Enantiopure sulfinylthiopyrans and related compounds from alkylsulfinylbuta-1,3-dienes

Article abstract of DOI:10.1016/S0957-4166(99)00410-3

Uncatalyzed and LiClO₄ catalyzed cycloadditions of (R(S))-1-{1-[(1S)- isoborneol-10-sulfinyl]vinyl}cyclohexene 1 and (R(S),E)-3-[(1S)-isoborneol- 10-sulfinyl]-1-methoxybuta-1,3-diene 2 with di(p-tolyl)- and di(p-anisyl)- thioketones 3 and 4 occur with complete regioselectivity. The lack of facial diastereoselectivity, observed in the cycloadditions of 1 with 3 or 4, appears to be a consequence of the sterical features of both diene and dienophile which, in the transition states, make the topological differentiation induced by the presence of the alkylsulfinyl group as chiral auxiliary uninfluential. No significant improvement in diastereoselectivity is observed in the LiClO₄ catalyzed reactions, but the obtained enantiopure cycloadducts are easily separated by column chromatography and isolated in high yields.

Full text of DOI:10.1016/S0957-4166(99)00410-3

Pergamon
Tetrahedron: Asymmetry 10 (1999) 3919–3929
Enantiopure sulfinylthiopyrans and related compounds from
alkylsulfinylbuta-1,3-dienes
Maria C. Aversa,a,∗ Anna Barattucci,a Paola Bonaccorsi,a Bianca F. Bonini,b
Placido Giannettoa and Francesco Nicolò c
aDipartimento di Chimica organica e biologica, Università degli Studi di Messina, Salita Sperone 31 (vill. S. Agata),
98166 Messina, Italy
bDipartimento di Chimica organica ‘A. Mangini’, Università degli Studi di Bologna, Viale Risorgimento 4,
40136 Bologna, Italy
cDipartimento 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 and LiClO4 catalyzed cycloadditions of (RS)-1-{1-[(1S)-isoborneol-10-sulfinyl]vinyl}cyclohexene
1 and (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-1-methoxybuta-1,3-diene 2 with di(p-tolyl)- and di(p-anisyl)-
thioketones 3 and 4 occur with complete regioselectivity. The lack of facial diastereoselectivity, observed in
the cycloadditions of 1 with 3 or 4, appears to be a consequence of the sterical features of both diene and
dienophile which, in the transition states, make the topological differentiation induced by the presence of the
alkylsulfinyl group as chiral auxiliary uninfluential. No significant improvement in diastereoselectivity is observed
in the LiClO4 catalyzed reactions, but the obtained enantiopure cycloadducts are easily separated by column
chromatography and isolated in high yields. © 1999 Elsevier Science Ltd. All rights reserved.
1. Introduction
Hetero-Diels–Alder (HDA) reactions give easy access to heterocycles which constitute the structural
skeleton of a large number of widespread natural compounds.1 Although the most common HDA
cycloadditions have been directed towards the synthesis of pyran derivatives as carbohydrate precursors,
conveniently substituted thiopyrans, obtained by using the HDA approach, have received special attention
as intermediates in the synthesis of biologically active agents.2–4
The most common thiodienophiles such as thioketones or thioaldehydes have been cycloadded
to a variety of suitable dienes, and the kinetics5,6 and stereochemistry of such reactions have been
investigated. The observed regioselectivity appears generally connected to the nature of substituents
∗
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)00410-3

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on C_S bond,7,8 and the endo/exo selectivity is moderate unless very bulky thiodienophiles are used.9
Studies on the facial diastereoselectivity have been performed for thioaldehydes bearing terpene moieties
as chiral auxiliaries, and the obtained results were not encouraging.10 Bonini et al. have extensively
investigated HDA reactions of enantiopure thioacylsilanes showing a silicon11 or carbon12 stereogenic
centre: appreciable diastereoselectivity, 50 and 80%, respectively, was observed. This article is concerned
with HDA cycloadditions, not yet described in the literature, of thiodienophiles with enantiomerically
pure dienes.
In continuing our research on the behaviour of enantiopure 2-alkylsulfinylbuta-1,3-dienes with hetero-
dienophiles with the intention of evaluating their synthetic potentiality,13 we turned our attention to
the HDA reactions of dienes 1 (Scheme 1) and 2 (Scheme 2) with dienophiles 3 and 4: these HDA
partners were chosen because they are easily accessible and quite stable compounds,14 unable to undergo
enethiolization. Dienes 115 and 216,17 had afforded very good stereochemical results in cycloadditions
with common carbodienophiles, generally showing a sensible increase in facial diastereoselectivity when
the reactions were catalyzed by suitable Lewis acids such as lithium perchlorate. Facial preference was
always controlled by the sulfur configuration.
Scheme 1.
In this paper we mainly describe the behaviour of sulfinyldienes 1 and 2 with sterically demanding
thiones 3 and 4 in both thermal and catalyzed HDA cycloadditions.

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
3921
Scheme 2.
Table 1
[4+2] Cycloadditions of dienes 1, 2 and 6 to thioketones 3, 4 and methyl acrylate 5 in CH2Cl2
2. Results and discussion
HDA reactions of dienes 1 and 2 with thioketones 3 and 4 were performed under argon atmosphere
in dry dichloromethane at reflux for diene 1 and at room temperature for the more reactive diene 2. The
results of these cycloadditions are reported in Table 1 together with the outcomes concerning Diels–Alder
(DA) cycloadditions of diene 1 with methyl acrylate 5 (Scheme 3) and sulfonyldiene 6 with thioketone
3 (Scheme 1). Longer reaction times are required for cycloadditions performed with diene 1, and/or in
the absence of lithium perchlorate.13,16,17 Yields are generally high, with some exceptions which involve
the cycloaddition of highly reactive sulfonyldiene 6, easily involved in side reactions at reflux (entry 11
in Table 1) and the cycloadditions of diene 1 with methyl acrylate 5 (entries 5 and 6 in Table 1) which
required very long reaction times at reflux, involving extensive diene decomposition.
The first HDA reaction performed on diene 1 and di(p-tolyl)thioketone 3 (Scheme 1) gave cycloadducts
7 and 8 in equal amounts (entry 1 in Table 1). The assignment of their structures was not obvious
until we performed a series of experiments which clearly demonstrated the complete regioselectivity
and null facial diastereoselectivity of the reaction. Sulfonyldiene 6, easily obtained by oxidation of
the corresponding sulfinyldiene 1, was cycloadded to thioketone 3, again giving equal amounts of the
two cycloadducts 9 and 10 (entry 11 in Table 1), which are undoubtedly facial diastereoisomers, as

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M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
Scheme 3.
Figure 1. X-Ray structure of adduct 7
demonstrated previously.16,18 Sulfonylbenzothiins 9 and 10 were separated by column chromatography
and individually oxidized to the bis-sulfones 11 and 12 (Scheme 1) which were also obtained as oxidation
products of sulfinylbenzothiins 7 and 8, respectively. These last results confirmed the stereochemical rela-
tionship between the diastereomeric cycloadducts 7 and 8. X-Ray crystallographic analysis, subsequently
performed on sulfinylbenzothiin 7, allowed the assignment of the (R) configuration to the new stereogenic
centre at C-8a (Fig. 1) and confirmed the regiochemistry of cycloadducts 7 and 8, previously proposed on
the basis of electronic characteristics of diene and dienophile19 substituents. Structures of cycloadducts
1
13 and 14 were correlated with those of 7 and 8 by comparison of suitable H NMR chemical shifts
(H2-3, 100, HA-5, H-8a, which are more affected by C-8a configuration (see Experimental)).
The lack of facial diastereoselectivity in HDA cycloaddition of diene 1 to thiobenzophenones 3 or 4
can be ascribed to the combined steric characteristics of the cyclohexene moiety of the diene and aryl
substituents of the dienophile in the transition states of the cycloadditions. These high steric requirements,
which are due in the dienophile to the approximately perpendicular disposition of the aryl groups with

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
3923
respect to the C_S plane,5 make the topological differentiation between the diene faces, induced by the
alkylsulfinyl auxiliary, uninfluential and poor stereochemical results are observed.†
In order to corroborate the above interpretation, we reacted thioketones 3 and 4 with the less sterically
demanding diene 2, and the facial diastereoselectivity value (19/20 and 21/22, 70:30, entries 7 and
9 in Table 1) was as expected for thermal cycloadditions of (RS,E)-3-[(1S)-isoborneol-10-sulfinyl]-3-
methoxybuta-1,3-diene 2. The attribution of the (R) configuration to the new stereogenic centre of the
major adducts 19 and 21 is based on the (R) configuration of the sulfur atom, which renders the Re face
of the diene 2 more easily approachable by the dienophile, as widely demonstrated before.13,16,17
Entries 5 and 6 in Table 1 are not strictly in line with the main subject of this paper, but the
previously discussed results concerning complete regioselectivity of HDA reactions of diene 1 with
thiobenzophenones allowed us to assign the structure to the four adducts which are products of the
cycloaddition between diene 1 and methyl acrylate 5, thus completing our study on the reactivity
of enantiopure 2-alkylsulfinylbuta-1,3-dienes towards acrylate.16,20 The reaction depicted in Scheme 3
occurs with complete regioselectivity, and the observed endo/exo and facial diastereoselectivities are in
accordance with previous results.16 Complete regioselectivity appears to be the more rational result of
the reaction between 1 and 5 if one considers that both complete facial and endo diastereoselectivities
were not observed even when 1 was reacted with the cyclic and endo-orientating N-phenylmaleimide as
dienophile.15
The tabulated results (entries 2, 6, 8 and 10 in Table 1) show that the presence of the Lewis acid
is unimportant for the stereochemical outcome of the cycloadditions under study. Lithium perchlorate
always shortened the reaction times but did not affect the facial diastereoselectivity. This result is general
for both dienes 1 and 2 involved in HDA reactions with thioketones 3 and 4, and suggests a coordination
of the catalyst to only one partner of the cycloaddition. The failed increase of facial diastereoselectivity in
the catalyzed cycloaddition of diene 1 with methyl acrylate 5 was unexpected on the basis of the results
obtained previously in the cycloaddition of diene 2 with the same dienophile 5 and in the presence of
the same catalyst.16 However, the previously observed coordination via lithium cation of both diene and
dienophile16 requires a suitable diene conformation in the transition state where the sulfinyl oxygen is
directed towards the dienophile; this situation could be too sterically demanding and thus unfavoured
when 1 and 5 are involved in a DA reaction.
In conclusion, the HDA cycloaddition of enantiopure alkylsulfinyldienes to thioketones constitutes
a possible route towards thiopyran derivatives having the desired absolute configuration, once the chiral
auxiliary is removed. Even if the observed facial diastereoselection was unsatisfactory (Scheme 2, entries
7–10 in Table 1) or completely absent (Scheme 1, entries 1–4), the easy separation and high yields of
cycloadducts can render this procedure attractive from a synthetic point of view.
3. Experimental
3.1. General methods and materials
Starting products 1–4 were prepared following literature methodologies.14,16,21 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 vanillin [vanillin
(1 g) dissolved in MeOH (60 ml) and conc. H2SO4 (0.6 ml)]. Silica gel used for column chromatography
†
In fact, a moderate increase of facial diastereoselection was observed when diene 1 was reacted with thiofluorenone.

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M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
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
1
a Siemens automated four-circle single-crystal diffractometer 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) and decoupling experiments. Proton and carbon indexes, marked with (0), pertain to
the isoborneol moiety. The symbol (00) identifies nuclei pertaining to aryl residues in compounds 7–14,
19–22, and vinyl nuclei in sulfonyldiene 6. 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. General procedure for Diels–Alder reactions in thermal conditions
A solution of the diene (0.35 mmol) in 3 ml of anhydrous CH2Cl2 was added to the neat dienophile
[an equimolar amount of thioketone dienophile was used, while an excess of methyl acrylate 5 was
reacted with diene 1 (6:1 molar ratio)]. The reaction mixture was stirred under argon until the diene
totally disappeared, as verified by TLC monitoring (light petroleum:ethyl acetate, 80:20). The solvent
was removed under vacuum and the crude mixture was column chromatographed. Reaction temperatures,
times and yields are shown in Table 1.
3.3. General procedure for Diels–Alder reactions in the presence of LiClO4
LiClO4 (0.28 mmol) was added to a solution of the diene (0.35 mmol) and thioketone dienophile (0.35
mmol) in anhydrous CH2Cl2 (3 ml) under argon (when methyl acrylate 5 was the dienophile, the relative
amounts of reagents were diene:dienophile:catalyst, 1:6:0.8). 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.
3.4. General procedure for MCPBA oxidations
Commercial MCPBA (90% after careful drying over P2O5) was slowly added to a solution of
substrate in anhydrous CH2Cl2 (10 ml/50 mg of substrate) at 0°C. The reaction mixture was allowed
to spontaneously reach the room temperature, and was maintained under stirring until the starting
product had totally disappeared, as verified by TLC monitoring (light petroleum:EtOAc, 75:25, as eluant
for observing the disappearance of diene 1, and CH2Cl2:EtOAc, 95:5, for the remaining substrates).
Anhydrous KF was added (25 mg/20 mg MCPBA) and the mixture stirred overnight. After filtration,
the evaporation of the solvent under reduced pressure gave the oxidation product, not needing any
purification. The yields were almost quantitative. Different MCPBA/substrate molar ratios were used:
1.5:1 for oxidation of sulfoxide 1 to sulfone 6, 3:1 for converting sulfonylthioethers 9 and 10 into bis-
sulfones 11 and 12, and 4.5:1 for obtaining the same bis-sulfones 11 and 12 from sulfinylthioethers 7 and
8, respectively.

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
3925
3.5. Cycloadducts from sulfinyldiene 1 and di-(p-tolyl)thioketone 3, reported in order of increasing
retention times (eluant CH2Cl2:EtOAc, 98:2)
3.5.1. (8aS,RS)-1,1-Di(p-tolyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfinyl]-1H-2-
benzothiin 8
Mp 145°C; [α]25 +371.7 (c 0.965) (found: C, 73.80; H, 7.83; C33H42O2S2 requires: C, 74.12;
D
0
0
0
H, 7.92%); δH: 7.2–7.0 (m, ArH), 4.05 (dd, J2 ,3 =8.2 and 4.2, H-2 ), 3.46 and 2.17 (AB system,
J10 A,10 B=13.2, H2-100), 3.34 (AB d, J3A,3B=17.5, HA-3), 2.96 (split d, J5A,5B=13.0, HA-5), 2.80 (split
dd, J8,8a=9.6 and 1.7, H-8a), 2.60 (split AB d, HB-3), 2.30 and 2.27 (two s, ArMe), 2.1–1.0 (m, H2-30,
50, 6, 60, 7, 8, H-40, HB-5), 1.09 (s, H3-80), 0.79 (s, H3-90); δC: 148.44 (C-4), 142.11 and 142.00 (C-
100), 136.26 (C-400), 130.63 (C-4a), 128.85 and 128.45 (C-200, 600), 127.96 and 127.27 (C-300, 500), 76.82
(C-20), 57.23 (C-100), 54.43 (C-1), 51.47 (C-10), 49.45 (C-8a), 48.14 (C-70), 45.01 (C-40), 38.35 (C-30),
32.33, 32.28, 31.09, 29.68, 27.10 and 26.42 (C-5, 50, 6, 60, 7, 8), 21.60 (C-3), 20.94, 20.90, 20.37 and
19.88 (Me); m/z (%): 535 (M+1, 18), 91 (86), 89 (82), 77 (100).
0
0
3.5.2. (8aR,RS)-1,1-Di(p-tolyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfinyl]-1H-2-
benzothiin 7
Mp 224°C; [α]25 −315.6 (c 0.890) (found: C, 73.69; H, 8.27; C33H42O2S2 requires: C, 74.12; H,
D
0
0
0
0
7.92%); δH: 7.2–7.0 (m, ArH), 4.00 (dd, J2 ,3 =7.9 and 4.0, H-2 ), 3.66 (AB d, J3A,3B=17.4, HA-3),
3.15 (split d, J5A,5B=12.7, HA-5), 2.97 and 1.84 (AB system, J10 A,10 B=13.3, H2-100), 2.88 (split dd,
3B,8a=2.4, J8,8a=10.9 and 2.3, H-8a), 2.44 (AB ddd, J3B,5B=2.4, HB-3), 2.30 and 2.29 (two s, ArMe),
0
J
2.1–1.0 (m, H2-30, 50, 6, 60, 7, 8, H-40, HB-5), 0.93 (s, H3-80), 0.81 (s, H3-90); δC: 148.64 (C-4), 142.34
and 141.61 (C-100), 136.29 and 136.21 (C-400), 131.56 (C-4a), 128.85 and 128.38 (C-200, 600), 128.16 and
127.25 (C-300, 500), 76.71 (C-20), 57.19 (C-100), 53.06 (C-1), 51.19 (C-10), 49.47 (C-8a), 48.14 (C-70),
44.93 (C-40), 38.31 (C-30), 33.01, 31.79, 30.74, 29.07, 27.07 and 26.44 (C-5, 50, 6, 60, 7, 8), 20.94, 20.85,
20.45 and 19.66 (Me), 19.75 (C-3); m/z (%): 535 (M+1, 4), 105 (46), 95 (47), 91 (53), 81 (78), 69 (80),
67 (46), 57 (58), 55 (100), 43 (69), 41 (69).
3.6. Cycloadducts from sulfinyldiene 1 and di-(p-anisyl)thioketone 4, reported in order of increasing
retention times (eluant light petroleum:Et2O, 80:20)
3.6.1. (8aR,RS)-1,1-Di(p-anisyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfinyl]-1H-2-
benzothiin 13
Mp 227–229°C; [α]25 −135.2 (c 0.304) (found: C, 69.99; H, 7.89; C33H42O4S2 requires: C, 69.93; H,
D
7.47%); δH: 7.2–6.7 (m, ArH), 4.00 (m, H-20), 3.78 and 3.77 (two s, OMe), 3.68 (AB d, J3A,3B=17.0, HA-
3), 3.14 (split d, J5A,5B=12.6, HA-5), 3.02 and 1.86 (AB system, J10 A,10 B=13.3, H2-100), 2.83 (split d,
0
0
J
8,8a=10.8, H-8a), 2.46 (split AB d, HB-3), 2.1–1.2 (m, H2-30, 50, 6, 60, 7, 8, H-40, HB-5), 0.95 (s, H3-80),
0.81 (s, H3-90); δC: 158.02 and 157.89 (C-400), 148.75 (C-4), 137.30 and 136.84 (C-100), 131.45 (C-4a),
129.50 and 128.39 (C-200, 600), 113.42 and 112.69 (C-300, 500), 76.75 (C-20), 56.69 (C-100), 55.22 and
55.18 (OMe), 53.16 (C-1), 51.28 (C-10), 49.83 (C-8a), 48.19 (C-70), 45.06 (C-40), 38.44 (C-30), 33.13,
32.02, 30.88, 29.17, 27.17 and 26.55 (C-5, 50, 6, 60, 7, 8), 20.63 (C-3), 19.88 (C-80, 90); m/z (%): 567
(M+1, 28), 259 (30), 258 (35), 155 (39), 149 (30), 138 (51), 137 (100), 107 (53), 91 (31), 89 (40), 77
(46).

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M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
3.6.2. (8aS,RS)-1,1-Di(p-anisyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfinyl]-1H-2-
benzothiin 14
Mp 109°C; [α]25 +265.8 (c 1.140) (found: C, 69.53; H, 7.22; C33H42O4S2 requires: C, 69.93; H,
D
7.47%); δH: 7.2–6.7 (m, ArH), 4.05 (m, H-20), 3.78 and 3.76 (two s, OMe), 3.47 and 2.17 (AB system,
J10 A,10 B=13.2, H2-100), 3.35 (AB d, J3A,3B=17.2, HA-3), 2.96 (split d, J5A,5B=12.6, HA-5), 2.75 (split d,
0
0
J
8,8a=10.2, H-8a), 2.61 (split AB d, HB-3), 2.1–1.2 (m, H2-30, 50, 6, 60, 7, 8, H-40, HB-5), 1.12 (s, H3-80),
0.83 (s, H3-90); δC: 158.08 and 157.97 (C-400), 148.55 (C-4), 137.18 and 137.14 (C-100), 130.60 (C-4a),
129.22 and 128.49 (C-200, 600), 113.43 and 113.03 (C-300, 500), 76.81 (C-20), 56.69 (C-100), 55.16 and
55.13 (OMe), 54.38 (C-1), 51.46 (C-10), 49.75 (C-8a), 48.14 (C-70), 45.00 (C-40), 38.34 (C-30), 32.33,
31.07, 29.66, 29.22, 27.09 and 26.41 (C-5, 50, 6, 60, 7, 8), 21.66 (C-3), 20.36 and 19.86 (C-80, 90); m/z
(%): 567 (M+1, 27), 259 (36), 258 (45), 155 (27), 149 (36), 138 (36), 137 (100), 135 (30), 107 (42), 91
(28), 89 (33), 81 (44), 77 (37).
3.7. 1-{1-[(1S)-Isoborneol-10-sulfonyl]vinyl}cyclohexene 6, obtained by MCPBA oxidation of diene 1
0
Oil; δH: 6.46 (m, H-2), 6.27 and 5.84 (two s, H2-200), 4.18 (dd, J2 ,3 =7.8 and 4.5, H-2 ), 3.39 and 2.94
0
0
(AB system, J10 A,10 B=13.5, H2-100), 2.3–1.1 (m, H2-3, 30, 4, 5, 50, 6, 60, H-40), 1.06 (s, H3-80), 0.80
(s, H3-90); δC: 151.44 (C-100), 131.82 (C-2), 130.16 (C-1), 123.01 (C-200), 76.28 (C-20), 52.45 (C-100),
50.93 (C-10), 49.17 (C-70), 44.26 (C-40), 39.05 (C-30), 30.42, 28.02, 27.56, 25.92, 22.71 and 21.50 (C-3,
4, 5, 50, 6, 60), 20.59 and 19.93 (C-80, 90); m/z (%): 307 (M+1−H2O, 7), 201 (19), 55 (100).
0
0
3.8. Cycloadducts from sulfonyldiene 6 and di(p-tolyl)thioketone 3, reported in order of increasing
retention times (eluant light petroleum:EtOAc, 98:2)
3.8.1. (8aR)-1,1-Di(p-tolyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfonyl]-1H-2-benzothiin 9
Mp 215°C (found: C, 71.80; H, 7.75; C33H42O3S2 requires C, 71.96; H, 7.69%); δH: 7.1–7.0 (m, ArH),
0
0
0
4.10 (dd, J2 ,3 =7.7 and 4.4, H-2 ), 3.84 (split d, J5A,5B=11.8, HA-5), 3.51 (AB d, J3A,3B=17.7, HA-3),
3.07 and 2.74 (AB system, J10 A,10 B=13.6, H2-100), 2.97 (split d, J8,8a=10.4, H-8a), 2.59 (split AB d,
HB-3), 2.30 and 2.29 (two s, ArMe), 2.2–1.1 (m, H2-30, 50, 6, 60, 7, 8, H-40, HB-5), 1.01 (s, H3-80),
0.84 (s, H3-90); δC: 158.20 (C-4), 141.95 and 141.37 (C-100), 136.51 and 136.45 (C-400), 130.25 (C-4a),
128.95 and 128.48 (C-200, 600), 127.96 and 127.12 (C-300, 500), 76.26 (C-20), 56.76 (C-100), 54.88 (C-1),
50.91 (C-8a), 50.90 (C-10), 49.14 (C-70), 44.15 (C-40), 38.81 (C-30), 34.33, 33.02, 30.73, 30.15, 27.53
and 26.35 (C-5, 50, 6, 60, 7, 8), 26.03 (C-3), 20.94, 20.91, 20.63 and 19.74 (Me).
0
0
3.8.2. (8aS)-1,1-Di(p-tolyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfonyl]-1H-2-benzothiin
10
Mp 189°C (found: C, 71.66; H, 7.70; C33H42O3S2 requires: C, 71.96; H, 7.69%); δH: 7.2–7.0 (m,
ArH), 4.11 (m, H-20), 3.82 (split d, J5A,5B=12.1, HA-5), 3.51 (AB d, J3A,3B=17.7, HA-3), 3.34 and 2.51
(AB system, J10 A,10 B=13.7, H2-100), 3.00 (split d, J8,8a=10.2, H-8a), 2.61 (split AB d, HB-3), 2.30 and
2.28 (two s, ArMe), 2.2–1.0 (m, H2-30, 50, 6, 60, 7, 8, H-40, HB-5), 1.10 (s, H3-80), 0.76 (s, H3-90); δC:
158.05 (C-4), 141.97 and 141.33 (C-100), 136.44 and 136.39 (C-400), 130.41 (C-4a), 128.96 and 128.51
(C-200, 600), 128.01 and 127.09 (C-300, 500), 76.31 (C-20), 56.80 (C-100), 54.63 (C-1), 50.91 (C-10), 50.82
(C-8a), 49.13 (C-70), 44.14 (C-40), 39.03 (C-30), 34.37, 33.07, 30.60, 30.14, 27.42 and 26.32 (C-5, 50, 6,
60, 7, 8), 25.99 (C-3), 20.93, 20.89, 20.38 and 19.99 (Me).
0
0

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
3927
3.9. (8aR)-1,1-Di(p-tolyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfonyl]-1H-2-benzothiin
2,2-dioxide 11, obtained by MCPBA oxidation of both 7 and 9
Mp 281°C; [α]25 −202.1 (c 1.225) (found: C, 67.97; H, 7.18; C33H42O5S2 requires: C, 68.01; H,
D
0
0
0
7.26%); δH: 7.3–7.1 (m, ArH), 4.12 (dd, J2 ,3 =7.1 and 3.7, H-2 ), 3.94 (split d, J5A,5B=12.6, HA-5), 3.77
0
0
(AB d, J3A,3B=17.6, HA-3), 3.4–3.3 (m, HB-3, H-8a), 3.39 and 2.91 (AB system, J10 A,10 B=13.7, H2-
100), 2.34 and 2.32 (two s, ArMe), 2.3–1.0 (m, H2-30, 50, 6, 60, 7, 8, H-40, HB-5), 1.06 (s, H3-80), 0.86
(s, H3-90); δC: 156.72 (C-4), 139.42 (C-100), 137.55 and 135.56 (C-400), 129.53 and 129.21 (C-200, 600),
129.00 and 128.28 (C-300, 500), 126.33 (C-4a), 76.22 (C-20), 73.54 (C-3), 55.33 (C-8a, 100), 50.89 (C-1),
49.30 (C-10), 47.33 (C-70), 44.13 (C-40), 39.13 (C-30), 33.60, 30.68, 29.66, 27.46 and 26.83 (C-5, 50, 6,
60, 7, 8), 21.01, 20.99, 20.62 and 19.83 (Me).
3.10. (8aS)-1,1-Di(p-tolyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfonyl]-1H-2-benzothiin
2,2-dioxide 12, obtained by MCPBA oxidation of both 8 and 10
Mp 121°C; [α]25 +156.6 (c 0.770) (found: C, 68.30; H, 7.70; C33H42O5S2 requires: C, 68.01; H,
D
0
0
0
7.26%); δH: 7.2–7.1 (m, ArH), 4.07 (dd, J2 ,3 =7.9 and 3.9, H-2 ), 3.94 (split d, J5A,5B=13.7, HA-5), 3.76
(AB d, J3A,3B=17.5, HA-3), 3.55 and 2.76 (AB system, J10 A,10 B=13.6, H2-100), 3.34 (m, H-8a), 3.30
(split AB d, HB-3), 2.34 and 2.32 (two s, ArMe), 2.3–1.0 (m, H2-30, 50, 6, 60, 7, 8, H-40, HB-5), 1.10 (s,
H3-80), 0.82 (s, H3-90); δC: 156.47 (C-4), 139.37 (C-100), 137.55 and 135.57 (C-400), 129.20 (C-200, 600),
128.98 (C-300, 500), 126.56 (C-4a), 76.07 (C-20), 73.59 (C-3), 55.48 (C-100), 55.23 (C-8a), 51.11 (C-1),
49.35 (C-10), 47.40 (C-70), 44.18 (C-40), 39.59 (C-30), 33.60, 30.74, 29.67, 27.38 and 26.80 (C-5, 50, 6,
60, 7, 8), 21.11, 21.01, 20.46 and 20.01 (Me).
0
0
3.11. Cycloadducts from sulfinyldiene 2 and di(p-tolyl)thioketone 3, reported in order of increasing
retention times (eluant light petroleum:EtOAc, 95:5)
3.11.1. (6S,RS)-3,6-Dihydro-2,2-di(p-tolyl)-4-[(1S)-isoborneol-10-sulfinyl]-6-methoxy-2H-thiin 20
Low-melting solid; δH: 7.6–7.1 (m, ArH), 6.81 (ddd, J3A,5= J5,6=2.2, J3B,5=2.3, H-5), 4.67 (ddd,
0
0 0
3A,6=2.2, J3B,6=2.3, H-6), 4.04 (dd, J2 ,3 =8.2 and 4.0, H-2 ), 2.90 (AB ddd, J3A,3B=17.2, HA-3), 3.11
J
(s, 6-OMe), 2.83 and 1.94 (AB system, J10 A,10 B=13.3, H2-100), 2.76 (AB ddd, HB-3), 2.32 (s, ArMe),
0
0
1.8–1.0 (m, H2-30, 50, 60, H-40), 1.03 (s, H3-80), 0.69 (s, H3-90).
3.11.2. (6R,RS)-3,6-Dihydro-2,2-di(p-tolyl)-4-[(1S)-isoborneol-10-sulfinyl]-6-methoxy-2H-thiin 19
Low-melting solid; [α]25 −77.2 (c 0.765); δH: 7.6–7.1 (m, ArH), 6.61 (ddd, J5,6=1.9, J3A,5=1.8,
D
0
0
0
J
3B,5=2.1, H-5), 4.72 (ddd, J3A,6=1.8, J3B,6=3.4, H-6), 3.98 (dd, J2 ,3 =7.7 and 3.8, H-2 ), 3.29 (AB
ddd, J3A,3B=17.6, HA-3), 3.08 (s, 6-OMe), 2.93 and 1.83 (AB system, J10 A,10 B=13.2, H2-100), 2.90 (AB
0
0
ddd, HB-3), 2.32 (s, ArMe), 1.8–1.0 (m, H2-30, 50, 60, H-40), 0.94 (s, H3-80), 0.76 (s, H3-90).
3.12. Cycloadducts from sulfinyldiene 2 and di(p-anisyl)thioketone 4, reported in order of increasing
retention times (eluant CH2Cl2:EtOAc, 98:2)
3.12.1. (6R,RS)-3,6-Dihydro-2,2-di(p-anisyl)-4-[(1S)-isoborneol-10-sulfinyl]-6-methoxy-2H-thiin 21
Low-melting solid; [α]25 −99.4 (c 0.815); δH: 7.6–6.8 (m, ArH), 6.61 (ddd, J3A,5=1.6, J3B,5=2.3,
D
0
0
0
J
5,6=1.8, H-5), 4.72 (ddd, J3A,6=1.6, J3B,6=3.6, H-6), 4.00 (dd, J2 ,3 =8.0 and 4.1, H-2 ), 3.81 and
3.80 (two s, ArOMe), 3.29 (AB ddd, J3A,3B=17.6, HA-3), 3.10 (s, 6-OMe), 2.97 and 1.86 (AB system,
J10 A,10 B=13.2, H2-100), 2.93 (AB ddd, HB-3), 0.96 (s, H3-80), 0.77 (s, H3-90).
0
0

3928
M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
3.12.2. (6S,RS)-3,6-Dihydro-2,2-di(p-anisyl)-4-[(1S)-isoborneol-10-sulfinyl]-6-methoxy-2H-thiin 22
Low-melting solid; δH: 7.6–6.8 (0m, ArH), 6.80 (m, H-5), 4.65 (ddd, J3A,6=1.6, J3B,6=J5,6=2.9, H-
0
0
6), 4.04 (dd, J2 ,3 =8.0 and 4.4, H-2 ), 3.79 (s, ArOMe), 3.12 (s, 6-OMe), 2.92 (AB ddd, J3A,3B=17.1,
J
3A,5=1.6, HA-3), 2.84 and 1.98 (AB system, J10 A,10 B=13.3, H2-100), 2.76 (AB ddd, J3B,5=2.1, HB-3),
0 0
1.03 (s, H3-80), 0.70 (s, H3-90).
3.13. Isolated cycloadducts from sulfinyldiene 1 and methyl acrylate 5, reported in order of increasing
retention times (eluant light petroleum:EtOAc, 95:5)
3.13.1. (2S,8aR,RS)-4-[(1S)-Isoborneol-10-sulfinyl]-2-methoxycarbonyl-1,2,3,5,6,7,8,8a-octahydrona-
phthalene 15
Oil; [α]25 −27.0 (c 1.365); δH: 4.09 (dd, J2 ,3 =8.1 and 4.0, H-2 ), 3.71 (s, OMe), 3.46 and 2.08 (AB
0
0
0
D
0
system, J10 A,10 B=12.9, H2-100), 3.1–1.1 (m, H2-1, 3, 5, 6, 7, 8, H-2, 8a), 1.09 (s, H3-80), 0.81 (s, H3-90);
δC: 174.08 (CO), 147.45 (C-4), 132.87 (C-4a), 76.87 (C-20), 52.18 (C-100), 51.61 (OMe), 51.35 (C-10),
48.12 (C-70), 45.07 (C-40), 43.71 (C-2), 41.62 (C-8a), 38.36 (C-30), 31.66, 30.87, 30.38, 28.34, 27.07,
26.14, 20.08 and 17.85 (C-1, 3, 5, 50, 6, 60, 7, 8), 20.51 and 19.92 (C-80, 90).
0
3.13.2. (2R,8aS,RS)-4-[(1S)-Isoborneol-10-sulfinyl]-2-methoxycarbonyl-1,2,3,5,6,7,8,8a-octahydrona-
phthalene 16
Oil; [α]25 +93.6 (c 0.850); δH: 4.09 (dd, J2 ,3 =8.3 and 4.3, H-2 ), 3.71 (s, OMe), 3.46 and 2.03 (AB
0
0
0
D
0
system, J10 A,10 B=13.2, H2-100), 2.9–1.1 (m, H2-1, 3, 5, 6, 7, 8, H-2, 8a), 1.12 (s, H3-80), 0.82 (s, H3-90);
δC: 174.03 (CO), 145.82 (C-4), 132.67 (C-4a), 76.84 (C-20), 53.30 (C-100), 51.57 (OMe), 51.38 (C-10),
48.08 (C-70), 45.04 (C-40), 43.10 (C-2), 41.47 (C-8a), 38.40 (C-30), 31.15, 31.06, 30.50, 28.39, 27.11,
26.02, 20.82 and 20.05 (C-1, 3, 5, 50, 6, 60, 7, 8), 20.41 and 19.90 (C-80, 90).
0
3.14. X-Ray analysis of (8aS,RS)-1,1-di(p-tolyl)-3,5,6,7,8,8a-hexahydro-4-[(1S)-isoborneol-10-sulfin-
yl]-1H-2-benzothiin 7‡
The space group of the monoclinic C33H42O2S2 crystal (from EtOAc, M=534.79) was P21 with
a=11.324(2), b=7.3923(9), c=18.455(3) Å, β=105.65(1)°. Other crystal parameters were as follows:
V=1487.6(4) Å3, Z=2, dcalc=1.194 g/cm3. The structure, solved by direct methods (SIR97),22 was
subsequently completed by a combination of least squares technique and Fourier syntheses, and refined
by the full-matrix least squares technique (SHELXTL PLUS) based on F.23 The H atoms were included
in the refinement following the ‘riding model’ with a unique common fixed isotropic displacement
parameter. The structure refinement, with all anisotropic non-H atoms, reached R(F)=0.0388 including a
parameter for extinction correction into the last cycles. The Flack enantiomorphic parameter converged
to the final value of 1.5(4), overestimated in comparison with the theoretical value +1 which characterizes
the assigned absolute configuration.24 The final Fourier difference maps revealed no significant residual
(<0.2 eÅ−3).
References
1. Tietze, L. F.; Kettschau, G. Top. Curr. Chem. 1997, 189, 1–120.
2. Vedejs, E.; Stults, J. S. J. Org. Chem. 1988, 53, 2226–2232.
‡
Tables of bond distances, bond angles, and positional and thermal parameters are available on request from the corresponding
author.

M. C. Aversa et al. / Tetrahedron: Asymmetry 10 (1999) 3919–3929
3929
3. Pinto, I. L.; Buckle, D. R.; Rami, H. K.; Smith, D. G. Tetrahedron Lett. 1992, 33, 7597–7600.
4. Wilde, R. G.; Billheimer, J. T.; Germain, S. J.; Hausner, E. A.; Meunier, P. C.; Munzer, D. A.; Stoltenborg, J. K.; Gillies, P.
J.; Burcham, D. L.; Huang, S. M.; Klaczkiewicz, J. D.; Ko, S. S.; Wexler, R. R. Bioorg. Med. Chem. 1996, 4, 1493–1513.
5. Rohr, U.; Schatz, J.; Sauer, J. Eur. J. Org. Chem. 1998, 2875–2883.
6. Barone, V.; Arnaud, R.; Chavant, P. Y.; Vallèe, Y. J. Org. Chem. 1996, 61, 5121–5129.
7. Vedejs, E.; Eberlein, T. H.; Mazur, D. J.; McClure, C. K.; Perry, D. A.; Ruggeri, R.; Schwarts, E.; Stults, J. S.; Varie, D.
L.; Wilde, R. G.; Wittenberger, S. J. Org. Chem. 1986, 5, 1556–1562.
8. Kirby, G. W.; McGregor, W. M. J. Chem. Soc., Perkin Trans. 1 1990, 3175–3182.
9. Vedejs, E.; Stults, J. S.; Wilde, R. G. J. Am. Chem. Soc. 1988, 110, 5452–5460.
10. Takahashi, T.; Kurose, N.; Koizumi, T. Heterocycles 1993, 36, 1601–1616.
11. Bonini, B. F.; Mazzanti, G.; Zani, P.; Maccagnani, G. J. Chem. Soc., Chem. Commun. 1988, 365–367.
12. Bonini, B. F.; Busi, F.; de Laet, R. C.; Mazzanti, G.; Thuring, J. F.; Zani, P.; Zwanenburg, B. J. Chem. Soc., Perkin Trans.
1 1993, 1011–1018.
13. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bruno, G.; Giannetto, P.; Panzalorto, M. Tetrahedron: Asymmetry 1997, 8,
2989–2995.
14. Lozac’h, N.; Guillouzo, G. Bull. Soc. Chim. Fr. 1957, 1221–1224.
15. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Nicolò, F.; Rizzo, S. Tetrahedron: Asymmetry 1999, 10,
3907–3917.
16. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Jones, D. N. J. Org. Chem. 1997, 62, 4376–4384.
17. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Panzalorto, M.; Rizzo, S. Tetrahedron: Asymmetry 1998, 9,
1577–1587.
18. Adams, H.; Jones, D. N.; Aversa, M. C.; Bonaccorsi, P.; Giannetto, P. Tetrahedron Lett. 1993, 34, 6481–6484.
19. Duus, F. In Comprehensive Organic Chemistry; Barton, D.; Ollis, D.; Jones, D. N., Eds.; Pergamon Press: Oxford, 1979;
Vol. 3; p. 376.
20. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Nicolò, F. J. Org. Chem. 1999, 64, 2114–2118.
21. Aversa, M. C.; Bonaccorsi, P.; Giannetto, P.; Jafari, S. M.A.; Jones, D. N. Tetrahedron: Asymmetry 1992, 3, 701–704.
22. Altomare, A.; Cascarano, O.; Giacovazzo, C.; Guagliardi, A.; Burla, M. C.; Polidori, G.; Camalli, M. J. Appl. Crystallogr.
1994, 27, 435–436.
23. Sheldrick, G. M. 1990, release 4.21/V, Siemens Analytical X-Ray Instruments Inc., Madison, Wisconsin, USA.
24. Flack, H. D. Acta Cryst. 1983, A39, 876–881.