Diels-Alder reactions of enantiopure [(1S)-isoborneol-10-sulfinyl]- and [(1S-exo)-2-bornylsulfinyl]vinylcyclohexenes with maleimides

Article abstract of DOI:10.1016/S0957-4166(99)00409-7

Uncatalyzed cycloadditions of enantiopure [(1S)-isoborneol-10-sulfinyl]- and [(1S-exo)-2-bornylsulfinyl]vinylcyclohexenes with N-phenylmaleimide occur with good facial diastereoselectivity, controlled by the sulfur configuration, even if the extent of this stereoselection appears influenced by the structural features of the terpene residue directly linked to the sulfoxide moiety. Complete endo diastereoselectivity is observed in LiClO₄ catalyzed cycloadditions of (R(S))-1-{1-[(1S)-isoborneol-10-sulfinyl]- and (S(S))-1-{1-[(1S-exo)-2-bornylsulfinyl]vinyl}cyclohexenes 4 and 5, respectively. The Diels-Alder reactivity of 5 and (S(S),E)-1-{2-[(1S-exo)-2- bornylsulfinyl]vinyl}cyclohexene 7, with the chiral auxiliary being in a different position with respect to the diene moiety, is also compared, and the results obtained confirm that 1-sulfinyldienes are less reactive than 2- sulfinyldienes. SnCl₄ catalyzed cycloaddition of 7 with N-methylmaleimide is also performed.

Full text of DOI:10.1016/S0957-4166(99)00409-7

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3907–3917
Diels–Alder reactions of enantiopure [(1S)-isoborneol-
10-sulfinyl]- and [(1S-exo)-2-bornylsulfinyl]vinylcyclohexenes
with maleimides
Maria C. Aversa,a,∗ Anna Barattucci,a Paola Bonaccorsi,a Placido Giannetto,a
Francesco Nicolò b and Simona Rizzo a
aDipartimento di Chimica organica e biologica, Chimica analitica e Chimica fisica, 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 August 1999; accepted 13 September 1999
Abstract
Uncatalyzed cycloadditions of enantiopure [(1S)-isoborneol-10-sulfinyl]- and [(1S-exo)-2-bornylsulfinyl]-
vinylcyclohexenes with N-phenylmaleimide occur with good facial diastereoselectivity, controlled by the
sulfur configuration, even if the extent of this stereoselection appears influenced by the structural features of
the terpene residue directly linked to the sulfoxide moiety. Complete endo diastereoselectivity is observed
in LiClO4 catalyzed cycloadditions of (RS)-1-{1-[(1S)-isoborneol-10-sulfinyl]- and (SS)-1-{1-[(1S-exo)-2-
bornylsulfinyl]vinyl}cyclohexenes 4 and 5, respectively. The Diels–Alder reactivity of 5 and (SS,E)-1-{2-[(1S-
exo)-2-bornylsulfinyl]vinyl}cyclohexene 7, with the chiral auxiliary being in a different position with respect to
the diene moiety, is also compared, and the results obtained comfirm that 1-sulfinyldienes are less reactive than
2-sulfinyldienes. SnCl4 catalyzed cycloaddition of 7 with N-methylmaleimide is also performed. © 1999 Elsevier
Science Ltd. All rights reserved.
1. Introduction
Enantiopure 3-(alkylsulfinyl)-1-methoxybuta-1,3-dienes 1 and 2 have provided stimulating results
in their Diels–Alder (DA) reactions with common carbo- and hetero-dienophiles; the stereochemical
outcome of thermal cycloadditions with cyclic dienophiles, such as N-phenylmaleimide (NPM),1 and
LiClO4 catalyzed cycloadditions with acyclic dienophiles, such as methyl acrylate2 and ethyl glyoxalate,3
evidence the great control exerted by the sulfinyl group on both π-facial and endo/exo selectivities. The
∗
Corresponding author. E-mail: aversa@imeuniv.unime.it
0957-4166/99/$ - see front matter © 1999 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(99)00409-7

3908
M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
strongly electron donating methoxy substituent and the sulfinyl group, the latter suitably positioned on
the diene system to support the OMe electronic characteristics, guarantee complete regioselectivity in
DA reactions of 1 and 2, and have a notable effect on their reactivity, allowing the occurrence of these
DA reactions under mild conditions and the production of enantiopure cycloadducts in high yields.
The synthetic strategy for the preparation of these enantiopure 2-(alkylsulfinyl)dienes is based on the
regio- and stereoselective addition of (E)- or (Z)-1-methoxybut-1-en-3-yne to enantiopure alkanesulfenic
acids, which can be easily obtained starting from commercially available terpene derivatives.4–6 The
structural features of the terpene residue, directly linked to the sulfur function, play a relevant role in this
synthetic strategy, in the chromatographic separation of the DA adducts and in the removal of the chiral
auxiliary, which appears less straightforward with respect to 1-(p-tolyl)sulfinylbutadienes.6,7
Synthesis and reactivity studies of (alkylsulfinyl)vinylcyclohexenes, such as 3–7 (Scheme 1), constitute
a challenging progression of our investigation into the behaviour of enantiopure sulfinyldienes in
asymmetric DA reactions. When one diene double bond participates in a six-membered ring, as in
vinylcyclohexenes 3–7, cycloadducts obtained by reacting 3–7 with suitable dienophiles can be converted
into polycyclic systems, useful precursors of molecules showing a steroid skeleton. The chiral auxiliaries
in 3–7 are structurally analogous, the isoborneolsulfinyl group (R*SO=isoB-SO) essentially differing
from the bornylsulfinyl one (R*SO=Born-SO) in the presence or absence of the hydroxy function: this is
in line with our interest in evaluating the influence that intramolecular hydrogen bonding6 and, in general,
the alkyl residue can have on the synthesis and reactivity of alkylsulfinyldienes. Finally, a comparison of
the reactivity of 1-sulfinyldiene 7 and 2-sulfinyldienes 3–6 in cycloadditions with maleimides enables us
to evaluate their potentialities in asymmetric DA reactions.
2. Results and discussion
The procedure based on the pericyclic addition of sulfenic acid 8 (coming from 9) to 1-
ethynylcyclohexene (Scheme 1), and already performed for the synthesis of 2-isoborneolsulfinyldienes 3
and 4,4 was adopted to obtain the 2-bornylsulfinyldienes 5 and 6, starting from the corresponding sulfenic
acid 10. The reaction, which is highly regioselective when 8 is reacted with 1-ethynylcyclohexene,
was performed on the sulfenic acid precursor 11 in neat enyne at 110°C and led to the formation of 5
and 6, together with the 1-sulfinyldiene 7, in 62.5:30:7.5 relative amounts and 80% total yield. Higher
temperatures (150°C) increased the reaction yield up to 90% in favour of the 2-sulfinyldiene 5 (67.8%)
and 1-sulfinyldiene 7 (16.7%), both having the sulfoxide in the (SS) configuration, to the detriment
of 2-sulfinyldiene 6 (15.5%). These data can be explained on the basis of an evaluation of the role
that the alkylsulfinyl moiety plays in the asymmetric induction characterizing the pericyclic addition
sulfenic acid/enyne. A temperature increase induces an increment of the thermodynamically favoured

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
3909
Scheme 1.
(SS) products 5 and 7; the decrease of (RS)-diene 6 and complete absence of the 1-sulfinyldiene with the
same sulfur configuration indicate that the higher steric requirements of the enantiopure bornylsulfinyl
auxiliary when the sulfoxide is in the (RS) configuration penalize the formation of the corresponding
sulfinyldienes.
Sulfur absolute configuration in bornylsulfinyldienes 5–7 has been attributed on the basis of pre-
viously observed stereochemical outcome of the sulfenic acid/enyne addition and dependence of C-
20, 30 chemical shifts on sulfur configuration.6 In (RS)-[(1S-exo)-2-bornylsulfinyl]vinylcyclohexenes
these two carbon resonances appear in the ranges 68–69 and 25–26 ppm, while in the (SR)-([1S-
exo)-2-bornylsulfinyl]vinylcyclohexenes C-20 and C-30 resonate in the ranges 71–78 and 32–33 ppm,
respectively.
Results concerning cycloadditions of 2-sulfinyldienes 3–6 with N-phenylmaleimide (NPM) in thermal
and catalyzed conditions (Scheme 2) are reported in Table 1. NPM was chosen to avoid regioselectivity
problems and because it is a highly reactive and endo-directing dienophile. Absolute configurations of
the new stereocentres in cycloadducts 12–24 have been assigned on the basis of NMR data and having
demonstrated that facial preference of DA attack is unambiguously controlled by sulfur configuration.1,2,6
Catalysis by lithium perchlorate, which was chosen for its good ability in enhancing facial
diastereoselectivity,1–3 shortened reaction times and induced complete diastereoselectivity endo/exo
in favour of the endo isomer (entries 3 and 5). The lack of influence on facial diastereoselectivity is
probably due to the great steric requirements of both diene and dienophile, which lead to very congested
transition states in catalyzed cycloadditions.1
It is noteworthy that the bornylsulfinyl auxiliary appears less efficient in the stereocontrol of cycload-
ditions with NPM than the isoborneolsulfinyl one (compare entries 1 with 4 or 2 with 6), an observation
which is in line with our previously reported results6 and those obtained in the synthesis of sulfinyldienes
3–7 (see above). These steric occurrences can again be ascribed to the relevant steric features of the
bornyl residue directly linked to the sulfinyl group.
The production of a fair amount of 1-sulfinyldiene 7 allowed for the first time a comparison of the
behaviour, in DA cycloadditions, of sulfinyldienes 5 and 7, differing only in the position of the chiral
auxiliary on the diene moiety. Compound 7 was added to NPM in dichloromethane, but no cycloaddition

3910
M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
Scheme 2.
Table 1
Asymmetric [4+2] cycloadditions of dienes 3–6 to NPM in CH2Cl2
products were observed in the reaction mixture after 15 days at reflux, thus confirming the lower reactivity
of 1-sulfinyldienes with respect to 2-sulfinyldienes.8
Cycloaddition of 7 with N-methylmaleimide (NMM) was also performed in the presence of SnCl4,
according to the procedure already described in the literature for (RS,E)-[2-(1-cyclohexenyl)vinyl]-p-
tolylsulfoxide, the latter showing the p-tolyl instead of the bornyl group as part of the sulfur chiral
auxiliary.9 The reaction outcome is depicted in Scheme 3: the expected meso-compound 259 was
obtained together with a mixture of the four diastereomeric sulfoxides 26. The major component of this
last mixture was isolated by column chromatography, subsequent crystallization (from EtOAc/ligroin),
and characterized by X-ray crystallography, which allowed its identification as (3S,SS)-3-[(1S-exo)-2-

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
3911
bornylsulfinyl]-1-methylsuccinimide.† The observation of compounds 26 was crucial in understanding
our reaction pathway, because they clearly come from trapping of the ‘stable’6 sulfenic acid 10 by
NMM, used in large excess (see Experimental). As described previously,8 DA adducts 27 evolve towards
sulfenate intermediates 28 through the well-known [2,3]-sigmatropic rearrangement.10,11 However, we
did not observe the corresponding allylic alcohol 29 since our reaction proceeded via sulfenic acid
trapping by NMM from sulfenates 28, to afford 26 and desulfurated endocyclic diene 30, the latter again
cycloadding NMM with the formation of compound 25.
Scheme 3.
In this paper we have shown that (alkylsulfinyl)vinylcyclohexenes are notable enantiopure dienes
which react easily in DA cycloadditions giving good stereochemical results. When reactions are per-
formed starting from 2-sulfinyldienes 3–6 the corresponding cycloadducts can be obtained in enan-
tiomerically pure form and subsequently transformed into molecules of synthetic interest, while the
use of 1-sulfinyldiene 7 is less productive from a synthetic point of view. Structural features of the
terpene residue linked to the sulfinyl auxiliary not only affect the synthesis of these dienes6 but also
the stereochemical outcome of their DA cycloadditions. However, the large number of terpene systems,
available as enantiopure starting products, gives the opportunity for designing numerous sulfinyldienes,
useful as efficient partners in stereocontrolled DA reactions.
†
The space group of the monoclinic C15H23NO3S crystal (M=297.42) was P21 with a=6.9717(8), b=10.2167(13), c=21.773(4)
Å, β=91.234(13)°. Other crystal parameters were as follows: V=1550.5(4) Å3, Z=4, dcalc=1.274 g/cm3. The structure refinement,
with all anisotropic non-H atoms, reached R(F)=0.0504 with a parameter for extinction correction included in the last cycles.
The absolute configuration of both independent molecules appearing into the crystallographic asymmetric unit was identical and
well-determined as evidenced by the final enantiomorph Flack parameter that converged to 0.06(13). Tables of bond distances,
bond angles, and positional and thermal parameters are available on request from the corresponding author.

3912
M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
3. Experimental
3.1. General methods and materials
Starting product (S-epimeric mixture) 11 was prepared following our own methodology.6 Solvents
were purified according to standard procedures. All reactions were monitored by TLC on commercially
available precoated plates (Aldrich silica gel 60 F 254) and the products were visualized with iodine
or vanillin [vanillin (1 g) dissolved in MeOH (60 ml) and conc. H2SO4 (0.6 ml)]. Silica gel used
for column chromatography was Aldrich 60. Mps were measured on a microscopic apparatus and
are uncorrected. Optical rotations were measured in CHCl3 solutions at 25°C and are given in 10−1
deg cm2 g−1; concentrations c are expressed in g/100 ml. Mass spectra were measured by fast atom
bombardment (FAB, m-nitrobenzyl alcohol as matrix) with a Finnigan MAT 90 instrument. X-Ray
diffraction analysis was performed on a Siemens automated four-circle single-crystal diffractometer
1
R3µ/V. H and 13C NMR spectra were recorded on a Varian Mercury 300 spectrometer at 300 and
75 MHz, respectively, in CDCl3 solutions with SiMe4 as internal standard; J values are given in
hertz; the attributions are supported by attached proton test (APT), heteronuclear shift-correlated and
homodecoupling experiments. Proton and carbon indexes, marked with (0), pertain to isoborneol or
bornyl moieties. The symbol (00) identifies vinyl nuclei in dienes 5–7 and aromatic nuclei in compounds
12–24. 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.
3.2. Thermolysis of sulfoxides 11 in the presence of 1-ethynylcyclohexene
Sulfoxides 4 (1.12 g, 4.7 mmol) were added to 1-ethynylcyclohexene (4.19 g, 39.5 mmol),
and the mixture maintained at 110°C. When the reaction appeared complete by TLC (1 h, eluant
EtOAc:hexane, 60:40) the enyne excess was removed under reduced pressure and the obtained reaction
mixture was separated by column chromatography, beginning the elution with hexane:Et2O (90:10)
and gradually increasing the Et2O percentage up to 30%. First was eluted (RS)-1-{1-[(1S-exo)-2-
25
bornylsulfinyl]vinyl}cyclohexene (6): oil; 24% yield; [α]D +16.0 (c 0.286); δ0H: 5.96 (dt, J2,3=4.1,
J
2,6=1.7, H-2), 5.71 and 5.59 (two s, H2-200), 2.58 (dd, J2 ,3 =9.2 and 7.4, H-2 ), 2.3–1.9 (m, H2-3,
0 0
6), 1.7–1.0 (m, H2-30, 4, 5, 50, 60, H-40), 1.14 (s, H3-100), 0.99 (s, H3-80), 0.86 (s, H3-90); δC: 152.87
(C-100), 132.08 (C-1), 128.26 (C-2), 112.21 (C-200), 68.47 (C-20), 50.31 (C-10), 46.71 (C-70), 45.18
(C-40), 39.65 and 27.35 (C-50, 60), 25.47 (C-30), 27.35 and 25.12 (C-3, 6), 22.45 and 21.88 (C-4, 5),
20.46 and 19.61 (C-80, 90), 13.43 (C-100). Then (SS)-1-{1-[(1S-exo)-2-bornylsulfinyl]vinyl}cyclohexene
25
(5) was eluted: low-melting solid; 50% yield; [α]D +78.0 (c 1.150); δH: 6.29 (m, H-2), 5.84 and
5.64 (two s, H2-200), 2.56 (m, H-20), 2.4–2.1 (m, H2-3, 6), 1.8–1.6 (m, HA-30, 50, 60, H-40, H2-4, 5),
1.4–1.1 (m, HB-30, 50, 60), 1.25 (s, H3-100), 0.94 (s, H3-80), 0.88 (s, H3-90); δC: 155.25 (C-100), 134.19
(C-1), 129.52 (C-2), 113.82 (C-200), 77.70 (C-20), 49.68 (C-10), 47.86 (C-70), 45.00 (C-40), 38.98 and
27.07 (C-50, 60), 31.95 (C-30), 27.02 and 25.59 (C-3, 6), 22.56 and 21.88 (C-4, 5), 20.11 and 19.46
(C-80, 90), 13.70 (C-100); m/z (%): 293 (M+1, 11), 137 (100), 95 (14), 81 (43). Finally, the less mobile
25
(SS,E)-1-{2-[(1S-exo)-2-bornylsulfinyl]vinyl}cyclohexene (7) was eluted: oil; 6% yield; [α]D +57.9
=15.4, H-200), 6.13 (d, H-100), 6.07 (t, J2,3=4.0, H-2), 2.66 (t, J2 ,3 =8.0,
0 0
00,200
(c 0.350); δH: 6.81 (d, J1
H-20), 2.2–2.1 (m, H2-3, 6), 1.8–1.1 (m, H2-30, 4, 5, 50, 60, H-40), 1.24 (s, H3-100), 0.97 (s, H3-80), 0.89
(s, H3-90); δC: 142.06 (C-200), 136.72 (C-100), 133.85 (C-1), 126.14 (C-2), 73.15 (C-20), 49.48 (C-10),
47.58 (C-70), 44.95 (C-40), 38.88 and 27.06 (C-50, 60), 32.19 (C-30), 26.17 and 24.39 (C-3, 6), 22.03 and
22.01 (C-4, 5), 20.07 and 19.70 (C-80, 90), 13.67 (C-100); m/z (%): 293 (M+1, 6), 137 (91), 81 (100), 55

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
3913
(85). When the thermolysis was carried out at 150°C, it was complete after 15 min with the following
yields of isolated dienes: 14% of compound 6, 61% of 5 and 15% of 7.
3.3. General procedure for Diels–Alder reactions of dienes 3–6 with NPM in thermal conditions
NPM (674.7 mg, 3.9 mmol) was added to a solution of the diene (0.65 mmol) in anhydrous CH2Cl2 (7
ml). The reaction mixture was refluxed until the diene totally disappeared, as verified by TLC monitoring
(EtOAc:hexane, 70:30). The solvent was removed under vacuum and the crude mixture was column
chromatographed beginning the elution with hexane:EtOAc (80:20) and gradually increasing the EtOAc
percentage up to 100%. Reaction times and yields are shown in Table 1.
3.4. General procedure for Diels–Alder reactions of dienes 4 and 5 with NPM in the presence of LiClO4
LiClO4 (29.8 mg, 0.28 mmol) was added to a solution of the diene (0.35 mmol) and NPM (363.7
mg, 2.1 mmol) in anhydrous CH2Cl2 (4 ml). The reaction mixture was stirred until the diene had totally
disappeared, as verified by TLC monitoring. Isolation and purification of cycloadducts were performed
as described previously. Reaction temperatures, times and yields are shown in Table 1.
3.5. Cycloadducts from (SS)-isoborneolsulfinyldiene 3 and NPM, reported in order of increasing reten-
tion times
3.5.1. (3aS,9aS,9bR,SS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S)-isoborneol-10-sulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 12
Mp 101–103°C (found: C, 69.54; H, 7.50. C28H35NO4S requires: C, 69.82; H, 7.32%); δH: 7.5–7.2
0
0
0
(m, Ph), 4.04 (t, J2 ,3 =5.5, H-2 ), 3.40 (m, H-3a, HA-4), 3.30 (dd, J3a,9b=8.3, J9a,9b=6.1, H-9b), 2.95 and
2.74 (AB system, J10 A,10 B=13.1, H2-100), 2.7–1.3 (m, H2-30, 50, 6, 60, 7–9, HB-4, H-40, 9a), 1.11 (s,
H3-80), 0.86 (s, H3-90); δC: 177.17 and 176.64 (C-1, 3), 147.07 (C-5), 132.71 (C-5a), 131.63 (C-100),
129.00 (C-200, 600), 128.44 (C-400), 126.47 (C-300, 500), 76.71 (C-20), 53.39 (C-100), 51.10 (C-10), 48.43
(C-70), 44.79 (C-40), 42.84 (C-9b), 41.05 (C-30), 39.42 and 38.95 (C-3a, 9a), 31.65, 27.59, 27.29, 25.94,
23.03, 22.90 and 19.12 (C-4, 50, 6, 60, 7–9), 20.48 and 20.43 (C-80, 90); m/z (%): 482 (M+1, 57), 329
(12), 55 (100).
0
0
3.5.2. (3aR,9aS,9bS,SS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S)-isoborneol-10-sulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 14
Mp 168–170°C (found: C, 69.77; H, 7.45. C28H35NO4S requires: C, 69.82; H, 7.32%); δH: 7.5–7.3 (m,
0
0
0
0
0
Ph), 3.98 (t, J2 ,3 =5.4, H-2 ), 3.4–3.1 (m, H-3a, 9b, HA-4), 2.91 and 2.77 (AB system, J10 A,10 B=13.4,
H2-100), 2.9–1.2 (m, H2-30, 50, 6, 60, 7–9, HB-4, H-40, 9a), 1.10 (s, H3-80), 0.87 (s, H3-90); δC: 177.75
and 177.40 (C-1, 3), 144.72 (C-5), 131.73 (C-100, 5a), 129.18 (C-400), 129.17 (C-200, 600), 126.16 (C-300,
500), 77.30 (C-20), 51.10 (C-10, 100), 48.68 (C-70), 44.96 (C-40), 44.84 (C-9b), 38.02 and 37.97 (C-3a,
9a), 35.75 (C-30), 31.87, 30.50, 30.44, 27.41, 27.34, 26.16 and 25.39 (C-4, 50, 6, 60, 7–9), 20.53 and
10.50 (C-80, 90).
3.5.3. (3aR,9aR,9bS,SS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S)-isoborneol-10-sulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 13
Mp 215–217°C (found: C, 69.50; H, 7.65. C28H35NO4S requires: C, 69.82; H, 7.32%); δH: 7.5–7.2
0
0
0
(m, Ph), 4.07 (t, J2 ,3 =5.5, H-2 ), 3.50 (dt, J3a,4A=1.2, J3a,4B=J3a,9b=8.3, H-3a), 3.38 (dd, J4A,4B=16.5,

3914
M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
HA-4), 3.33 (dd, J9a,9b=6.8, H-9b), 2.79 and 2.50 (AB system, J10 A,10 B=13.3, H2-100), 2.7–1.1 (m, H2-
30, 4, 50, 6, 60, 7–9, H-40, 9a), 0.90 (s, H3-80), 0.75 (s, H3-90); δC: 177.84 and 176.48 (C-1, 3), 147.12
(C-5), 133.50 and 131.58 (C-100, 5a), 129.11 (C-200, 600), 128.63 (C-400), 126.29 (C-300, 500), 77.21 (C-
20), 53.70 (C-100), 51.14 (C-10), 48.39 (C-70), 44.87 (C-40), 43.10 (C-9b), 41.19 (C-30), 39.84 and 39.41
(C-3a, 9a), 31.78, 27.30, 26.30, 25.01, 22.20, 21.99 and 20.00 (C-4, 50, 6, 60, 7-9), 20.32 (C-80, 90).
0
0
3.6. Cycloadducts from (RS)-isoborneolsulfinyldiene 4 and NPM, reported in order of increasing reten-
tion times
3.6.1. (3aS,9aR,9bR,RS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S)-isoborneol-10-sulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione (17)
Mp 222–224°C (found: C, 69.79; H, 7.40. C28H35NO4S requires: C, 69.82; H, 7.32%); δH: 7.5–7.2
0
(m, Ph), 4.10 (dd, J2 ,3 =8.1 and 4.3, H-2 ), 3.51 and 2.07 (AB system, J10 A,10 B=12.6, H2-100), 3.4–1.4
0
0
0
0
(m, H-3a, 40, 9b, H2-30, 4, 50, 6, 60, 7–9), 1.13 (s, H3-80), 0.83 (s, H3-90).
3.6.2. (3aR,9aR,9bS,RS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S)-isoborneol-10-sulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione (15)
25
Mp 210–212°C; [α]D −47.1 (c 0.955) (found: C, 69.44; H, 7.70. C28H35NO4S requires: C, 69.82;
0
0
0
H, 7.32%); δH: 7.5–7.2 (m, Ph), 4.08 (dd, J2 ,3 =8.3 and 4.1, H-2 ), 3.41 (m, H-3a), 3.40 and 2.12 (AB
system, J10 A,10 B=13.0, H2-100), 3.30 (dd, J3a,9b=8.3, J9a,9b=6.4, H-9b), 2.7–1.1 (m, H2-30, 4, 50, 6, 60,
7–9, H-40, 9a), 1.10 (s, H3-80), 0.80 (s, H3-90); δC: 176.97 and 176.46 (C-1, 3), 147.68 (C-5), 131.96 and
131.56 (C-100, 5a), 128.99 (C-200, 600), 128.43 (C-400), 126.37 (C-300, 500), 76.76 (C-20), 52.65 (C-100),
51.25 (C-10), 48.09 (C-70), 44.92 (C-40), 42.74 (C-9b), 39.32 and 38.87 (C-3a, 9a), 38.37 (C-30), 30.88,
27.36, 27.05, 25.94, 23.00, 22.85 and 18.92 (C-4, 50, 6, 60, 7–9), 20.37 and 19.81 (C-80, 90); m/z (%):
482 (M+1, 24), 135 (37), 95 (50), 81 (70), 69 (100).
0
0
3.6.3. (3aS,9aS,9bR,RS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S)-isoborneol-10-sulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione (16)
Mp 180–182°C; [α]D25 +89.3 (c 0.740) (found: C, 69.90; H,07.55. C28H35NO4S requires: C, 69.82; H,
0
0
7.32%); δH: 7.5–7.2 (m, Ph), 4.04 (dd, J2 ,3 =8.1 and 4.2, H-2 ), 3.50 (dt, J3a,4A=2.1, J3a,4B=J3a,9b=8.1,
H-3a), 3.44 and 1.70 (AB system, J10 A,10 B=13.2, H2-100), 3.36 (dd, J4A,4B=16.5, HA-4), 3.33 (dd,
9a,9b=7.9, H-9b), 2.7–1.1 (m, H2-30, 50, 6, 60, 7–9, HB-4, H-40, 9a), 1.00 (s, H3-80), 0.52 (s, H3-90);
0
0
J
δC: 177.50 and 176.32 (C-1, 3), 148.52 (C-5), 131.54 (C-100, 5a), 129.14 (C-200, 600), 128.62 (C-400),
126.00 (C-300, 500), 76.89 (C-20), 53.00 (C-100), 51.25 (C-10), 48.21 (C-70), 44.97 (C-40), 43.00 (C-9b),
39.75 and 39.55 (C-3a, 9a), 38.38 (C-30), 31.06, 27.15, 26.11, 24.81, 21.99, 21.86 and 20.32 (C-4, 50, 6,
60, 7–9), 20.00 and 19.57 (C-80, 90); m/z (%): 482 (M+1, 67), 149 (60), 135 (100), 107 (52), 91 (52), 55
(59).
3.7. Cycloadducts from (SS)-bornylsulfinyldiene 5 and NPM, reported in order of increasing retention
times
3.7.1. (3aS,9aS,9bR,SS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S-exo)-2-bornylsulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 18
25
Mp 83–85°C; [α]D +109.3 (c 1.480) (found: C, 72.00; H, 7.64. C28H35NO3S requires: C, 72.22; H,
7.58%); δH: 7.4–7.2 (m, Ph), 3.37 (dt, J3a,4A=2.1, J3a,4B=J3a,9b=8.6, H-3a), 3.37 (dd, J4A,4B=15.4, HA-4),
3.30 (dd, J9a,9b=5.5, H-9b), 2.7–1.1 (m, H-20, 40, 9a, HB-4, H2-30, 50, 6, 60, 7–9), 1.27 (s, H3-100), 0.90 (s,

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
3915
H3-80, 90); δC: 176.98 and 176.50 (C-1, 3), 151.24 (C-5), 131.64 and 130.88 (C-100, 5a), 128.97 (C-200,
600), 128.96 (C-400), 126.61 (C-300, 500), 70.03 (C-20), 48.90 (C-10), 47.54 (C-70), 44.79 (C-40), 43.13
(C-9b), 39.74 and 38.94 (C-3a, 9a), 38.66, 32.29, 27.34, 22.14, 21.86, 20.28 and 20.26 (C-4, 50, 6, 60,
7–9), 27.03 (C-30), 19.93 and 19.33 (C-80, 90), 13.38 (C-100); m/z (%): 466 (M+1, 5), 137 (51), 81 (100).
3.7.2. (3aR,9aS,9bS,SS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S-exo)-2-bornylsulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 20
Mp 66–68°C (found: C, 71.90; H, 7.38. C28H35NO3S requires: C, 72.22; H, 7.58%); δH: 7.5–7.3 (m,
Ph), 3.4–1.1 (m, H-20, 3a, 40, 9a, 9b, H2-30, 4, 50, 6, 60, 7–9), 1.25 (s, H3-100), 0.92 (s, H3-80), 0.89 (s,
H3-90); δC: 177.66 and 177.40 (C-1, 3), 147.68 (C-5), 131.71 and 129.64 (C-100, 5a), 129.11 (C-200, 600),
128.50 (C-400), 126.03 (C-300, 500), 69.55 (C-20), 49.09 (C-10), 47.61 (C-70), 44.74 (C-40), 44.65 (C-9b),
38.24 and 37.99 (C-3a, 9a), 38.80, 35.32, 31.55, 29.63, 26.95, 26.21 and 17.63 (C-4, 50, 6, 60, 7–9), 25.16
(C-30), 19.45 and 19.40 (C-80, 90), 13.48 (C-100); m/z (%): 466 (M+1, 4), 137 (20), 95 (50), 81 (65), 69
(73), 55 (100).
3.7.3. (3aS,9aR,9bR,SS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S-exo)-2-bornylsulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 21
Mp 188–190°C (found: C, 72.00; H, 7.70. C28H35NO3S requires: C, 72.22; H, 7.58%); δH: 7.5–7.2
(m, Ph), 3.45 (dt, J3a,4A=2.6, J3a,4B=J3a,9b=8.8, H-3a, HA-4), 3.35 (dd, J9a,9b=7.7, H-9b), 3.07 (dd,
J
4A,4B=17.3), 2.9–1.2 (m, H-20, 40, 9a, HB-4, H2-30, 50, 6, 60, 7–9), 1.22 (s, H3-100), 0.92 (s, H3-80),
0.86 (s, H3-90); δC: 177.84 and 176.45 (C-1, 3), 149.83 (C-5), 131.61 and 130.18 (C-100, 5a), 128.93
(C-200, 600), 128.40 (C-400), 125.90 (C-300, 500), 68.27 (C-20), 49.18 (C-10), 47.56 (C-70), 44.68 (C-40),
42.15 (C-9b), 39.31 and 38.63 (C-3a, 9a), 38.82, 31.12, 29.60, 27.48, 24.24, 23.54 and 17.83 (C-4, 50, 6,
60, 7–9), 26.70 (C-30), 19.46 and 19.42 (C-80, 90), 13.54 (C-100); m/z (%): 466 (M+1, 5), 137 (65), 55
(100).
3.7.4. (3aR,9aR,9bS,SS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S-exo)-2-bornylsulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 19
Mp 140–142°C (found: C, 72.25; H, 7.63. C28H35NO3S requires: C, 72.22; H, 7.58%); δH: 7.5–7.2
(m, Ph), 3.4–3.3 (m, H-3a, HA-4), 3.30 (dd, J3a,9b=8.9, J9a,9b=5.6, H-9b), 2.7–1.2 (m, H-20, 40, 9a, HB-4,
H2-30, 50, 6, 60, 7–9), 1.23 (s, H3-100), 0.88 (s, H3-80, 90); m/z (%): 466 (M+1, 23), 312 (30), 137 (100),
81 (70).
3.8. Cycloadducts from (RS)-bornylsulfinyldiene 6 and NPM, reported in order of increasing retention
times
3.8.1. (3aR,9aR,9bS,RS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S-exo)-2-bornylsulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 22
Mp 193–195°C; [α]D25 −19.0 (c 0.835) (found: C, 72.21; H, 7.70. C28H35NO3S requires: C, 72.22; H,
7.58%); δH: 7.5–7.2 (m, Ph), 3.37 (dt, J3a,4A=2.3, J3a,4B=J3a,9b=8.6, H-3a), 3.29 (dd, J9a,9b=5.6, H-9b),
3.27 (split dd, J4A,4B=15.8, HA-4), 2.7–1.0 (m, H-20, 40, 9a, HB-4, H2-30, 50, 6, 60, 7–9), 0.99 (s, H3-80),
0.95 (s, H3-100), 0.85 (s, H3-90); δC: 177.05 and 176.60 (C-1, 3), 147.83 (C-5), 134.25 and 131.68 (C-
100, 5a), 129.04 (C-200, 600), 128.47 (C-400), 126.62 (C-300, 500), 68.80 (C-20), 49.96 (C-10), 47.28 (C-70),
45.22 (C-40), 43.25 (C-9b), 39.78 and 39.05 (C-3a, 9a), 39.18, 29.65, 27.41, 26.89, 22.45, 21.78 and
20.37 (C-4, 50, 6, 60, 7–9), 25.06 (C-30), 19.88 and 19.86 (C-80, 90), 13.28 (C-100); m/z (%): 466 (M+1,
4), 312 (7), 279 (4), 205 (9), 55 (100).

3916
M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
3.8.2. (3aS,9aR,9bR,RS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S-exo)-2-bornylsulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 23
Mp 94–96°C (found: C, 72.26; H, 7.38. C28H35NO3S requires: C, 72.22; H, 7.58%); δH: 7.5–7.3 (m,
Ph), 3.31 (ddd, J3a,4A=7.6, J3a,4B=8.7, J3a,9b=5.7, H-3a), 3.19 (ddd, J6A,6B=11.3, J6A,7=3.7 and 1.5, HA-
6), 3.02 (ddd, J4A,4B=18.5, HA-4), 2.86 (dd, J9,9a=4.6, J9a,9b=9.1, H-9a), 2.72 (dd, H-9b), 2.6–1.1 (m,
H-20, 40, H2-30, 50, 60, 7–9, HB-4, 6), 0.98 (s, H3-80), 0.90 (s, H3-100), 0.84 (s, H3-90); δC: 177.90 and
177.38 (C-1, 3), 145.08 (C-5), 133.06 and 131.78 (C-100, 5a), 129.15 (C-200, 600), 128.55 (C-400), 126.09
(C-300, 500), 68.56 (C-20), 49.99 (C-10), 47.37 (C-70), 45.36 (C-40), 44.68 (C-9b), 39.03 and 38.37 (C-3a,
9a), 25.50 (C-30), 38.85, 30.99, 30.96, 29.23, 27.40, 26.50 and 18.07 (C-4, 50, 6, 60, 7–9), 19.94 and
19.75 (C-80, 90), 13.28 (C-100).
3.8.3. (3aR,9aS,9bS,RS)-1,3,3a,4,6,7,8,9,9a,9b-Decahydro-5-[(1S-exo)-2-bornylsulfinyl]-2-
phenylbenz[e]isoindole-1,3-dione 24
Mp 75–77°C (found: C, 72.11; H, 7.68. C28H35NO3S requires: C, 72.22; H, 7.58%); δH: 7.5–7.2 (m,
Ph), 3.5–3.1 (m, H-3a, 9b, HA-4), 2.7–1.0 (m, H-20, 40, H2-30, 50, 6, 60, 7–9, HB-4), 0.96 (s, H3-80), 0.86
(s, H3-100), 0.80 (s, H3-90).
3.9. Reaction of (SS,E)-1-{2-[(1S-exo)-2-bornylsulfinyl]vinyl}cyclohexene (7) with NMM in the presence
of SnCl4
SnCl4 (0.064 ml, 0.55 mmol) was added to a solution of the diene 7 (200 mg, 0.685 mmol) and NMM
(456 mg, 4.1 mmol) in anhydrous CH2Cl2 (5 ml) under stirring at room temperature. When the reaction
appeared complete by TLC (48 h, eluant hexane:EtOAc, 70:30) further CH2Cl2 (5 ml) was added, and
the organic layer washed with H2O for SnCl4 removal, and dried over Na2SO4. The solvent was then
evaporated under vacuum and the crude mixture was column chromatographed beginning the elution
with hexane:EtOAc (90:10) and gradually increasing the EtOAc percentage up to 40%. First the dia-
stereomeric mixture of four sulfoxides 26 (55% yield) was eluted. The crystallization from EtOAc:ligroin
of suitable combined fractions gave (3S,SS)-3-[(1S-exo)-2-bornylsulfinyl]-1-methylsuccinimide (main
25
product among sulfoxides 26): mp 143–145°C; [α]D +159.1 (c 0.215) (found: C, 60.50; H, 7.75.
C15H23NO3S requires: C, 60.58; H, 7.79%); δH: 3.80 (dd, J3,4A=4.7, J3,4B=9.1, H-3),0 3.46 (AB dd,
0 0
3A,3B=18.1, HA-4), 3.02 (1-Me), 2.73 (AB dd, HB-4), 2.54 (dd, J2 ,3 =9.2 and 6.7, H-2 ), 1.9–1.2 (m,
J
H2-30, 50, 60, H-40), 1.19 (s, H3-100), 1.02 (s, H3-80), 0.91 (s, H3-90); δC: 174.48 and 173.50 (C-2, 5),
69.23 (C-20), 56.74 (C-3), 49.98 (C-10), 47.72 (C-70), 44.82 (C-40), 39.18 (C-4), 31.54 and 24.01 (C-50,
60), 26.91 (C-30), 25.49 (1-Me), 20.02 and 19.74 (C-80, 90), 13.59 (C-100); MS/FAB in the presence of
NaI: m/z (%): 320 (M+Na, 73), 137 (44), 81 (45), 41 (45), 23 (100). The final fractions of the column con-
tained meso-2,12-dimethyl-1,2,3,3a,4,6,7,8,9a,9b,10,11,12,14-tetradecahydro-4,9a[30 ,40]-endo-pyrrolo-
benz[e]isoindole-1,3,11,13-tetrone 259 (20% yield): δH: 5.69 (dt, J4,5=6.3, J5,6=2.0, H-5), 3.67 (dt,
J
3a,4=J4,10=3.0, H-4), 2.93 (dd, J3a,9b=J10,14=8.1, H-3a, 10), 2.90 (s, Me), 2.75 (t, J8,9=6.9, H2-9), 2.71
(d, H-9b, 14), 2.10 (dt, J6,7=6.4, H2-6), 1.8–1.3 (m, H2-7, 8).
References
1. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Panzalorto, M.; Rizzo, S. Tetrahedron: Asymmetry 1998, 9,
1577–1587.
2. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Jones, D. N. J. Org. Chem. 1997, 62, 4376–4384.

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3907–3917
3917
3. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bruno, G.; Giannetto, P.; Panzalorto, M. Tetrahedron: Asymmetry 1997, 8,
2989–2995.
4. Aversa, M. C.; Bonaccorsi, P.; Giannetto, P.; Jafari, S. M. A.; Jones, D. N. Tetrahedron: Asymmetry 1992, 3, 701–704.
5. Aversa, M. C.; Bonaccorsi, P.; Giannetto, P.; Jones, D. N. Tetrahedron: Asymmetry 1994, 3, 805–808.
6. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Nicolò, F. J. Org. Chem. 1999, 64, 2114–2118.
7. Arce, E.; Carreño, M. C.; Cid, M. B.; García Ruano, J. L. J. Org. Chem. 1994, 59, 3421–3426.
8. Carreño, M. C.; Cid, M. B.; García Ruano, J. L.; Santos, M. Tetrahedron: Asymmetry 1997, 8, 2093–2097.
9. Carreño, M. C.; Cid, M. B.; Colobert, F.; García Ruano, J. L.; Solladié G. Tetrahedron: Asymmetry 1994, 5, 1439–1442.
10. Evans, D. A.; Andrews, G. C. J. Am. Chem. Soc. 1972, 94, 3672–3674.
11. Abbott, D. J.; Stirling, C. J. M. J. Chem. Soc. (C) 1969, 818–821.