(±)-3,3-Diethoxycarbonyl-2-p-tolylsulfinylacrylonitrile as dienophile: Relationship between the barrier for pyramidal inversion of vinyl sulfoxides and the electronic effects of the substituents at the double bond

Article abstract of DOI:10.1016/S0040-4020(02)00149-7

The dienophilic behavior of (±)-3,3-diethoxycarbonyl-2-p-tolylsulfinylacrylonitrile (6) is reported and compared with that of trialkoxycarbonyl sulfinylethylene (3). The change of a CO₂R group by a CN one increases both the reactivity and the stereoselectivity of the cycloaddition. It seems that the linear structure of the CN group increases the planarity of the system reinforcing its electron-withdrawing power and therefore improving its dienophilic behavior. Otherwise, the low configurational stability at room temperature of the sulfoxide 6, which is obtained as a racemic from its optically pure precursor, must also be a consequence of this strong electronic demand of the substituents which results in an unusually small energetic barrier for pyramidal inversion of the sulfinyl sulfur in compound 6 (ΔG^?=16.3kcalmol^-1 at T_c=25°C, determined by dynamic NMR spectroscopy). This is the first evidence of the existing relationship between racemization barrier of vinyl sulfoxides and the electron-withdrawing power of the groups joined to the double bond.

Full text of DOI:10.1016/S0040-4020(02)00149-7

TETRAHEDRON
Pergamon
Tetrahedron 58 32002) 2613±2620
ꢀ^)-3,3-Diethoxycarbonyl-2-p-tolylsul®nylacrylonitrile
as dienophile: relationship between the barrier for pyramidal
inversion of vinyl sulfoxides and the electronic effects
of the substituents at the double bond
a,p
Francisco Yuste, Benjamõn Ortiz, J. Israel Perez, Angel Rodrõguez-Hernandez,
a
a
a
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Ruben Sanchez-Obregon, Fernando Walls and Jose L. Garcõa Ruano
Â
b,p
a
a
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a
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Instituto de Quõmica, Universidad Nacional Autonoma de Mexico, Circuito Exterior, Cd. Universitaria, Coyoacan 04510, Mexico
b
  Â
Departamento de Quõmica Organica %C-I), Universidad Autonoma de Madrid, Cantoblanco, 28049-Madrid, Spain
Received 9 October 2001; revised 26 December 2001; accepted 1 February 2002
AbstractÐThe dienophilic behavior of 3^)-3,3-diethoxycarbonyl-2-p-tolylsul®nylacrylonitrile 36) is reported and compared with that of
trialkoxycarbonyl sul®nylethylene 33). The change of a CO2R group by a CN one increases both the reactivity and the stereoselectivity of the
cycloaddition. It seems that the linear structure of the CN group increases the planarity of the system reinforcing its electron-withdrawing
power and therefore improving its dienophilic behavior. Otherwise, the low con®gurational stability at room temperature of the sulfoxide 6,
which is obtained as a racemic from its optically pure precursor, must also be a consequence of this strong electronic demand of the
substituents which results in an unusually small energetic barrier for pyramidal inversion of the sul®nyl sulfur in compound 6
³
3DG ˆ16.3 kcal mol21 at Tcˆ258C, determined by dynamic NMR spectroscopy). This is the ®rst evidence of the existing relationship
between racemization barrier of vinyl sulfoxides and the electron-withdrawing power of the groups joined to the double bond. q 2002
Elsevier Science Ltd. All rights reserved.
1. Introduction
acyclic dienes due to their polymerization) the reactivity is
rather moderate 3similar to that of 1). Additionally, the low
regioselectivity detected in the elimination of the sul®nyl
group from the resulting adducts restricted their usefulness.
The incorporation of a third alkoxycarbonyl group to the
double bond was unable to solve these problems and thus
compound 3 exhibited a reactivity lower than 2 and 1,
as well as low endo/exo and p-facial selectivities.15 Two
alternative explanations can be postulated to account for
this behavior. The ®rst one would assume that steric
interactions hindering the coplanarity of the alkoxycarbonyl
The asymmetric Diels±Alder reaction is one of the most
important methods to prepare optically enriched six
membered ring systems due to its ability to create up to
four chiral centers in one step with a high degree of stereo-
control.1±5 The sul®nyl group has proved to be one of the
most ef®cient chiral auxiliaries when located either at diene
or dienophile, due to its ability to control the stereo-
selectivity of the cycloaddition process.6±8 Concerning the
use of sul®nylethylenes as dienophiles, their reactivity and
endo-selectivity are both moderate or low unless they bear
additional electron-withdrawing groups at the double bond,
alkoxycarbonyl ones having been the most widely studied.
In this ®eld, one of us has described the Diels±Alder reac-
tions of vinyl sulfoxides 1,9±11 2,12±14 and 315 3Scheme 1),
which are mono, di, and trialkoxycarbonyl derivatives,
respectively. The reactivity and stereoselectivity of sul®nyl-
maleates 2 were highly satisfactory, mainly when reactions
were conducted under TiCl4 catalysis,12±14 but in the
absence of this catalyst 3which cannot be used with many
Keywords: vinyl sulfoxides; Diels±Adler reactions; racemization; stereo-
electronic effects.
p
Corresponding authors. Fax: 134-91-397-3966;
e-mail: yustef@servidor.unam.mx; joseluis.garcia.ruano@uam.es
Scheme 1.
0040±4020/02/$ - see front matter q 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020302)00149-7

2614
F. Yuste et al. / Tetrahedron 58 %2002) 2613±2620
Scheme 2.
groups reduce their activating ability 3as well as their endo-
orientating character). Thus, the expected improvement in
the reactivity when the number of the alkoxycarbonyl
groups at the double bond increases, would be compensated
by the decrease in their activating ability produced by the
steric interactions distorting their coplanarity 3such a dis-
tortion would be very important for trialcoxycarbonyl
derivative 3). The second explanation would involve
the assumption that the sul®nyl group could act as an
electron-donating or -withdrawing group depending on the
nature of the other groups present at the double bond. This
dual behavior would be due to the fact that the 1M effect of
the lone electron pair at the sul®nyl sulfur 3whose electronic
description usually only considers its 2M and 2I effects,
thus only considering it as an electron-withdrawing group)
was operative and eventually became its predominant
electronic effect when it was required by other strongly
electron-demanding groups at the double bond. According
to this description, the sul®nyl group could be considered as
a buffer of the electronic density of the double bond, and the
increase in dienophilic reactivity expected from the increase
in the number of groups such as esters at the double bond
could be compensated by an inversion of the electronic
in¯uence of the sul®nyl group. Both explanations do not
exclude each other.
restricting their planarity. Thus we envisioned that sul®nyl-
acrylonitriles should be better dienophiles than sul®nyl-
acrylates, which could be demonstrated by studying the
dienophilic behavior of several enantiopure 3Z)-3-p-tolyl-
sul®nylacrylonitriles 416±17 3Scheme 1). The reactivity of
these nitriles, although higher than that of the corresponding
acrylates 5,18±22 was rather moderate thus suggesting that
the increase in the reactivity produced by the nitrile could be
partially compensated by the sul®nyl group, now acting as
an electron donor group. In order to con®rm this ®rst
evidence and thus clarify on the electronic behavior of the
sul®nyl group, the study of other systems with more
activated vinyl sulfoxides was necessary. In this sense we
decided to study the dienophilic behavior of the 3,3-di-
ethoxycarbonyl-2-p-tolylsul®nylacrylonitrile 6 because it
has a structure similar to 3 but with a linear CN group
instead of that of the trigonal alkoxycarbonyl groups, thus
suggesting an improvement in reactivity and stereoselec-
tivity. In this paper we report the results obtained in this
study which con®rm the above-mentioned assumptions and
what is more important, we provide the ®rst evidence of the
existing relationship between the con®gurational stability of
the vinyl sulfoxides and the electronic character of the
substituents joined to the dienophilic double bond.
In order to check the ®rst explanation, the substitution of the
ester groups by the cyano ones seemed to be appropriate
because the linear structure of the latter suggested the
absence of steric interactions with the ¯anking groups
2. Results and discussion
The synthesis of 3,3-diethoxycarbonyl-2-p-tolylsul®nyl-
acrylonitrile 6, was carried out as depicted in Scheme 2,
Figure 1. X-Ray structures for compounds 6 and endo-8.

F. Yuste et al. / Tetrahedron 58 %2002) 2613±2620
2615
Table 1. Diels±Alder reactions of dienophiles 6 and 3 3values in brackets taken from Ref. 15) with cyclopentadiene
b
b
Entry
Catalyst 31.2 equiv.)
T 38C)
t 3h)
Yield 3%)a
endo-8b
endo-80
exo-9b
exo-90
endo/exoRatio
1
2
3
4
±
20 320)
220 30)
220 3210)
278 3278)
2.5 372)
2 32)
2 32)
80 383)
79 377)
84 389)
±c376)
80 362)
89 362)
92 355)
±c390)
±38)
±38)
±3±)
±c34)
20 330)
11 330)
8 345)
±c36)
±3±)
±3±)
±3±)
±c3±)
4.0 32.3)
8.1 32.3)
11.5 31.2)
±c315.6)
Eu3fod)3
ZnBr2
TiCl4
±c31)
a
Of pure adducts after chromatographic puri®cation.
Isomer ratio determined by 1H NMR.
Slow decomposition of the dienophile 6 was observed in the presence of this catalyst.
b
c
using a synthetic sequence parallel to that used for the
preparation of 3.15 Deprotonation of 3R)-31)-cyanomethyl-
p-tolyl sulfoxide23 with LHMDS 31.2 equiv.) in THF and
further reaction of the resulting anion with diethyl oxo-
malonate at 2788C furnished the diastereomerically pure
3its con®guration was not determined) alcohol 7 in 78%
yield after ¯ash chromatography. Dehydration of 7 was
performed by treatment with tri¯ic anhydride±diisopropyl-
ethylamine or with MsCl±diisopropylethylamine in CH2Cl2
at 2788C affording the pure vinyl sulfoxide 6 in 46 and 66%
yield, respectively 3after chromatography). Surprisingly, the
optical purity of 6 [[a]Dˆ10.9 3c 1, acetone)] was very low
3ee#5%, determined by 1H NMR in the presence of
Yb3hfc)3), despite its precursor 7 was optically active
[[a]Dˆ193.4 3c 1, acetone)]. We will return to this inter-
esting ®nding later.
modes of the reagents or the stereochemistry of the adducts
using as a reference the sul®nyl group 3present in 3 and 6),
despite the right name could be the opposite according to the
sequence rules.
From the results depicted in Table 1, it can be established
that the reactions of dienophile 6 with cyclopentadiene
under different conditions yielded a mixture of only two
adducts 3endo-8 and exo-9), which were separated and puri-
®ed by column chromatography. The endo structure and the
con®guration of the major adduct 38)24 were unequivocally
determined by an X-ray diffraction study 3Fig. 1).
The stereochemistry of the minor adduct 9 was established
as exo from the fact that the sulfone 11, resulting from its
oxidation with m-CPBA, exhibits a 1H NMR spectrum
different to sulfone 10 obtained by oxidation of sulfoxide
endo-8, which revealed that both sulfones must display
different endo or exo con®guration. It allowed us to assign
the exo stereochemistry to compound 11 and therefore to its
precursor 9, because that for 10 must be endo since it derives
from endo-8. The complete p-facial selectivity observed in
these reactions for the endo approach suggests that dia-
stereotopic dienophilic faces must be clearly different,
which must also be the case for the exo approach. Therefore,
we could expect that the diene attack was predominant to
the same face in both endo and exo approaches. It allowed to
assign compound exo-9 the relative con®guration shown in
Table 1.
The X-ray diffraction analysis of 6 3Fig. 1), which con®rms
its racemic nature,24 reveals that the ester group in cis-
arrangement with respect to the CN one is almost coplanar
with the double bond 3the dihedral angle C4±C2±C1±O2ˆ
178, Fig. 1) thus con®rming our predictions about the scarce
in¯uence exerted by the linear cyano group in the conju-
gation of the ¯anking groups. By contrast, the planarity of
the second ester group is strongly restricted 3dihedral angle
C4±C2±C3±O4ˆ58.58), maybe due to its steric and elec-
tronic interactions with the ¯anking sul®nyl and ester
groups. Finally, the conformational arrangement around
the C±S bond is the one wherein the p-tolyl group is
oriented in an almost perpendicular plane 3dihedral angle
C2±C4±S1±C10ˆ21108) with respect to that of the dieno-
philic double bond and the sul®nyl oxygen O35) is oriented
towards a face different to that of the carbonyl oxygen O34).
This conformation, which determines the steric course of
the cycloadditions of compound 6 3see later), could also
be predominant in solution as it minimizes the electronic
repulsion between O34) and O35).
The comparison of the results obtained from 6 with those
from 3 3see Table 1 and Ref. 15), indicates that the reactivity
of 6 is the highest one, but the most signi®cant difference is
observed in the stereoselectivity 3see Table 1), compound 6
exhibiting a complete p-facial selectivity in both endo and
exo approaches 3in compound 3 this was the case only for
the exo approach), and an endo/exo selectivity higher than
those observed for compound 3, mainly in the presence of
catalysts such as Eu3fod)3 and ZnBr2 3entries 2 and 3,
Table 1).
The results obtained in reactions of dienophile 6 with an
excess of cyclopentadiene using CH2Cl2 as the solvent,
under different conditions, are presented in Table 1. We
have also included, for comparative purposes, the results
obtained from enantiopure triester 3 under similar con-
ditions.15 In order to make easier this comparison, the
endo or exo terms used in this paper describe the approach
Taking into account that the planarity of the three alkoxy-
carbonyl groups at 3 must be distorted due to steric and
electronic interactions, hence minimizing their in¯uence
in the reactivity of the double bond, the higher reactivity

2616
F. Yuste et al. / Tetrahedron 58 %2002) 2613±2620
butadiene and Danishefsky's diene. These reactions were
carried out under thermal conditions 3Schemes 4 and 5).
As in the case of the reactions of dienophiles 212±14 and 315
with acyclic dienes, the adducts derived from 6 were not
stable and rapidly evolved to the desul®nylated compounds
resulting from the syn-pyrolytic elimination of the sul®nyl
group. As depicted in Scheme 4, the cycloaddition of 6 with
1-methoxy-1,3-butadiene gave the adduct 12, which could
not be detected and rapidly evolved into the cyclohexadiene
13, obtained as the sole product in 58% yield. This
evolution, which precludes to obtain any stereochemical
information, indicates that the regioselectivity of the reac-
tion is complete and exclusively controlled by the vinyl
carbon supporting the gem-diester function. This regio-
selectivity is not unexpected because it is just the same to
that observed with dienophile 3. On the other hand,
the Diels±Alder reaction of 6 with trans-1-methoxy-3-
3trimethylsilyloxy)-1,3-butadiene afforded the regioisomers
18 and 19 in 61 and 13% yields, respectively 3Scheme 5),
the formation of which can be explained by spontaneous
desul®nylation of the initially formed adducts 14 and 15
and concomitant hydrolysis of the resulting enol silyl ethers
16 and 17 during the work-up.
Scheme 3.
of compound 6 can be easily explained by assuming that it
must adopt a similar spatial arrangement in solution and in
the solid state 3see Fig. 1), the CN group scarcely affecting
the planarity of the ¯anking ester, which will be more
ef®cient in increasing the dienophilic reactivity.
Concerning the stereoselectivity, the complete p-facial
selectivity observed in the cycloaddition of nitrile 6 in
both endo and exo approaches, is not unexpected if we
take into account the almost normal arrangement of the
aryl group and the orientation of O34), which completely
precludes the approach of the diene from the face that they
both occupy 3Fig. 1). On the other hand, the clear pre-
dominance of the endo sul®nyl approach is intriguing.
From an electronic point of view, it could be expected
that the endo orientating character of the CN and ester
groups in a cis-arrangementÐthe latter almost coplanar
with the double bondÐwere higher than that of the
SOTol and CO2Et group lacking such planarity. We assume
that the interactions between the methylene bridge of the
cyclopentadiene with the sul®nyl and alkoxycarbonyl
oxygens O33) and O35), oriented towards the face suffering
the diene approach yielding exo-9, are the main responsible
for the observed preference for the endo sul®nyl approach
3Scheme 3). The increase in the endo selectivity in the
presence of Lewis acids, which are able to associate with
such oxygens 3mainly the sul®nyl one), thus increasing their
size and therefore the magnitude of their steric interactions,
reinforces this explanation.
The decrease in the regioselectivity observed for the
1,3-disubstituted diene is unexpected from an electronic
point of view 3both substituents reinforce the same orien-
tation), which suggests that steric factors involving the
substituent at C-3 in the diene and those of the dienophile
in the favored endo or exo approach must be signi®cant in
the regioselectivity control.
The surprising racemization observed in the formation of
compound 6 from its optically active precursor 7 is a fact
that had some precedents. Thus it had been previously
observed in the synthesis of trans-3-p-tolylsul®nyl-2-pro-
penal.25 In this case we were not able to ®nd reproducible
reaction conditions allowing the preparation of the optically
pure compound. A similar but fortunately easy to control
situation was observed in the synthesis of cyclic vinyl-p-
tolylsul®limines.26 Taking into account that reaction con-
ditions used in the synthesis of these compounds were not
stronger enough to justify a chemical racemization, but all of
them exhibit strong electron-withdrawing groups connected
to the double bonds, we reasoned that the lack of optical
activity could be a consequence of the decrease in the
energetic barrier for the inversion at the sul®nyl sulfur. In
order to evaluate such a barrier we have realized a NMR
experiment.
Next, we studied the reactions of 6 with 1-methoxy-1,3-
Scheme 4.
Scheme 5.

F. Yuste et al. / Tetrahedron 58 %2002) 2613±2620
2617
Figure 2. 300 MHz 1H NMR signals of the methyl protons of the ethyl ester groups of 3^)-6 in the presence of two-fold molar amount of 32)-TFAE in CDCl3.
3A): at 2608C. 3B): at 08C. 3C): at 258C.
It is known that a number of compounds cannot be obtained
in their optically pure form because of their rapid inter-
conversion of its enantiomers at room temperature.
Although the chirality of the enantiomers in racemic
mixtures cannot be proved by optical methods, it can be
demonstrated indirectly by dynamic NMR spectroscopy
by using an appropriate chiral solvating agent.27 Thus,
different NMR spectra can be observed for enantiomers
which undergo a suf®ciently strong interaction with a
optically active compound. By measuring nonequivalence
as a function of the temperature it is possible to determine
the interconversion rates of enantiomers.28 This approach
has been used to determine the barrier to pyramidal
must increase 3the conjugation of the lone electron pair at
sulfur is more ef®cient when it occupies a p orbital of one
planar sp2 hybridized sulfur) thus lowering its energetic
barrier for the pyramidal inversion, as it is observed.
Additionally the fact that the sul®nyl group becomes as
electron-donating in this and similar compounds, can contri-
bute to decrease their dienophilic reactivity, as it has also
been observed 3Section 1). A systematic study about the
in¯uence of different electron-withdrawing groups on the
racemization barrier of the vinyl sulfoxides is in course
and will be published in further papers.
1
inversion of the enantiomers of 6. The H NMR signals of
3. Conclusion
the methyl protons of the ethyl ester groups of 3^)-6 in
CDCl3 at 300 MHz in the presence of two molar equivalents
of 3R)-32)-2,2,2-tri¯uoro-1-39-anthryl)-ethanol [32)-TFAE]
at three different temperatures are presented in Fig. 2. As it
can be observed, at 2608C 3Fig. 23A)), the triplets of the
methyl protons of the two enantiomers appears splitted with
a Ddˆ3 Hz. An increase in the temperature causes a rapid
interconversion 3Fig. 23B)) and the methyl signals coalesce
at 258C 3Fig. 23C)). If the coalescence temperature Tc is
In summary, we have demonstrated that the substitution of
one of the alkoxycarbonyl groups of the triester 3 by the
cyano one improves both reactivity and stereoselectivity.
On the other hand, the presence of strongly electron-with-
drawing groups at the double bond of vinyl sulfoxides
causes a decrease in the energy barrier for the pyramidal
inversion of the sul®nyl sulfur, thus making its racemization
easier. This is the ®rst evidence about the in¯uence of the
electronic effects of the substituents at double bond in the
con®gurational stability of vinyl sulfoxides.
258C, from these values we obtain a rate constant kcˆ
³
6.6 s21 and DG ˆ16.3 kcal mol21
.
³
The unexpectedly low DG value for pyramidal inversion of
the sul®nyl sulfur 3for dialky, diaryl, and alkyl aryl sulf-
³
4. Experimental
4.1. General
oxides the values are DG ˆ35±42 kcal mol21 29
)
must be
related to the electronic in¯uence of the substituents at the
double bond in compound 6. The increase in the planarity of
the system enhances the electron-withdrawing power of the
substituents, thus favoring that the lone electron pair at
sulfur was shifted towards the double bond, in order to
compensate for its electronic de®ciency. It determines that
the sul®nyl group can exhibit a 1M effect, which is not
usually considered. Two are the consequences of this elec-
tronic shifting. First of all, the planarity of the sul®nyl sulfur
Melting points were determined in a Culatti apparatus. All
moisture sensitive reactions were performed in ¯ame-dried
glassware equipped with rubber septa under positive argon
pressure and monitored by TLC. Solvents were dried
according to literature procedures. Optical rotations were
measured on a digital polarimeter at 208C 3concentration
1
in g/100 mL). H and 13C NMR spectra were obtained at

2618
F. Yuste et al. / Tetrahedron 58 %2002) 2613±2620
300 and 75 MHz, respectively, on deuterochloroform using
TMS as the internal standard. Mass spectra were measured
at 70 eV and 1908C.
2.44 3s, 3H), 4.36 3dq, Jˆ3.0, 7.2 Hz, 2H), 4.46 3q, Jˆ
7.2 Hz, 2H), 7.39 and 7.79 3AA0BB0 system, 4H). 13C
NMR 3CDCl3): d 13.7, 14.0, 21.6, 63.7, 63.8, 109.0,
125.3, 130.6, 136.8, 139.4, 144.0, 159.5, 161.1. EIMS:
335 3M1, 10), 139 3100), 123 310), 91 313), 77 36). Anal.
Calcd for: C16H17NO5S: C, 57.30; H, 5.11; N, 4.18. Found:
C, 57.52; H, 5.20; N, 4.31.
Analytical thin layer chromatography was performed on
Alugram 0.25 mm silica gel 60 sheets 3Macherey±Nagel).
Visualization was accomplished with UV light absorption,
iodine vapor or ethanolic fosfomolybdic acid solution
followed by heating. Flash chromatography was
performed with silica gel 60 Merck, 3230±400 mesh). 3R)-
31)-cyanomethyl-p-tolyl sulfoxide was prepared as
described.23
4.2. Diels±Alder reactions of 6with cyclopentadiene
Uncatalyzed reaction. To a solution of 6 30.1 g, 0.30 mmol,
1 equiv.) in CH2Cl2 32 mL), at room temperature under
argon, cyclopentadiene 3149 mL, 1.79 mmol, 6 equiv.) was
added. The resulting solution was stirred for 2.5 h. Evapo-
ration of the volatiles under vacuum afforded a residue that
was analyzed by 1H NMR 3endo-8/exo-9 ratioˆ80:20). The
8 and 9 isomers were separated and puri®ed by ¯ash chro-
matography using hexane±ethyl acetate 85:15 as the eluent.
4.1.1.
ꢀRS)-ꢀ1)-3,3-Diethoxycarbonyl-3-hydroxy-2-p-
tolylsul®nylpropionitrile ꢀ7). A solution of 3R)-31)-cyano-
methyl-p-tolyl sulfoxide 31.0 g, 5.6 mmol, 1.0 equiv.) in
THF 310 mL) was added, under argon, to a solution of
LHMDS 3prepared from a 1.1 M solution of n-BuLi
36.7 mmol, 1.2 equiv.) and hexamethyldisilazane 31.42
mL, 6.7 mmol, 1.2 equiv.) in THF 340 mL) at 08C) cooled
at 2788C. After stirring for 30 min, a solution of diethyl
oxomalonate 30.945 mL, 6.2 mmol, 1.1 equiv.) was slowly
added. Stirring was continued at 2788C for 2 h. Then, a
saturated ammonium chloride solution 316 mL) was
added. The organic layer was separated and the aqueous
layer was extracted with CH2Cl2 32£15 mL). The combined
organic extracts were dried 3Na2SO4) and concentrated. The
residue was puri®ed by column chromatography 3hexane±
ethyl acetate 60:40) to produce 1.52 g 378%) of 7 as white
crystals, mp 121±1248C, [a]Dˆ193.4 3c 1, acetone). IR
3CHCl3): 3496, 2987, 2941, 2908, 2248, 1764, 1747,
Lewis acid promoted reactions. A solution of 6 30.05 g,
0.15 mmol, 1 equiv.) in CH2Cl2 32 mL) was added to a
suspension of the Lewis acid 30.18 mmol, 1.2 equiv.) in
CH2Cl2 32 mL) cooled at 2208C, under argon. The mixture
was stirred for 10 min, and then 75 mL 389 mmol, 6 equiv.)
of cyclopentadiene was added. Stirring was continued for
2 h at 2208C. After the addition of 5% HCl 3Eu3fod)3) or
10% NaHCO3 3ZnBr2), the aqueous layer was separated and
extracted with CH2Cl2. The combined organic extracts were
washed with water, dried, and concentrated. The obtained
mixtures 3see Table 1) were analyzed by 1H NMR, separated
and puri®ed by ¯ash chromatography.
1
1597, 1066 cm21. H NMR 3CDCl3): d 1.30 3t, Jˆ7.2 Hz,
3H), 1.39 3t, Jˆ7.2 Hz, 3H), 1.65 3bs, 1H, interchangeable
with D2O), 2.46 3s, 3H), 4.27±4.47 3m, 4H), 4.59 3s, 1H),
7.40 and 7.72 3AA0BB0 system, 4H). 13C NMR 3CDCl3): d
13.8, 14.0, 21.6, 62.1, 64.2, 64.3, 77.3, 112.3, 125.4, 130.3,
137.7, 144.1, 166.4, 166.6. EIMS: 353 3M1, 18), 139 3100),
131 310), 91 312), 77 34).
4.2.1. ꢀ^)-ꢀ1R,2S,4S)-3,3-Diethoxycarbonyl-2-ꢀp-tolyl-
sul®nyl)bicyclo[2.2.1]hept-5-ene-2-carbonitrile ꢀendo-8).
Mp 111±1138C 3dec.). IR 3CHCl3): 3003, 2996, 2939, 2231,
1
1738, 1463, 1049 cm21. H NMR 3CDCl3): d 0.87 3t, Jˆ
7.2 Hz, 3H), 1.27 3t, Jˆ7.2 Hz, 3H), 1.93 3dt, Jˆ1.8,
10.2 Hz, 1H), 2.20 3dt, Jˆ1.5, 10.2 Hz, 1H), 2.40 3s, 3H),
3.68 3m, 1H), 3.82 3m, 1H), 3.98 3m, 2H), 4.22 3m, 2H), 6.35
3dd, Jˆ3.0, 5.7 Hz, 1H), 6.76 3dd, Jˆ3.0, 5.7 Hz, 1H), 7.30
and 7.93 3AA0BB0 system, 4H). 13C NMR 3CDCl3): d 13.2,
14.0, 21.4, 47.7, 52.8, 54.5, 62.5, 63.9, 69.1, 76.4, 117.0,
127.3, 129.1, 137.2, 138.2, 139.5, 142.2, 167.1, 167.4.
EIMS: 402 3M111, 8), 401 3M1, 7), 385 320), 262 388),
234 369), 206 3100), 188 373), 144 350), 123 330), 91 323).
Anal. Calcd for C21H23NO5S: C, 62.82; H, 5.77; N, 3.49.
Found: C, 62.58; H, 5.80; N, 3.42.
4.1.2. ꢀ^)-3,3-Diethoxycarbonyl-2-p-tolylsul®nylacrylo-
nitrile ꢀ6). Method A. To a solution of 7 31.34 g,
3.8 mmol, 1 equiv.) in CH2Cl2 325 mL) stirred at 2788C
under argon, tri¯ic anhydride 30.912 mL, 4.18 mmol,
1.1 equiv.) and diisopropylethylamine 31.32 mL, 7.6
mmol, 2 equiv.) were successively added. The mixture
was stirred at 2788C for 1 h, and then H2O 330 mL) was
added. The organic layer was separated and the aqueous
layer was extracted with CH2Cl2 32£20 mL). The combined
organic layers were dried 3Na2SO4) and concentrated. The
residue was puri®ed by column chromatography 3hexane±
ethyl acetate 80:20) to give a solid that was recrystallized
from hexane±CH2Cl2 to produce 0.584 g 346%) of 6 as
yellow crystals, mp 102±1048C.
4.2.2. ꢀ^)-ꢀ1S,2S,4R)-3,3-Diethoxycarbonyl-2-ꢀp-tolyl-
sul®nyl)bicyclo[2.2.1]hept-5-ene-2-carbonitrile ꢀexo-9).
Mp 93±958C 3dec.). IR 3CHCl3): 3003, 2996, 2939, 2236,
1737, 1598, 1194, 1081 cm21. 1H NMR 3CDCl3): d 1.03 3t,
Jˆ7.2 Hz, 3H), 1.31 3t, Jˆ7.2 Hz, 3H), 1.61 3t, Jˆ1.8 Hz,
1H), 1.64 3t, Jˆ1.8 Hz, 1H), 2.43 3s, 3H), 3.58 3m, 2H), 4.04
3m, 2H), 4.31 3q, Jˆ7.2 Hz, 2H), 6.39 3dd, Jˆ3.0, 5.4 Hz,
1H), 6.58 3dd, Jˆ3.0, 5.4 Hz, 1H), 7.35 and 7.84 3AA0BB0
system, 4H). 13C NMR 3CDCl3): d 13.5, 13.9, 21.5, 44.9,
50.6, 52.1, 62.4, 63.1, 69.4, 71.7, 116.5, 127.3, 129.4, 137.5,
137.7, 140.8, 143.2, 166.4, 167.8. EIMS: 401 3M1, 6), 385
317), 262 382), 234 365), 206 3100), 188 375), 144 353), 123
340), 91 320). Anal. Calcd for C21H23NO5S: C, 62.82; H,
5.77; N, 3.49. Found: C, 62.68; H, 5.82; N, 3.47.
Method B. To a solution of 7 31.64 g, 4.7 mmol, 1 equiv.) in
CH2Cl2 365 mL) stirred at 2788C under argon, mesyl
chloride 31.46 mL, 18.8 mmol, 4 equiv.) and diisopropyl-
ethylamine 33.24 mL, 18.8 mmol, 4 equiv.) were added.
The mixture was stirred at 2788C for 2 h. Usual work-up
and puri®cation as above described produced 0.934 g 366%)
of 6 as yellow crystals, mp 102±1048C. IR 3CHCl3): 2960,
1
2939, 2875, 2250, 1735, 1650, 1595, 1033 cm21. H NMR
3CDCl3): d 1.34 3t, Jˆ7.2 Hz, 3H), 1.41 3t, Jˆ7.2 Hz, 3H),

F. Yuste et al. / Tetrahedron 58 %2002) 2613±2620
2619
4.3. General method for the oxidation of sulfoxides endo-
8 and exo-9
1H), 6.40 3ddd, Jˆ0.6, 5.1, 9.6 Hz, 1H), 6.86 3dd, Jˆ0.6,
5.7 Hz, 1H). 13C NMR 3CDCl3): d 13.7, 13.9, 57.0, 59.6,
62.5, 62.7, 72.4, 108.6, 117.7, 123.7, 129.2, 138.7, 165.3,
165.4. EIMS: 279 3M1, 7), 372 34), 206 3100), 178 370), 160
373), 148 330), 130 377), 102 320).
To a stirred solution of m-CPBA 380±85%) 30.054 g,
0.25 mmol, 2 equiv.) in CH2Cl2 32 mL) at 08C a solution
of sulfoxide 38 or 9) 30.050 g, 0.12 mmol, 1 equiv.) in
CH2Cl2 32 mL) was added. The mixture was stirred at 08C
for 6 h. Then, a 10% Na2S2O3 solution 35 mL) was added.
The organic layer was separated, and the aqueous layer was
extracted with CH2Cl2 33£10 mL). The combined organic
layers were washed with water 35 mL), brine 35 mL), dried
3Na2SO4), and evaporated under vacuum. The residue was
puri®ed by ¯ash chromatography using hexane±ethyl
acetate 75:25 as the eluent to yield 10 382%) and 11
380%), respectively.
4.4.2. ꢀ^)-3-Cyano-4,4-diethoxycarbonyl-5-methoxy-2-
cyclohexen-1-one ꢀ18). It was obtained from the reaction
of 6 with trans-1-methoxy-3-3trimethylsilyloxy)-1,3-buta-
diene. Yield: 61%, mp 71±748C. IR 3CHCl3): 2986, 2938,
2832, 2250, 1741, 1704, 1260, 1094 cm21 1H NMR
.
3CDCl3): d 1.34 3t, Jˆ7.2 Hz, 3H), 1.35 3t, Jˆ7.2 Hz,
3H), 2.97±3.01 3m, 2H), 3.32 3s, 3H), 4.28±4.45 3m, 4H),
4.54 3t, Jˆ3.0 Hz, 1H), 6.68 3s, 1H). 13C NMR 3CDCl3): d
13.7, 13.9, 38.3, 57.4, 60.5, 63.1, 63.6, 78.6, 115.9, 124.3,
140.5, 164.5, 164.8, 192.8. EIMS: 295 3M1, 12), 222 3100),
194 358), 181 342), 164 355).
4.3.1. ꢀ^)-ꢀ1R,2S,4S)-3,3-Diethoxycarbonyl-2-ꢀp-tolyl-
sulfonyl)bicyclo[2.2.1]hept-5-ene-2-carbonitrile ꢀ10). Mp
120±1228C. IR 3CHCl3): 3003, 2987, 2935, 2235, 1743,
4.4.3. ꢀ^)-4-Cyano-5,5-diethoxycarbonyl-3-methoxy-2-
cyclohexen-1-one ꢀ19). It was obtained from the reaction
of 6 with trans-1-methoxy-3-3trimethylsilyloxy)-1,3-buta-
diene. Yield: 13%, oil. IR 3CHCl3): 2983, 2940, 2250,
1
1597, 1341, 1254, 1154 cm21. H NMR 3CDCl3): d 1.29
3t, Jˆ7.2 Hz, 3H), 1.30 3t, Jˆ7.2 Hz, 3H), 1.67 3dt, Jˆ
10.2, 1.8 Hz, 1H), 1.96 3d, Jˆ10.2 Hz, 1H), 2.47 3s, 3H),
3.16 3m, 1H), 3.70 3m, 1H), 4.20±4.40 3m, 4H), 6.35 3dd,
Jˆ3.0, 5.4 Hz, 1H), 6.64 3dd, Jˆ3.0, 5.4 Hz, 1H), 7.40 and
8.02 3AA0BB0 system, 4H). 13C NMR 3CDCl3): d 13.7 32C),
21.7, 46.9, 51.6, 56.3, 62.7, 63.3, 71.5, 74.4, 118.3, 129.6,
130.8, 133.1, 135.1, 139.1, 146.1, 165.1, 167.3. EIMS: 417
3M1, 3), 372 34), 306 322), 262 367), 216 3100), 188 323),
170 374), 144 312), 139 338), 91 342).
1
1739, 1670, 1623, 1456, 1349 cm21. H NMR 3CDCl3): d
1.23 3t, Jˆ7.2 Hz, 3H), 1.33 3t, Jˆ7.2 Hz, 3H), 3.00 and
3.22 3AB system, Jˆ17.1 Hz, 2H), 3.82 3s, 3H), 4.20±
4.39 3m, 4H), 4.40 3s, 1H), 5.45 3s, 1H). 13C NMR
3CDCl3): d 13.8, 13.9, 36.4, 39.2, 56.7, 57.3, 63.4, 63.5,
103.4, 114.6, 165.9, 166.7, 167.7, 191.9. EIMS: 295 3M1,
10), 222 3100), 194 397), 176 372), 150 330), 123 361).
4.3.2. ꢀ^)-ꢀ1S,2S,4R)-3,3-Diethoxycarbonyl-2-ꢀp-tolyl-
sulfonyl)bicyclo[2.2.1]hept-5-ene-2-carbonitrile ꢀ11). Mp
125±1288C. IR 3CHCl3): 3003, 2986, 2939, 2240, 1744,
Acknowledgements
1
1597, 1340, 1255, 1153 cm21. H NMR 3CDCl3): d 1.27
Â
We thank M. I. Chavez, R. GavinÄo, S. Hernandez-Ortega,
R. PatinÄo, M. A. PenÄa, J. Perez, B. Quiroz, H. Rõos, R. A.
Â
3t, Jˆ7.2 Hz, 3H), 1.34 3t, Jˆ7.2 Hz, 3H), 1.68 3dt, Jˆ
10.2, 1.5 Hz, 1H), 2.49 3s, 3H), 2.72 3dt, Jˆ10.2, 1.5 Hz,
1H), 3.17 3m, 1H), 3.75 3m, 1H), 4.18±4.42 3m, 4H), 6.33
3dd, Jˆ3.0, 5.4 Hz, 1H), 6.39 3dd, Jˆ3.0, 5.4 Hz, 1H),
7.42 and 7.98 3AA0BB0 system, 4H). 13C NMR 3CDCl3):
d 13.6, 13.8, 21.8, 45.5, 52.0, 54.3, 62.7, 63.3, 68.8, 73.7,
116.8, 129.9, 131.1, 133.5, 138.4, 140.1, 146.5, 166.2,
166.3. EIMS: 417 3M1, 4), 372 33), 306 314), 262 395),
234 332), 216 3100), 206 348), 170 345), 144 336), 139
327), 91 345).
Â
Â
Toscano, L. Velasco for their technical assistance, and the
Â
Consejo Nacional de Ciencia y Tecnologõa 3CONACYT-
Mexico, Project 26375-E) and DGICYT, Spain 3Project
Â
BQU2000-0246) for partial ®nancial support.
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