New S,O-acetals from (1R)-(-)-myrtenal as chiral auxiliaries in nucleophilic additions

Article abstract of DOI:10.1016/j.tetlet.2004.01.046

Treatment of hydroxythiol 4 with α,α-diethoxyacetophenone at room temperature yielded a mixture of epimeric S,O-acetals 6 and 7 (1:4, 92% yield), which were efficiently separated by flash chromatography. The OTBS derivatives 8 and 9 were treated with several Grignard reagents to afford carbinols 10 and 13 respectively (85-99% yield, >95% dr). After successive hydrolysis and reduction of 10 and 13 it is possible to obtain either enantiomer of diols 16 in high optical purity (>95% er).

Full text of DOI:10.1016/j.tetlet.2004.01.046

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 2141–2145
New S,O-acetals from (1R)-())-myrtenal as chiral auxiliaries in
nucleophilic additions
a
Luis Chacon-Garcıa, Selene Lagunas-Rivera, Salvador Perez-Estrada,
a
a
ꢀ
ꢀ
ꢀ
a
b
a
ꢀ
ꢀ
M. Elena Vargas-Dıaz, Pedro Joseph-Nathan, Joaquın Tamariz
and L. Gerardo Zepedaa,*
aDepartamento de Quꢀımica Orgꢀanica, Escuela Nacional de Ciencias Biolꢀogicas, Instituto Politꢀecnico Nacional,
Prol. de Carpio y Plan de Ayala, Mꢀexico, D.F. 11340, Mexico
b
ꢀ
ꢀ
ꢀ
Departamento de Quımica, Centro de Investigacion y de Estudios Avanzados del Instituto Politecnico Nacional,
Apartado 14-740, Mꢀexico, D.F. 07000, Mexico
Received 19 October 2003; revised 23 December 2003; accepted 12 January 2004
Abstract—Treatment of hydroxythiol 4 with a,a-diethoxyacetophenone at room temperature yielded a mixture of epimeric S,O-
acetals 6 and 7 (1:4, 92% yield), which were efficiently separated by flash chromatography. The OTBS derivatives 8 and 9 were
treated with several Grignard reagents to afford carbinols 10 and 13 respectively (85–99% yield, >95% dr). After successive
hydrolysis and reduction of 10 and 13 it is possible to obtain either enantiomer of diols 16 in high optical purity (>95% er).
ꢀ 2004 Elsevier Ltd. All rights reserved.
As part of our research to develop new chiral auxiliaries,
we described the synthesis of 2-acyl-1,3-oxathianes,1
which have been proven as useful synthetic tools for the
enantioselective preparation of several chiral 1,1-dial-
kyl-1,2-ethanodiols.2 These compounds are key inter-
mediates for constructing chiral a-hydroxycarbonyl
derivatives possessing important biological activities
(Chart 1).3 In the precedent papers1;2 of this series we
described the synthesis of oxathiane 1 and acyloxathi-
anes 2a and 2b in 35%, 45%, and 32% isolated yield,
respectively (Chart 1). Further, in a recent work Sol-
ꢀ
ladie-Cavallo et al. described the synthesis of 2-substi-
tuted alkyl oxathianes by condensing the anion of
oxathiane 1 with acetaldehyde and benzaldehyde.4 The
OR
R1
RO
R2MgX
O
R1
R1
OH
SH
OH
S
S
O
O
O
R2
S
R
S
R
O
O
R1
OH
1
R = H
2a R = COPh
2b R = COMe
3a R = H
HO
R2
3b R = COPh
3cR = COMe
Chart 1.
Keywords: (1R)-())-Myrtenal; Diastereoselective nucleophilic additions; S,O-acetals; Chiral 1,2-diols.
* Corresponding author. Tel.: +52-55-57296300; fax: +52-55-53963503; e-mail: lzepeda@woodward.encb.ipn.mx
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.01.046

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L. Chacꢀon-Garcıa et al. / Tetrahedron Letters 45 (2004) 2141–2145
2142
successful preparation of the anion of oxathiane 1 and
its condensation with several electrophiles4 added syn-
thetic value to oxathiane 1 because it enhances the
possibility to obtain a major variety of enantiomerically
pure a-hydroxycarbonyl derivatives. In spite of the
almost quantitative preparation of hydroxythiol 4
(Scheme 1) from (1R)-())-myrtenal,1;2 chemical yields of
oxathiane 1 and acyloxathianes 2a and 2b, ranging 35–
45%, remained as a challenge to be improved. This work
presents recent advances in this direction, and the use of
new S,O-acetals as chiral auxiliaries to be used in pur-
suing the same molecular targets obtained by using
oxathianes 1 and 3a, and acyloxathianes 2a,b and 3b,c
prepared by us1;2 and by ElielÕs group,5 respectively.
The OTBS derivatives 8 and 9 were treated with several
representative nucleophiles, giving the corresponding
adducts 10a–g and 11a–g (Table 1), as well as 12a,b,e
and 13a,b,e, respectively.9 As can be seen, diastereo-
selective ratios were excellent with Grignard reagents,
and are similar to those described for acyloxathianes 2a
and 2b.1;2 As described in additions to acyloxathianes
2a and 2b, a small amount of alcohol 10g was detected
in the above reactions.10 The higher stereoselectivities
shown with Grignard reagents, as compared to those
with n-BuLi and LiAlH4 (entries 7 and 8) agree with the
ability of the metal to form C@O–M–O interactions,
which in turn favor the formation of the highly stereo-
selective Cram chelated transition state.11
In a search to improve the chemical yield of benzoyl-
oxathiane 2a, we carried out the coupling of hydroxy-
thiol 4 with a-ketoacetal 5 in CH2Cl2 at room
temperature using p-TsOH as catalyst, affording, almost
quantitatively, the S,O-acetals 6 and 7 in 1:4 ratio, which
were readily separated by flash chromatography (6: Rf
0.16; 7: rf 0.25; TLC, hexane–EtOAc 4:1). The reaction
outcome was easily equaled to 1:1 by treated the original
mixture with NaHCO3 in THF at room temperature
(Scheme 1).
The absolute configuration of the new stereogenic center
was established by chemical correlation with com-
pounds of known absolute stereochemistry. Thus, the
oxidative hydrolysis of adducts 10a–g proceeded in 80–
95% yielding mixtures of the corresponding a-hydroxy-
aldehydes (R)-14a–g with the dimeric disulfide 15, which
is favored over the expected sultine12 due to angular
strain. The reduction of this mixture with LiAlH4, or
NaBH4, followed by flash chromatography, provided
the corresponding diols 16a–g (85–93% yield) and
regenerated hydroxythiol 4, or the OTBS protected thiol
4a (75–85% yield).13 The optical rotations of diols 16a–g
were compared with those previously described, allow-
ing to know both their optical purity and absolute
configuration, which was established as (R).2;14a–c Com-
plementarily, Ag2O oxidation of the reaction mixture of
(R)-14a and 15 afforded (R)-())-atrolactic acid and the
nonfurther oxidized disulfide 15. This chemical corre-
lation, together with that of diols (R)-16a–b, also con-
stitutes evidence for the absolute configuration of the
nonisolated aldehydes 14a–g.
The structural analogy of these compounds with oxa-
thiane 2a is evident; therefore this finding encouraged us
to evaluate them as chiral auxiliaries in diastereoselec-
tive additions to their keto group, as was done for
oxathianes 2a and 2b.1;2 In order to achieve such addi-
tions, the OH groupof S,O-acetals 6 and 7 was pro-
tected with tert-butyldimethylsilyl chloride (TBSCl) in
the presence of imidazole in anhydrous CH2Cl2, giving
the nonequilibrated S,O-acetals 8 (Rf 0.84; hexane–
EtOAc 9:1) and 9 (Rf 0.79 in TLC; hexane/EtOAc 9:1) in
95%.6 It is worth noting that Rf values of 8 and 9 are
closer than those of the unprotected S,O-acetals 6 and 7;
nevertheless, these compounds are efficiently separated
by flash or radial chromatography.7 In addition, the
reversed polarity in TLC of S,O-acetals 8 and 9, with
regard to S,O-acetals 6 and 7, should be noted.8
In order to gain further stereochemical information
concerning diastereoselectivities, adducts 13a,b,e were
also submitted to hydrolysis, giving aldehydes (S)-
14a,b,e and dimer 15. These aldehydes were efficiently
reduced with NaBH4 to the corresponding diols (S)-
CHCl3, reflux
p-TsOH,78%
OEt
OEt
Ph
Ph
H
OEt
O
EtO
EtO
EtO
H
5
O
O
5
SH
OH
+
S
S
OH
S
CH2Cl2, r.t.
p-TsOH, 92%
C6H6, reflux
p-TsOH, 38%
O
OH
(1)
O
4
O
(4)a
(1)b
2a
6
7
NaHCO3
THF, r.t.
(1)
CH2Cl2
95%
(CH2O)n,
C6H6
TBSCl
CH2Cl2
95%
TBSCl
p-TsOH
imidazole
imidazole
S
S
H
S
OTBS
OEt
EtO
S
OTBS
H
+
S
O
O
O
O
O
1
22
8
9
Scheme 1. Preparation of S,O-acetals 8 and 9 from hydroxythiol 4, which is a key precursor for the synthesis of chiral auxiliaries 1 and 2a. Numbers
in parentheses indicate the 6:7 ratio: aobtained from the crude reaction, and bafter equilibration with NaHCO3.

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L. Chacꢀon-Garcıa et al. / Tetrahedron Letters 45 (2004) 2141–2145
2143
Table 1. Use of S,O-acetals as chiral auxiliaries in diastereoselective nucleophilic additions and its chemical correlation with diols of known absolute
configuration
R
R
S
R
2
R
S
R
2
R
S
1
1
2
1
R
R
R
3
3
3
11
11
R M
4
+
R
OH
HO
R
4
4
R
O
R
R
10 R = OTBS; R = OEt;
8 R = OTBS; R = OEt; R = H; R = Ph
11 R = OTBS; R = OEt;
1
1
2
3
1
R =H; R = Ph; R = H, alkyl
9 R = OTBS; R = H; R = OEt; R = Ph
R = H; R = Ph; R = H, alkyl
2
3
4
1
2
3
2
3
4
12 R = OTBS; R = H;
17R = OH; R = OMe; R = H; R = Me
13 R = OTBS; R = H; R = OEt;
1
1
2
3
1
2
R = OEt; R = Ph; R = H, alkyl
18R = OH; R = H; R = OMe; R = Me
R = Ph ; R = H, alkyl
i
2
3
4
1
2
3
4
3
20 R = OTBS; R = OMe; R = H;
19R = OTBS; R = OMe; R = H; R = Me
21 R = OTBS; R = OMe; R = H;
1
2
1
2
3
1
2
R = Me; R = Ph
R = Me; R = Ph
3
4
4
3
AgNO NCS
3
O
R
3
R
NaBH
3
4
SH
R
HO
+
+
R
H
HO
S
R
4
R
4
HO
(R)-16a-g R = Ph; R = H, alkyl
(S)-16a,b,e R = Me, Et, vin; R = Ph
4 R = OH
(R)-14a-g R = Ph; R = H, alkyl
3 4
3
4
2
4aR = OTBS
(S)-14a,b,e R = Me, Et, vin; R = Ph
3
4
15R = OTBS
3
4
Entry
S,O-Acetal
R4M
R4
Adducts (% ratio,
% yield)a
Diol, % yieldb
Abs. config., % Erf
1
8
8
8
8
8
8
8
8
9
9
9
19
MeMgBr
EtMgBr
Me
Et
10a:11a (>99:1, 99)
10b:11b (>99:1, 99)
10c:11c (>99:1, 74)c
10d:11d (>99:1, 82)c
10e:11e (>99:1, 88)
10a:11a (>99:1, 99)d
10f:11f (>90:10, 74)
10g:11g (80:20, 96)
12a:13a (1:>99, 99)
12b:13b (1:>99, 99)
12e:13e (1:>99, 86)
20:21 (>99:1, 96)e
16a, 90
16b, 86
16c, 72
16d, 76
16e, 88
16a, 82
16f, 63
16g, 68
16a, 92
16b, 90
16e, 85
16a, 76
(R), >95
(R), >95
(R), >95
(R), >95
(R), >95
(R), >95
(R), 89
2
3
i-PrMgBr
i-BuMgBr
CH2@CHMgBr
MeLi
i-Pr
i-Bu
4
5
CH2@CH
Me
6
7
n-BuLi
LiAlH4
n-Bu
H
8
(R), 80
9
MeMgBr
EtMgBr
Me
Et
(S), >95
(S), >95
(S), >95
(S), >95
10
11
12
CH2@CHMgBr
PhMgBr
CH2@CH
Ph
a The ratio was measured by integrating H-11 in the NMR (300 MHz) spectra of the crude reaction mixture, and the yield was calculated as the
mixture of both diastereomers.
b Calculated from the hydrolysis of the precursor adducts.
c Chemical yield was diminished due to the formation of adduct 10g as by-product.
d MeLi gave the same adduct as MeMgBr starting with 8.
e Only S,O-acetal 19 was treated with PhMgBr to corroborate the stereochemistry at C-11 of compounds 17 and 18. At scheme (i) 17 fi 19: TBSCl,
imidazole, CH2Cl2, rt, 95% yield.
f Absolute configuration and % er were determined according to Refs. 2,14a–c.
16a,b,e. Once the absolute configuration of diols (R)-
16a–g and (S)-16a,b,e were known from their optical
rotations,2;14a it was possible to assign the absolute
configuration at C-11 of S,O-acetals 6 and 7, being (S)
and (R), respectively. This finding was further sustained
by assuming that nucleophilic additions on 8 and 9 took
place in agreement with the Cram chelated mechanism,
as is observed in acyloxathianes.1;2;5 In this sense, the
higher conformational freedom of S,O-acetals 8 and 9,
as compared to acyloxathianes, seems not to be an
obstacle to attain a chelated transition state. Neverthe-
less, such conformational freedom could be responsible
for the larger tendency of 8 and 9 to be epimerized in
comparison to acyloxathianes.9 In other words, the
corresponding anions of 8 and 9, which presumably are
formed before the nucleophilic addition takes place,
cannot reach the typical equatorial preference15 as can
anions of oxathianes 14 and 3a,16 since the former are
acyclic S,O-thioacetals and the later are cyclic S,O-
thioacetals. This means that anions of 8 and 9, or 6 and
7 are probably quite close in energy.
In order to extend the scope for the formation of S,O-
acetals, treatment of hydroxythiol 4 with pyruvic alde-
hyde dimethyl acetal under the above reaction condi-
tion, led to a 2:1 mixture of S,O-acetals 17 and 18,
respectively, in 95% yield. In spite of their close rf values
(17, Rf 0.20; 18, Rf 0.26; hexane–EtOAc 7:3) they were
efficiently separated by radial chromatography. Thus,
diastereomerically pure S,O-acetal 17 was also treated
with TBSCl affording the protected S,O-acetal 19 in 95%
yield. Following the same reaction conditions used to
obtain adducts 10a–g, compound 19 was treated with
PhMgBr yielding adducts 20 and 21 in >99:1 ratio and
96% yield. The hydrolysis of adduct 20, and subsequent
reduction of the intermediate aldehyde (S)-14a, (Table 1,

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L. Chacꢀon-Garcıa et al. / Tetrahedron Letters 45 (2004) 2141–2145
2144
entry 12) led to diol (S)-16a, which possesses the same
configuration as diol obtained from adduct 13a (Table 1,
entry 9). Therefore, and as was stated for S,O-acetals 6
and 7, this result indicates that the stereochemistry at C-
11 in S,O-acetals 17 and 18 is (S) and (R), respectively. It
is noteworthy that S,O-acetals 8 (R3 ¼ Ph) and 19
(R3 ¼ Me) afford the a-hydroxycarbonyl derivatives
possessing the opposite absolute configuration than
those obtained with oxathianes 2a and 3b, or oxathianes
2b and 3c, respectively. This fact represents a synthetic
complement when acyloxathianes are used as chiral
auxiliaries, since to obtain a given enantiomeric pair it
was necessary to interchange the R groupof the acyl
moiety followed by addition of the appropriate Grig-
nard reagent.5
the above S,O-acetals are opening a new avenue to
substantially improve the synthesis of the corresponding
acyloxathianes. Spectroscopic data for compounds 8
and 10a are showed.19;20
Acknowledgements
This work was supported by CONACyT (grant 35013E)
and CGPI-IPN (grant 20030702). L.C.-G., M.E.V.-D.
and S.L.-R. thank CONACyT (92069, 125225 and
165282, respectively) and CGPI/IPN (PIFI) post-
graduate fellowships. S.P.-E. acknowledges CGPI/IPN
(PIFI) for undergraduate fellowship.
Although the chiral auxiliary is recovered in good yield,
either as 4, 4a or 15, the main shortcoming of this
methodology is that in the next cycle of induction, when
reusing the chiral auxiliary 4, the separation of S,O-
acetals 6 and 7 (when using 4), or 8 and 9 (if 4a is used)
should be faced. Therefore, at that stage it should be
decided if equilibration of the crude mixture of 6 and 7
will be carried out or not, depending on the desired
absolute configuration of the target compound.
References and notes
ꢀ
ꢀ
ꢀ
ꢀ
1. Martınez-Ramos, F.; Vargas-Dıaz, M. E.; Chacon-Garcıa,
L.; Tamariz, J.; Joseph-Nathan, P.; Zepeda, L. G.
Tetrahedron: Asymmetry 2001, 12, 3095.
ꢀ
ꢀ
ꢀ
ꢀ
2. Vargas-Dıaz, M. E.; Chacon-Garcıa, L.; Velazquez, P.;
Tamariz, J.; Joseph-Nathan, P.; Zepeda, L. G. Tetrahe-
dron: Asymmetry 2003, 14, 3225.
3. For some a-phenyl-a-hydroxycarbonyl derivatives, see: (a)
Yasohara, Y.; Miyamoto, K.; Kizaki, N.; Hasegawa, J.;
Ohashi, T. Tetrahedron Lett. 2001, 42, 3331; (b) Nakajima,
Y.; Takeyama, T.; Furusato, T.; Ooya, H.; Nakayama,
M.; Sasabe, S. JP Patent 06220049 A2 19940809, 1994;
Chem. Abstr. 1995, 122, 133170; (c) Hoechst-Schering, DE
Patent, 4319887 A1 19941222, 1994; Chem. Abstr. 1995;
122, 132777.
On the other hand, taking advantage of the isolation of
S,O-acetals 6 and 7, and assuming their intermediacy in
the formation of oxathiane 2a, they were converted to
the last compound in 78% isolated yield by refluxing in
CHCl3 in the presence of p-TsOH during 1 h (Scheme 1).
This result is a notable yield improvement concerning
the synthesis of benzoyloxathiane 2a.
ꢀ
4. Solladie-Cavallo, A.; Balaz, M.; Salisova, M.; Welter, R.
J. Org. Chem. 2003, 68, 6619.
5. Lynch, J. E.; Eliel, E. L. J. Am. Chem. Soc. 1984, 106,
2943.
From the last reaction were isolated dimeric com-
pounds17 in roughly 10% yield, which are structurally
related to dimer 22 isolated from the treatment of
hydroxythiol 4 with paraformaldehyde (Scheme 1).4;18
As mentioned above, such behavior could be explained
in terms of angular strain. In other words, the lower
conformational freedom of hydroxythiol 4, that is, as
compared to hydroxythiol prepared from pulegone,5
partially precludes the formation of an additional ring
(in this case the oxathiane ring), affording dimeric
compounds with less content of angular strain. This is
the reason why dimer 15 is likely formed in lieu of the
sultine,12 which was not previously isolated.1;2
6. Starting from diastereomerically pure S,O-acetal, certain
degree of epimerization at C-11 is observed when CH2Cl2
is not anhydrous. OTBS protection in DMF as solvent
should also be avoided due to epimerization of pure S,O-
acetal.
7. S,O-Acetals 6 and 7 are easier separated by flash chroma-
tography than compounds 8 and 9 because their larger Rf
value differences; however, the later can be efficiently
separated by applying the following typical procedure: In
a chromatography column (id ¼ 3.5 cm) packed with 90 cm
of flash silica gel, 584 mg of the crude mixture of S,O-
acetals 8 and 9 were eluted with a mixture of EtOAc–
hexane (1:49) at 15 psi, giving 344 mg (59%) of 8, 192 mg
(33%) of 9 and 46 mg (8%) of a mixture of both
compounds.
8. This was corroborated by converting diastereomerically
pure 6–8 and comparing its Rf values with the crude
mixture of 8 and 9.
9. Grignard reagents should be freshly prepared; otherwise
epimerization of pure 8 or 9 at C-11 occurs before addition
takes place, affording mixtures of adducts 10 and 11, or 12
and 13, respectively, in unpredictable ratios.
In search to improve the synthesis of acetyloxathiane 2b,
the above protocol was applied to the crude mixture of
S,O-acetals 17 and 18. However, in this case the yield of
the desired oxathiane 2b resulted similar to that
described without previous isolation of S,O-acetals 17
and 18.1
In conclusion, the synthesis of S,O-acetals 6, 7, 17, and
18 provides clear evidence that our experimental pro-
tocol can be extended to the preparation of a wide
variety of analogous S,O-acetals. In addition, was
demonstrated that such compounds represent an
attractive synthetic alternative to prepare the some times
desirable enantiomeric pair of molecules in high optical
purity. Finally, was demonstrated that the isolation of
10. This by-product is formed by hydride transfer from the b-
position of the Grignard reagent: Hamelin, A. Bull. Soc.
Chim. Fr. 1961, 1211.
11. (a) Cram, D. J.; Kopecky, K. R. J. Am. Chem. Soc. 1959,
81, 2748; For evidence of Cram-chelated transition state,
see: (b) Frye, S. V.; Eliel, E. L.; Cloux, R. J. Am. Chem.
Soc. 1987, 109, 1862; (c) Frye, S. V.; Eliel, E. L. J. Am.

ꢀ
L. Chacꢀon-Garcıa et al. / Tetrahedron Letters 45 (2004) 2141–2145
2145
Chem. Soc. 1988, 110, 484; (d) Chen, X.; Hortelano, E. R.;
Eliel, E. L. J. Am. Chem. Soc. 1990, 112, 6130.
12. The expected sultine would be 9,9-dimethyl-4-oxa-5-thia-
tricyclo[6.1.1.0 [2,6]]decane 5-oxide.
13. The reduction of the mixture of aldehydes 13 and dimer 15
with NaBH4 provides the corresponding diol and thiol 4a;
however, when LiAlH4 is used, hydroxythiol 4 and the
corresponding diol are obtained.
14. (a) 16a–c,e: Colombo, L.; Di Giacomo, M.; Brusotti, G.;
Milano, E. Tetrahedron Lett. 1995, 2863; (b) 16g: Dale, J.
A.; Mosher, H. S. J. Org. Chem. 1970, 35, 4002; (c) Gaul,
J ¼ 9:2, 7.2 Hz, OCHb), 3.38 (t, 1H, J ¼ 10:0 Hz, H-10a),
3.20 (dd, 1H, J ¼ 10:0, 4.2 Hz, H-10b), 2.85 (m, 1H, H-3),
2.77 (m, 1H, H-4eq), 2.38 (m, 1H, H-7eq), 2.18 (m, 1H, H-
5), 2.11 (ddd, 1H, J ¼ 13:8, 5.9, 2.4 Hz, H-4ax), 1.91 (m,
1H, H-1), 1.86 (m, 1H, H-2), 1.29 (t, 3H, J ¼ 7:2 Hz,
OCH2CH3), 1.17 (s, 3H, Me-9), 0.98 (s, 3H, Me-8), 0.94 (d,
1H, J ¼ 10:0 Hz, H-7ax), 0.77 (s, 9H, t-Bu), )0.12 (s, 3H,
Me–Si), )0.14 ppm (s, 3H, Me–Si). IR (CH2Cl2): mmax 3059,
2926, 2857, 1686, 1597, 1579, 1250, 1087.2, 836.2,
776 cmÀ1. MS m=z: 357 (Mþ)105, 8), 135 (100), 133 (16),
105 (44), 79 (93), 41 (19), 29 (18). Calcd for C26H42O3SSi:
€
C.; Scharer, K.; Seebach, D. J. Org. Chem. 2001, 66, 3059.
C, 67.51; H, 9.09; S, 6.92. Found: C, 67.69; H, 8.83; S, 7.20.
24
D
15. (a) Eliel, E. L.; Hartmann, A. A. J. Am. Chem. Soc. 1971,
93, 2572; (b) Abatjoglou, A. G.; Eliel, E. L.; Kuyper, L. F.
J. Am. Chem. Soc. 1977, 99, 8262; (c) Epiotis, N. D.;
Yates, R. L.; Bernardi, F.; Wolfe, S. J. Am. Chem. Soc.
1976, 98, 5435.
16. Eliel, E. L.; Lynch, J. E. Tetrahedron Lett. 1981, 2855.
17. cis- and trans-5,15-Dibenzoyl-10,10,20,20-tetramethyl-4,6-
dioxa-14,16-dithiapentacyclo[4.9.4.1. 1;191.9;160.2;1708;13]eicos-
ane.
20. Compound 10a: ½aŠ +25.7ꢁ (c 0.9, CHCl3). 1H NMR
(300 MHz, CDCl3): d 7.40–7.20 (m, 5H, Ar), 4.59 (s, 1H,
H-11), 3.88 (dq, 1H, J ¼ 9:9, 7.1 Hz, OCHa), 3.65 (dd, 1H,
J ¼ 9:9, 4.7 Hz, H-10b), 3.54 (t, 1H, J ¼ 10:0 Hz, H-10a),
3.26 (dq, 1H, J ¼ 9:9, 7.1 Hz, OCHb), 3.17 (br s, 1H, OH),
2.95 (m, 1H, H-3), 2.50–2.31 (m, 2H, H-4eq, H-7eq), 2.19
(m, 1H, H-1), 2.12–1.86 (m, 3H, H-5, H-4ax, H-2), 1.62 (s,
3H, Me-13), 1.19 (s, 3H, Me-9), 1.13 (t, 3H, J ¼ 7:1 Hz,
OCH2CH3), 1.17 (s, 3H, Me-9), 0.99 (d, 1H, J ¼ 9:8 Hz,
H-7ax), 0.90 (s, 3H, Me-8), 0.88 (s, 9H, t-Bu), 0.03 (s, 3H,
Me–Si), 0.02 ppm (s, 3H, Me–Si). IR (CH2Cl2): mmax 3467,
2928, 2857, 1447, 1079, 699, 620 cmÀ1. LRMS (EI) m=z:
460 (Mþ)18, 1), 375 (21), 357 (57), 135 (100), 133 (71), 105
(58), 73 (36). HRMS (FABþ) calcd for C27H46O3SSiNa:
501.2835, found: 501.2827.
18. In fact, spectroscopic and X-ray data of this dimer were
ꢀ
described: Vargas-Dıaz, M. E. M. Sc. dissertation, Escuela
Nacional de Ciencias Biologicas-IPN, Mexico City, 2002.
ꢀ
28
19. Compound 8: ½aŠ )4.4ꢁ (c 0.40, CHCl3). 1H NMR
D
(300 MHz, CDCl3): d 8.10–7.40 (m, 5H, Ar), 5.84 (s, 1H,
H-11), 4.01 (dq, 1H, J ¼ 9:2, 7.2 Hz, OCHa), 3.60 (dq, 1H,