Synthesis of chiral 1- and 2-(p-tolylsulfinyl)-3-trimethylsilyloxybuta-1,3-dienes and their behaviour in Diels-Alder cycloadditions

Article abstract of DOI:10.1016/S0957-4166(00)00039-2

The synthesis of (±)-(E)-1-(p-tolylsulfinyl)-3-trimethylsilyloxybuta-1,3-diene 1 and (S(S))-2-(p-tolylsulfinyl)-3-trimethylsilyloxybuta-1,3-diene 2 and their reactions with cyclic dienophiles are described. Cycloaddition of diene 1 with N-methylmaleimide

Full text of DOI:10.1016/S0957-4166(00)00039-2

Tetrahedron: Asymmetry 11 (2000) 1217±1225
Synthesis of chiral 1- and 2-(p-tolylsul®nyl)-
3-trimethylsilyloxybuta-1,3-dienes and their behaviour
in Diels±Alder cycloadditions
M. Teresa Aranda,a Maria C. Aversa,b,* Anna Barattucci,a,b Paola Bonaccorsi,b
M. Carmen Carreno,a,* M. Belen Cida and Jose L. Garcõa Ruanoa,*
a
Â
Departamento de Quõmica Organica (C-I), Universidad Autonoma, Cantoblanco, 28049 Madrid, Spain
Â
Dipartimento di Chimica organica e biologica, Universita degli Studi di Messina, Salita Sperone 31 (vill. S. Agata),
Â
b
Á
98166 Messina, Italy
Received 3 January 2000; accepted 20 January 2000
Abstract
The synthesis of (‹)-(E)-1-(p-tolylsul®nyl)-3-trimethylsilyloxybuta-1,3-diene 1 and (SS)-2-(p-tolylsulf-
inyl)-3-trimethylsilyloxybuta-1,3-diene 2 and their reactions with cyclic dienophiles are described.
Cycloaddition of diene 1 with N-methylmaleimide 10 was performed under pressure a€ording a complex
reaction mixture from which two epimers at C-30, (‹)-11a and (‹)-11b [2,3,3a,4,5,7a-hexahydro-2-methyl-
7a-(1-methylsuccinimide-3-yl)-1H-isoindole-1,3,5-triones], were isolated in equal amounts. Diene (‹)-1
cycloadded to the more reactive 4-methyl-1,2,4-triazoline-3,5-dione 14 at atmospheric pressure and room
temperature. However, nothing can be said about the stereochemical outcome of this addition since the
loss of the chiral auxiliary via the sulfoxide±sulfenate rearrangement gave the bicyclic a,b-unsaturated
ketone 17 (2-methyl-2,3,5,6-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1,3,6-trione). Diels±Alder cyclo-
addition of enantiopure diene 2 with 10 occurred under pressure leading to a diastereomeric mixture of
adducts where the trimethylsilyl enol ether moiety spontaneously evolved to the ketone function. The major
enantiopure product 18a [(3aS,6S,7aR,RS)-2-methyl-6-(p-tolylsul®nyl)perhydroisoindole-1,3,5-trione] was
isolated and characterized. Cycloadditions of both dienes to dienophile 10 appear highly stereoselective.
# 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
During recent years the sul®nyl group has shown its stereodi€erentiating power if linked to a
diene moiety involved in Diels±Alder (DA) reactions, so that numerous reports have appeared
concerning the synthesis of sul®nyl-substituted 1,3-butadienes1 and their reactivity as DA partners.2
* Corresponding authors. E-mail: aversa@imeuniv.unime.it, carmen.carrenno@uam.es,
joseluis.garcia.ruano@uam.es
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00039-2

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M. T. Aranda et al. / Tetrahedron: Asymmetry 11 (2000) 1217±1225
The relevant in¯uence exerted by the sul®nyl group position with respect to the conjugated system
has been pointed out for (sul®nylvinyl)cyclohexenes:3 2-sul®nyldienes exhibit a higher reactivity
in DA cycloadditions than 1-sul®nyldienes. According to this observation, it seemed important to
compare the reactivity of open-chain 1- and 2-sul®nyldienes possessing a highly DA activating
substituent such as the trimethylsilyloxy group. The simultaneous presence of this substituent and
the p-tolylsul®nyl group as a chiral auxiliary on a diene system should guarantee a high degree of
stereocontrol in DA cycloadditions, an easy removal of the chiral auxiliary from the DA pro-
ducts, and an easy functionalization of the derivatives thus obtained, due to the facile transfor-
mation of the trimethylsilyl enol ether into a carbonyl group. On this basis, we reasoned that (E)-
1-(p-tolylsul®nyl)-3-trimethylsilyloxybuta-1,3-diene 1 and (SS)-2-(p-tolylsul®nyl)-3-trimethylsilyl-
oxybuta-1,3-diene 2 (Scheme 1) could be synthetically useful reagents for asymmetric cycloaddi-
tions. The previously unknown diene 1 shows the same substituent localization characterized by
the Danishefsky diene,4 and the advantage of being a precursor of cycloadducts in which chiral
auxiliary removal should be easily accomplished. The enantiopure diene 2, prepared by us fol-
lowing a synthetic approach di€erent from that reported previously,1b has the sul®nyl group
linked to the C-2, thus ensuring, in principle, good reactivity towards common dienophiles.2f The
synthesis of both dienes 1 and 2 and their DA cycloadditions with cyclic dienophiles are reported
in this paper. We were particularly interested in evaluating the role that the 1,3- or 2,3-relation-
ships between the two substituents can play in the reactivity of these butadienes, and their
synthetic potentiality for the building of functionalized cyclohexenes.
Scheme 1.
2. Results and discussion
The synthesis of diene 1 was accomplished starting from commercially available methyl vinyl
ketone 3 (Scheme 1). The racemic b-sul®nyl a,b-unsaturated ketone 4 was prepared from 3 in
three steps, according to literature procedures.5 When the 7:3 (E:Z) mixture of sul®des 56 was
oxidized by m-chloroperbenzoic acid (MCPBA), the sulfoxide 4 obtained had an (E)-con®gura-
tion, in line with previous results.5b The enolate anion, generated by treating 4 with potassium
bis(trimethylsilyl)amide (KHMDS) in THF/toluene, was trapped by chlorotrimethylsilane7
a€ording racemic diene 1 which can be stored at 20ꢀC for several weeks, but rapidly decom-
poses to ketone 4 on standing at room temperature.
The ®rst asymmetric synthesis of diene 2, involving three steps from non-commercially avail-
able (RS)-p-tolyl vinyl sulfoxide, was published by Maignan et al. in 1992.1b The low overall yield

M. T. Aranda et al. / Tetrahedron: Asymmetry 11 (2000) 1217±1225
1219
of this approach (ꢁ30%) prompted us to exploit the alternative method shown in Scheme 1.
Condensation of commercial (RS)-methyl p-tolylsulfoxide 6 with ethyl acetate gave sul®nylketone
7 (88% yield) according to the procedure of Solladie and Ghiatou.8 Compound 7 was reacted
with formaldehyde and dimethylamine to give 8 as a mixture of epimers, which evolved into the
enantiopure ketosulfoxide 99 via Hofmann degradation. The combined yield for the transforma-
tion of 7!9 was 97%. Finally, sulfoxide 9 was subjected to Nakagawa's enolization7 without any
puri®cation, leading to enantiopure diene 2.
Dienes 1 and 2 were used in DA reactions without chromatographic puri®cation since both
easily undergo spontaneous decomposition. NMM 10 was chosen as a typically highly reactive
dienophile involving no regiochemistry problems.
Cycloaddition of (‹)-1 with NMM 10 required the use of high pressure (13 Kbar), a€ording a
complex mixture of products from which only two diastereoisomers (‹)-11a,b could be isolated
and their structures (Scheme 2) unequivocally assigned on the basis of their spectroscopic para-
meters. The formation of (‹)-11a,b may be the result of a three-step reaction sequence. The ®rst
one involves NMM addition to the less hindered face of diene 1 where the sul®nyl group adopts
the spatial arrangement which minimizes the electrostatic repulsive interactions between sul®nyl
and carbonyl oxygen atoms.2a The second step is the elimination of p-toluenesulfenic acid from
adduct (‹)-12 giving trimethylsilyloxydiene (‹)-13, which, in the last step, acts as a nucleophile
towards NMM 10. A 1:1 racemic mixture of epimers at C-30, (‹)-11a and (‹)-11b, was obtained.
Taking into account the behaviour of several 1-sul®nyl dienes previously involved in DA reactions
with NMM 102a and the present results [(‹)-11a and (‹)-11b di€er only in the con®guration of the
stereogenic centre formed during the last step of the reaction sequence] we suggest that the reaction
shown in Scheme 2 was accomplished with a very high stereoselectivity, even if the complexity of
the crude reaction mixture does not allow for certainty about complete stereoselectivity.2a
Scheme 2.
The more reactive 4-methyl-1,2,4-triazoline-3,5-dione 14 was then reacted with diene (‹)-1
(Scheme 3) and the reaction was accomplished at room temperature within 1 h. An inspection of
1
the crude reaction product showed the almost unique presence of sulfenate 15, by H NMR
analysis: apart from the typical resonances of the O±S±Tol and O±TMS groups, we could observe
H2-5 resonating as an AB system centred at ꢀ 3.96 (J5A,5B=15.0) and H-7,8 resonating as two

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M. T. Aranda et al. / Tetrahedron: Asymmetry 11 (2000) 1217±1225
Scheme 3.
broad doublets at ꢀ 4.90 and 6.42, respectively (J7,8=5.0). The intermediate 15 was obtained by
initial [2,3]-sigmatropic rearrangement of cycloadduct 16, subsequently spontaneously evolved to
the a,b-unsaturated ketone 17. This latter compound was isolated and characterized.
Cycloaddition of 2 with NMM 10 occurred only in dichloromethane under pressure (4.5 Kbar)
a€ording a 2:1 diastereomeric mixture of compounds 18 (Scheme 4), from which the major dia-
stereoisomer 18a was isolated in enantiomerically pure form by crystallization from hexane/ethyl
acetate. All the attempts to isolate 18b by chromatography were unsuccessful because of the
decomposition of the mixture which occurred during chromatography. Chemical shifts and
coupling constants from the 1H NMR spectrum of compound 18a are given in Table 1. The spin±
spin coupling constants of the bridgehead nuclei H-3a,7a suggest a preferred extended boat con-
formation of the fused bicyclic system (Fig. 1), as shown previously for racemic compounds of
similar structure.10 The chemical shifts of H2-7 appear in line with the conformational preference
around the C±S bond shown in Fig. 1, and already observed for 2-sul®nyl cyclohexanones, where
the equatorial HB-7 is clearly shielded by the anisotropic e€ect of the aromatic ring in 1,3-parallel
arrangement.11 On the basis of these data, for 18a we suggest the stereochemistry depicted in Fig. 1,
with all cis substituents, and assign the (3aS,6S,7aR,RS) absolute con®guration to its stereogenic
1
centres. Moreover, an accurate inspection of the H NMR absorptions of the 2:1 mixture of
18a:18b allowed us to identify 18b as the epimer of 18a at C-6:11 in particular, we were able
Scheme 4.

M. T. Aranda et al. / Tetrahedron: Asymmetry 11 (2000) 1217±1225
1221
Table 1
Selected H NMR parameters of compound 18a
1
Figure 1. Conformational preferences for compound 18a
unequivocally to identify H-6 of 18b resonating as a doublet of doublets at ꢀ 3.52 (J6,7=10.2 and
6.1), together with further signi®cant resonances. All of these results cogently support a cycload-
dition between 2 and 10 (Scheme 4) occurring in a completely stereoselective manner, followed by
a less diastereoselective Si±O bond cleavage.
In this paper we have reported the synthesis of the previously unknown diene (‹)-1 and ®rst
studies of its DA reactivity in comparison with that of diene 2. The presence of the 3-OTMS
substituent on the diene skeleton does not modify the DA reactivity or stereoselectivity of 1-
sul®nyldienes, in line with previously reported results,2a but strongly decreases the reactivity of 2-
sul®nyldienes.2b,f We suggest that the lower reactivity of 2 is a result of its diculty in adopting
the s-cis conformation required by DA transition states, because of the proximity of the highly
sterically demanding p-tolylsul®nyl and trimethylsilyloxy substituents on the diene moiety. Gen-
erally, dienes 1 and 2 are dicult to handle. The severe reaction conditions required by DA
cycloadditions of dienes 1 and 2 with NMM 10 caused further evolution of the initial adducts
towards mixtures of diastereoisomers, thereby limiting their use in asymmetric synthesis.
3. Experimental
3.1. General methods and materials
Solvents were puri®ed according to standard procedures. All reactions were monitored by TLC
on commercially available precoated plates (Merck silica gel 60 F254), and the products were
visualized with a UV light, phosphomolybdic acid and 2,4-dinitrophenylhydrazine. Merck silica gel
(230±400 mesh ASTM) was used for column chromatography. Preparative TLC separations were
performed on Merck neutral alumina plates. Mps were measured on a microscopic apparatus and
are uncorrected. Elemental analyses were performed by the Servicio Interdepartamental de

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M. T. Aranda et al. / Tetrahedron: Asymmetry 11 (2000) 1217±1225
Investigacion (SIdI) de la Universidad Autonoma de Madrid with a Perkin±Elmer 2400 CHNS/
O. Speci®c rotations [ꢁ]D were measured in CHCl3 solutions at room temperature and are given
1
in 10 1 deg cm2 g ; concentrations (c) are expressed in g/100 ml. 1H and 13C NMR spectra were
recorded on a Bruker AC-200 spectrometer at 200.1 and 50.3 MHz, respectively, in CDCl3 solutions
with SiMe4 as the internal standard; J values are given in hertz; the attributions are supported by
double resonance experiments. IR spectra were obtained in CHCl3 solutions with a Philips PU-9716
instrument. Mass spectra were measured by electron impact (EI, 70 eV) with a VG AutoSpec
instrument. Cycloadditions under pressure were realized using a UNIPRESSEQUIPMENT 101 LV
30/16.
3.2. 4-(p-Tolylthio)-2-butanone 1912
Et3N (311 ml, 2.2 mmol) was added dropwise at 15ꢀC to a stirred solution of methyl vinyl
ketone 3 (15.65 g, 223 mmol) and p-thiocresol (40 ml, 334 mmol) in CHCl3 (40 ml). After stirring
for 12 h at room temperature, the mixture was diluted with Et2O and washed with 5% aqueous
K2CO3 and half-saturated brine. The organic layers were dried (Na2SO4) and the solvent was
evaporated under vacuum. The crude mixture was puri®ed by column chromatography eluting
with hexane:EtOAc (91:9) to give 4-(p-tolylthio)-2-butanone 19: oil; 90% yield; 1H NMR ꢀH 7.3±
7.1 (AA0BB0 system, ArH), 3.10 (t, J3,4=7.5, H2-4), 2.74 (t, H2-3), 2.34 (s, MeAr), 2.14 (s, H3-1);
13C NMR ꢀC 206.4, 136.3, 131.7, 130.2, 129.6, 42.9, 29.8, 27.9, 20.8; IR ꢂmax 2810, 1710, 1490,
1
1360, 1170 cm ; EIMS m/z (%) 194 (M, 100), 151 (17), 137 (19), 124 (52), 91 (33).
3.3. (E)-4-(p-Tolylthio)-3-buten-2-one 5a6
NCS (14.11 g, 106 mmol) was slowly added to a solution of 4-(p-tolylthio)-2-butanone 19
(17.11 g, 88 mmol) in CCl4 (150 ml) at 0ꢀC. The mixture was allowed to spontaneously reach
room temperature, stirred for 2 h and ®ltered. The solvent was removed under vacuum and the
resulting oily residue was dissolved in CHCl3 (150 ml) and treated with Et3N (1.2 ml). The solu-
tion was then heated at re¯ux and after 45 min cooled to room temperature. The reaction mixture
was washed with 10N HCl and a half-saturated brine solution. The organic layers were dried
(Na2SO4) and concentrated under vacuum. The oily residue was puri®ed by column chromat-
ography beginning the elution with hexane:acetone (96:4) and gradually increasing the acetone
percentage up to 100%. 4-(p-Tolylthio)-3-buten-2-one 5 was obtained (64% yield) as a 67:33
mixture of (E)- and (Z)-isomers, respectively, and this mixture was used for preparing racemic
sulfoxide 4 (see below). However, crystallization of the mixture 5 from hexane/Et2O gave (E)-4-
(p-tolylthio)-3-buten-2-one 5a: mp 59±60ꢀC (found: C, 68.32; H, 6.18; S, 16.76. C11H12OS
requires: C, 68.71; H, 6.29; S, 16.67%); H NMR ꢀH 7.67 (d, J3,4=15.2, H-4), 7.4±7.2 (AA0BB0
1
system, ArH), 5.92 (d, H-3), 2.38 (s, MeAr), 2.19 (s, H3-1); ꢀC 194.5, 147.2, 139.3, 132.9, 130.3, 129.4,
1
124.2, 27.0, 20.9; IR ꢂmax 2910, 1650, 1540, 1220, 950, 760 cm . (Z)-4-(p-tolylthio)-3-buten-2-one
5b: ꢀH 7.67 (d, J3,4=9.6, H-4), 7.4±7.2 (AA0BB0 system, Jortho=8.3, ArH), 6.35 (d, H-3), 2.36 (s,
MeAr), 2.27 (s, H3-1); 13C NMR ꢀC 196.1, 149.4, 137.9, 130.5, 130.1, 126.0, 119.7, 26.7, 20.8.
3.4. (‹)-(E)-4-(p-Tolylsul®nyl)-3-buten-2-one 4
MCPBA (4.5 g, 26 mmol) was dissolved in CH2Cl2 (100 ml) and slowly added to a stirred
solution of 4-(p-tolylthio)-3-buten-2-one 5 (5 g, 26 mmol) in CH2Cl2 (300 ml) at 0ꢀC. The reaction

M. T. Aranda et al. / Tetrahedron: Asymmetry 11 (2000) 1217±1225
1223
mixture was stirred for 30 min, diluted with Et2O and washed with a saturated solution of
NaHCO3 and with a half-saturated brine solution. The organic phase was dried (Na2SO4), the
solvent evaporated under vacuum and the crude mixture was puri®ed by column chromatography
eluting with hexane:EtOAc (96:4). Crystallization from hexane/Et2O gave (‹)-(E)-4-(p-tolyl-
sul®nyl)-3-buten-2-one 4: mp 78±80ꢀC (found: C, 63.35; H, 5.73; S, 15.43. C11H12O2S requires: C,
63.44; H, 5.81; S, 15.39%); 63% yield; H NMR ꢀH 7.5±7.3 (AA0BB0 system, ArH), 7.32 (d,
1
J3,4=15.1, H-4), 6.97 (d, H-3), 2.42 (s, MeAr), 2.34 (s, H3-1); 13C NMR ꢀC 195.0, 149.4, 142.6,
1
138.0, 130.4, 130.0, 124.9, 26.2, 21.4; IR ꢂmax 2910, 1680, 1580, 1210, 1050, 960, 750 cm .
3.5. (‹)-1-(p-Tolylsul®nyl)-3-trimethylsilyloxybuta-1,3-diene 1
A 0.5 M solution of KHMDS in toluene (10.44 ml, 5.2 mmol) was added dropwise to (‹)-(E)-
4-(p-tolylsul®nyl)-3-buten-2-one 4 (0.730 g, 3.5 mmol) in toluene/THF at 78ꢀC under stirring.
TMSCl (662 ml, 5.2 mmol) and H2O (15 ml) were consecutively added at short intervals of 10 min
each. The crude product was extracted with hexane (3Â20 ml) and the combined organic layers
were dried (Na2SO4). After evaporation of the solvent, (‹)-1-(p-tolylsul®nyl)-3-trimethylsilyl-
oxybuta-1,3-diene 1 was obtained and used without further puri®cation: oil; 60% yield; 1H NMR
ꢀH 7.6±7.3 (AA0BB0 system, ArH) 6.86 and 6.55 (AB system, J1,2=14.5, H-1,2), 4.67 and 4.60
(two broad s, H2-4), 2.44 (s, MeAr), 0.16 (s, Me3Si).
3.6. (RS)-4-(N,N-Dimethylamino)-3-(p-tolylsul®nyl)-2-butanone 8
A 40% solution of Me2NH in H2O (0.192 ml) and a 37% aqueous solution of HCHO (0.114
ml) were added to (RS)-1-(p-tolylsul®nyl)-2-propanone 78,13 (0.01 g, 0.51 mmol) in MeCN (2.5
ml) at 0ꢀC. After stirring (10 min), the solution was diluted with H2O (10 ml) and extracted with
CH2Cl2 (3Â10 ml). The organic layers were dried (Na2SO4) and the solvent evaporated under
vacuum to give an epimeric mixture of (RS)-4-(N,N-dimethylamino)-3-(p-tolylsul®nyl)-2-but-
1
anone 8 which was used for the next steps without further puri®cation: oil; H NMR ꢀH 7.5±7.3
(two AA0BB0 systems, ArH), 3.99 (m, H-3 of one epimer), 3.62 (m, H-3 of the other epimer), 2.94
(m, H2-4 of one epimer), 2.78 (m, H2-4 of the other epimer), 2.41 (s, MeAr), 2.25 and 2.22 (two s,
NMe2), 2.10 (s, H3-1 of one epimer), 2.09 (s, H3-1 of the other epimer).
3.7. (SS)-3-(p-Tolylsul®nyl)-3-buten-2-one 99
(RS)-4-(N,N-Dimethylamino)-3-(p-tolylsul®nyl)-2-butanone 8 (0.129 g, 0.51 mmol) in MeCN
(2.5 ml) and MeI (0.16 ml, 2.5 mmol) were consecutively added to CaCO3 (0.153 g, 1.53 mmol) at
0ꢀC. The suspension was stirred for 1.5 h and then H2O (20 ml) was added. The aqueous solution
was extracted with CH2Cl2 (3Â30 ml) and the organic layers were dried (Na2SO4). After
evaporation of the solvent, (SS)-3-(p-tolylsul®nyl)-3-buten-2-one 9 was obtained, not needing
puri®cation: oil; 97% yield from sulfoxide 7; [ꢁ]D +355 (c 1.0) {lit.9 [ꢁ]D +294 (c 0.72 in acetone)}.
Spectral data are in accordance with the literature.9
3.8. (SS)-2-(p-Tolylsul®nyl)-3-trimethylsilyloxybuta-1,3-diene 21b
Anhydrous TMSCl (92 ml, 0.73 mmol) was added to a solution of (SS)-3-(p-tolylsul®nyl)-3-
buten-2-one 9 (0.10 g, 0.5 mmol) in toluene/THF (1.76/1.60 ml) at 78ꢀC under argon. After 5

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M. T. Aranda et al. / Tetrahedron: Asymmetry 11 (2000) 1217±1225
min of stirring, a 0.5 M solution of KHMDS in toluene (1.44 ml) was added to the mixture which
was maintained under stirring for a further 30 min. The work-up of the reaction was carried out
by adding H2O (10 ml) and extracting the aqueous phase with hexane (3Â20 ml). The organic
layers were combined and dried (Na2SO4) to obtain (SS)-2-(p-tolylsul®nyl)-3-trimethylsilyl-
oxybuta-1,3-diene 2 which was used without further puri®cation: oil; 80% yield (estimated on the
basis of spectral data in accordance with the literature).1b
3.9. 2,3,3a,4,5,7a-Hexahydro-2-methyl-7a-(1-methylsuccinimide-3-yl)-1H-isoindole-1,3,5-triones 11
A solution of NMM 10 (0.133 g, 1.2 mmol) in anhydrous CH2Cl2 (1 ml) was added to racemic
1-(p-tolylsul®nyl)-3-trimethylsilyloxybuta-1,3-diene 1 (0.112 g, 0.4 mmol) dissolved in anhydrous
CH2Cl2 (1 ml) and the reaction was performed in a polyethylene vial under pressure (13 Kbar for
64 h). After evaporation of the solvent, the crude reaction mixture was puri®ed by column
chromatography and preparative TLC eluting with hexane:acetone 80:20 to give, in low yields,
about equal amounts of the two racemic mixtures 11a and 11b, mutually epimers at C-30 [the
symbol (0) identi®es atoms pertaining to the succinimide substituent]. (‹)-11a: oil; H NMR ꢀH
1
0
6.71 (dd, J6,7=10.5, J4A,7=1.1, H-7), 6.27 (d, H-6), 3.72 (dd, J3 ,4 A=9.5, J3 ,4 B=6.0, H-3'), 3.24
0
0
0
(br AB d, J4A,4B=18.8, HA-4), 3.13 (br d, J3a,4B=9.3, H-3a), 3.07 and 3.02 (two s, 2ÂMe), 2.97
(AB dd, J4 A,4 B=18.3, HA-40), 2.71 (AB dd, HB-4), 2.66 (AB dd, HB-40); EIMS m/z (%) 290 (M,
5), 233 (15), 205 (77), 178 (96), 120 (52), 113 (94), 92 (100), 65 (37); HRMS calcd for C14H14N2O5:
0
0
1
290.0903; found: 290.0909. (‹)-11b: oil; H NMR ꢀH 6.70 (dd, J6,7=10.9, J4A,7=1.6, H-7), 6.27
0
0
0
(d, H-6), 3.93 (br d, J3a,4B=8.1, H-3a), 3.33 (dd, J3 ,4 =9.1 and 5.9, H-3 ), 3.22 (br AB d,
J4A,4B=18.0, HA-4), 3.02 and 3.00 (two s, 2ÂMe), 3.01 (m, H2-40), 2.58 (AB dd, HB-4); EIMS m/z
(%) 290 (M, 2), 205 (21), 178 (61), 120 (23), 113 (100), 92 (47), 91 (48), 65 (26), 57 (42), 55 (30).
3.10. 2-Methyl-2,3,5,6-tetrahydro-1H-[1,2,4]triazolo[1,2-a]pyridazine-1,3,6-trione 17
A solution of 4-methyl-1,2,4-triazoline-3,5-dione 14 (0.051 g, 0.45 mmol) in CH2Cl2 (5 ml) was
slowly added to racemic 1-(p-tolylsul®nyl)-3-trimethylsilyloxybuta-1,3-diene 1 (0.126 g, 0.45
mmol) dissolved in anhydrous CH2Cl2 (5 ml), under argon. After stirring (1 h) the solvent was
evaporated under vacuum and the reaction mixture puri®ed by preparative TLC eluting with
hexane:acetone 75:25 to give the bicyclic compound 17: 33% yield; 1H NMR ꢀH 7.75 (d, J7,8=8.3,
H-8), 5.59 (d, H-7), 4.37 (s, H2-5), 3.18 (s, Me); 13C NMR ꢀC 184.5, 150.8, 146.5, 132.9, 105.0,
1
50.6, 25.6; IR ꢂmax 2910, 1790, 1730, 1600, 1470, 1310, 1270, 760 cm ; EIMS m/z (%) 181 (M,
37), 126 (10), 96 (100), 68 (7), 56 (21).
3.11. (3aS,6S,7aR,RS)-2-Methyl-6-(p-tolylsul®nyl)perhydroisoindole-1,3,5-trione 18a
A solution of NMM 10 (0.143 g, 1.29 mmol) in anhydrous CH2Cl2 (1 ml) was added to (SS)-2-
(p-tolylsul®nyl)-3-trimethylsilyloxy-1,3-butadiene 2 (0.120 g, 0.43 mmol) dissolved in anhydrous
CH2Cl2 (1 ml), and the reaction was performed in a polyethylene vial under pressure (4.5 Kbar
for 5 days). After evaporation of the solvent, the reaction mixture was puri®ed by column
chromatography eluting with CH2Cl2:EtOAc 90:10. 2-Methyl-6-(p-tolylsul®nyl)perhydroisoindole-
1,3,5-trione 18 was obtained as a 1:2 diastereoisomeric mixture which was crystallized from
hexane:EtOAc to give (3aS,6S,7aR,RS)-2-methyl-6-(p-tolylsul®nyl)perhydroisoindole-1,3,5-trione
18a: mp 150±151ꢀC; [ꢁ]D +538 (c 0.9); H NMR ꢀH 7.4±7.3 (AA0BB0 system, ArH), 3.21 (dd,
1

M. T. Aranda et al. / Tetrahedron: Asymmetry 11 (2000) 1217±1225
1225
J6,7A=12.5, J6,7B=5.6, H-6), 3.14 (ddd, J3a,4A=7.0, J3a,4B=11.8, J3a,7a=8.8, H-3a), 3.03 (s,
NMe), 3.01 (dd, J4A,4B=14.0, HA-4), 2.89 (ddd, J7a,7A=12.5, J7a,7B=5.6, H-7a), 2.59 (dd, HB-4),
2.44 (s, MeAr), 2.42 (dt, J7A,7B=14.2, HA-7), 1.95 (dt, HB-7); 13C NMR ꢀC 203.0, 177.1, 176.7,
142.3, 136.9, 130.2, 123.9, 68.8, 38.9, 37.6, 36.7, 25.1, 21.4, 18.5; EIMS m/z (%) 319 (M, 4), 303
(9), 179 (30), 139 (49), 124 (49), 91 (89), 66 (100).
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