Diels-Alder reactions of (R(s))-3-[(1S)-isoborneol-10-sulfinyl]- 1- methoxybuta-1,3-dienes with electron-deficient carbodienophiles. The effects of Lewis acid catalysis

Article abstract of DOI:10.1016/S0957-4166(98)00138-4

Uncatalyzed cycloadditions of (R(S),E)-1 and (R(S),Z)-3-[(1S)- isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene 2 with maleimide and N- phenylmaleimide occurred with complete endo and very high facial diastereoselectivities. The effects of Lewis acid catalysis on these Diels- Alder reactions have been evaluated. LiClO₄ catalyzed cycloaddition of 1 with dimethyl maleate gave cyclohexene 13 as the unique product with complete control of endo and π-facial diastereoselectivities exerted by the sulfinyl group. A significant improvement in diastereoselectivity was also observed in the LiClO₄ catalyzed cycloaddition of 1 with dimethyl fumarate.

Full text of DOI:10.1016/S0957-4166(98)00138-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 9 (1998) 1577–1587
Diels–Alder reactions of (RS)-3-[(1S)-isoborneol-10-sulfinyl]-
1-methoxybuta-1,3-dienes with electron-deficient
carbodienophiles. The effects of Lewis acid catalysis
Maria C. Aversa,a,∗ Anna Barattucci,a Paola Bonaccorsi,a Placido Giannetto,a
Manuela Panzalorto b and Simona Rizzo a
aDipartimento di Chimica organica e biologica, Università degli Studi di Messina, Salita Sperone 31 (vill. S. Agata),
98166 Messina, Italy
bDipartimento di Chimica inorganica, chimica analitica e chimica fisica, Università degli Studi di Messina, Salita Sperone 31
(vill. S. Agata), 98166 Messina, Italy
Received 3 March 1998; accepted 2 April 1998
Abstract
Uncatalyzed cycloadditions of (RS,E)-1 and (RS,Z)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene 2
with maleimide and N-phenylmaleimide occurred with complete endo and very high facial diastereoselectivities.
The effects of Lewis acid catalysis on these Diels–Alder reactions have been evaluated. LiClO4 catalyzed
cycloaddition of 1 with dimethyl maleate gave cyclohexene 13 as the unique product with complete control of endo
and π-facial diastereoselectivities exerted by the sulfinyl group. A significant improvement in diastereoselectivity
was also observed in the LiClO4 catalyzed cycloaddition of 1 with dimethyl fumarate. © 1998 Elsevier Science
Ltd. All rights reserved.
1. Introduction
Since the first publication reporting the involvement of enantiomerically pure sulfinyldienes in
Diels–Alder reactions,1 stimulating results have been achieved in this field.2 The experimental data
obtained have emphasized the sulfinyl group efficiency in controlling π-facial diastereoselectivity and
the synthetic potential of conjugate sulfinyldienes in the field of natural product chemistry. Electron-
deficient cyclic dienophiles, such as maleimides and maleic anhydride, have been widely used in
cycloadditions with enantiomerically pure 1- and 2-sulfinyldienes, and complete endo and very high
facial diastereoselectivities were observed.2a,c–f The results concerning π-facial selectivity have been
explained on the basis of strong electrostatic repulsions between the sulfinyl oxygen atom of the diene
∗
Corresponding author. E-mail: aversa@imeuniv.unime.it
0957-4166/98/$19.00 © 1998 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(98)00138-4

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and the carbonyl oxygen atoms of the dienophile in the transition state. Nevertheless, 1-sulfinyldienes
have shown low reactivity by comparison with 2-sulfinyldienes, since cycloadditions of the former com-
pounds with cyclic electron-deficient dienophiles need high pressures and/or longer reaction times to be
completed.3 Recently, Diels–Alder reactions of 1-sulfinyldienes with either acyclic electron-deficient or
cyclic electron-rich dienophiles have been described, and the low reactivity of 1-sulfinyldienes with both
types of partners has been attributed to simultaneous electron-donating (+M) and electron-withdrawing
(−I) effects of the sulfinyl group which mutually compensate and have minimal influence on both
LUMO’s and HOMO’s energies of these dienes.4 Following analogous arguments, 2-sulfinyl dienes such
as 1 and 2 (Scheme 1 and Scheme 2), which possess a strongly electron-donating methoxy substituent
and the sulfinyl group suitably positioned to support the electronic characteristics of the OMe substituent,
should be significantly more electron rich than 1-sulfinyldienes and therefore more reactive with electron-
deficient dienophiles. However, less attention has been directed towards the Diels–Alder behaviour of
these 2-sulfinyldienes, even if they should act as more effective partners in such cycloadditions.3
Scheme 1.
In this paper we report the results obtained in Diels–Alder reactions of enantiopure dienes 1 and 2 with
maleimide 3 and N-phenylmaleimide (NPM, 4) (Scheme 1) which corroborate the expected remarkable
reactivity of these diene sulfoxides. Acyclic electron-deficient dienophiles, such as dimethyl maleate 5
and fumarate 6, have also been reacted with diene 1 (Scheme 2) in order to open the way towards the
synthesis of enantiopure cyclohexenes, with at least three stereogenic centres, useful intermediates in the
total synthesis of natural products. The role of different Lewis acids in affecting the stereoselectivity of
these Diels–Alder reactions has been investigated and a rationalization of the obtained results is proposed.
2. Results and discussion
Enantiomerically pure (RS,E)-diene 1 reacted under mild conditions with maleimide 3, NPM 4
(Scheme 1), dimethyl maleate 5 and dimethyl fumarate 6 (Scheme 2), giving in each case cycloadducts
in high yields.
The results obtained are summarized in Table 1 and deserve some comments. The reactivity of the
systems under study, as deduced from the reaction times, corresponded to expectation, i.e. the cyclic

M. C. Aversa et al. / Tetrahedron: Asymmetry 9 (1998) 1577–1587
1579
Scheme 2.
electron-deficient dienophiles reacted faster than the acyclic ones. Moreover, a comparison with literature
data on cycloadditions of different 1- and 2-sulfinyl dienes with maleimides2a,d clearly showed the higher
reactivity of 1 and encouraged us to test the cycloaddition of (RS,Z)-diene 2 to NPM 4. Diene 2 strongly
prefers the antiperiplanar conformation and, as a consequence, a reduced reactivity of such a diene in
concerted cycloadditions is well stated.2i,5 However this reaction would open up access to cyclohexenes
showing configurations at the new-formed asymmetric centres not easily accessible in other ways. In
fact the cycloaddition between 2 and 4 (Scheme 1) occurred in a reasonable length of time and mild
conditions (entry 10), in line with the high reactivity of the diene systems under study.
An inspection of Table 1 underlines the complete endo selectivity in the cycloadditions under investiga-
tion, apart from the special case of dimethyl fumarate. The maleimide planarity can be responsible for its
strong endo orientating character,6 and results shown in entries 1, 3, 4 and 10 confirm the expectations.
Moreover, literature data on cycloadditions of dimethyl maleate 5 with (E)-1-methoxybuta-1,3-diene
report the formation of endo:exo products in an approximately 70:30 ratio.5 Our observation (entry 11)
of complete endo diastereoselectivity in the reaction between 1 and 5 illustrates the remarkable control
exerted by the sulfinyl group on the endo selectivity when the dienophile is suitably substituted.2i,4
High π-facial diastereoselectivity was observed when maleimides 3 and 4 were used as dienophiles
in uncatalyzed cycloadditions (entries 1, 3, 4 and 10). The nearly exclusive formation of 7, 9, and 11
evidenced the great control exerted by the sulfinyl group on the π-facial selectivity: the cyclic dienophiles
approach dienes 1 and 2 on their Re faces, which are the more electron rich sides, opposite to the sulfinyl
oxygen, the dienes adopting the less sterically hindered conformation along the C–S bond.2i LiClO4
catalyzed cycloadditions of diene 1 with 3 and 4 showed a decrease in facial diastereoselectivity, more
evident when NPM was the dienophile (entries 2 and 8). On this basis we undertook an investigation of
cycloadditions of diene 1 with dienophile 4 in the presence of different Lewis acids (Table 1): all of them
led to a diminished facial selectivity which turned over in favour of diastereoisomer 10 when Eu(fod)3
was the catalyst (entry 9). The stereochemical outcome of these catalyzed reactions can be interpreted
by considering the endo approach of the dienophile once again on the Re face of the diene, which adopts
the conformation (a) where the catalyst is able to co-ordinate both a carbonyl oxygen of the dienophile

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Table 1
Asymmetric [4+2] cycloadditions of dienes 1 and 2 to carbodienophiles, in CH2Cl2 as a solvent
and the sulfinyl oxygen of the diene.2i However the dienophile approach to the Si face of the diene in
conformation (b) also becomes effective owing to the catalyst participation and steric requirements of a
conformationally biased dienophile such as NPM: conformation (b) appears electronically less favoured
than (a), but this adverse characteristic is counterbalanced in part by reduced steric congestion in the
transition state. If it is true, the size of the Lewis acid2f should influence the relative stabilities of the
transition states originated from the NPM endo approach to conformations (a) or (b): in fact the approach
to the Si face of the diene 1 in its conformation (b) becomes the favourite one when the bulky Eu(fod)3
catalyzes the cycloaddition (entry 9).
(RS,E)-Diene 1 was reacted with dimethyl maleate at room temperature to avoid possible E/Z
isomerization.5 When the cycloaddition was catalyzed by a suspension of LiClO4, π-facial diastereo-
selectivity was complete (entry 12), giving 13 as the unique cycloadduct. The interpretation of these
stereochemical results is similar to the one previously suggested for the asymmetric cycloaddition of
diene 1 and ethyl glyoxalate.2h For synthetic purposes it is useful to emphasize that cycloadduct 14 can
be obtained as the unique compound of the LiClO4 catalyzed cycloaddition of dimethyl maleate with
(SS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene,2i which is the epimer of diene 1 at the
sulfur atom.

M. C. Aversa et al. / Tetrahedron: Asymmetry 9 (1998) 1577–1587
1581
Fig. 1. X-Ray structure of 9
Cycloaddition of 1 with dimethyl fumarate yielded a mixture of four cycloadducts with trans arrange-
ment of the methoxycarbonyl groups at C-4 and C-5. The mixture of the four cycloadducts was column
chromatographed on silica gel, and cycloadduct 15, the major product of the reaction which is also
the chromatographically more mobile, and cycloadduct 18, which is the less mobile, were obtained in
enantiomerically pure form and fully characterized. LiClO4 catalysis shortened the reaction time and
improved facial diastereoselectivity for adduct 15 (entry 14).
The absolute configuration of cycloadduct 9 was firmly established by X-ray crystallographic analysis
(Fig. 1) while the absolute configurations were assigned to the remaining cycloadducts by analogy with
9, on the basis of NMR data and unambiguous demonstration that the sulfur configuration controls the
configurations of the newly-formed asymmetric centres.2i Significant spin–spin coupling constants from
1H NMR spectra of cycloadducts under study are collected in Table 2, together with the corresponding
data measured for the epimeric adducts 19 and 20.2i The reported values support the relative configura-
tions assigned to the stereogenic centres in the cyclohexene ring of the adducts 13, 15 and 17 (and their
facial diastereomers) owing to the conformational preferences observed in CDCl3 solution. For instance,
the 3-methoxycarbonyl substituent prefers the equatorial position in 15 and 17 (adducts from fumarate)
and 19 and 20 (from acrylate) while it appears axially situated in the adduct 13, obtained from dimethyl
maleate. Moreover, the C-3 chemical shift appears strictly related to 3-OMe conformational preference:
C-3 resonates at 76–77 ppm in compounds 13, 14, 17 and 20 (equatorial 3-OMe) and 72 ppm in 15 and
19, where 3-OMe is axial.
The high degree of stereocontrol found in cycloadditions of electron-deficient cyclic and acyclic
dienophiles with sulfinyldienes points out that these enantiopure diene sulfoxides may fulfil a useful
role in enantioselective synthesis. In particular, the presence and mutual placement of methoxy and
sulfinyl substituents in our enantiopure 3-hydroxyalkylsulfinyl-1-methoxybuta-1,3-dienes,2i such as 1
and 2, seem to have notable effects on their reactivity as syn-periplanar conjugate systems, allowing
the use of mild conditions in Diels–Alder reactions and obtainment of sterically resolved cycloadducts
in high yields. We are now working to transfer all the potential of these enantiopure products in the
synthesis of naturally occurring compounds.

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Table 2
Selected coupling constants in the 1H NMR spectra of compounds 13, 15, 17, 19 and 20
3. Experimental
(RS,E)- and (RS,Z)-3-[(1S)-Isoborneol-10-sulfinyl]-1-methoxybuta-1,3-dienes 1 and 2 were prepared
following our previous methodology.2i Solvents were purified according to standard procedures, com-
mercial dimethyl maleate was column chromatographed eluting with light petroleum:ethyl acetate 95:5
just before its use, the remaining commercial dienophiles and the Lewis acids were used without further
purification. All reactions were monitored by TLC on commercially available precoated plates (Aldrich
silica gel 60 F 254) and the products were visualized with vanillin [vanillin (1 g) dissolved in MeOH (60
ml) and H2SO4 conc. (0.6 ml)]. Silica gel used for column chromatography was Aldrich 60. Reaction
temperatures, times, and yields are shown in Table 1. Mps were measured on a microscopic apparatus and
20
are uncorrected. Optical rotations [α]D were measured in CHCl3 solutions and are given in 10−1 deg
cm2 g−1; concentrations c are expressed in g/ml. Elemental analyses were performed by REDOX, Milano
(Italy). IR spectra were taken with a Perkin–Elmer 1600 FT spectrophotometer in CHCl3 solutions. Mass
spectra were measured by Fast Atom Bombardment (FAB, m-nitrobenzyl alcohol as the matrix) with
a Finnigan MAT 90 instrument. X-Ray diffraction analysis was performed on a Siemens automated
1
four-circle single-crystal diffractometer R3µ/V. H and 13C NMR spectra were recorded on a Varian
Gemini 300 spectrometer at 300 and 75 MHz respectively in CDCl3 solutions with SiMe4 as the internal
standard; J values are given in Hz; the attributions are supported by Attached Proton Test (APT) and
decoupling experiments. Diastereomeric adduct ratios were established by integration of well-separated
proton signals of the diastereomers in the crude adduct mixtures and are listed in Table 1.

M. C. Aversa et al. / Tetrahedron: Asymmetry 9 (1998) 1577–1587
1583
3.1. General procedure for Diels–Alder reactions in thermal conditions
A solution of the diene 1 (or 2) (100 mg, 0.35 mmol) in 2 ml of anhydrous dichloromethane was
added to 2.1 mmol of neat dienophile. The reaction mixture was stirred under argon until the diene
totally disappeared, as verified by TLC monitoring (light petroleum:ethyl acetate=1:1). The solvent
was removed under vacuum and the crude mixture was column chromatographed eluting with light
petroleum:ethyl acetate (8:2).
3.2. General procedure for Diels–Alder reactions in the presence of Lewis acids
Lewis acid (0.42 mmol) was added to a solution of diene 1 (150 mg, 0.53 mmol) and dienophile (3.18
mmol) in anhydrous dichloromethane (3 ml) under argon. The reaction mixture was stirred until the diene
had totally disappeared, as verified by TLC monitoring. Isolation and purification of cycloadducts were
performed as previously described.
3.3. Cycloadducts from diene 1 and maleimide 3, reported in order of increasing retention times
3.3.1. (1S,2S,6S,RS)-4-[(1S)-Isoborneol-10-sulfinyl]-2-methoxy-8-azabicyclo[4.3.0]non-3-ene-7,9-
dione 8
0
0
Low melting solid; δH 6.90 (dd, J2,3 5.5, J3,5A 2.6, H-3), 4.52 (dd, J1,2 4.5, H-2), 4.12 (dd, J2 ,3 7.9 and
3.3, H-20), 3.32 (s, OMe), 3.26 (m, H-6), 3.10 (dd, J1,6 10.0, H-1), 3.01 and 2.55 (AB system, J10 A,10 B
13.0, H2-100), 2.70 (AB ddd, J5A,5B 15.9, J5A,6 7.2, HA-5), 2.53 (AB ddd, J5B,6 9.0, HB-5), 1.9–1.1 (m,
H2-30,50,60, H-40), 1.08 (s, H3-80), 0.86 (s, H3-90).
0
0
3.3.2. (1R,2R,6R,RS)-4-[(1S)-Isoborneol-10-sulfinyl]-2-methoxy-8-azabicyclo[4.3.0]non-3-ene-7,9-
dione 7
Mp 72–73°C; [α]D20 +125.0 (c 0.0137); δH 6.82 (dd, J2,3 5.0, J3,5B 2.1, H-3), 4.44 (dd, J1,2 4.9, H-2),
4.09 (dd, J2 ,3 8.1 and 4.0, H-20), 3.32 (s, OMe), 3.29 and 2.28 (AB system, J10 A,10 B 12.9, H2-100), 3.26
(m, H-6), 3.17 (dd, J1,6 9.8, H-1), 2.87 (AB dd, J5A,5B 16.3, J5A,6 8.3, HA-5), 2.78 (AB ddd, J5B,6 7.0,
HB-5), 1.9–1.1 (m, H2-30,50,60, H-40), 1.09 (s, H3-80), 0.83 (s, H3-90); δC 178.45 and 175.28 (C-7,9),
147.49 (C-4), 130.98 (C-3), 76.90 (C-20), 71.84 (C-2), 57.56 (OMe), 53.52 (C-100), 51.40 (C-10), 48.37
(C-70), 46.08 and 45.03 (C-1,40), 38.45 (C-30), 38.28 (C-6), 30.84 and 27.12 (C-50,60), 20.51 (C-80),
19.85 (C-90), 18.96 (C-5); m/z (%) 382 (M+1, 47), 149 (100), 135 (75).
0
0
0
0
3.4. Cycloadducts from diene 1 and NPM 4, reported in order of increasing retention times
3.4.1. (1S,2S,6S,RS)-4-[(1S)-Isoborneol-10-sulfinyl]-2-methoxy-8-phenyl-8-azabicyclo[4.3.0]non-
3-ene-7,9-dione 10
20
Mp 204–205°C; [α]D −110 (c 0.0001); δH 7.5–7.3 (m, Ph), 6.95 (dd, J2,3 5.2, J3,5A 2.6, H-3), 4.62
(dd, J1,2 4.6, H-2), 4.12 (dd, J2 ,3 7.6 and 3.6, H-20), 3.35 (s, OMe), 3.34 (m, H-6), 3.20 (dd, J1,6 9.9,
0
0
H-1), 3.01 and 2.58 (AB system, J10 A,10 B 13.0, H2-100), 2.79 (AB ddd, J5A,5B 16.1, J5A,6 7.0, HA-5),
2.64 (AB dd, J5B,6 9.3, HB-5), 1.9–1.1 (m, H2-30,50,60, H-40), 1.06 (s, H3-80), 0.84 (s, H3-90); δC 177.92
and 174.75 (C-7,9), 148.13 (C-4), 131.78 (C-100), 129.22 (C-3), 128.81 (C-200,400,600), 126.55 (C-300500),
76.70 (C-20), 71.89 (C-2), 57.45 (OMe), 54.68 (C-100), 51.51 (C-10), 48.36 (C-70), 45.50 and 45.14 (C-
1,40), 38.46 (C-30), 37.22 (C-6), 30.99 and 27.13 (C-50,60), 21.67 (C-5), 20.48 (C-80), 19.79 (C-90); m/z
(%) 458 (M+1, 47), 149 (60), 135 (100).
0
0

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M. C. Aversa et al. / Tetrahedron: Asymmetry 9 (1998) 1577–1587
3.4.2. (1R,2R,6R,RS)-4-[(1S)-Isoborneol-10-sulfinyl]-2-methoxy-8-phenyl-8-azabicyclo[4.3.0]non-
3-ene-7,9-dione 9
20
Mp 213–214°C; [α]D +210 (c 0.0001) (found: C, 65.49; H, 6.79; C25H31NO5S requires C, 65.62;
H, 6.83%); δH 7.5–7.3 (m, Ph), 6.87 (dd, J2,3 5.1, J3,5B 2.5, H-3), 4.54 (dd, J1,2 4.7, H-2), 4.10 (m, H-20),
3.38 (m, H-6), 3.34 (s, OMe), 3.33 and 2.30 (AB system, J10 A,10 B 12.8, H2-100), 3.24 (dd, J1,6 9.8, H-1),
3.01 (AB dd, J5A,5B 16.5, J5A,6 9.0, HA-5), 2.88 (AB ddd, J5B,6 6.9, HB-5), 1.9–1.1 (m, H2-30,50,60, H-40),
1.09 (s, H3-80), 0.81 (s, H3-90); δC 177.72 and 174.65 (C-7,9), 148.17 (C-4), 131.77 (C-100), 130.56 (C-
3), 129.17 (C-200,600), 128.75 (C-400), 126.49 (C-300500), 76.92 (C-20), 71.98 (C-2), 57.61 (OMe), 53.59
(C-100), 51.43 (C-10), 48.35 (C-70), 45.13 and 45.04 (C-1,40), 38.43 (C-30), 36.99 (C-6), 30.85 and 27.11
(C-50,60), 20.46 (C-80), 19.85 (C-90), 18.90 (C-5); νmax 3500 (OH), 3007, 2954, 1716 (CO), 1388, 1096,
1078 cm−1; m/z (%) 458 (M+1, 65), 137 (99), 135 (100).
0
0
3.5. Cycloadducts from diene 2 and NPM 4, reported in order of increasing retention times
3.5.1. (1R,2S,6R,RS)-4-[(1S)-Isoborneol-10-sulfinyl]-2-methoxy-8-phenyl-8-azabicyclo[4.3.0]non-
3-ene-7,9-dione 12
Mp 205–207°C; δH 7.5–7.2 (m, Ph), 6.94 (dd, J2,3 5.7, J3,5A 3.0, H-3), 4.60 (dd, J1,2 2.3, H-2), 4.08
(dd, J2 ,3 7.7 and 3.5, H-20), 3.67 (dd, J1,6 8.8, H-1), 3.45 (m, H-6), 3.42 (s, OMe), 2.95 (AB ddd, J5A,5B
0
0
15.8, J5A,6 7.4, HA-5), 2.74 and 2.65 (AB system, J10 A,10 B 13.1, H2-100), 2.68 (AB dd, J5B,6 2.3, HB-5),
1.9–1.1 (m, H2-30,50,60, H-40), 0.88 (s, H3-80), 0.71 (s, H3-90); δC 177.88 and 175.26 (C-7,9), 149.15
(C-4), 131.33 (C-100), 129.31 (C-200,600), 129.00 (C-3), 128.19 (C-400), 126.20 (C-300,500), 76.86 (C-20),
72.22 (C-2), 57.17 (OMe), 54.12 (C-100), 51.43 (C-10), 48.36 (C-70), 45.93 and 45.12 (C-1,40), 38.50
(C-30), 37.77 (C-6), 30.90 and 27.10 (C-50,60), 22.70 (C-5), 20.18 (C-80), 19.54 (C-90); m/z (%) 458
(M+1, 18), 138 (58), 137 (100).
0
0
3.5.2. (1S,2R,6S,RS)-4-[(1S)-Isoborneol-10-sulfinyl]-2-methoxy-8-phenyl-8-azabicyclo[4.3.0]non-
3-ene-7,9-dione 11
Mp 152–153°C; [α]D20 +50 (c 0.0001); δH 7.5–7.2 (m, Ph), 6.84 (dd, J2,3 5.7, J3,5A 2.4, H-3), 4.58 (dd,
J1,2 2.4, H-2), 4.08 (dd, J2 ,3 8.2 and 4.0, H-20), 3.65 (dd, J1,6 8.8, H-1), 3.47 (m, H-6), 3.45 (s, OMe),
0
0
3.15 and 2.36 (AB system, J10 A,10 B 13.0, H2-100), 2.87 (AB ddd, J5A,5B 15.6, J5A,6 7.3, HA-5), 2.78
(AB dd, J5B,6 2.6, HB-5), 1.9–1.1 (m, H2-30,50,60, H-40), 1.07 (s, H3-80), 0.79 (s, H3-90); δC 177.43 and
175.17 (C-7,9), 148.13 (C-4), 131.34 (C-100), 129.23 (C-200,600), 129.06 (C-3), 128.93 (C-400), 126.18
(C-300,500), 76.96 (C-20), 72.25 (C-2), 57.17 (OMe), 54.11 (C-100), 51.46 (C-10), 48.36 (C-70), 45.53 and
45.08 (C-1,40), 38.45 (C-30), 37.89 (C-6), 30.96 and 27.13 (C-50,60), 22.38 (C-5), 20.40 (C-80), 19.80
(C-90); νmax 3500 (OH), 3009, 2954, 1713 (CO), 1387, 1088, 1078 cm−1; m/z (%) 458 (M+1, 48), 137
(41), 135 (100).
0
0
3.6. Cycloadducts from diene 1 and dimethyl maleate 5, reported in order of increasing retention times
3.6.1. (3S,4S,5S,RS)-4,5-Dimethoxycarbonyl-1-[(1S)-isoborneol-10-sulfinyl]-3-methoxycyclohexene 14
Mp 170–172°C; [α]D20 +8.2 (c 0.0062); δH 6.50 (ddd, J2,3 2.1, J2,6A 2.8, J2,6B 1.4, H-2), 4.24 (ddd, J3,4
6.2, J3,6A 2.8, J3,6B 1.4, H-3), 4.11 (dd, J2 ,3 8.2 and 4.2, H-20), 3.74 and 3.72 (two s, 2×CO2Me), 3.63
0
0
(dd, J4,5 3.6, H-4), 3.53 (s, 3-OMe), 3.20 and 2.58 (AB system, J10 A,10 B 13.4, H2-100), 3.03 (ddd, J5,6A
10.3, J5,6B 6.0, H-5), 2.85 (AB ddt, J6A,6B 16.7, HA-6), 2.42 (AB ddt, HB-6), 1.9–1.0 (m, H2-30,50,60,
H-40), 1.09 (s, H3-80), 0.86 (s, H3-90); δC 172.02 and 170.40 (2×CO), 143.21 (C-1), 126.28 (C-2), 77.07
(C-20), 76.11 (C-3), 57.67 (3-OMe), 54.31 (C-100), 52.47 and 51.83 (2×CO2Me), 51.52 (C-10), 48.35
0
0

M. C. Aversa et al. / Tetrahedron: Asymmetry 9 (1998) 1577–1587
1585
(C-70), 45.15 (C-40), 43.31 (C-4), 40.39 (C-5), 38.43 (C-30), 30.95 and 27.19 (C-50,60), 23.58 (C-6),
20.57 (C-80), 19.88 (C-90); m/z (%) 429 (M+1, 38), 135 (100), 107 (36).
3.6.2. (3R,4R,5R,RS)-4,5-Dimethoxycarbonyl-1-[(1S)-isoborneol-10-sulfinyl]-3-methoxycyclohexene
13
20
Mp 135–137°C; [α]D +43.4 (c 0.0268) (found: C, 58.68; H, 7.51; C21H32O7S requires C, 58.86; H,
7.53%); δH 6.34 (br d, J2,3 2.2, H-2), 4.22 (br d, J3,4 6.5, J3,6A 2.1, H-3), 4.07 (dd, J2 ,3 8.3 and 4.2, H-20),
3.76 and 3.71 (two s, 2×CO2Me), 3.66 (dd, J4,5 2.6, H-4), 3.52 (s, 3-OMe), 3.50 and 2.40 (AB system,
0
0
J10 A,10 B 13.2, H2-100), 3.0–2.8 (m, H-5, H2-6), 1.9–0.9 (m, H2-30,50,60, H-40), 1.11 (s, H3-80), 0.83 (s,
H3-90); δC 172.12 and 170.39 (2×CO), 143.76 (C-1), 129.92 (C-2), 76.97 (C-20), 76.36 (C-3), 57.75
(3-OMe), 52.69 (C-100), 52.46 and 51.80 (2×CO2Me), 51.34 (C-10), 48.26 (C-70), 45.07 (C-40), 42.55
(C-4), 39.82 (C-5), 38.42 (C-30), 30.75 and 27.11 (C-50,60), 20.48 (C-80), 19.88 (C-90), 19.85 (C-6); νmax
3400 (OH), 3002, 2854, 1737 (CO), 1438, 1072, 1004 cm−1; m/z (%) 429 (M+1, 100), 149 (44), 135
(61), 57 (43).
0
0
3.7. Isolated cycloadducts from diene 1 and dimethyl fumarate 67 reported in order of increasing
retention times
3.7.1. (3R,4R,5S,RS)-4,5-Dimethoxycarbonyl-1-[(1S)-isoborneol-10-sulfinyl]-3-methoxycyclohexene
15
Low melting solid; [α]D20 +120.8 (c 0.0078); δH 6.75 (br dd, J2,3 4.4, J2,6A 0.8, J2,6B 2.5, H-2), 4.27 (t,
3,4 4.4, H-3), 4.10 (dd, J2 ,3 7.5 and 3.7, H-20), 3.76 (s, 2×CO2Me), 3.40 (s, 3-OMe), 3.18 (dt, J4,5=J5,6B
0
0
J
11.3, J5,6A 5.0, H-5), 3.11 and 2.41 (AB system, J10 A,10 B 12.9, H2-100), 3.07 (dd, H-4), 2.56 (AB ddd,
0
0
J
6A,6B 17.0, HA-6), 2.20 (AB ddd, HB-6), 1.9–1.1 (m, H2-30,50,60, H-40), 1.08 (s, H3-80), 0.84 (s, H3-90);
δC 174.85 and 171.19 (2×CO), 144.54 (C-1), 125.70 (C-2), 77.20 (C-20), 72.10 (C-3), 57.83 (3-OMe),
53.81 (C-100), 52.33 and 52.06 (2×CO2Me), 51.49 (C-10), 48.40 (C-70), 47.32 (C-40), 45.10 (C-4), 38.44
(C-30), 37.00 (C-5), 30.84 and 27.14 (C-50,60), 26.89 (C-6), 20.53 (C-80), 19.86 (C-90); νmax 3400 (OH),
2367, 1734 (CO), 1540 cm−1; m/z (%) 429 (M+1, 100), 149 (88), 135 (77).
3.7.2. (3R,4S,5R,RS)-4,5-Dimethoxycarbonyl-1-[(1S)-isoborneol-10-sulfinyl]-3-methoxycyclohexene
17
Low melting solid; [α]D20 +23.9 (c 0.0116); δH 6.52 (br dt, J2,3 2.4, J2,6A 1.0, J2,6B 2.4, H-2), 4.30 (dt,
J3,4 8.3, J3,6A 1.7, J3,6B 2.9, H-3), 4.08 (m, H-20), 3.77 and 3.73 (two s, 2×CO2Me), 3.42 (s, 3-OMe),
3.10 (m, J4,5 10.8, J5,6A 5.4, J5,6B 9.8, H-5), 3.34 and 2.34 (AB system, J10 A,10 B 13.0, H2-100), 2.95
(dd, H-4), 2.78 (AB ddt, J6A,6B 17.5, HA-6), 2.50 (AB ddt, HB-6), 1.9–1.1 (m, H2-30,50,60, H-40), 1.10 (s,
H3-80), 0.84 (s, H3-90); δC 173.13 and 172.25 (2×CO), 143.22 (C-1), 129.19 (C-2), 77.19 (C-20,3), 57.21
(3-OMe), 53.41 (C-100), 52.46 and 52.44 (2×CO2Me), 51.45 (C-10), 48.37 (C-70), 47.36 (C-40), 45.09
(C-4), 40.88 (C-5), 38.45 (C-30), 30.80 and 27.13 (C-50,60), 22.86 (C-6), 20.54 (C-80), 19.90 (C-90); m/z
(%) 429 (M+1, 37), 149 (100), 135 (56), 69 (38), 57 (39), 55 (46).
0
0
3.8. X-Ray structure determination of (1R,2R,6R,RS)-4-[(1S)-isoborneol-10-sulfinyl]-2-methoxy-
8-phenyl-8-azabicyclo[4.3.0]non-3-ene-7,9-dione 9
Suitable crystals of compound 9 have been obtained by slow evaporation of an ethyl acetate solution.
A summary of crystallographic data, collected at room temperature, and structure refinement is given
in Table 3. Reflection intensities were evaluated by profile fitting of a 96-step peak scan among 2θ

1586
M. C. Aversa et al. / Tetrahedron: Asymmetry 9 (1998) 1577–1587
Table 3
Crystal data and measurements conditions for the adduct 9
shells procedure8 and then corrected for Lorentz polarization effects. Standard deviations σ(I) were
estimated from counting statistics. The structure was solved by direct methods subsequently completed
by a combination of least squares technique and Fourier syntheses (SHELXTL-PLUS9) and refined
by the full-matrix least squares technique (SHELXL-9710) based on F2. H atoms were constrained to
idealized geometries: assigned isotropic displacement parameters were 1.5 times the Uiso value of their
C atoms for methyl hydrogens and 1.2 Uiso for all the other H atoms. Data reduction, structure solution
and drawings were performed with SHELXTL-PLUS package,9,10 and the geometrical calculations were
obtained from PARST programme,11 respectively. All calculations were performed on a µ-VAX 3400
and an AXP DecStation 3000/400.
Acknowledgements
Financial support by MURST and Regione Siciliana are gratefully acknowledged.
References
1. Adams, H.; Jones, D. N.; Aversa, M. C.; Bonaccorsi, P.; Giannetto, P. Tetrahedron Lett. 1993, 34, 6481–6484.
2. (a) Gosselin, P.; Bonfand, E.; Hayes, P.; Retoux, R.; Maignan, C. Tetrahedron: Asymmetry 1994, 5, 781–784; (b) Aversa,
M. C.; Bonaccorsi, P.; Giannetto, P.; Jones, D. N. Tetrahedron: Asymmetry 1994, 5, 805–808; (c) Carreño, M. C.; Cid, M.
B.; Colobert, F.; García Ruano, J. L.; Solladié, G. Tetrahedron: Asymmetry 1994, 5, 1439–1442; (d) Arce, E.; Carreño, M.

M. C. Aversa et al. / Tetrahedron: Asymmetry 9 (1998) 1577–1587
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C.; Cid, M. B.; García Ruano, J. L. J. Org. Chem. 1994, 59, 3421–3426; (e) Carren´o, M. C.; Cid, M. B.; García Ruano,
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1996, 37, 4537–4540; (g) Gosselin, P.; Bonfand, E.; Maignan, C. J. Org. Chem. 1996, 61, 9049–9052; (h) Aversa, M. C.;
Barattucci, A.; Bonaccorsi, P.; Bruno, G.; Giannetto, P.; Panzalorto, M. Tetrahedron: Asymmetry 1997, 8, 2989–2995; (i)
Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Jones, D. N. J. Org. Chem. 1997, 62, 4376–4384.
3. Compare Ref. 1 with Ref. 4, and Ref. 2a with Ref. 2d.
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6. García Ruano, J. L.; Carretero, J. C.; Carreño, M. C.; Martín Cabrejas, L. M.; Urbano, A. Pure & Appl. Chem. 1996, 68,
925–930.
7. Minor products 16 and 18 were recognized in the crude adduct mixture by typical 1H NMR resonances such as vinyl
proton multiplets at δ 6.72 and 6.57 respectively.
8. Diamond, R. Acta Crystallogr., Sect. A 1969, 25, 43–55.
9. SHELXTL-PLUS 1991, V.4.2, Siemens Analytical X-Ray Instruments Inc., Madison, Wisconsin.
10. Sheldrick, G. M. 1997, SHELXL-97, Program for the Refinement of Crystal Structures, University of Göttingen, Germany.
11. Nardelli, M. Comput. Chem. 1983, 7, 95–98 (locally modified version).