Enantiopure arenesulfenic acids as intermediates in stereoselective synthesis

Article abstract of DOI:10.1016/j.tet.2005.09.052

New transient arenesulfenic acids were involved in the synthesis of enantiopure 2-arylsulfinyl-1,3-dienes, showing central or axial chirality of the substituted arene residue, apart from the chirality related to the stereogenic sulfur atom. Some of the obtained dienes, that is, (S_a,S _S)- and (S_aR_S)-2-(2′-hydroxy-1,1′- binaphthalen-2-sulfinyl)-3-methyl-1,3-butadienes, were subjected to diastereoselective Diels-Alder cycloadditions with N-methylmaleimide. Removal of the arylsulfoxide auxiliary, in the major adduct, was accomplished by reductive cleavage with Raney nickel.

Full text of DOI:10.1016/j.tet.2005.09.052

Tetrahedron 61 (2005) 11902–11909
Enantiopure arenesulfenic acids as intermediates in
stereoselective synthesis
b
c
Maria C. Aversa,a Paola Bonaccorsi,a, Cristina Faggi, Giuseppe Lamanna
*
and Stefano Menichettic,
*
a
`
Dipartimento di Chimica organica e biologica, Universita degli Studi di Messina, Salita Sperone 31 (vill. S. Agata), 98166 Messina, Italy
b
`
Centro interdipartimentale di Cristallografia, Universita degli Studi di Firenze, via della Lastruccia 13, 50019 Sesto Fiorentino,
Firenze, Italy
`
Dipartimento di Chimica organica ‘Ugo Schiff’, Universita degli Studi di Firenze, via della Lastruccia 13, 50019 Sesto Fiorentino,
c
Firenze, Italy
Received 15 July 2005; revised 7 September 2005; accepted 15 September 2005
Available online 4 October 2005
Abstract—New transient arenesulfenic acids were involved in the synthesis of enantiopure 2-arylsulfinyl-1,3-dienes, showing central or
axial chirality of the substituted arene residue, apart from the chirality related to the stereogenic sulfur atom. Some of the obtained dienes,
that is, (Sa,SS)- and (SaRS)-2-(20-hydroxy-1,10-binaphthalen-2-sulfinyl)-3-methyl-1,3-butadienes, were subjected to diastereoselective Diels–
Alder cycloadditions with N-methylmaleimide. Removal of the arylsulfoxide auxiliary, in the major adduct, was accomplished by reductive
cleavage with Raney nickel.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
It has been widely demonstrated that chemo and regio-
selective syn-addition of a sulfenic acid to conjugated
enynes represents a convenient synthetic strategy for the
preparation of diene sulfoxides, significant partners in
Diels–Alder (DA) cycloadditions, with the sulfinyl group
acting as chiral auxiliary.1 The syn-addition is a thermal six-
electron process whose intrinsic nature does not imply any
acid or basic conditions, so ensuring formation of the
sulfoxide moiety even in the presence of pH sensitive
functional groups. Good to high yields are generally
observed. Sulfenic acids, that are generated in situ from
opportune precursors, can be obtained in enantiomerically
pure form, providing access to enantiopure sulfinyl dienes.
Camphorsulfonic and mandelic acids, readily available
members of the chiral pool, were choosen as starting
compounds in the preparation of precursors of enantiopure
sulfenic acids 1–3 for the contiguity of a hydroxy function to
the sulfur atom (Fig. 1). This contiguity guarantees an
intramolecular hydrogen bond, between the hydroxy group
Keywords: Arenesulfenic acids; Diastereofacial selectivity; Diels–Alder
cycloadditions; N-methylmaleimide; Sulfinyl dienes.
*
Corresponding authors. Tel.: C39 090 6765187; fax: C39 090 393895
(P.B.); tel.: C39 055 4573535; fax: C39 055 4573531 (S.M.);
e-mail addresses: paolab@isengard.unime.it; stefano.menichetti@unifi.it
Figure 1. Transient enantiopure sulfenic acids.
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.09.052

M. C. Aversa et al. / Tetrahedron 61 (2005) 11902–11909
11903
and the oxygen atom of the sulfoxide moiety, that facilitates
the chromatographic separation of diastereoisomers and in
some cases enhances stereoselection in concerted
processes.2 The high steric demands of the camphor
skeleton are maintained in the commercially available
[(1S)-endo]-(K)-borneol that was easily transformed into a
precursor of the enantiopure sulfenic acid 6, showing no
possibilities of intramolecular hydrogen bonding.2d–g
Indeed, an intramolecular hydrogen bonding, also useful
in preventing self-condensation of sulfenic acids, can
present some disadvantages due to unexpected and
undesired reactions of the hydroxy function in the
subsequent synthetic transformations of the sulfoxides
obtained from sulfenic acids such as 1–3.2f,3 L-cysteine
and a- and b-D-1-thioglycopyranose are stimulating starting
products for the generation of transient sulfenic acids 4, 5, 7,
8 that allowed the synthesis of enantiopure sulfinyl dienes
showing the L-cysteine or 1-thio-D-glycopyranose S-oxide
frameworks as chiral auxiliaries where the stereo-
differentiating moiety is also a biologically active residue.4
Almost all the sulfinyl dienes, including the chiral above-
mentioned S-alkyl residues, have been involved in DA
reactions that afforded the expected cycloadducts, easily
obtainable in enantiomerically pure forms and good yields.
However, removal from these adducts of the sulfoxide
function, directly linked to an alkyl group on one side, and
to an unsaturated carbon on the other, represented a big
challenge. Desulfurization by nickel reagents or sodium
amalgam failed on several occasions and indirect method-
ologies were exploited for reaching this goal.2d,5
In this paper we describe the synthesis of new sulfinyl
dienes in which an enantiopure aryl group is directly linked
to the sulfur atom. These S-arylsulfinyl dienes have been
obtained via the corresponding sulfenic acids, possessing
central or axial chirality, and their addition to opportune
enynes. Some of the obtained dienes have been subjected to
DA cycloaddition with N-methylmaleimide (NMM),
followed by removal of the arylsulfoxide auxiliary that
was accomplished by Raney nickel desulfurization, making
straightforward and efficient the overall synthetic process
towards functionalized enantiopure cyclic molecules.
Scheme 1. Reagents and conditions: (a) MenCl, K2CO3, 50 8C, 46 h;
(b) PhtNSCl, CHCl3, 0 8C, 20 min; (c) LAH, THF, rt, 1 h; (d) CH2]
CHCN, Et3N, THF, rt, 20 h; (e) m-CPBA, CH2Cl2, 0 8C, 20 min (1:1
S-epimers); (f) 1-ethynylcyclohexene, 130 8C, 1 h (1:1 S-epimers).
The commercially available (K)-chloromethyl menthyl
ether (MenCl) was used to link a chiral auxiliary to one
hydroxy function in 9, since the Men residue has the
advantage of possessing no reactive groups that could
interfere during the whole synthetic pathway. The reaction
between resorcinol (9) and MenCl was performed in the
presence of potassium carbonate, in a molar ratio of 5:1:3,
respectively (Scheme 1).
2. Results and discussion
Enantiopure phenol 10 was then subjected to completely
regioselective sulfenylation with PhtNSCl, at 0 8C to avoid
ether cleavage, and compound 11 was obtained as the
unique product. LAH reduction, conjugate addition onto
acrylonitrile, and m-CPBA oxidation led to epimeric
sulfoxides 13, that are precursors of the enantiopure
arenesulfenic acid 14. Thermolysis of nitrile mixture 13
was performed in neat 1-ethynylcyclohexene, at 130 8C for
1 h. The completely chemo- and regioselective addition of
sulfenic acid 14 to the triple bond of ethynylcyclohexene
gave the epimeric mixture of sulfinyl dienes 15 in 1:1 ratio.
These two epimeric sulfoxides appeared as a single spot by
TLC, although several different solvent systems were
evaluated. Column chromatography of the mixture 15
allowed the isolation of only small quantities of each of
the two enantiopure epimers 15 that were fully
Two main reasons gave rise to the selection of resorcinol (9)
as starting material for the preparation of enantiopure dienes
15 via sulfenic acid 14 showing central chirality (Scheme 1):
(i) an electron-rich aromatic ring was necessary for the
chosen synthetic sequence [sulfenylation with phtalimide-
sulfenyl chloride (PhtNSCl)6 of 10 followed by LAH
reduction] that allowed the introduction of a thiol function
onto the benzene nucleus; (ii) only one of the two hydroxy
functions in 9 could be easily derivatized, with a
commercial enantiopure reagent, for the generation of the
enantiopure arenesulfenic acid 14, where the remaining free
hydroxy substituent, opportunely placed onto the aromatic
ring, would provide an intramolecular hydrogen bonding
with the oxygen atom in the sulfenic function, so mitigating
the heavy disposition of sulfenic acids to self-condensation.

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M. C. Aversa et al. / Tetrahedron 61 (2005) 11902–11909
characterized. However, this difficulty in isolation prompted
us to drop the project of involving enantiopure dienes 15 in
DA cycloadditions. The very difficult separation of sulfinyl
dienes 15 appears as a consequence of their similar
chromatographic features, due to the distance between the
stereodifferentiating menthyl substituent and the sulfinyl
group.
the use of temperatures between 40 and 140 8C, in
dependence of the structure of the sulfoxide precursor.8
Nucleophilic addition of thiol 16 onto acrylonitrile in the
presence of triethylamine, followed by m-CPBA oxidation,
led to sulfoxides 18 (1:1 S-epimers). Thermolysis of 18 to
19 was performed in the presence of commercially available
2-methyl-1-buten-3-yne, at 110 8C for 1.5 h, and gave
sulfinyl dienes 20 and 21 in 1:1 ratio and 75% total yield.
The epimeric mixture of the two sulfinyl dienes 20 and 21
was subjected to column chromatography, and they were
easily separated and fully characterized. The configuration
at sulfur atom of sulfoxides 20 and 21, shown in Scheme 2,
was inferred from X-ray crystallographic analysis of
cycloadduct 25 (Fig. 2). The obtained results confirmed
expectations based on the intramolecular hydrogen bonding,
between the hydroxy function of the binaphtyl residue and
the sulfoxide oxygen, and its relationship with the difference
in chromatographic mobility2c observed between the two
epimeric sulfinyl dienes 20 and 21.
Our attention then turned to S-arylsulfinyl dienes whose aryl
substituent could possess an intrinsic chirality. Enantiopure
dienes 20 and 21 in Scheme 2 show not only the central
chirality due to the stereogenic sulfur atom but also the axial
chirality coming from the atropoisomeric binaphthyl moiety
linked to the sulfoxide group. The synthesis of 20 and 21
was performed starting from enantiopure (Sa)-20-mercapto-
1,10-binaphthalen-2-ol (16), easily prepared from com-
mercial (Sa)-(K)-1,10-bi-2-naphthol.7 Thiol 16 can be
warmed up to 250 8C without racemization, thus allowing
the safe generation of sulfenic acid 19 in enantiomerically
pure form by the well-assessed thermal strategy that implies
Figure 2. Perspective view of the structure of 25 crystallized with a
molecule of ethyl acetate in the asymmetric unit.
Actually (Sa,RS)-2-(20-hydroxy-1,10-binaphthalen-2-sul-
finyl)-3-methyl-1,3-butadiene (21) was reacted with NMM
in dichloromethane to give the two diastereoisomeric
cycloadducts 24 and 25 in 3:2 ratio and 69% total yield
(Scheme 2). Column chromatography furnished the major
adduct 24 as first eluted product, followed by minor adduct
25. The two cycloadducts 24 and 25 were separately
subjected to several recrystallizations, but only minor
cycloadduct 25 afforded crystals suitable for X-ray analysis
from ethyl acetate (Fig. 2). Results of crystallographic
analysis allowed assignment of configurations at the newly
formed stereocentres C-3a and C-7a of cycloadducts 24
(Sa,RS,3aR,7aS) and 25 (Sa,RS,3aS,7aR). The stereochemical
outcome of the cycloaddition between enantiopure diene 21
and NMM can be rationalized as follows. Low diastereo-
facial selectivity was observed, in favour of cycloadduct 24,
which came from NMM approaching the (Si) face of diene
21 preferentially adopting the A conformation in the DA
transition state (Fig. 3).9 The appreciable formation of the
minor adduct 25 by NMM approach to the (Re) face of diene
Scheme 2. Reagents and conditions: (a) CH2]CHCN, Et3N, THF, rt, 72 h;
(b) m-CPBA, CH2Cl2, K50 8C, 1 h (1:1 S-epimers); (c) 2-methyl-1-buten-
3-yne, 110 8C, 1.5 h (20/21 1:1); (d) N-methylmaleimide, CH2Cl2, 40 8C
(22/23 2:1, 24/25 3:2).

M. C. Aversa et al. / Tetrahedron 61 (2005) 11902–11909
11905
3. Conclusions
In this paper, we have reported an useful development of the
well-assessed methodology to build up diene skeletons,
bearing a chiral sulfinyl substituent.1–5 New transient
arenesulfenic acids were involved in the synthesis of
enantiopure 2-arylsulfinyl-1,3-dienes, showing central or
axial chirality of the substituted arene residue, apart from
the chirality related to the stereogenic sulfur atom. Some of
the obtained dienes show a binaphthyl moiety linked to the
sulfoxide group and were easily prepared from (Sa)-20-
mercapto-1,10-binaphthalen-2-ol (16). Both enantiopure
(Sa)-2-(20-hydroxy-1,10-binaphthalen-2-sulfinyl)-3-methyl-
1,3-butadienes 20 and 21 were subjected to DA reaction
with NMM, and the diastereomeric mixtures of cyclo-
adducts were easily separated by column chromatography.
The binaphthyl residue conferred crystallinity to all the
obtained cycloadducts. Although low diastereofacial
selectivity was recorded in DA reactions of dienes 20 and
21, the preferred face of dienophile approach is the one,
which was expected on the basis of previously reported
considerations concerning the stereochemical outcome of
sulfinyl diene cycloadditions.9 The actual work gives new
support to our previous statement that the sulfur configur-
ation is not the only controller of the diastereofacial
selectivity, but further structural features of diene, dieno-
phile, and non-diene group linked to the sulfoxide sulfur
contribute significantly to the process of facial discrimi-
nation. Finally, removal of the arylsulfoxide auxiliary from
adduct 24 was easily accomplished by Raney nickel
desulfurization method.
Figure 3. Conformational preferences in Diels–Alder transition states of
diene 21.
21 in its B conformation, where sulfur oxygen is maintained
transoid to C-1/C-2 double bond, is a consequence of the
steric features of both the binaphthyl group linked to
the sulfoxide sulfur and the 3-methyl substituent on the
2-sulfinyl-1,3-diene skeleton. These two factors, together
with the steric requirement of the dienophile, reduce the
topological differentiation between the diene faces, induced
by the sulfinyl group.10
DA cycloaddition of (Sa,SS)-2-(20-hydroxy-1,10-bina-
phthalen-2-sulfinyl)-3-methyl-1,3-butadiene (20) with
NMM led to cycloadducts 22 (chromatographically more
mobile) and 23 in 2:1 ratio, respectively, and 87% overall
yield (Scheme 2). This diastereoselection amount is in line
with the one measured in the DA cycloaddition of diene 21
(see above). The configuration at C-3a and C-7a shown in
Scheme 2 for adducts 22 and 23 is determined by the sulfur
configuration in 20, so that the diene 20 (SS)/NMM
approaches are opposite to the ones observed in the DA
reaction of diene 21 (RS).
Desulfurization of the major adduct 24 was realized in 5 h
by commercial W-2 Raney nickel (Scheme 3). (3aS,7aR)-
3a,4,7,7a-tetrahydro-2,5-dimethyl-1H-isoindole-1,3(2H)-
dione (26) and (3aS,7aR)-hexahydro-2,5-dimethyl-1H-iso-
indole-1,3(2H)-diones 27 (6:1 epimeric mixture) were
obtained in 55% overall yield, separated by column
chromatography, and identified by comparison with
literature data.11 Despite the formation of 27, together
with the enantiopure compound 26, was unsatisfactory but
predictable in the reductive cleavage of aryl(ethenyl)sulf-
oxide 24, the use of a S-aryl substituted chiral auxiliary
ensured an easy desulfurization process.
4. Experimental
4.1. General
All reactions were monitored by TLC on commercially
available precoated plates (silica gel 60 F 254) and the
products were visualized with iodine or acid vanillin
solution. Silica gel 60, 230–400 mesh, was used for
column chromatography. Petrol refers to light petroleum,
bp 30–40 8C. Melting points were measured on a
microscopic apparatus and are uncorrected. Optical
rotations were measured in CHCl3 solutions unless
1
otherwise stated. H and 13C NMR spectra were recorded
at 300 and 75 MHz, respectively, in CDCl3 solutions (unless
otherwise stated) with TMS as internal standard. IR spectra
were recorded in nujol. Mass spectrum was measured by
FAB (m-nitrobenzyl alcohol as matrix).
X-ray crystallography. The analysis was carried out with a
Goniometer Oxford Diffraction KM4 Xcalibur2 at room
temperature. Graphite-monochromated Mo Ka radiation
(40 mA/K40 KV) and a KM4 CCD/SAPPHIRE detector
were used for cell parameter determination and data
collection. The integrated intensities, measured using the
u scan mode, were corrected for Lorentz and polarization
effects.12 The substantial redundancy in data allows
empirical absorption corrections (SADABS13) to be applied
using multiple measurements of symmetry-equivalent
reflections. Structure was solved by direct methods of
Scheme 3. Reagents and conditions: (a) Raney nickel, THF, rt, 5 h (26/27
2:1).

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M. C. Aversa et al. / Tetrahedron 61 (2005) 11902–11909
SIR9714 and refined using the full-matrix least squares on F2
(40 mL) was added, at 0 8C under Ar, to a suspension of
LAH (0.90 g, 23.72 mmol) in anhydrous THF (25 mL).
After 1 h of stirring at room temperature, the mixture was
quenched with HCl 1 N (50 mL) and ice. The resulting
suspension was extracted with Et2O (3!100 mL) and
the organic phase dried over Na2SO4. Evaporation of
the solvent under reduced pressure gave the crude
5-[(1R,2S,5R)-menthoxymethoxy]-2-mercapto-phenol
(1.49 g) that was used in the next step without purification;
1H NMR d 7.35 (d, JZ8.7 Hz, 1H), 6.67 (d, JZ2.7 Hz, 1H),
6.54 (dd, JZ8.7, 2.7 Hz, 1H), 6.39 (s, 1H), 5.29 (d, JZ
7.2 Hz, 1H), 5.19 (d, JZ7.2 Hz, 1H), 3.46 (dt, JZ10.5,
4.2 Hz, 1H), 2.82 (s, 1H), 2.1–2.0 (m, 1H), 1.7–1.6 (m, 2H),
1.4–1.2 (m, 2H), 1.0–0.7 (m, 4H), 0.90 (d, JZ6.6 Hz, 3H),
0.84 (d, JZ7.2 Hz, 3H), 0.62 (d, JZ7.2 Hz, 3H). The
solution of the crude 5-[(1R,2S,5R)-menthoxymethoxy]-2-
mercapto-phenol (1.49 g, 4.8 mmol about) in anhydrous
THF (40 mL), was added under Ar to a solution of
acrylonitrile (3.16 mL, 48.00 mmol) and Et3N (0.64 mL,
4.59 mmol) in anhydrous THF (15 mL). The mixture was
stirred at room temperature for 20 h, then quenched with
saturated NH4Cl solution (40 mL) and extracted with Et2O
(2!40 mL). The organic phase was washed with H2O (2!
100 mL) and dried over Na2SO4. After removal of the
solvent under reduced pressure, the crude product was
purified by column chromatography (petrol/EtOAc 3:1) to
nitrile 12 as an orange solid (0.95 g, 2.61 mmol, 66% from
provided by SHELXL97.15
Crystallographic data (excluding structure factors) for the
structure in this paper have been deposited with the
Cambridge Crystallographic Data Center as supplementary
publication number CCDC 278055. Copies of the data can
be obtained, free of charge, on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK [fax: C44 1223
336033 or e-mail: deposit@ccdc.cam.ac.uk].
4.1.1. 3-[(1R,2S,5R)-menthoxymethoxy]-phenol (10). To
a mixture of resorcinol (9) (2.42 g, 21.98 mmol) and
anhydrous K2CO3 (1.82 g, 13.17 mmol) in anhydrous
DMF (30 mL) MenCl (0.92 mL, 4.41 mmol) was added
under Ar. After being stirred at 50 8C for 46 h, the reaction
mixture was allowed to reach spontaneously the room
temperature and quenched with saturated NH4Cl solution
(60 mL). The aqueous layer was extracted with CH2Cl2 (4!
60 mL), the organic phases were recollected, washed with
H2O (6!250 mL) and dried over Na2SO4. Evaporation of
the solvent gave a crude mixture that was purified by
column chromatography (CH2Cl2/MeOH 50:1) to obtain
phenol 10 as an orange solid (1.05 g, 3.77 mmol, 85% from
MenCl), mp 62–64 8C; [a]2D4K154.6 (c 0.1); 1H NMR d 7.10
(t, JZ8.1 Hz, 1H), 6.58 (ddd, JZ8.1, 2.1, 0.9 Hz, 1H), 6.54
(t, JZ2.1 Hz, 1H), 6.47 (ddd, JZ8.1, 2.1, 0.9 Hz, 1H), 6.32
(br s, 1H), 5.30 (d, JZ7.2 Hz, 1H), 5.22 (d, JZ7.2 Hz, 1H),
3.49 (dt, JZ10.8, 4.2 Hz, 1H), 2.1–2.0 (m, 2H), 1.7–1.6 (m,
2H), 1.4–1.3 (m, 1H), 1.3–1.2 (m, 1H), 1.1–0.8 (m, 3H),
0.90 (d, JZ6.6 Hz, 3H), 0.84 (d, JZ6.9 Hz, 3H), 0.63 (d,
JZ6.9 Hz, 3H); 13C NMR d 158.7, 156.9, 129.9, 108.6,
107.9, 103.4, 91.1, 78.1, 48.1, 41.1, 34.3, 31.5, 25.2, 22.9,
22.2, 21.0, 15.5. Anal. Calcd for C17H26O3: C, 73.34; H
9.41. Found: C, 73.26; H, 9.32.
1
11), mp 64–66 8C; [a]2D5K95.4 (c 0.3); H NMR d 7.36 (d,
JZ8.7 Hz, 1H), 6.71 (d, JZ2.7 Hz, 1H), 6.55 (s, 1H), 6.59
(dd, JZ8.4, 2.7 Hz, 1H), 5.31 (d, JZ7.2 Hz, 1H), 5.22 (d,
JZ7.2 Hz, 1H), 3.46 (dt, JZ10.5, 4.2 Hz, 1H), 2.85 (t, JZ
7.2 Hz, 2H), 2.51 (t, JZ7.2 Hz, 2H), 2.1–2.0 (m, 2H), 1.7–
1.6 (m, 2H), 1.4–1.3 (m, 1H), 1.3–1.2 (m, 1H), 1.0–0.8 (m,
3H), 0.90 (d, JZ6.6 Hz, 3H), 0.83 (d, JZ7.2 Hz, 3H), 0.60
(d, JZ6.6 Hz, 3H); 13C NMR d 160.9, 158.3, 137.1, 117.8,
109.5, 107.7, 102.9, 91.1, 78.4, 48.1, 41.0, 34.3, 31.8, 31.5,
25.2, 22.9, 22.2, 21.0, 17.9, 15.6; IR nmax 2360 (CN) cmK1
.
4.1.2. 2-{2-Hydroxy-4-[(1R,2S,5R)-menthoxymethoxy]-
phenylsulfanyl}-1H-isoindole-1,3(2H)-dione (11). To a
solution of phenol 10 (1.90 g, 6.82 mmol) in anhydrous
CHCl3 (70 mL) kept at 0 8C under Ar, a PhtNSCl solution6
(1.46 g, 6.82 mmol) in anhydrous CHCl3 (70 mL) was
added dropwise. The reaction mixture was stirred at 0 8C for
20 min, then quenched with saturated NaHCO3 solution
(100 mL). The organic phase was extracted with CH2Cl2
(100 mL), washed with H2O (2!150 mL), and dried over
Na2SO4. The solvent was removed at reduced pressure.
Column chromatography (CH2Cl2) afforded compound 11
as a white solid (1.79 g, 3.93 mmol, 58%), mp 128–130 8C;
Anal. Calcd for C20H29NO3S: C, 66.08; H, 8.04; N, 3.85.
Found: C, 65.86; H, 7.96; N, 3.77.
4.1.4. 3-{2-Hydroxy-4-[(1R,2S,5R)-menthoxymethoxy]-
phenylsulfinyl}-propanenitriles 13 (two S-epimers). To
a solution of sulfide 12 (0.95 g, 2.61 mmol) in anhydrous
CH2Cl2 (130 mL) at 0 8C m-CPBA (0.64 g 70%,
2.60 mmol) was added. The solution was stirred at 0 8C
for 20 min, diluted with CH2Cl2 (100 mL) and washed with
saturated NaHCO3 solution (2!150 mL). The organic
phase was dried over Na2SO4 and concentrated. The crude
product was purified by column chromatography (petrol/
EtOAc 1:1), to give an inseparable 1:1 mixture of sulfur
epimers 13 as a white solid (0.76 g, 2.00 mmol, 77%), mp
1
[a]2D4K70.5 (c 0.3); H NMR d 8.33 (s, 1H), 7.9–7.7 (m,
4H), 7.74 (d, JZ8.7 Hz, 1H), 6.66 (d, JZ2.4 Hz, 1H), 6.52
(dd, JZ8.7, 2.4 Hz, 1H), 5.28 (d, JZ7.2 Hz, 1H), 5.17 (d,
JZ7.2 Hz, 1H), 3.42 (dt, JZ10.8, 4.2 Hz, 1H), 2.1–2.0 (m,
2H), 1.6 (m, 2H), 1.4–1.3 (m, 1H), 1.2–1.1 (m, 1H), 1.0–0.7
(m, 3H), 0.87 (d, JZ6.6 Hz, 3H), 0.81 (d, JZ6.9 Hz, 3H),
0.59 (d, JZ6.9 Hz, 3H); 13C NMR d 168.5, 162.9, 160.4,
139.4, 134.7, 131.8, 124.1, 110.8, 108.9, 103.5, 91.3, 78.7,
48.0, 41.1, 34.2, 31.4, 25.1, 22.8, 22.2, 20.9, 15.5. Anal.
Calcd for C25H29NO5S: C, 65.91; H, 6.42; N, 3.07. Found:
C, 65.68; H, 6.21; N, 3.11.
1
128–131 8C; H NMR d 9.81 (s, 1H), 7.00 (d, JZ8.7 Hz,
1H), 6.7–6.6 (m, 2H), 5.32 (d, JZ7.5 Hz, 1H), 5.23 (d, JZ
7.5 Hz, 1H), 3.46 (dt, JZ10.5, 4.2 Hz, 1H), 3.4–3.2 (m,
2H), 3.0–2.9 (m, 1H), 2.7–2.6 (m, 1H), 2.1–2.0 (m, 2H),
1.7–1.6 (m, 2H), 1.4–1.3 (m, 1H), 1.3–1.2 (m, 1H), 1.0–0.8
(m, 3H), 0.92 (d, JZ6.3 Hz, 3H), 0.84 (d, JZ6.9 Hz, 3H),
0.61 (d, JZ6.9 Hz, 3H); 13C NMR d 162.2, 160.0, 126.6,
116.8, 112.6, 108.9, 106.1, 91.2, 78.7, 49.0, 48.1, 41.1, 34.3,
31.5, 25.3, 23.0, 22.2, 20.9, 15.6, 10.7. Anal. Calcd for
C20H29NO4S: C, 63.30; H, 7.70; N, 3.69. Found: C, 63.01;
H, 7.55; N, 3.51.
4.1.3. 3-{2-Hydroxy-4-[(1R,2S,5R)-menthoxymethoxy]-
phenylsulfanyl}-propanenitrile (12). A solution of thio-
derivative 11 (1.79 g, 3.93 mmol) in anhydrous THF

M. C. Aversa et al. / Tetrahedron 61 (2005) 11902–11909
11907
4.1.5. 1-(1-Cyclohexen-1-yl)-1-{2-hydroxy-4-[(1R,2S,
5R)-menthoxymethoxy]-phenylsulfinyl}-ethene 15 (two
S-epimers). A mixture of sulfoxides 13 (0.20 g, 0.53 mmol)
and 1-ethynylcyclohexene (0.50 mL, 4.25 mmol) was
heated at 130 8C under Ar. After 1 h of stirring, the mixture
was allowed to reach spontaneously the room temperature
and then was diluted with CH2Cl2 (10 mL). Evaporation of
the solvent under reduced pressure gave a crude product
that was purified by column chromatography (petrol/EtOAc
7:1). An oily 1:1 mixture of epimers 15 was isolated (0.11 g,
0.25 mmol, 47%). Anal. Calcd for C25H36O4S: C, 69.41; H,
8.39. Found: C, 69.78; H, 8.15. Further attempts of
chromatographic separation of the two epimers allowed
the isolation of very small amounts of enantiopure
sulfoxides. More mobile sulfur epimer 15 was obtained
4.1.7. (Sa)-3-(20-hydroxy-1,10-binaphthalen-2-sulfinyl)-
propanenitriles 18 (two S-epimers). To a solution of
sulfide 17 (1.11 g, 3.12 mmol) in CH2Cl2 (50 mL), at
K50 8C, a solution of m-CPBA (0.73 g 70%, 2.96 mmol) in
CH2Cl2 (80 mL) was added dropwise. After 1 h of stirring,
the mixture was diluted with CH2Cl2 (50 mL) and treated
with 10% Na2S2O3 solution (150 mL). The organic phase
was washed with saturated NaHCO3 solution (2!150 mL)
and H2O (2!150 mL), dried over Na2SO4, and evaporated
under reduced pressure to give sulfoxides 18 as a 1:1
mixture (1.07 g, 2.88 mmol, 92%) of two S-epimers. The
epimers were separated by column chromatography
(CH2Cl2/EtOAc, 20:1). More mobile sulfur epimer 18 was
obtained as a white solid, mp 78–80 8C; [a]2D6K193.0 (c 0.3,
1
THF); H NMR d 8.18 (d, JZ8.7 Hz, 1H), 8.07 (d, JZ
1
as an oil; [a]2D5K119.0 (c 0.1); H NMR d 9.92 (s, 1H),
8.7 Hz, 1H), 7.97 (d, JZ8.1 Hz, 1H), 7.91 (d, JZ8.7 Hz,
1H), 7.86 (d, JZ8.1 Hz, 1H), 7.6–7.5 (m, 1H), 7.4–7.2 (m,
5H), 6.95 (d, JZ8.4 Hz, 1H), 6.57 (s, 1H), 3.0–2.8 (m, 2H),
2.7–2.6 (m, 1H), 2.5–2.4 (m, 1H); 13C NMR d 152.0, 138.1,
135.1, 133.0, 132.5, 132.2, 131.6, 130.2, 128.8, 128.7,
128.3, 128.2, 127.9, 127.7, 125.8, 124.1, 123.9, 119.7,
117.7, 117.5, 113.4, 47.9, 9.5. Anal. Calcd for C23H17NO2S:
C, 74.37; H, 4.61; N, 3.77. Found: C, 74.58; H, 4.60; N,
3.57. Then less mobile sulfur epimer 18 was eluted as a
6.96 (dd, JZ8.4, 0.6 Hz, 1H), 6.6–6.5 (m, 2H), 5.93 (br
s, 2H), 5.65 (br s, 1H), 5.28 (d, JZ7.2 Hz, 1H), 5.20 (d,
JZ7.2 Hz, 1H), 3.44 (dt, JZ10.5, 4.2 Hz, 1H), 2.2–2.0
(m, 5H), 1.7–1.2 (m, 10H), 1.0–0.8 (m, 2H), 0.89 (d,
JZ6.6 Hz, 3H), 0.82 (d, JZ7.2 Hz, 3H), 0.58 (d,
JZ7.2 Hz, 3H); 13C NMR d 161.5, 161.4, 152.6,
131.6, 129.9, 128.1, 113.2, 112.9, 107.5, 106.0, 90.9,
78.4, 48.2, 41.1, 34.4, 31.5, 28.6, 25.4, 25.3, 23.1, 22.4,
22.2, 21.6, 21.0, 15.6. Less mobile sulfur epimer 15 was
obtained as an oil; [a]2D5K58.2 (c 0.02); 1H NMR d
9.95 (s, 1H), 6.96 (d, JZ9.0 Hz, 1H), 6.50 (m, 2H),
5.93 (br s, 2H), 5.65 (br s, 1H), 5.28 (d, JZ7.5 Hz,
1H), 5.20 (d, JZ7.2 Hz, 1H), 3.45 (dt, JZ10.5, 4.2 Hz,
1H), 2.2–2.0 (m, 5H), 1.7–1.2 (m, 10H), 1.0–0.8 (m,
2H), 0.89 (d, JZ6.6 Hz, 3H), 0.82 (d, JZ6.9 Hz, 3H),
0.58 (d, JZ7.2 Hz, 3H); 13C NMR d 161.5, 161.5,
152.6, 131.6, 129.9, 128.1, 113.3, 112.9, 107.2, 106.3,
91.0, 78.4, 48.2, 41.1, 34.4, 31.5, 28.6, 25.4, 25.3, 23.1,
22.4, 22.2, 21.6, 21.0, 15.5.
white solid, mp 98–100 8C; [a]2D6C377.4 (c 0.8, THF); H
1
NMR (CD3CN) d 8.27 (d, JZ8.4 Hz, 1H), 8.14 (d, JZ
8.7 Hz, 1H), 8.04 (d, JZ8.1 Hz, 1H), 7.98 (d, JZ9.0 Hz,
1H), 7.92 (d, JZ7.8 Hz, 1H), 7.7–7.6 (m, 1H), 7.4–7.2 (m,
5H), 6.79 (d, JZ8.4 Hz, 1H), 5.93 (br s, 1H), 2.6–2.5 (m,
2H), 2.5–2.3 (m, 2H); 13C NMR [(CD3)2SO] d 152.6, 139.3,
134.5, 133.7, 132.7, 132.0, 130.9, 129.3, 128.6 (2C), 127.8,
127.7, 127.4, 127.2, 125.7, 123.3, 123.0, 120.0, 118.5,
118.3, 112.5, 47.0, 8.8. Anal. Calcd for C23H17NO2S: C,
74.37; H, 4.61; N, 3.77. Found: C, 74.27; H, 4.72; N, 3.80.†
4.1.8. (Sa)-2-(20-hydroxy-1,10-binaphthalen-2-sulfinyl)-3-
methyl-1,3-butadienes 20 and 21 (two S-epimers). To a
suspension of sulfoxides 18 (0.18 g, 0.48 mmol) in toluene
(12 mL) 2-methyl-1-buten-3-yne (0.70 mL, 7.36 mmol) was
added and the reaction mixture refluxed and stirred for 1.5 h.
The resulting yellow solution was cooled to room
temperature and the 1:1 mixture of dienes 20 and 21 was
obtained as a white precipitate (0.14 g, 0.36 mmol, 75%
total yield). The epimers were separated by column
chromatography (initial elution with CH2Cl2, then
CH2Cl2/EtOAc 9:1). First eluted was (Sa,SS)-2-(20-
hydroxy-1,10-binaphthalen-2-sulfinyl)-3-methyl-1,3-buta-
diene (20) as a white solid, mp 173 8C dec; [a]2D4K206.7 (c
1.0, THF); 1H NMR d 8.14 (d, JZ9.0 Hz, 1H), 7.98 (d, JZ
7.2 Hz, 1H), 7.96 (d, JZ8.1 Hz, 1H), 7.87 (d, JZ8.1 Hz,
1H), 7.60 (m, 1H), 7.4–7.2 (m, 6H), 7.11 (d, JZ8.1 Hz, 1H),
5.92 (s, 1H), 5.68 (s, 1H), 4.88 (s, 1H), 4.81 (s, 1H), 1.65 (s,
3H); 13C NMR [DCON(CD3)2] d 154.8, 154.4, 141.6, 137.5,
137.3, 135.5, 135.0, 133.2, 131.2, 130.3, 129.0, 128.9,
4.1.6. (Sa)-3-(20-hydroxy-1,10-binaphthalen-2-sulfanyl)-
propanenitrile (17). To a solution of (Sa)-20-mercapto-
1,10-binaphthalen-2-ol7,16 (16) (2.00 g, 6.61 mmol) in
anhydrous THF (60 mL), acrylonitrile (4.38 mL,
66.53 mmol) and Et3N (0.92 mL, 6.61 mmol) were added
under N2. The reaction mixture was stirred at room
temperature for 72 h. The resulting yellow-orange solution
was diluted with CH2Cl2 (200 mL) and washed with
saturated NH4Cl solution (3!200 mL) and H2O (2!
200 mL). The organic layer was dried over Na2SO4, and
the solvent removed under reduced pressure. Column
chromatography (eluant: from petrol/CH2Cl2 1:1 to pure
CH2Cl2) gave nitrile 17 as a white solid (1.77 g, 4.98 mmol,
1
75%), mp 93–95 8C; [a]2D4K67.8 (c 1.0, THF); H NMR
(CD3CN) d 8.05 (d, JZ8.7 Hz, 1H), 7.97 (d, JZ8.7 Hz,
1H), 7.94 (d, JZ9.3 Hz, 1H), 7.89 (d, JZ8.1 Hz, 1H), 7.73
(d, JZ8.7 Hz, 1H), 7.47 (dt, JZ7.4, 1.1 Hz, 1H), 7.29 (m,
3H), 7.21 (dt, JZ7.7, 1.2 Hz, 1H), 7.04 (d, JZ8.7 Hz, 1H),
6.83 (d, JZ8.7 Hz, 1H), 3.12 (t-like, JZ7.1 Hz, 2H), 2.57
(t-like, JZ7.1 Hz, 2H); 13C NMR [(CD3)2CO] d 153.3,
135.5, 134.8, 134.5, 134.4, 133.4, 130.6, 129.65, 129.59,
128.9, 127.6, 127.5, 127.2, 126.7, 126.5, 124.9, 123.7,
119.1, 118.1, 29.4, 18.6. Anal. Calcd for C23H17NOS: C,
77.72; H, 4.82; N, 3.94. Found: C, 77.35; H, 4.80; N, 4.00.
The same chromatography 0allowed the isolation of small
amounts (4%) of bis[(Sa)-2 -hydroxy-1,10-binaphthyl-2-yl]
disulfide; [a]2D7K87.3 (c 1.0).7
† When sulfide 17 was oxidized with an equimolar amount of m-CPBA at
K15 8C, the 1:1 mixture of epimeric sulfoxides 18 was obtained in 73%
total yield, together with (Sa)-3-(20-hydroxy-1,10-binaphthalen-2-sul-
fonyl)-propanenitrile (14%), mp 204–206 8C, more mobile than
sulfoxides 18 (column chromatography with CH2Cl2/EtOAc 19:1); 1H
NMR d 8.34 (d, JZ8.8 Hz, 1H), 8.22 (d, JZ8.8 Hz, 1H), 8.04 (d, JZ
8.3 Hz, 1H), 8.03 (d, JZ9.0 Hz, 1H), 7.93 (split d, JZ7.8 Hz, 1H), 7.68
(ddd, JZ8.3, 6.9, 1.3 Hz, 1H), 7.4–7.3 (m, 4H), 7.22 (split d, JZ8.5 Hz,
1H), 6.74 (split d, JZ8.4 Hz, 1H), 3.0–2.5 (m, 4H).

11908
M. C. Aversa et al. / Tetrahedron 61 (2005) 11902–11909
128.7, 128.6, 127.8, 127.4, 127.3, 124.9, 123.6, 121.7,
118.8, 117.0 (2C), 115.5, 22.1; IR nmax 3280 (OH), 1007
(SO) cmK1. Anal. Calcd for C25H20O2S: C, 78.09; H, 5.24.
Found: C, 77.88; H, 5.25. Then (Sa,RS)-2-(20-hydroxy-1,10-
binaphthalen-2-sulfinyl)-3-methyl-1,3-butadiene (21) was
eluted as a white solid, mp 124–126 8C; [a]2D5C378.4 (c
1.0, THF); 1H NMR d 8.04 (d, JZ8.7 Hz, 1H), 7.91 (d, JZ
8.4 Hz, 1H), 7.82 (m, 2H), 7.53 (t, JZ7.0 Hz, 1H), 7.47 (d,
JZ9.0 Hz, 1H), 7.4–7.1 (m, 5H), 6.76 (d, JZ8.4 Hz, 1H),
6.23 (s, 1H), 5.87 (s, 1H), 4.34 (s, 1H), 4.26 (s, 1H), 1.59 (s,
3H); 13C NMR [DCON(CD3)2] d 155.7, 154.0, 142.2, 137.4,
136.1, 135.4, 135.1, 133.2, 131.2, 130.0, 129.1, 128.9,
128.8, 128.4, 127.7, 127.4, 126.8, 125.7, 123.4, 121.7,
119.1, 116.5, 116.4, 115.4, 22.0; IR nmax 3250 (OH), 1015
(SO) cmK1. Anal. Calcd for C25H20O2S: C, 78.09; H, 5.24.
Found: C, 78.20; H, 5.12.
(0.18 g, 0.36 mmol, 69% overall yield). First eluted was the
major adduct (3aR,7aS,Sa,RS)-3a,4,7,7a-tetrahydro-5-(20-
hydroxy-1,10-binaphthalen-2-sulfinyl)-2,6-dimethyl-1H-
isoindole-1,3(2H)-dione (24), white solid, mp 175–177 8C;
[a]2D7C179.7 (c 0.5); 1H NMR [(CD3)2SO] d 10.00 (s, 1H),
8.32 (d, JZ8.7 Hz, 1H), 8.10 (d, JZ8.7 Hz, 2H), 7.94 (d,
JZ9.0 Hz, 1H), 7.88 (d, JZ8.1 Hz, 1H), 7.58 (t, JZ7.4 Hz,
1H), 7.39 (d, JZ9.0 Hz, 1H), 7.33 (t, JZ7.6 Hz, 1H), 7.27
(t, JZ7.2 Hz, 1H), 7.15 (t, JZ7.2 Hz, 1H), 6.96 (d, JZ
8.4 Hz, 1H), 6.41 (d, JZ8.4 Hz, 1H), 2.9–2.7 (m, 2H), 2.67
(s, 3H), 1.8–1.7 (m, 2H), 1.3–1.2 (m, 2H), 0.51 (s, 3H); 13C
NMR [(CD3)2SO] d 178.9, 178.4, 152.6, 144.2, 139.4,
134.2, 133.8, 133.2, 132.2, 132.1, 130.4, 128.5, 128.1,
128.0, 127.3, 127.1, 126.5, 125.4, 123.5, 122.8, 120.4,
118.7, 113.3, 38.7, 38.5, 30.7, 30.0, 24.5, 19.9, 18.1; IR nmax
3100 (OH), 1780 and 1698 (CO), 985 (SO) cmK1. Anal.
Calcd for C30H25NO4S: C, 72.71; H, 5.08; N, 2.83. Found:
C, 72.92; H, 5.05; N, 2.83. Less mobile was the minor
adduct (3aS,7aR,Sa,RS)-3a,4,7,7a-tetrahydro-5-(20-hydroxy-
1,10-binaphthalen-2-sulfinyl)-2,6-dimethyl-1H-isoindole-
1,3(2H)-dione (25), white solid, mp 154–156 8C; [a]2D7C
4.1.9. (Sa,SS)-3a,4,7,7a-tetrahydro-5-(20-hydroxy-1,10-
binaphthalen-2-sulfinyl)-2,6-dimethyl-1H-isoindole-1,
3(2H)-diones 22 and 23 0 (two diastereomers). To a
suspension of (Sa,SS)-2-(2 -hydroxy-1,10-binaphthalen-2-
sulfinyl)-3-methyl-1,3-butadiene (20) (0.21 g, 0.55 mmol)
in CH2Cl2 (40 mL) NMM (1.19 g, 10.71 mmol) was added,
and the mixture was refluxed and stirred for 72 h. After
removal of the solvent, the crude product was purified by
column chromatography (eluant: from CH2Cl2/EtOAc 1.5:1
to pure EtOAc) to give the two diastereomeric cycloadducts
22 and 23, in 2:1 ratio (0.24 g, 0.48 mmol, 87% overall
yield). First eluted was the major adduct (3aS,7aR,Sa,SS)-
3a,4,7,7a-tetrahydro-5-(20-hydroxy-1,10-binaphthalen-2-
sulfinyl)-2,6-dimethyl-1H-isoindole-1,3(2H)-dione (22),
white solid, mp 183 8C dec; [a]2D5K226.5 (c 0.8); 1H
NMR d 8.3–8.1 (m, 2H), 7.9–7.7 (m, 3H), 7.5–7.4 (m, 1H),
7.3–7.1 (m, 5H), 6.99 (d, JZ8.4 Hz, 1H), 2.8–2.5 (m, 4H),
2.71 (s, 3H), 2.3–2.2 (m, 2H), 1.02 (s, 3H). Anal. Calcd for
C30H25NO4S: C, 72.71; H, 5.08; N, 2.83. Found: C, 73.06;
H, 5.10; N, 2.87. Less mobile was the0 minor adduct
(3aR,7aS,Sa,SS)-3a,4,7,7a-tetrahydro-5-(2 -hydroxy-1,10-
binaphthalen-2-sulfinyl)-2,6-dimethyl-1H-isoindole-
1,3(2H)-dione (23), white solid, mp 164–166 8C; [a]2D5K
151.8 (c 0.6); 1H NMR [(CD3)2SO] d 9.53 (s, 1H), 8.31 (d,
JZ8.8 Hz, 1H), 8.16 (d, JZ8.8 Hz, 1H), 8.09 (d, JZ
8.4 Hz, 1H), 7.93 (d, JZ8.8 Hz, 1H), 7.88 (d, JZ8.1 Hz,
1H), 7.58 (t, JZ7.0 Hz, 1H), 7.36 (t, JZ8.2 Hz, 1H), 7.3–
7.2 (m, 3H), 7.10 (d, JZ8.7 Hz, 1H), 6.87 (d, JZ8.1 Hz,
1H), 3.0–2.9 (m, 1H), 2.8–2.6 (m, 2H), 2.66 (s, 3H), 2.35
(dd, JZ15.3, 7.8 Hz, 1H), 2.04 (dd, JZ15.0, 10.4 Hz, 1H),
1.63 (t-like, JZ12.3 Hz, 1H), 1.05 (s, 3H); MS m/z (%) 496
(29, MC1), 268 (15), 239 (8), 95 (49), 81 (51), 69 (82), 55
(100), 43 (76); IR nmax 3200 (OH), 1770 and 1701 (CO),
1005 (SO) cmK1. Anal. Calcd for C30H25NO4S: C, 72.71;
H, 5.08; N, 2.83. Found: C, 73.00; H, 5.18; N, 2.90.
1
168.0 (c 0.5); H NMR [(CD3)2SO] d 9.99 (br s, 1H), 8.30
(d, JZ8.4 Hz, 1H), 8.15 (d, JZ8.7 Hz, 1H), 8.09 (d, JZ
8.1 Hz, 1H), 7.94 (d, JZ9.0 Hz, 1H), 7.86 (d, JZ8.1 Hz,
1H), 7.57 (t, JZ7.4 Hz, 1H), 7.38 (d, JZ9.0 Hz, 1H), 7.32
(t, JZ7.7 Hz, 1H), 7.23 (t, JZ7.4 Hz, 1H), 7.00 (t, JZ
7.5 Hz, 1H), 6.95 (d, JZ8.4 Hz, 1H), 6.32 (d, JZ8.1 Hz,
1H), 2.68 (s, 3H), 1.81 (dd, JZ15.4, 7.9 Hz, 2H), 1.5–1.4
(m, 2H), 1.01 (dd, JZ15.2, 8.6 Hz, 2H), 0.55 (s, 3H); 13C
NMR [(CD3)2SO] d 178.6, 178.5, 152.5, 144.5, 139.6,
134.2, 133.8, 133.0, 132.1, 130.4, 128.6, 128.4, 128.1,
128.0, 127.2, 127.0, 126.5, 125.5, 123.4, 122.7, 120.3,
118.6, 113.5, 37.8, 30.0, 24.2, 19.4, 17.6. Anal. Calcd for
C30H25NO4S: C, 72.71; H, 5.08; N, 2.83. Found: C, 72.51;
H, 5.10; N, 3.22.
X-ray structural analysis of 25, CCDC no. 278055: formula
C34H33NO6S (C30H25NO4SCC4H8O2), MZ583.67, ortho-
˚
rhombic, space group P 21 21 21, aZ10.517(2) A,
3
˚
˚
˚
bZ12.410(2) A, cZ22.803(7) A, VZ2976(1) A , ZZ4,
DcZ1.303, mZ0.156 mmK1, F(000)Z1232. Reflections
(4700) were collected with a 2.63!q!21.36 range with a
completeness to q 95.3%; 3107 were independent, the
parameters were 385, and the final R index was 0.0839 for
reflections having IO2s(I), and 0.1559 for all data.
Compound 25 crystallizes with a molecule of EtOAc in
the asymmetric unit. The positions of EtOAc carbon and
oxygen atoms in are not well defined so that their
coordinates have been splitted, they were refined as
isotropic, and the relative hydrogen atoms were not
assigned. The non-hydrogen atoms of compound 25 were
refined anisotropically whereas its hydrogen atoms were
refined as isotropic and assigned in calculated positions.
4.1.10. (Sa,RS)-3a,4,7,7a-tetrahydro-5-(20-hydroxy-1,10-
binaphthalen-2-sulfinyl)-2,6-dimethyl-1H-isoindole-1,
3(2H)-diones 24 and 25 (two diastereomers). To a
solution of (Sa,RS)-2-(20-hydroxy-1,10-binaphthalen-2-sul-
finyl)-3-methyl-1,3-butadiene (21) (0.20 g, 0.52 mmol) in
CH2Cl2 (25 mL) NMM (1.18 g, 10.62 mmol) was added and
the mixture refluxed for 72 h. After removal of the solvent,
the crude product was purified by column chromatography
(eluant: from CH2Cl2/EtOAc 2.3:1 to pure EtOAc) to give
the two diastereomeric cycloadducts 24 and 25 in 3:2 ratio
4.2. Desulfurization of (3aR,7aS,Sa,RS)-3a,4,7,7a-tetra-
hydro-5-(20-hydroxy-1,10-binaphthalen-2-sulfinyl)-2,6-
dimethyl-1H-isoindole-1,3(2H)-dione (24)
To a solution of cycloadduct 24 (0.10 g, 0.20 mmol) in
anhydrous THF (20 mL) a suspension of commercial W-2
Raney nickel (nickel sponge, suspension in water, 1.80 mL)
in anhydrous THF (10 mL) was added. The reaction mixture
was stirred at room temperature for 5 h and then filtered

M. C. Aversa et al. / Tetrahedron 61 (2005) 11902–11909
11909
4. (a) Aucagne, V.; Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.;
¨
Giannetto, P.; Rollin, P.; Tatibouet, A. J. Org. Chem. 2002, 67,
through a Celite pad. The Celite cake was washed with
EtOAc and the resulting clear solution was concentrated
under reduced pressure. The crude mixture was purified by
two consecutive column chromatographies (petrol/EtOAc
2.3:1) to give, in order of increasing retention times (2:1
molar ratio, 55% overall yield), (3aS,7aR)-hexahydro-2,5-
dimethyl-1H-isoindole-1,3(2H)-diones 27 (6:1 epimeric
mixture, 6.7 mg, 0.04 mmol), followed by (3aS,7aR)-
3a,4,7,7a-tetrahydro-2,5-dimethyl-1H-isoindole-1,3(2H)-
dione (26) (13.3 mg, 0.07 mmol). The analytical and
spectroscopic data, measured for 26 and 27, were fully
consistent with the ones reported in the literature.11
6925–6930. (b) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.;
Giannetto, P. J. Org. Chem. 2005, 70, 1986–1992. (c) Aversa,
M. C.; Barattucci, A.; Biliardo, M. C.; Bonaccorsi, P.;
¨
Giannetto, P.; Rollin, P.; Tatibouet, A. J. Org. Chem. 2005,
70, 7389–7396.
5. (a) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bruno, G.;
Giannetto, P.; Policicchio, M. Tetrahedron Lett. 2000, 41,
4441–4445. (b) Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.;
Giannetto, P. Tetrahedron 2002, 58, 10145–10150.
6. (a) Capozzi, G.; Falciani, C.; Menichetti, S.; Nativi, C. J. Org.
Chem. 1997, 62, 2611–2615. (b) Capozzi, G.; Delogu, G.;
Fabbri, D.; Marini, M.; Menichetti, S.; Nativi, C. J. Org.
Chem. 2002, 67, 2019–2026.
Acknowledgements
7. Azad, S. M.; Bennett, S. M. W.; Brown, S. M.; Green, J.; Sinn,
E.; Topping, C. M.; Woodward, S. J. Chem. Soc., Perkin
Trans. 1 1997, 687–694.
Work carried out in the framework of the National Project
‘Stereoselezione in Sintesi Organica. Metodologie ed
Applicazioni’, supported by MIUR (Ministero Istruzione
`
Universita e Ricerca) and Universities of Firenze and
Messina.
8. Adams, H.; Anderson, J. C.; Bell, R.; Jones, D. N.; Peel, M. R.;
Tomkinson, N. C. O. J. Chem. Soc., Perkin Trans. 1 1998,
3967–3974.
9. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Faggi, C.; Gacs-
Baitz, E.; Marrocchi, A.; Minuti, L.; Taticchi, A. Tetrahedron
2005, 61, 7719–7726.
10. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bonini, B. F.;
`
Giannetto, P.; Nicolo, F. Tetrahedron: Asymmetry 1999, 10,
References and notes
3919–3929.
11. Vijn, R. J.; Hiemstra, H.; Kok, J. J.; Knotter, M.; Speckamp,
W. N. Tetrahedron 1987, 43, 5019–5030.
1. Reviews on the topic: Aversa, M. C.; Barattucci, A.;
Bonaccorsi, P.; Giannetto, P. Tetrahedron: Asymmetry 1997,
8, 1339–1367. Recent Res. Dev. Org. Chem. 2002, 6, 87–101.
Arkivoc 2002, 79–98.
12. Walker, N.; Stuart, D. Acta Cystallogr. Sect. A: Found.
Crystallogr. 1983, 39, 158–166.
13. Sheldrick, G. M. SADABS: Program for Empirical Absorption
2. (a) Aversa, M. C.; Bonaccorsi, P.; Giannetto, P.; Jafari,
S. M. A.; Jones, D. N. Tetrahedron: Asymmetry 1992, 3,
701–704. (b) Aversa, M. C.; Bonaccorsi, P.; Giannetto, P.;
Jones, D. N. Tetrahedron: Asymmetry 1994, 5, 805–808. (c)
Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.;
Jones, D. N. J. Org. Chem. 1997, 62, 4376–4384. (d) Aversa,
¨ ¨ ¨
Correction, version 2.03; Universitat Gottingen: Gottingen,
Germany, 1997–2001.
14. Altomare, A.; Burla, M. C.; Camalli, M.; Cascarano, G. L.;
Giacovazzo, C.; Guagliardi, A.; Moliterni, A. G. G.; Polidori,
G.; Spagna, R. J. Appl. Crystallogr. 1999, 32, 115–119.
15. Sheldrick, G. M. SHELXL97: Program for Crystal Structure
`
M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Nicolo, F.
J. Org. Chem. 1999, 64, 2114–2118. (e) Aversa, M. C.;
¨
Refinement; Institut fu¨r Anorganische Chemie der Universitat
¨ ¨
Gottingen: Gottingen, Germany, 1987.
`
Barattucci, A.; Bonaccorsi, P.; Giannetto, P.; Nicolo, F.;
Rizzo, S. Tetrahedron: Asymmetry 1999, 10, 3907–3917. (f)
Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Giannetto, P.;
Policicchio, M. J. Org. Chem. 2001, 66, 4845–4851. (g)
Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bruno, G.;
Caruso, F.; Giannetto, P. Tetrahedron: Asymmetry 2001, 12,
2901–2908. (h) Aversa, M. C.; Barattucci, A.; Bilardo, M. C.;
Bonaccorsi, P.; Giannetto, P. Synthesis 2003, 2241–2248.
3. Aversa, M. C.; Barattucci, A.; Bonaccorsi, P.; Bruno, G.;
16. (a) Bandarage, U. K.; Simpson, J.; Smith, R. A. J.; Weavers,
R. T. Tetrahedron 1994, 50, 3463–3472. (b) Fabbri, D.;
Delogu, G.; De Lucchi, O. J. Org. Chem. 1995, 60,
6599–6601. (c) Green, J.; Woodward, S. Synlett 1995,
155–156. (d) Fabbri, D.; Pulacchini, S.; Gladiali, S. Synlett
1996, 1054–1056. (e) Bennet, S. M. W.; Brown, S. M.; Conole,
G.; Dennis, M. R.; Fraser, P. K.; Radojevic, S.; McPartlin, M.;
Topping, C. M.; Woodward, S. J. Chem. Soc., Perkin Trans. 1
1999, 3127–3132.
`
Giannetto, P.; Nicolo, F. J. Chem. Soc., Perkin Trans. 2 1997,
273–277.