New 1,3-oxathianes derived from Myrtenal: Synthesis and reactivity

Article abstract of DOI:10.1021/jo034404w

2-Methyl- and 2-phenyl-substituted oxathianes derived from Myrtenal have been synthesized in satisfying yields. Lithiation of 2-methyl-substituted oxathiane could not be done, but lithiation of 2-phenyl-substituted and non-substituted oxathianes could be

Full text of DOI:10.1021/jo034404w

New 1,3-Oxa th ia n es Der ived fr om Myr ten a l: Syn th esis a n d
Rea ctivity
Arlette Solladie´-Cavallo,*,† Milan Balaz,†,‡ Marta Salisova,*,‡ and Richard Welter§
De´partement de Chimie Organique Fine, ECPM/ Universite´ Louis Pasteur, 67087-Strasbourg, France,
Department of Organic Chemistry, Comenius University, 842 15-Bratislava, Slovakia, and
Laboratoire DECMET, UMR 7513, Universite´ Louis Pasteur, 67000 Strasbourg
salisova@fns.uniba.sk.
Received March 28, 2003
2-Methyl- and 2-phenyl-substituted oxathianes derived from Myrtenal have been synthesized in
satisfying yields. Lithiation of 2-methyl-substituted oxathiane could not be done, but lithiation of
2-phenyl-substituted and non-substituted oxathianes could be performed with s-BuLi. Quenching
with D2O, TMSCl, and/or a carbonyl compound always provides the equatorial product in consistency
with a prefered equatorial orientation of the lithium in the lithiated derivatives. A model is proposed
to rationalize the diastereoselectivities observed at C5′ during reaction of aldehydes with lithiated
non-substituted oxathiane. The model is based on the hypothesis that the lithium, being linked
simultaneously to the carbon and the oxygen, is shifted toward the oxygen side, making the steric
hindrance of this side more effective. Dimeric side products were observed during formation of
these oxathianes (condensation of various aldehydes with the corresponding hydroxythiol), which
had not been reported for other oxathianes (derived from pulegone and/or camphorsulfonic acid).
Chiral 1,3-oxathianes 1-4 have been used at the
SCH2O bridge1-3 for diastereoselective synthesis of bio-
active compounds4 or at the sulfur atom5,6 as a precursor
of chiral ylides. Concerning the reactivity of the SCH2O-
bridge of oxathianes it appeared that lithiation was easily
performed with n-BuLi in the case of 1-trans1c and 2-cis3
while s-BuLi had to be used with 3-trans.1a
oxathianes and that these compounds (often major) have
dimeric structures.
We present here two new oxathianes 4a and 4b,
derived from myrtenal, a study of the reactivity of these
oxathianes, as well as the first successful lithiation of
oxathiane 4c which could not be lithiated yet. It is
reported also that, unlike for oxathianes 1-3, side
products are observed during the synthesis of type 4
Syn th esis a n d Id en tifica tion of Oxa th ia n es 4a
a n d 4b a n d of th e Sid e P r od u cts. Oxathianes 4a and
4b have been synthesized from hydroxythiol 7 using
p-toluenesulfonic acid (0.05 equiv) in benzene at room
temperature, Scheme 1, or using BF3:OEt2 (0.5 equiv) in
CH2Cl2 at 0 °C, Table 1. The hydroxythiol 7 was obtained
from (-)-myrtenal 5 according to the usual procedure;
however, DBU had to be used as base instead of pyridine
to obtain 99% yield and 99% diastereoselectivity. Then
LiAlH4 reduction of 6 provided the desired hydroxythiol
7 in 90% isolated yield and as a single diastereomer,
Scheme 1.
It is worth noting that this reaction is not as clean as
it is usually for the synthesis of oxathianes 1-3. A dimer
8a (17%) has also been obtained (as a ∼1/1 mixture of
the two possible diastereomers) together with traces of
a new compound 9a (5%) in the case of condensation of
7 with acetaldehyde, while in the case of condensation
† ECPM/Universite´ Louis Pasteur.
‡ Comenius University.
§ Universite´ Louis Pasteurg. E-mail: welter@chimie.u-strasbg.fr.
(1) (a) Eliel, E. L.; Frazee, W. J . J . Org. Chem. 1979, 44, 3598. (b)
Eliel, E. L.; Lynch, J . E. Tetrahedron Lett. 1981, 22, 2855. (c) Lynch,
J . E.; Eliel, E. L. J . Am. Chem. Soc. 1984, 106, 2943.
(2) Martinez-Ramos, F.; Vargas-Diaz, M. E.; Chacon-Garcia, L.;
Tamariz, J .; J oseph-Nathan, P.; Zepeda, L. G. Tetrahedron: Asymmetry
2001, 12, 3095.
(3) (a) Solladie´-Cavallo, A.; Balaz, M.; Salisova, M.; Suteu, C.; Nafie,
L. A.; Cao, X.; Freedman T. B. Tetrahedron: Asymmetry 2001, 12, 2605.
(b) Solladie´-Cavallo, A.; Balaz, M.; Salisova, M. Eur. J . Org. Chem.
2003, 337.
(4) For some examples of the use of oxathianes for the preparation
of bioactive compounds, see: (a) Eliel, E. L.; Soai, K. Tetrahedron Lett.
1981, 22, 2859. (b) Frye, S. V.; Eliel, E. L. J . Org. Chem. 1985, 50,
3402. (c) Ohwa, M.; Kogure, T.; Eliel, E. L. J . Org. Chem. 1986, 51,
2599. (d) Cervantes-Cuevas, H.; J oseph-Nathan, P. Tetrahedron Lett.
1988, 29, 5535. (e) Kaulen, J . Angew. Chem., Int. Ed. Engl. 1989, 28,
462. (f) Nemoto, H.; Matsuhashi, N.; Imaizumi, M.; Nagai, M.;
Fukumoto, K. J . Org. Chem. 1990, 55, 5626. (g) Bai, X.; Eliel, E. L. J .
Org. Chem. 1991, 56, 2086.
(5) (a) Solladie´-Cavallo, A.; Adib, A. Tetrahedron 1992, 48, 2453.
(b) Solladie´-Cavallo, A.; Diep-Vohuule, A. J . Org. Chem. 1995, 60, 3494.
(c) Solladie´-Cavallo, A.; Diep-Vohuule, A.; Sunjic, V.; Vinkovic, V.
Tetrahedron: Asymmetry 1996, 7, 1783. (d) Solladie´-Cavallo, A.; Diep-
Vohuule, A.; Isarno, T. Angew. Chem., Int. Ed. Engl. 1998, 37, 1689.
(6) (a) Aggarwal, V. K.; Thompson, A., J ones, R. V. H.; Standen, M.
Tetrahedron: Asymmetry 1995, 6, 2557. (b) Aggarwal, V. K.; Smith,
H. W.; Hynd, G.; J ones, R. V. H.; Fieldhouse, R.; Spey, S. E. J . Chem.
Soc., Perkin Trans. 1 2000, 3267. (c) Aggarwal, V. K.; Ferrara, M.;
O’Brien, C. J .; Thompson, A.; J ones, R. V. H.; Fieldhouse, R. J . Chem.
Soc., Perkin Trans. 1 2001, 1635.
10.1021/jo034404w CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/19/2003
J . Org. Chem. 2003, 68, 6619-6626
6619

Solladie´-Cavallo et al.
SCHEME 1
TABLE 1. P r ep a r a tion of Oxa th ia n es 4a a n d 4b fr om
Hyd r oxyth iol 7
% in
weight
unidentified
product
4 (%
aldehyde catalyst recovereda
4/8/9
recovered)b
MeCHO p-TsOH
BF3:OEt2
PhCHO p-TsOH
BF3:OEt2
75
60
95
90
78/17/5
72/13/15
42/0/58
19/0/81
no
yes
no
no
60
36
23
10
a
Percent in weight of material recovered compared to the mass
used for the reaction (correspond to samples after filtration of
solids and/or after extraction and containing no solvent). Percent
F IGURE 1. NOE in compounds 4a , 4b, and 4c.
b
isolated of oxathiane 4 (in mol), after chromatography.
Moreover, NOE experiments, with positive effects
between proton H5 and protons H7 and H3axial, Figure
1, showed that the R-groups have equatorial orientation
in both oxathianes 4a and 4b, as we already observed in
the case of type 2 oxathianes.3
of 7 with benzaldehyde (under identical conditions) 9b
was major (58%) and 8b was not observed.
Moreover, the use of BF3:OEt2 in CH2Cl2, which worked
perfectly for the preparation of 2-substituted oxathi-
anes of type 2 (Me: 90%; Ph: 80%)3 and 3 (Me: 99%;
Ph: 84%),7 provided lower yields in the preparation of
oxathiane 4a and 4b, Table 1.
Compounds 8a , 9a , and 9b have been identified by
comparison with compound 8c, for which an X-ray
1
structure could be performed (cf. bellow), and using H
NMR, 13C NMR, and MS.
After chromatography on silica gel, 60% of 4a and 23%
of 4b were isolated.
Oxa th ia n e 4c a n d Id en tifica tion of Dim er 8c. The
synthesis of 4c (already prepared by Zepeda et al.2) was
done using the same route but when the hydroxythiol 7
was treated with paraformaldehyde in the presence of a
catalytic amount of p-toluenesulfonic acid in refluxing
benzene, dimer 8c was the major product (56% in mole)
and only a trace amount of compound 10 was obtained
(2 mol %) as determined by 1H NMR on CH2 signals (2H).
No starting 7 was detected, indicating a full conversion,
Scheme 2. After chromatography on NEt3 pretreated
silica gel 30% of 4c, 63% of dimer 8c and traces of 10
(∼1%) were isolated.
Assignment of all the proton signals of oxathianes 4a
and 4b has been done using COSY experiments. The
large value (10 Hz) of the coupling constant observed
between protons H2 and H7 in both cases is consistent
with a trans structure. This trans structure was then
corroborated by the presence of positive nuclear Over-
hauser effects between one of the methyl protons (singlet
at 1.14 ppm for 4a and 1.22 ppm for 4b) and protons H7
and H3axial or between proton H11axial and H2, Figure 1.
It is worth noting that, in both cases, proton H7
appears as a quadruplet with three coupling constants
of similar value (∼10 Hz) due to the dihedral angles8 (see
X-ray of 8c).
The 1H and 13C NMR spectra of trans-oxathiane 4c are
identical to the literature and consistent with those of
trans-oxathianes 4a and 4b. It is worth noting that
proton H7 appears also as a quadruplet with three
coupling constants of similar values (∼10 Hz) due to the
dihedral angles8 (see X-ray of 8c).
(7) Aggarwal, V. K.; Ford, J . G.; Fonquerna, S.; Adams, H.; J ones,
R. V. H.; Fieldhouse, R. J . Am. Chem. Soc. 1998, 120, 8328.
(8) From the Karplus-Conroy curve it appears immediately that
the values of 3J coupling constants corresponding to dihedral angles
The 1H NMR spectrum of compound 8c, Figure 2,
exhibits two singlets (at 3.70 and 4.48 ppm) correspond-
ing to two protons each (CH2) together with all the signals
of the starting hydroxythiol skeleton 7 (but multiplied
of about 20° (3J H7-H8eq
)
3J ≈ 20) and 140° (3J H7-H2 and 3J H7-
H8ax ) 3J ≈ 140) can be predicted to be similar and in the range 8-11
Hz which is the case. See: Gu¨nter, H. NMR Spectroscopy (translated
by Gleason, R. W.); J ohn Wiley & Sons: Chichester, 1980; p 107.
6620 J . Org. Chem., Vol. 68, No. 17, 2003

New 1,3-Oxathianes Derived from Myrtenal
F IGURE 2. 1H NMR of compound 8c.
F IGURE 3. Molecular structure of compound 8c; ORTEP with atom numbering. Thermal ellipsoids are drawn at 50% probability
level. Hydrogen atoms are omitted for clarity.
SCHEME 2
by two). Moreover, the equivalence of the protons in both
of the CH2 groups suggested the presence in the molecule
of a C2 axis. Mass spectroscopy of 8c indicated a dimeric-
type structure with a parent ion M+ ) 396 corresponding
to C22H36O2S2.
After crystallization from hexane a selected single
crystal of compound 8c was submitted to X-ray diffraction
analysis. The structure obtained, Figure 3, is the expected
dimer 8c with a C2 axis. It appears also that the
substituents at C13 (or C1) and C21 (or C9), using the
ORTEP numbering, are in a trans relationship. More-
over, flattering of the ring appears clearly and the
dihedral angles C15-C14-C13-C21 (or C3-C2-
C1-C9) and C14-C13-C21-C20 (or C2-C1-C9-C8)
values are 19.0(2)° and 23.0(2)°, respectively, which
explains the similar values for the 3J H7-H8eq,
3
3J H7-H8ax, and J H7-H2 coupling constants.8
Lit h ia t ion a n d Qu en ch in g of Oxa t h ia n es 4a -c.
Although lithiation of 4c with BuLi had failed,2 we
succeeded to obtain the lithium derivative of 4c using
s-BuLi in THF at -78 °C as seen from the quantita-
tive yield in monodeuterated oxathiane 11c obtained,
Scheme 3.
Quenching with TMSCl also provided compound 12c
in quantitative yield.
Quenching of the lithiated oxathiane 4c with
PhCHO and PhCOMe, Scheme 3, provided the desired
alcohols 13c and 14c in 94% and 83% yield, respectively,
J . Org. Chem, Vol. 68, No. 17, 2003 6621

Solladie´-Cavallo et al.
SCHEME 3
TABLE 2. Dia ster eoselectivity a t C5′ for Oxa th ia n e 4c
a n d /or a t C2′ for Oxa th ia n es 1 a n d 2 (d u r in g
con d en sa tion of ca r bon yl r ea gen t on to lith ia ted
oxa th ia n es)
SCHEME 4
4c 5′R/5′S
1a 2′R/2′S
2a 2′R/2′S
PhCHO
PhCOMe
62/38
53/47
67/33
70/30
70/30
80/20
a
For 1, see ref 11; for 2, see ref 3b.
and as a mixture of two diastereomers (over the four
possible).
keto-derivative 15, reaction which is known to proceed
through a Cram’s approach9 with entrance of the hydride
from the oxygen side, thus providing the S-configuration
at C5′, Scheme 5.
The keto-derivative 15 was synthesized through con-
densation of benzonitrile onto lithiated oxathiane 4c
followed by HCl hydrolysis.10
NOE experiments exhibit in all cases positive effects
between proton H5 and protons H7 and H3axial, indicating
that the remaining proton at C5 has an axial orientation.
Therefore, the deuterium in 11c and the SiMe3 group in
12c have an equatorial position. Likewise, in both dia-
stereomers of 13c and 14c the CH(OH)Ph and CMe(OH)-
Ph groups are also equatorial.
From the synthesis of diastereomer 13cII having the
S-configuration at C5′ (cf. below), the R-configuration has
been assigned to the major diastereomer 13cI obtained
during the condensation of benzaldehyde on lithiated 4c,
Scheme 3.
Isom er 13cII having the S-configuration at C5′ is
3
characterized by a triplet (3J 5-5′ ) J 5′-OH ) 3.5 Hz) at
5.01 ppm for H5′ and a doublet (3J 5-5′ ) 3.5 Hz) at 5.17
ppm for H5; while, in 13cI, H5′ is a double-doublet (3J 5-5′
3
) 7.5 Hz, J 5′-OH ) 2 Hz) at 4.73 ppm and H5 a doublet
(3J 5-5′ ) 7.5 Hz) at 4.98 ppm.
However, no deuterium exchange was observed when
oxathiane 4a was treated with s-BuLi in THF (at -78
°C and/or at -30 °C) followed by quenching with D2O.
Only the starting oxathiane was recovered and in quan-
titative yield. Although some decomposition was observed
when the reaction time for formation of the lithiated
derivative was too long (40 min instead of 15 min).
Oxathiane 4b, treated with s-BuLi in THF at -78 °C,
afforded, after quenching with D2O, the monodeuterated
oxathiane 11b in quantitative yield, Scheme 4.
Quenching with TMSCl also provided compound 12b
in 43% yield.
Discu ssion a n d Con clu sion
Postulating that condensations of PhCHO and
PhCOMe undergo the same stereochemical approach, one
can conclude that the major diastereomer I of 13c and
14c has the R-configuration at C5′.
The diastereoselectivities observed at C5′ with oxa-
thiane 4c (62/38 and 53/47) are much smaller compared
to those obtained under similar conditions with oxa-
thianes 23 and/or 1,11 but the configuration at the carbon
undergoing addition for all the major isomers is R at
carbon C5′ or C2′, Table 2.
Positive nuclear Overhouser effects were observed
between the ortho protons of the phenyl group and
protons H7 and H3axial, indicating that the phenyl ring,
in 11b and 12b, has an axial orientation. Therefore, the
deuterium atom and the SiMe3 group were introduced
in the equatorial position.
Assign m en t of Absolu te Con figu r a tion a t C5′ of
Com p ou n d s 13cI fr om 13cII. Assignment of the con-
figuration at C5′ has been done by preparation of
compound 13cII using LiAlH4 reduction of the desired
(9) Ko, K. Y.; Frazee, W. J .; Eliel, E. L. Tetrahedron 1984, 40, 1333.
(10) Eliel, E. L.; Bai, X.; Abdel-Magid, A. F.; Hutchins, R. O. J . Org.
Chem. 1990, 55, 4951.
6622 J . Org. Chem., Vol. 68, No. 17, 2003

New 1,3-Oxathianes Derived from Myrtenal
F IGURE 4.
SCHEME 5
Close examination of the models that we proposed
recently3 shows that, in lithiated oxathiane 2, the oxygen
side is significantly more hindered than the sulfur side
(because of the aromatic ring and of the folding of the
molecule), causing approach I (with the large group RL
away from the concave part of the molecule) to be favored
over approach II , Figure 4.
In lithiated oxathiane 1, the O-side and S-side are
similarly hindered (with an equatorial Me on the S-side
versus an equatorial CH2 on the O-side) and should
provide low enantioselectivities, which is not the case.
With the propensity of lithium (in carbanions) to interact
more with an oxygen present in the molecule than with
the carbanion-carbon being well-known, at least in the
solid state,12 and its propensity to link to a sulfur atom
being weaker,13 one can reasonably postulate that the
lithium atom in lithiated oxathianes interacts both with
the carbon and the oxygen, Figure 5, and is shifted
toward the O-side, making the hindrance at this side
F IGURE 5.
closer and therefore more effective, leading in oxathiane
1 to an increase of the contribution of approach I
compared to approach II and a larger diastereoselectivity
as observed.
In oxathiane 4c the S-side is more hindered than the
O-side (with a CH2 equatorial on the S-side versus a H
equatorial on the O-side), and approach II should be
favored. The R preference, but with a low diastereose-
lectivity, is consistent with the hypothesis of a shift of
the lithium toward the O-side and a smaller than
expected influence of the hindrance located on the S-side
on the diastereoselectivity.
(11) Eliel, E. L.; Morris-Natschke, S. J . Am. Chem. Soc. 1984, 106,
2937.
In conclusion, 2-methyl- and 2-phenyl-substituted oxa-
thianes 4a and 4b have been synthesized in satisfying
yields. Lithiation of 2-methyl-substituted 4a could not
be done (n-BuLi or s-BuLi), although lithiation of 2-phen-
yl-substituted 4b and nonsubstituted 4c have been
successfully performed with s-BuLi. Quenching with D2O,
TMSCl, and/or a carbonyl compound always provides the
(12) In the crystal of lithiosulfones and lithiosulfoxides the lithium
was found to be linked to the oxygen atom, see: Gais, H. J .; Lindner,
H. J .; Vollhardt, J . Angew. Chem., Int. Ed. Engl. 1985, 24, 859 and
Boche, G.; Marsch, M.; Harms, K.; Sheldrick, G. M. Angew. Chem.,
Int. Ed. Engl. 1985, 24, 573.
(13) In lithiated thioethers, dimerization may occur through a (Li-
C-Li-C) four-membered ring or through
a (Li-C-S-Li-C) six-
membered ring, see: Amstutz, R.; Laube, T.; Schweizer, W. B.;
Seebach, D.; Dunitz, J . D. Helv. Chim. Acta 1984, 67, 224.
J . Org. Chem, Vol. 68, No. 17, 2003 6623

Solladie´-Cavallo et al.
C5 equatorial products (deuterium, SiMe3, CR1(OH)R2
are introduced in the equatorial orientation), consistent
with a preferred equatorial orientation of the lithium in
the lithiated derivatives.14,15
34.8 (CH2), 35.0 (CH), 35.8 (CH2), 37.4 (CH), 37.9 (CH), 38.0
(CH2), 38.1 (CH2), 40.0 (CH2), 41.6 (CH2), 42.3 (CH), 42.5 (CH),
43.0 (CH), 46.3 (CH), 46.48 (CH), 46.52 (SCHS), 46.8 (SCHS),
47.2 (CH), 47.4 (CH), 49.4 (CH), 51.0 (CH), 51.4 (CH), 52.2
(CH), 67.6 (CH2O), 68.5 (CH2O), 68.8 (CH2O), 69.6 (CH2O), 99.0
(O-CH2-O), 99.1 (O-CH2-O). MS: M+ ) 424.
A model is proposed to rationalize the diastereoselec-
tivities observed at C5′ during reaction of aldehydes with
lithiated oxathianes. The model is based on the hypoth-
esis that the lithium, being linked simultaneously to the
carbon and the oxygen, is shifted toward the oxygen side,
making the steric hindrance of this side more effective.
Moreover, dimeric side products were observed in all
cases (oxathianes 4a -c) during condensation of various
aldehydes (CH2O, RCHO) with the starting hydroxythiol,
which was not observed in the case of other oxathianes
such as 1, 2, and 3.
9a : Colorless oil; [R]20 ) +224 (CHCl3, c ) 1). 1H NMR
(CDCl3) δ: 0.97 (3H, s, Me), 0.98 (3H, s, Me), 1.13 (2H, d, J )
10 Hz), 1.21 (6H, s, 2‚Me), 1.66 (3H, d, J ) 7 Hz, Me), 2.00
(2H, m), 2.06-2.22 (6H, m), 2.43 (4H, m), 2.55 (2H, dddd, J )
13 Hz, J ) 9.5 Hz, J ) 3 Hz, J ) 2 Hz), 3.30 (2H, ddd, J ) 9.5
Hz, J ) 7.5 Hz, J ) 5.5 Hz), 3.63 (2H, m), 3.79 (2H, dt, J )
10.5 Hz, J ) J ) 8 Hz), 4.16 (1H, q, J ) 7 Hz). 13C NMR
(CDCl3) δ: 24.0 (Me), 24.1 (Me), 24.6 (Me), 27.83 (Me), 27.86
(Me), 33.27 (CH2), 33.29 (CH2), 36.1 (CH), 37.0 (CH), 38.6
(CH2), 38.8 (C), 40.0 (CH2), 42.45 (CH), 42.46 (CH), 44.1 (CH),
44.2 (CH), 45.7 (SCHS), 52.2 (CH), 53.0 (CH), 67.30 (CH2),
67.35 (CH2). MS: M+ ) 398
4b: White solid, mp 74-76 °C. [R]20D ) -36 (CHCl3, c ) 1).
1H NMR (CDCl3) δ: 1.08 (1H, d, J ) 9.5 Hz, H11ax), 1.22 (3H,
s, Me), 1.31 (3H, s, Me), 1.78 (1H, dd, J ) 13 Hz, J ) 10 Hz,
H8ax), 1.89 (1H, t, J ) 6 Hz, H1), 2.10 (1H, q, J ) J ) J ) 6
Hz, H9), 2.40 (1H, dddd, J ) 13 Hz, J ) 10 Hz, J ) 6 Hz, J )
2 Hz, H8eq), 2.64 (2H, m), 3.80 (1H, t, J ) 11 Hz, H3ax), 3.96
(1H, q, J ) 10 Hz, H7), 4.17 (1H, dd, J ) 11 Hz, J ) 3 Hz,
H3eq), 5.95 (1H, s, H5), 7.29-7.39 (3H, m), 7.49 (2H, dd, J ) 8
Hz, J ) 2 Hz). 13C NMR (CDCl3) δ: 24.6 (Me), 29.7 (Me), 33.4
(CH2), 39.0 (C), 39.6 (CH2), 42.4 (CH), 43.5 (CH), 45.9 (CH),
51.5 (CH), 76.7 (CH2O), 87.7 (OCHS), 126.2 (CH), 128.4 (CH),
128.4 (CH), 139.2 (C). Anal. Calcd for C17H22OS: C, 74.41; H,
8.08. Found: C, 74.24; H, 8.00.
Exp er im en ta l Section
Commercially available reagents were used without further
purification; all solvents were dried and distilled before use.
1D proton and 13C NMR, recorded at 300 MHz for 1H and 75
MHz for 13C, were referenced to solvent (7.26/77.0 for CDCl3);
2D experiments (COSY and NOESY) were recorded at 400
MHz. Mass spectra were run by EI ionization (70 eV). Rotation
were determined at room temperature. All characteristics of
the starting hydroxythiol 7 were identical to the literature
values.2
Cycliza tion of 7 w ith Ald eh yd es. A solution of hydroxy-
thiol 7-trans (3.2 mmol, 1 equiv), the desired aldehyde (3.5
mmol, 1.1 equiv), and p-TsOH (0.16 mmol, 0.05 equiv) in
benzene (30 mL) was stirred at the desired temperature under
an argon atmosphere (reflux for 30 min for paraformaldehyde;
at room temperature for 4.5 h for acetaldehyde; at room
temperature for 2 h for benzaldehyde). The solution was stirred
with anhydrous K2CO3 overnight, filtered, and concentrated.
The crude product was purified by flash chromatography over
silica gel pretreated with 5% Et3N and using a hexane:ether
mixture (40:1) as the eluent.
9b: Colorless oil. [R]20 ) +102 (CHCl3, c ) 1). 1H NMR
D
(CDCl3) δ: 0.81 (3H, s, Me), 0.95 (3H, s, Me), 1.09 (1H, d, J )
10 Hz), 1.14 (1H, d, J ) 10 Hz), 1.18 (3H, s, Me), 1.20 (3H, s,
Me), 1.91-2.19 (8H, m), 2.40 (4H, m), 2.65 (2H, bs, OH), 2.81
(1H, ddd, J ) 9.5 Hz, J ) 7 Hz, J ) 5.5 Hz), 3.22 (1H, ddd, J
) 9.5 Hz, J ) 7.5 Hz, J ) 5.5 Hz), 3.43 (1H, dd, J ) 10.5 Hz,
3
3
J ) 7.5 Hz), 3.59 (2H, dd, J ) 10 Hz, J ) 7 Hz), 3.72 (1H,
dd, J ) 10.5 Hz, J ) 7 Hz), 5.18 (1H, s), 7.22-7.35 (3H, m,
HPh), 7.47 (2H, d, J ) 8 Hz, HPh). 13C NMR (CDCl3) δ: 23.4
(Me), 23.5 (Me), 27.45 (Me), 27.49 (Me), 32.4 (CH2), 32.7 (CH2),
37.1 (CH), 37.4 (CH2), 37.7 (CH), 37.9 (CH2), 38.2 (C), 38.3 (C),
41.7 (CH), 41.9 (CH), 43.3 (CH), 43.4 (CH), 51.9 (SCHS), 52.8
(CH), 53.0 (CH), 66.3 (CH2), 66.5 (CH2), 127.6 (CH), 127.9 (CH),
4a : Colorless oil; [R]20 ) -63.0 (CHCl3, c ) 1). 1H NMR
D
(CDCl3) δ: 1.01 (1H, d, J ) 9.5 Hz, H11ax), 1.14 (3H, s, Me),
1.26 (3H, s, Me), 1.50 (3H, d, J ) 6 Hz, Me), 1.72 (1H, dd, J )
12.5 Hz, J ) 10 Hz, H8ax), 1.81 (1H, t, J ) 6 Hz, H1), 2.10 (1H,
q, J ) 6 Hz, H9), 2.34 (1H, dddd, J ) 12.5 Hz, J ) 10 Hz, J )
6 Hz, J ) 2 Hz, H8eq), 2.41 (1H, dt, J ) J ) 10 Hz, J ) 3 Hz,
H2), 2.60 (1H, dtd, J ) 9.5 Hz, J ) J ) 6 Hz, J ) 2 Hz, H11eq),
3.60 (1H, t, J ) 10 Hz, H3ax), 3.75 (1H, q, J ) 10 Hz, H7), 3.97
(1H, dd, J ) 10 Hz, J ) 3 Hz, H3eq), 4.99 (1H, q, J ) 6 Hz, H5).
13C NMR (CDCl3) δ: 21.8 (Me), 24.5 (Me), 29.7 (Me), 33.5
(CH2), 39.0 (C), 39.6 (CH2), 41.4 (CH), 43.3 (CH), 45.8
(CH), 51.4 (CH), 76.2 (CH2O), 82.4 (OCHS). Anal. Calcd for
128.5 (CH), 140.4 (C). MS: M+ ) 460.
1
4c: Colorless oil; [R]20 ) -26.4 (c ) 1.4, CHCl3). H NMR
D
(CDCl3) δ: 1.03 (1H, d, J ) 10 Hz, H11ax), 1.17 (3H, s, Me),
1.27 (3H, s, Me), 1.73 (1H, ddd, J ) 13 Hz, J ) 10 Hz, J ) 1.5
Hz, H8ax), 1.78 (1H, t, J ) 6 Hz, H1), 2.11 (1H, dq, J ) 6 Hz,
J ) 1.5 Hz, H9), 2.36 (1H, dddd, J ) 13 Hz, J ) 10 Hz, J ) 6
Hz, J ) 2 Hz, H8eq), 2.51 (1H, ddd, J ) 11 Hz, J ) 10 Hz, J )
3 Hz, H2), 2.59 (1H, dtd, J ) 10 Hz, J ) J ) 6 Hz, J ) 2 Hz,
H11eq), 3.60 (1H, t, J ) 11 Hz, H3ax), 3.73 (1H, q, J ) 10 Hz,
H7), 3.96 (1H, dd, J ) 11 Hz, J ) 3 Hz, H3eq), 4.95 (2H, AB
system, J AB ) 12 Hz, ∆νAB ) 7 Hz, H5). 13C NMR (CDCl3) δ:
24.5 (C12), 29.6 (C13), 33.6 (C8), 39.1 (C10), 39.6 (C11), 42.1 (C7),
43.5 (C1), 46.2 (C9), 52.5 (C2), 74.0 (C5), 76.6 (C3).
C
12H20OS: C, 67.87; H, 9.49. Found: C, 68.00; H, 9.25.
8a : White solid; mp 113-115 °C. [R]20 ) +219 (CHCl3, c )
D
1). 1/1 mixture of 8a I and 8a II: 1H NMR (CDCl3) δ 1.00 (3H,
s, Me), 1.01 (3H, s, Me), 1.02 (3H, s, Me), 1.03 (1H, d, J ) 9.5
Hz), 1.07 (3H, s, Me), 1.10 (1H, d, J ) 9.5 Hz), 1.16 (2H, d, J
) 9.5 Hz), 1.22 (12H, s, 4‚Me), 1.28 (6H, d, J ) 5.5 Hz), 1.29
(6H, d, J ) 5.5 Hz), 1.64 (6H, d, J ) 7 Hz, 2‚Me), 1.66 (6H, d,
J ) 7 Hz, 2‚Me), 1.90-2.20 (15H, m), 2.32 (1H, ddt, J ) 7 Hz,
J ) J ) 5 Hz, J ) 2 Hz), 2.38-2.59 (8H, m), 3.41 (1H, ddd, J
) 10 Hz, J ) 7 Hz, J ) 5.5 Hz), 3.46-3.57 (4H, m), 3.60-3.75
(5H, m), 3.87 (1H, t, J ) 5 Hz), 3.89 (1H, dd, J ) 5.5 Hz, J )
4.5 Hz), 4.17 (1H, q, J ) 5.5 Hz, SCHS), 4.26 (1H, q, J ) 5.5
Hz, SCHS), 4.64 (1H, q, J ) 5.5 Hz, OCHO), 4.66 (1H, q, J )
5.5 Hz, OCHO). 13C NMR (CDCl3) δ: 19.5 (Me), 19.6 (Me), 24.3
(Me), 24.5 (Me), 24.9 (Me), 25.1 (Me), 25.3 (Me), 27.9 (Me), 28.1
(Me), 28.2 (Me), 28.3 (Me), 33.5 (CH2), 33.6 (CH), 34.2 (CH2),
8c: White solid, mp 130-132 °C, [R]20 ) +427.6 (CHCl3, c
D
) 1). 1H NMR (CDCl3) δ: 1.01 (6H, s, 2×Me), 1.05 (2H, d, J )
9.5 Hz, 2‚H6ax), 1.21 (6H, s, 2‚Me), 1.96 (4H, m), 2.05 (4H, m),
2.48 (4H, m), 3.52 (2H, dd, J ) 9.5 Hz, J ) 3.5 Hz, 2‚H2′eq),
3.77 (2H, dt, J ) J ) 9.5 Hz, J ) 6 Hz, 2‚H3), 3.78 (2H, s,
SCH2S), 3.90 (2H, dd, J ) 9.5 Hz, J ) 3.5 Hz, 2×H2′ax), 4.55
(2H, s, OCH2O). 13C NMR (CDCl3) δ: 24.5 (Me), 28.1 (Me),
32.9 (CH), 33.4 (SCH2S), 35.5 (CH2), 37.2 (CH2), 38.7 (C), 42.3
(CH), 47.3 (CH), 49.3 (CH), 70.1 (CH2O), 93.8 (OCH2O). MS:
M+ ) 396.
1
10: Colorless oil. H NMR and 13C NMR (CDCl3) identical
to literature.2
Typical P r ocedu r e for th e Lith iation of 1,3-Oxath ian es.
To a solution of the desired 1,3-oxathiane (0.227 mmol, 1 equiv)
in 1 mL of anhydrous THF was added a 0.8 M cyclohexane
(14) Eliel, E. L.; Koskimies, J . K.; Lohri, B. J . Am. Chem. Soc. 1978,
100, 1614.
(15) Lehn, J . M.; Wipff, G. J . Am. Chem. Soc. 1976, 98, 7489.
6624 J . Org. Chem., Vol. 68, No. 17, 2003

New 1,3-Oxathianes Derived from Myrtenal
solution of s-BuLi (0.295 mmol, 1.3 equiv) at -78 °C under an
argon atmosphere. After being stirred for 40 min at -78 °C,
the quenching is done.
product (94% conversion) was purified by flash chromatogra-
phy and provided the following: 13c (86%, colorless oil,
mixture of two diastereoisomers 62:38) using a gradient
hexane:ether mixture (9:1f3:1) as eluent and/or 14c (76%,
colorless oil, mixture of two diastereoisomers. 53:47) using an
hexane:ether (9:1) mixture as eluent.
Qu en ch in g of 4b-Li a n d 4c-Li w ith D2O. D2O (1 mL)
was added dropwise, and the bath was removed. The resulting
mixture was extracted with ether to give 11b (100%, colorless
1
13c: Colorless oil. 13cI (62%): 1H NMR (CDCl3) δ: 1.00
(1H, d, J ) 9.5 Hz, H11ax), 1.11 (3H, s, Me), 1.26 (3H, s, Me),
1.69 (1H, ddd, J ) 13 Hz, J ) 11 Hz, J ) 1 Hz, H8ax), 1.83
(1H, t, J ) 6 Hz, H1), 2.08 (1H, dq, J ) J ) J ) 6 Hz, J ) 1
Hz, H9), 2.26 (1H, dddd, J ) 13 Hz, J ) 8.5 Hz, J ) 6 Hz, J )
2 Hz, H8eq), 2.44 (1H, dt, J ) J ) 10.5 Hz, J ) 3 Hz, H2), 2.59
(1H, dtd, J ) 10 Hz, J ) J ) 6 Hz, J ) 2 Hz, H11eq), 3.13 (1H,
d, J ) 2.5 Hz, OH), 3.65 (1H, dt, J ) J ) 10.5 Hz, J ) 8.5 Hz,
H7), 3.68 (1H, t, J ) 10.5 Hz, H3ax), 4.10 (1H, dd, J ) 10.5 Hz,
J ) 3 Hz, H3eq), 4.73 (1H, dd, J ) 7.5 Hz, J ) 2.5 Hz, H5′),
4.98 (1H, d, J ) 7.5 Hz, H5), 7.30-7.45 (5H, m). 13C NMR
(CDCl3) δ: 24.5 (Me), 29.6 (Me), 33.5 (CH2), 39.5 (CH2), 39.0
(C), 41.2 (CH), 43.4 (CH), 45.7 (CH), 51.5 (CH), 76.4 (CH), 76.2
(CH2), 89.9 (CH), 127.1 (CH), 128.4 (CH), 128.6 (CH), 138.9
oil) and/or 11c (100%, colorless oil). H NMR analysis of both
compounds indicated quantitative incorporation of deuterium
at C-5.
1
11b: Colorless oil. [R]20 ) -127 (CHCl3, c ) 1). H NMR
D
(CDCl3) δ: 1.05 (3H, s, Me), 1.10 (1H, d, J ) 9.5 Hz, H11ax),
1.25 (3H, s, Me), 1.81 (1H, ddd, J ) 13.5 Hz, J ) 10 Hz, J )
1.5 Hz, H8ax), 1.85 (1H, t, J ) 6 Hz, H1), 2.10 (1H, dq, J ) J )
J ) 6 Hz, J ) 1.5 Hz, H9), 2.34 (1H, dddd, J ) 13.5 Hz, J ) 9
Hz, J ) 6 Hz, J ) 2 Hz, H8eq), 2.61 (1H, dtd, J ) 9.5 Hz, J )
J ) 6 Hz, J ) 2 Hz, H11eq), 2.87 (1H, ddd, J ) 12 Hz, J ) 11
Hz, J ) 6 Hz, H2), 3.78 (1H, dd, J ) 12 Hz, J ) 11 Hz, H3ax),
3.95 (2H, m, H7 + H3eq), 5.95 (1H, s, H5), 7.28-7.40 (3H, m),
7.56 (2H, m). 13C NMR (CDCl3) δ: 23.7 (Me), 29.4 (Me), 32.9
(CH2), 34.4 (CH), 38.6 (CH2), 39.0 (C), 43.3 (CH), 44.1 (CH),
48.4 (CH), 70.2 (CH2O), 79.5 (t, CD), 126.8 (CH), 128.1 (CH),
128.4 (CH), 139.6 (CH).
(C). IR (neat): 3390 (OH) cm-1
.
13cII (38%): 1H NMR (CDCl3) δ: 1.08 (1H, d, J ) 9.5 Hz,
H11ax), 1.11 (3H, s, Me), 1.25 (3H, s, Me), 1.70 (1H, ddd, J )
13 Hz, J ) 11 Hz, J ) 1 Hz, H8ax), 1.81 (1H, t, J ) 6 Hz, H1),
2.08 (1H, dq, J ) J ) J ) 6 Hz, J ) 1 Hz, H9), 2.27 (1H, dddd,
J ) 13 Hz, J ) 8.5 Hz, J ) 6 Hz, J ) 2 Hz, H8eq), 2.44 (1H, dt,
J ) J ) 11 Hz, J ) 3 Hz, H2), 2.58 (1H, dtd, J ) 9.5 Hz, J )
J ) 6 Hz, J ) 2 Hz, H11eq), 2.78 (1H, d, J ) 3.5 Hz, OH), 3.64
(1H, dt, J ) J ) 11 Hz, J ) 8.5 Hz, H7), 3.69 (1H, t, J ) 11
Hz, H3ax), 4.06 (1H, dd, J ) 11 Hz, J ) 3 Hz, H3eq), 5.01 (1H,
t, J ) 3.5 Hz, H5′), 5.17 (1H, d, J ) 3.5 Hz, H5), 7.30-7.45
(5H, m, HPh). 13C NMR (CDCl3) δ: 24.5 (Me), 29.6 (Me), 33.6
(CH2), 39.0 (CH2), 39.4 (C), 40.8 (CH), 43.4 (CH), 45.7 (CH),
51.5 (CH), 75.3 (CH), 76.4 (CH2), 90.8 (CH), 126.3 (CH), 128.0
(CH), 128.2 (CH), 139.0 (C). IR (neat): 3390 (OH) cm-1. Anal.
Calcd for C18H24O2S: C, 71.01; H, 7.95. Found: C, 71.26; H,
8.06.
11c: Colorless oil. [R]20 ) -9.8 (CHCl3, c ) 1). 1H NMR
D
(CDCl3) δ: 1.04 (1H, d, J ) 10 Hz, H11ax), 1.17 (3H, s, Me),
1.27 (3H, s, Me), 1.77 (2H, m, H8ax + H1), 2.12 (1H, dq, J ) 6
Hz, J ) 1.5 Hz, H9), 2.37 (1H, dddd, J ) 13 Hz, J ) 9 Hz, J )
6 Hz, J ) 2 Hz, H8eq), 2.51 (1H, dt, J ) J ) 10 Hz, J ) 3 Hz,
H2), 2.60 (1H, dtd, J ) 10 Hz, J ) J ) 6 Hz, J ) 2 Hz, H11eq),
3.60 (1H, t, J ) 10 Hz, H3ax), 3.73 (1H, dt, J ) J ) 10 Hz, J )
9 Hz, H7), 3.97 (1H, dd, J ) 10 Hz, J ) 3 Hz, H3eq), 4.96 (1H,
s, H5). 13C NMR (CDCl3) δ: 24.4 (Me), 29.6 (Me), 33.6 (CH2),
39.0 (C), 39.5 (CH2), 42.0 (CH), 43.4 (CH), 46.1 (CH), 52.4 (CH),
73.7 (t, J CD ) 24 Hz, CHD), 76.5 (CH2O).
Qu en ch in g of 4b-Li a n d 4c-Li w ith TMSCl. Trimethyl-
silyl chloride (0.413 mmol, 1.3 equiv) was added dropwise.
After 80 min, aqueous Na2CO3 was added and the resulting
mixture was extracted with ether to give 12b (43%), which
was separated from starting 4b (52%) by flash chromatography
using a hexane:ether (19:1) mixture as eluent and/or 12c (99%,
14c: Colorless oil. 14cI (53%): 1H NMR (CDCl3) δ: 0.98
(1H, d, J ) 9.5 Hz, H11ax), 1.10 (3H, s, Me), 1.25 (3H, s, Me),
1.65 (3H, s, Me), 1.61 (1H, m, H8ax), 1.81 (1H, t, J ) 6 Hz, H1),
2.07 (1H, dq, J ) J ) J ) 6 Hz, J ) 1 Hz, H9), 2.27 (1H, m,
H8eq), 2.42 (1H, dt, J ) J ) 11 Hz, J ) 3 Hz, H2), 2.58 (1H, m,
H11eq), 2.92 (1H, s, OH), 3.65 (2H, m, H3ax + H7), 4.09 (1H, dd,
J ) 11 Hz, J ) 3 Hz, H3eq), 5.11 (1H, s, H5), 7.27-7.39 (3H,
m), 7.48-7.53 (2H, m). 13C NMR (CDCl3) δ: 24.7 (Me), 27.3
(Me), 29.6 (Me), 33.54 (CH2), 39.1 (C), 39.4 (CH2), 40.9 (CH),
43.36 (CH), 45.6 (CH), 51.3 (CH), 75.8 (CH2O), 76.5 (C-OH),
93.4 (OCHS), 125.3 (CH), 127.3 (CH), 128.00 (CH), 143.8 (C);
1
pure by H NMR, colorless oil, no purification).
1
12b: Colorless oil. [R]20 ) -134 (CHCl3, c ) 1). H NMR
D
(CDCl3) δ: 0.01 (9H, s, CH3Si), 0.70 (3H, s, Me), 1.04 (1H, d,
J ) 10 Hz, H11ax), 1.15 (3H, s, Me), 1.66 (2H, m, H8ax + H1),
2.10 (1H, dq, J ) J ) J ) 6 Hz, J ) 1 Hz, H9), 2.14 (1H, dddd,
J ) 13 Hz, J ) 8.5 Hz, J ) 6 Hz, J ) 2 Hz, H8eq), 2.53 (1H,
dtd, J ) 10 Hz, J ) J ) 6 Hz, J ) 2 Hz, H11eq), 2.58 (1H, td,
J ) J ) 10 Hz, J ) 3 Hz, H2), 3.42 (1H, td, J ) 10 Hz, J ) 8.5
Hz, H7), 3.65 (1H, dd, J ) 11 Hz, J ) 3.5 Hz, H3eq), 3.84 (1H,
dd, J ) 11 Hz, J ) 10 Hz, H3ax), 7.19 (1H, tt, J ) 7.5 Hz, J )
1.5 Hz), 7.35 (2H, t, J ) 7.5 Hz), 7.55 (2H, d, J ) 7.5 Hz). 13C
NMR (CDCl3) δ: -3.6 (Me3Si), 24.4 (Me), 30.0 (Me), 34.1 (CH2),
36.6 (CH), 39.8 (CH2), 38.9 (C), 44.0 (CH), 46.6 (CH), 52.8 (CH),
70.2 (CH2O), 87.8 (O-C-S), 126.3 (CH), 128.2 (CH), 128.6
(CH), 141.6 (CH).
IR: (neat) 3500 (OH) cm-1
.
14cII (47%): 1H NMR (CDCl3) δ: 1.01 (1H, d, J ) 9.5 Hz,
H11ax), 1.11 (3H, s, Me), 1.25 (3H, s, Me), 1.66 (3H, s, Me), 1.65
(1H, m, H8ax), 1.80 (1H, t, J ) 6 Hz, H1), 2.09 (1H, dq, J ) J
) J ) 6 Hz, J ) 1 Hz, H9), 2.27 (1H, m, H8eq), 2.39 (1H, dt, J
) J ) 11 Hz, J ) 3 Hz, H2), 2.58 (1H, m, H11eq), 3.07 (1H, s,
OH), 3.65 (2H, m, H3ax + H7), 4.03 (1H, dd, J ) 11 Hz, J ) 3
Hz, H3eq), 5.05 (1H, s, H5), 7.27-7.39 (3H, m), 7.48-7.53 (2H,
m). 13C NMR (CDCl3) δ: 24.4 (Me), 27.3 (Me), 29.6 (Me), 33.50
(CH2), 39.1 (C), 39.5 (CH2), 41.1 (CH), 43.39 (CH), 45.7 (CH),
51.5 (CH), 75.9 (CH2O), 77.2 (C-OH), 93.7 (OCHS), 125.7
(CH), 127.4 (CH), 128.02 (CH), 144.2 (C). IR (neat): 3500 (OH)
12c: Colorless oil. [R]20 ) -42 (CHCl3, c ) 1). 1H NMR
D
(CDCl3) δ: 0.11 (9H, s, Me3Si), 1.04 (1H, d, J ) 9.5 Hz, H11ax),
1.16 (3H, s, Me), 1.25 (3H, s, Me), 1.73 (2H, m, H8ax + H1),
2.10 (1H, qd, J ) J ) J ) 6 Hz, J ) 1 Hz, H9), 2.35 (1H, dddd,
J ) 13 Hz, J ) 8.5 Hz, J ) 6 Hz, J ) 2 Hz, H8eq), 2.48 (1H, dt,
J ) J ) 10 Hz, J ) 3 Hz, H2), 2.58 (1H, dtd, J ) 9.5 Hz, J )
J ) 6 Hz, J ) 2 Hz, H11eq), 3.55 (1H, t, J ) 10 Hz, H3ax), 3.76
(1H, dt, J ) J ) 10 Hz, J ) 8.5 Hz, H7), 3.98 (1H, dd, J ) 10
Hz, J ) 3 Hz, H3eq), 4.78 (1H, s, H5). 13C NMR (CDCl3) δ: -3.6
(Me3Si), 24.4 (Me), 29.7 (Me), 33.9 (CH2), 39.0 (C), 39.6 (CH2),
43.6 (CH), 43.8 (CH), 46.4 (CH), 51.7 (CH), 78.7 (CH2O), 81.5
(CH).
cm-1
.
P r ep a r a tion of 15. To oxathiane 4c (0.43 mmol, 1 equiv)
in dry THF (1.7 mL) under argon at -78 °C was added
dropwise (through a syringe) a solution of s-BuLi 0.5 M in
cyclohexane (0.56 mmol, 1.3 equiv). After stirring for 40 min,
PhCN (0.56 mmol, 1.3 equiv) was added dropwise, and stirring
was maintained for 45 min at -78 °C. Then a 2 M HCl solution
(1 mL) was added, and the mixture was stirred briefly at room
temperature until two clear phases appeared. The organic
layer was separated, and the aqueous layer was extracted with
diethyl ether. The combined organic solutions were washed
with water, dried over Na2SO4, and concentrated under
Qu en ch in g of 4c-Li w ith Ca r bon yl Com p ou n d s. The
desired carbonyl compound (1.5 equiv) was added dropwise to
4c-Li prepared as described above. After 2 h of stirring, the
reaction mixture was quenched with aqueous NH4Cl and
extracted with ether. The joined organic phases were dried
over Na2SO4 and concentrated under vacuum. The crude
J . Org. Chem, Vol. 68, No. 17, 2003 6625

Solladie´-Cavallo et al.
vacuum. Purification by column chromatography using a
hexane:ether mixture (5:1) as the eluent gave the desired
ketone 15 (30%).
The mixture was extracted with diethyl ether; the joined
organic phases were dried over Na2SO4 and concentrated
under vacuum to afford 13c (99%, colorless oil) as a mixture
of 13cII (95%) and 13cI (5%).
15: Colorless oil. [R]20 ) -44.8 (CHCl3, c ) 1). 1H NMR
D
(CDCl3) δ: 1.07 (1H, d, J ) 10 Hz, H11ax), 1.22 (3H, s, Me),
1.30 (3H, s, Me), 1.80 (1H, ddd, J ) 13 Hz, J ) 10.5 Hz, J )
1 Hz, H8ax), 1.88 (1H, t, J ) 6 Hz, H1), 2.16 (1H, qd, J ) 6 Hz,
J ) 1 Hz, H9), 2.41 (1H, dddd, J ) 13 Hz, J ) 9 Hz, J ) 6 Hz,
J ) 2 Hz, H8eq), 2.64 (2H, m, H2 + H11eq), 3.80 (1H, t, J ) 11
Hz, H3ax), 3.99 (1H, td, J ) J ) 10.5 Hz, J ) 9 Hz, H7), 4.22
(1H, dd, J ) 11 Hz, J ) 3 Hz, H3eq), 6.21 (1H, s, H5), 7.46 (2H,
t, J ) 8 Hz), 7.60 (1H, tt, J ) 7.5 Hz, J ) 1 Hz), 8.11 (2H, dd,
J ) 8 Hz, J ) 1 Hz). 13C NMR (CDCl3) δ: 24.6 (Me), 29.5 (Me),
33.4 (CH2), 39.0 (C), 39.5 (CH2), 42.6 (CH), 43.4 (CH), 45.7
(CH), 51.2 (CH), 76.4 (CH2O), 87.0 (O-C-S), 128.4 (CH), 129.5
(CH), 133.7 (CH), 133.8 (C). IR (neat): 1694 (CO) cm-1. Anal.
Calcd for C18H22O2S: C, 71.49; H, 7.33. Found: C, 71.31; H,
7.49.
Ack n ow led gm en t. We are grateful to the French
Government (Sous-Direction des Boursiers Etrangers et
des Affaires Internationales) for a grant to M.B. (No.
19991885) and the Ambassade de France a` Bratislava-
Service de Coope´ration et d’Action Culturelle (M. B.
Paqueteau) for encouragement and financial support to
M.B. and M.S., and we cordially thank M. Schmitt
(ECPM) for NMR spectral assistance and P. Wehrung
(ECPM) for Mass Spectra.
Su p p or tin g In for m a tion Ava ila ble: 1D and 2D (COSY
and NOESY) 1H and 13C spectra of all new compounds; X-ray
crystallographic data. This material is available free of charge
via the Internet at http://pubs.acs.org.
Red u ction of 15. A well-stirred solution of 15 (0.07 mmol,
1 equiv) in 1 mL of dry THF under argon was treated with
LiAlH4 (0.14 mmol, 2 equiv) at -78 °C. After stirring for 2 h
at the same temperature, the excess reducing agent was
quenched at -78 °C with saturated aqueous NH4Cl solution.
J O034404W
6626 J . Org. Chem., Vol. 68, No. 17, 2003