornene (10 g, 106 mmol) in CH2Cl2 (50 mL). After a few
minutes, the solvent was removed under reduced pressure and the
residue was purified by flash chromatography (eluent: n-hexane).
Colourless oil (17.7 g, 70% yield). IR (neat, NaCl): ν˜ ϭ 3078, 3050,
1
2967, 2874, 1591, 1485, 1446, 1308, 780, 755, 696 cmϪ1. H NMR
2,3-Bis(phenylsulfonyl)-1,4-dihydro-1,4-methanonaphthalene
(6c).
(200 MHz, CDCl3): δ ϭ 2.11Ϫ1.32 (m, 6 H), 2.25Ϫ2.37 (m, 1 H),
2.45Ϫ2.57 (m, 1 H), 3.11 (td, 1 H, J ϭ 3.0, 1.6 Hz), 4.05 (td, 1 H,
J ϭ 2.4, 1.6 Hz), 7.19Ϫ7.46 (m, 5 H, Ar) ppm. 13C NMR (50 MHz,
CDCl3): δ ϭ 21.75, 28.81, 35.81, 43.68, 44.21, 59.03, 67.15, 126.60,
128.90, 130.56, 135.28 ppm. C13H15ClS (238): calcd. C 65.39, H
6.33; found C 65.51, H 6.14.
Method A (from 5c): A solution of mCPBA (5.4 g, 70% purity
mixed with H2O, 31.6 mmol) in CH2Cl2 (40 mL) was cautiously
added to a solution of 5c (2.27 g, 6.33 mmol) in CH2Cl2 (10 mL),
stirred at 0 °C and monitored by TLC (CH2Cl2). After 3 h, the
reaction mixture was diluted with CH2Cl2 (40 mL) and the organic
phase was washed with Na2CO3 (3 ϫ 20 mL of a 10% aqueous
solution) and brine (2 ϫ 20 mL), dried (MgSO4) and concentrated
under reduced pressure. The residue, after recrystallisation from
2-endo-Chloro-3-exo-(phenylthio)-1,2,3,4-tetrahydro-1,4-methano-
naphthalene (7c): The reaction conditions previously described for
Et2O, gave pale yellow needles (2.0 g, 75% yield). Method B (from the preparation of 7a were adopted. From a solution of PhSCl
11c): The reaction was performed with 11c (0.5 g, 1.28 mmol),
mCPBA (0.66 g, 70% mixture in H2O, 3.8 mmol) and CH2Cl2
(3.05 g, 21.1 mmol) in n-hexane (20 mL), and a solution of
benzonorbornadiene (3.0 g, 21.1 mmol) in CH2Cl2 (20 mL), a col-
Eur. J. Org. Chem. 2002, 4024Ϫ4031
4029

P. Peluso, C. Greco, O. De Lucchi, S. Cossu
FULL PAPER
ourless oil (4.0 g, 70% yield) was obtained after flash chromato-
133.23, 146.03, 147.94, 165.96 ppm. C13H14O2S (234): calcd. C
graphy (eluent: n-hexane/CH2Cl2, 9:1). IR (neat, NaCl): ν˜ ϭ 3078, 66.64, H 6.02; found C 66.78, H 6.29.
3065, 2986, 2947, 1591, 1492, 1275, 801, 769, 748, 696 cmϪ1 1H
.
NMR (200 MHz, CDCl3): δ ϭ 2.31 (dt, J ϭ 10.0, 1.1 Hz, 1 H, 1/
2 AB system), 2.32 (dt, J ϭ 10.0, 1.1 Hz, 1 H, 1/2 AB system), 3.20
(t, J ϭ 4.0 Hz, 1 H), 3.40Ϫ3.44 (m, 1 H), 3.58Ϫ3.64 (m, 1 H), 4.46
(t, J ϭ 4.0 Hz, 1 H), 7.22Ϫ7.55 (m, 9 H, Ar) ppm. 13C NMR
(50 MHz, CDCl3): δ ϭ 46.58, 50.06, 51.55, 57.39, 64.14, 120.82,
124.59, 126.27, 126.79, 126.98, 129.03, 130.50, 135.01, 142.80,
145.70 ppm. C17H15ClS (286): calcd. C 71.19, H 5.27; found C
70.91, H 5.04.
2-(Phenylsulfonyl)-1,4-dihydro-1,4-methanonaphthalene (10c): The
reaction conditions described above for the preparation of 6a were
adopted. With a solution of 8c (2.0 g, 8.0 mmol) in CH2Cl2 (30 mL)
and a solution of mCPBA (3.96 g, 70% mixture in H20, 16 mmol)
in the same solvent (40 mL) the reaction was complete after 1 h at 0
°C (TLC, eluent CH2Cl2). By recrystallisation from Et2O/n-hexane,
colourless crystals (1.8 g, 83% yield) were collected; m.p. 121 °C.
IR (KBr disk): ν˜ ϭ 3086, 3008, 29895, 2985, 2953, 1579, 1454,
1
1321, 1150, 1087, 767, 728, 701, 673, cmϪ1. H NMR (200 MHz,
2-(Phenylthio)bicyclo[2.2.1]heptene (8a): A solution of tBuOK
(16.6 g, 149 mmol) in THF (80 mL) was slowly added over 30 min
to a solution of 7a (17.7 g, 74.2 mmol) in the same solvent (25 mL),
stirred under argon at room temperature. The mixture was then
heated at reflux temperature for 3 h. After the mixture had cooled
to room temperature, the solvent was removed under reduced pres-
sure, H2O (60 mL) was added, and the mixture was extracted with
Et2O (3 ϫ 40 mL). The combined organic layers were washed with
H2O (2 ϫ 30 mL) and brine (2 ϫ 30 mL), dried (MgSO4) and con-
centrated under reduced pressure. The residue was purified by flash
chromatography (eluent: n-hexane), giving a pale yellow oil (10.5 g,
70% yield). IR (neat, NaCl): ν˜ ϭ 3072, 2973, 2881, 1591, 1564,
1492, 1453, 827, 748, 696 cmϪ1. 1H NMR (200 MHz, CDCl3): δ ϭ
1.05Ϫ1.84 (m, 6 H), 2.85 (br. s, 1 H), 2.98 (br. s, 1 H), 6.02 (d, J ϭ
3.6 Hz, 1 H, vin.), 7.16Ϫ7.40 (m, 5 H, Ar) ppm. 13C NMR
(50 MHz, CDCl3): δ ϭ 24.73, 26.87, 43.64, 46.26, 46.82, 126.26,
128.78, 129.71, 135.77, 139.73 ppm. C13H14S (202): calcd. C 77.18,
H 6.98; found C 77.41, H 7.16.
CDCl3): δ ϭ 2.33 (dd, J ϭ 7.5, 1.2 Hz, 1 H, 1/2 AB system), 2.56
(dt, J ϭ 8.0, 1.2 Hz, 1 H, 1/2 AB system), 3.99Ϫ4.06 (m, 1 H),
4.08Ϫ4.18 (m, 1 H), 7.21 (d, J ϭ 6.8 Hz, 1 H, vin.), 6.65Ϫ6.97,
7.37Ϫ7.78 (series of m, 9 H, Ar) ppm. 13C NMR (50 MHz,
CDCl3): δ ϭ 50.70, 51.22, 69.54, 122.03, 122.32, 124.71, 125.08,
127.92, 129.09, 133.22, 138.87, 146.85, 148.62, 152.45, 156.33 ppm.
C17H14O2S (282): calcd. C 72.32, H 5.00; found C 72.24, H 5.12.
2-(Phenylsulfonyl)-3-(phenylthio)bicyclo[2.2.1]heptene (11a): A well-
stirred solution of LDA [freshly prepared under standard reaction
conditions from
a
solution of diisopropylamine (0.3 mL,
2.21 mmol) in THF (10 mL) and nBuLi (0.9 mL of a 2.5  solution
in hexanes, 2.21 mmol)] was treated at Ϫ78 °C under argon with a
solution of 10a (0.2 g, 0.85 mmol) in THF (5 mL). After the mix-
ture had been kept for 30 min at Ϫ78 °C, a solution of PhSSPh
(0.48 g, 2.21 mmol) in THF (10 mL) was added at the same temper-
ature and the mixture was stirred for 3 h at Ϫ78 °C and then for
an additional 12 h at room temperature. The crude reaction mix-
ture was treated with brine (1 mL), concentrated under reduced
pressure and diluted with Et2O (40 mL). The organic phase was
washed with H2O (3 ϫ 20 mL) and brine (2 ϫ 10 mL), dried
(MgSO4) and concentrated under reduced pressure. The residue
was purified by flash chromatography (eluent: n-hexane/ethyl acet-
ate, 95:5) and recrystallised from Et2O, to afford colourless crystals
(0.2 g, 70% yield); m.p. 153 °C. IR (KBr disk): ν˜ ϭ 3085, 2999,
2-(Phenylthio)-1,4-dihydro-1,4-methanonaphthalene (8c): The reac-
tion conditions described above for the preparation of 8a were ad-
opted. From a solution of 7c (6.38 g, 22.2 mmol) in THF (10 mL)
and a solution of tBuOK (3.73 g, 33.3 mmol) in the same solvent
(40 mL), a pale yellow oil (3.9 g, 70% yield) was obtained after
flash chromatography (eluent: n-hexane/CH2Cl2, 97:3). IR(neat,
NaCl): ν˜ ϭ 3085, 3012, 2980, 2933, 2868, 1591, 1479, 1446, 1275,
2947, 2881, 1538, 1453, 1301, 1150, 1077, 729, 715, 696, 623 cmϪ1
.
781, 768, 742, 643 cmϪ1 1H NMR (200 MHz, CDCl3): δ ϭ 2.33
.
1H NMR (200 MHz, CDCl3): δ ϭ 1.05Ϫ1.75 (m, 6 H), 2.70Ϫ2.83
(m, 1 H), 3.24Ϫ3.35 (m, 1 H), 7.35Ϫ7.66, 7.99Ϫ8.09 (10 H, series
of m, Ar) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 25.74, 27.08,
46.01, 46.19, 49.23, 127.05, 129.16, 129.04, 129.30, 131.05, 133.07,
133.98, 134.44, 141.86, 157.45 ppm. C19H18O2S2 (342): calcd. C
66.64, H 5.30; found C 66.81, H 5.47.
(dt, J ϭ 7.4, 1.5 Hz, 1 H, 1/2 AB system), 2.50 (dt, J ϭ 7.4, 1.5 Hz,
1 H, 1/2 AB system), 3.73 (br. s, 1 H), 4.00 (br. s, 1 H), 6.66 (d,
J ϭ 3.0 Hz, 1 H, vin.), 6.90Ϫ7.46 (m, 9 H, Ar) ppm. 13C NMR
(50 MHz, CDCl3): δ ϭ 51.23, 54.28, 67.35, 120.85, 121.69, 124.07,
124.55, 126.70, 128.75, 130.49, 131.00, 140.14, 149.51, 150.00,
150.42 ppm. C17H14S (250): calcd. C 81.56, H 5.64; found C 81.27,
H 5.50.
2-(Phenylsulfonyl)-3-(phenylthio)1,4-dihydro-1,4-methano-
naphthalene (11c): The reaction conditions described for the pre-
paration of 11a were employed. With LDA [freshly prepared from
a solution of diisopropylamine (0.64 mL, 4.6 mmol) in THF (7 mL)
and nBuLi (1.84 mL of a 2.5  solution in hexanes, 4.6 mmol)], 10c
2-(Phenylsulfonyl)bicyclo[2.2.1]heptene (10a).[14] A) The reaction
conditions described above for the preparation of 6b were adopted.
Through the use of a solution of 8a (0.4 g, 2.0 mmol) in CH2Cl2
(10 mL) and TBA-OXONE (5.0 g, 6.0 mmol) (1 h, room temper-
ature) and purification by rapid percolation through a short silica (0.5 g, 1.77 mmol) in THF (10 mL) and diphenyl disulfide (1.0 g,
gel column (eluent CH2Cl2) a pale yellow oil (0.45 g, 97% yield)
was obtained. B) The reaction conditions described above for the
preparation of 6a were adopted. Through the use of a solution of
8a (0.2 g, 1.0 mmol) in CH2Cl2 (10 mL) and a solution of mCPBA
(0.3 g of a 70% mixture in H2O, 1.28 mmol), the reaction was com-
4.6 mmol) in THF (30 mL), an oil was obtained and purified by
flash chromatography (eluent: n-hexane/CH2Cl2, 9:1) and recrys-
tallised from Et2O, to afford pale yellow crystals. 0.5 g; 74% yield;
m.p. 190Ϫ192 °C. IR (KBr disk): ν˜ ϭ 3078, 3023, 2984, 2922, 1766,
1454, 1321, 1157, 759, 696, 610 cmϪ1 1H NMR (200 MHz,
.
plete after 2 h at 0 °C (0.21 g, 90% yield); m.p. 49Ϫ50 °C (n-hexane/ CDCl3): δ ϭ 2.06 (dd, J ϭ 7.8, 1.3 Hz, 1 H, 1/2 AB system), 2.46
Et2O) (ref.[14] 47.5Ϫ48.5 °C). IR (KBr disk): ν˜ ϭ 2986, 2970, 2881, (dd, J ϭ 7.8, 1.3 Hz, 1 H, 1/2 AB system), 3.65 (br. s, 1 H), 4.15
1
1584, 1453, 1321, 1295, 1183, 1156, 1091, 768, 735, 689 cmϪ1. H
(br. s, 1 H), 6.66Ϫ6.90, 7.34Ϫ7.59, 7.73Ϫ7.80 (14 H, series of m,
NMR (200 MHz, CDCl3): δ ϭ 0.87Ϫ1.87 (m, 6 H), 3.09 (br. s, 1 Ar) ppm. 13C NMR (50 MHz, CDCl3): δ ϭ 52.56, 56.23, 64.93,
H), 3.14 (br. s, 1 H), 6.93 (d, J ϭ 3.2 Hz, 1 H, vin), 7.48Ϫ7.66 (m,
121.13, 121.88, 124.60, 124.95, 126.86, 128.70, 129.22, 129.72,
3 H, Ar), 7.85Ϫ7.94 (m, 2 H, Ar) ppm. 13C NMR (50 MHz, 129.96, 132.82, 135.30, 138.26, 140.14, 145.26, 148.20, 164.97 ppm.
CDCl3): δ ϭ 24.73, 24.82, 43.05, 43.67, 49.38, 127.74, 129.14, C23H18O2S2 (390): calcd. C 70.74, H 4.65; found C 70.63, H 4.60.
4030
Eur. J. Org. Chem. 2002, 4024Ϫ4031

Synthesis of 2-Mono- and 2,3-Disubstituted Polycyclic Alkenes
FULL PAPER
Tranmer, W. Tam, J. Org. Chem. 2001, 66, 5113. [2h] T. G. Back,
Tetrahedron 2001, 57, 5263. [2i] For a review on enantioselective
desymmetrisation processes see: M. C. Willis, J. Chem. Soc.,
Perkin Trans. 1 1999, 1765.
Acknowledgments
This work was co-funded by the MURST (Rome) within the na-
tional project ‘‘Stereoselezione in Sintesi Organica. Metodologie e
Applicazioni’’ and by the ‘‘Universita Ca’ Foscari’’ of Venice
(Fondi ex 60%). Grateful thanks are due to Mr. A. Canu of the
University of Sassari for microanalytical determinations.
[3]
[3a] U. Azzena, S. Cossu, O. De Lucchi, G. Melloni, Tetrahedron
`
[3b]
Lett. 1989, 30, 1845.
S. Cossu, O. De Lucchi, Gazz. Chim.
[3c]
`
A. Riera, M. Martı, A. Moyiano, M.
It. 1990, 120, 569.
[3d]
`
Pericas, A. Santamaria, Tetrahedron Lett. 1990, 31, 2173.
L. Pasquato, O. De Lucchi, L. Krotz, Tetrahedron Lett. 1991,
[1]
[3e]
T.-L. Ho, in Symmetry, A Basis for Synthesis Design, Wiley
32, 2177.
R. Gleiter, F. Ohlbach, T. Oeser, H. Irngartinger,
[1a]
Interscience, New York, 1995. See as example:
G. Helmchen, A. Krotz, H.-P. Neumann, M. L. Ziegler, Liebigs
Antibiotics:
Liebigs Ann. 1996, 785.
[4] [4a]
Benzonorbornadiene: T. F. Mich, E. J. Nienhouse, T. E.
Ann. Chem. 1993, 1313. C. Le Drian, A. E. Greene, J. Am.
Farina, J. J. Tuffariello, J. Chem. Educ. 1968, 45, 272. [4b] Naph-
thonorbornadiene: M. N. Paddon-Row, Synthesis 1986, 328.
[1b]
Chem. Soc. 1982, 104, 5473.
Antitumour agents: E. Härri,
[4c]
W. Loeffler, H. P. Sigg, H. Stähelin, C. Tamm, Helv. Chim.
5,8-Dimethoxybenzonorbornadiene: A. P. Marchand, S.
[4d]
Acta 1963, 46, 1235. K. Sakai, M. Yamashita, Y. Shibata,
Chem. Lett. 1986, 353.
Alihodzie, R. Shukla, Synth. Commun. 1988, 28, 541.
G.
[1c]
[4e]
HIV inhibitors: J. Reymond, P. Vo-
Schmid, J. Rabai, Synthesis 1988, 332.
K. C. Caster, C. G.
gel, Tetrahedron Lett. 1989, 30, 705. C. A. Fletcher, H. Hilpert,
P. L. Myers, S. Roberts, R. Storer, J. Chem. Soc., Chem. Com-
mun. 1989, 1707. [1d] Prostaglandins: E. J. Corey, X.-M. Cheng,
in The Logic of Chemical Synthesis, John Wiley & Sons, USA,
1989. [1e]Alkaloids: A. R. Battersby, The Alkaloids in Specialist
Periodical Reports (Ed.: J. E. Saxton), The Chemical Society,
London, 1971, vol. 1, p. 31. D. B. McLean, in The Chemistry of
the Alkaloids, Van Nostrand Reinholds Co., New York, 1970,
chapter 16. W. L. Scott, D. A. Evans, J. Am. Chem. Soc. 1972,
94, 4779. P. T. W. Cheng, S. McLean, Can. J. Chem. 1989, 67,
261. [1f] Terpenes: M. E. Jung, C. A. McCombs, Y. Takeda, Y.-
G. Pan, J. Am. Chem. Soc. 1981, 103, 6677. M. Asaoka, K.
Ishibashi, N. Yanagida, H. Takei, Tetrahedron Lett. 1983, 24,
5127. M. Demuth, S. Chandrasekhar, K. Schaffner, J. Am.
Chem. Soc. 1984, 106, 1092. T. Rajamannar, K. K. Balasubra-
manian, Tetrahedron Lett. 1988, 29, 5789. Y.-J. Wu, D. J. Bur-
nell, Tetrahedron Lett. 1988, 29, 1988. [1g] Glycosides and deriv-
atives: T. Suami, S. Ogawa, K. Nakamoto, I. Kasahara, Car-
bohydr. Res. 1977, 58, 240. S. Ogawa, I. Kasahara, T. Suami,
Bull. Chem. Soc. Jpn. 1979, 52, 118. A. K. Saksena, A. T.
McPhail, K. D. Onan, Tetrahedron Lett. 1981, 2067. A. K. Sak-
sena, A. K. Ganguly, Tetrahedron Lett. 1981, 5227. H. A. J.
Carless, O. Z. Oak, Tetrahedron Lett. 1989, 30, 1719. J. R.
Keck, R. D. Walls, J. Org. Chem. 2001, 66, 2932.
[5] [5a]
J. Kenndoff, K. Polborn, G. Szeimies, J. Am. Chem. Soc.
[5b]
1990, 112, 6117.
G. K. Tranmer, C. Yip, S. Handerson, R.
W. Jordan, W. Tam, Can. J. Chem. 2000, 78, 527.
[6]
[7]
J. W. Wilt, P. J. Chenier, J. Org. Chem. 1970, 35, 1562.
[7a] H. Kwart, L. Kaplan, J. Am. Chem. Soc. 1970, 75, 3356. [7b]
S. Cossu, O. De Lucchi, V. Lucchini, G. Valle, M. Balci, A.
[7c]
Dastan, B. Demirci, Tetrahedron Lett. 1997, 38, 5319.
C.
Zonta, S. Cossu, O. De Lucchi, Eur. J. Org. Chem. 2000, 1965.
[7d]
A. Altundas, A. Dastan, M. McKee, M. Balci, Tetrahedron
[7e]
2000, 56, 6115.
A. Dastan, Tetrahedron 2001, 57, 8725.
[8]
R. Durr, S. Cossu, O. De Lucchi, Synth. Commun. 1997, 27,
1369.
[9] [9a]
M. Hudlicky, in Oxidation in Organic Chemistry, A. C. S.
Publ., Washington, 1990. [9b]B. M. Trost, R. Braslau, J., Org.
Chem. 1988, 53, 532.
[10] [10a]
See for a review: G. Capozzi, G. Modena, L. Pasquato, in
The Chemistry of Sulphenic Acids and their Derivatives (Ed.: S.
Patai), Wiley & Sons Ltd., Chichester, U.K., 1990, chapter 10,
[10b]
pp. 403.
N. S. Zefirov, A. S. Koz’min, V. Kirin, V. Zhdan-
kin, R. Caple, J. Org. Chem. 1981, 46, 5264 and references cited
[10c]
therein.
S. Cossu, O. De Lucchi, F. Dilillo, Gazz. Chim.
[10d]
Ital. 1989, 119, 519.
O. Arjona, R. F. de la Pradilla, J.
[1h]
Billinge, O. Z. Oak, Tetrahedron Lett. 1989, 30, 3113.
Plumet, A. Viso, J. Org. Chem. 1991, 56, 6227.
[11]
[12]
Pancratistatine: M. Binwala, P. Vogel, Helv. Chim. Acta 1989,
72, 1825. P. Vogel, D. Fattori, F. Gasparini, C. Le Drian, Syn-
lett 1990, 173. E. Reynard, J.-L. Reymond, P. Vogel, Synlett
1991, 469 J. L. Acen˜a, O. Arjona, J. Plumet, Tetrahedron:
Asymmetry 1996, 7, 3535; (ϩ)-pinitol: J. L. Acen˜a, O. Arjona,
F. Iradier, J. Plumet, Tetrahedron Lett. 1996, 37, 105.
Each (phenylsulfonyl)-substituted sp2-carbon atom of a meso-
bis(phenylsulfonyl)-substituted polycyclic alkene is equivalent
to a latent carbonyl functionality. The term ‘‘symmetrisation’’
has been adopted in this sense.
F. Fernandez, X. Garcia-Mera, J. E. Rodriguez-Borges, Tetra-
[12a]
hedron: Asymmetry 2001, 12, 365. As recent example:
H.
[2] [2a]
S. Cossu, O. De Lucchi, P. Pasetto, Angew. Chem. Int. Ed.
Nagata, M. Kawamura, K. Ogasawara, Synthesis 2000, 1825.
[2b]
[12b]
Engl. 1997, 36, 1504.
S. Cossu, O. De Lucchi, P. Peluso, R.
P. Conti, A. P. Kozikowski, Tetrahedron Lett. 2000, 41,
[2c]
´
Volpicelli, Tetrahedron Lett. 1999, 40, 8705.
C. Najera, M.
4053.
[2d]
[13]
[14]
Yus, Tetrahedron 1999, 55, 10547.
S. Cossu, O. De Lucchi,
L. A. Paquette, K. S. Learn, J. L. Romine, H.-S. Lin, J. Am.
Chem. Soc. 1988, 110, 879.
[2e]
Phosphorus, Sulfur Silicon 1999, 153Ϫ154, 41.
S. Cossu, O.
De Lucchi, P. Peluso, R. Volpicelli, Tetrahedron Lett. 2000, 41,
P. B. Hopkins, P. L. Fuchs, J. Org. Chem. 1978, 43, 1208.
[2f]
7263.
K. Peters, E.-M. Peters, R. Volpicelli, S. Cossu, O.
Received June 14, 2002
[2g]
De Lucchi, P. Peluso, Z. Kristallogr. 2000, 215, 231.
G. K.
[O02323]
Eur. J. Org. Chem. 2002, 4024Ϫ4031
4031