Highly stereoselective additions of sulfur stabilized carbanions to [(S)R]-2-(p-tolylsulfinyl)cyclohexanones

Article abstract of DOI:10.1016/S0957-4166(00)00407-9

We describe the addition reactions of α-thiocarbanions derived from sulfoxides, thioethers, and sulfones to 2-(p-tolylsulfinyl)cyclohexanones. The high stereoselectivity observed in the formation of the chiral hydroxylic carbon is controlled by the configuration of the sulfinyl group at the substrate, but it is modulated by the nature of the sulfur function at the reagent (SOTol>SO₂Ph>SPh). The highly stereoselective formation of the second stereogenic center generated in these reactions from prochiral anions is only achieved with sulfinylcarbanions, the configuration of which controls that of such a center. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00407-9

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 11 (2000) 4385–4395
Highly stereoselective additions of sulfur stabilized
carbanions to [(S)R]-2-(p-tolylsulfinyl)cyclohexanones
Jose´ L. Garc´ıa Ruano,a,* David Barros,a M. Carmen Maestro,a,* Ana M. Mart´ın Castrob,†
and Paul R. Raithbyb
aDepartamento de Qu´ımica Orga´nica (C-I), Universidad Auto´noma, 28049 Madrid, Spain
bDepartment of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK
Received 29 September 2000; accepted 9 October 2000
Abstract
We describe the addition reactions of a-thiocarbanions derived from sulfoxides, thioethers, and sulfones
to 2-(p-tolylsulfinyl)cyclohexanones. The high stereoselectivity observed in the formation of the chiral
hydroxylic carbon is controlled by the configuration of the sulfinyl group at the substrate, but it is
modulated by the nature of the sulfur function at the reagent (SOTol>SO2Ph>SPh). The highly
stereoselective formation of the second stereogenic center generated in these reactions from prochiral
anions is only achieved with sulfinylcarbanions, the configuration of which controls that of such a center.
© 2000 Elsevier Science Ltd. All rights reserved.
1. Introduction
Recently our group has demonstrated the high efficiency of the sulfinyl group in the
stereochemical control of the reduction,1–5 alkylation,6–9 and hydrocyanation10–12 reactions on
b-ketosulfoxides. The results obtained from substrates with an additional stereogenic center in
the a-position have a special significance because the stereoselectivity at the hydroxylic center is
controlled mainly by the configuration at sulfur and therefore their reactions can be carried out
on the epimeric mixture at C-a. The reactions of the [(S)R]-2-(p-tolylsulfinyl)cyclohexanones 1
with lithium ester enolates13,14 have special relevance because they are stereocontrolled aldol
reactions using ketones as the electrophiles. Starting from prochiral nucleophiles, the control of
the C-2 stereogenic center (Scheme 1) was only possible in reactions from lactone enolates.
The easy generation of sulfur-stabilized carbanions and their successful reactivity with a
variety of electrophiles, along with the synthetic versatility of the sulfur functions,15–17 determine
that these reagents are valuable nucleophiles in CꢀC bond-forming reactions.18,19 In this sense,
* Corresponding authors. E-mail: joseluis.garcia.ruano@uam.es; carmen.maestro@uam.es
†
Author for X-ray analysis. E-mail: martin.castro@uam.es
0957-4166/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00407-9

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J. L. Garc´ıa Ruano et al. / Tetrahedron: Asymmetry 11 (2000) 4385–4395
Scheme 1.
chiral sulfinyl carbanions are especially interesting because the sulfinyl group can act as a chiral
auxiliary. However, it is well established that the addition of simple a-sulfinylcarbanions to
ketones takes place with satisfactory 1,2-induction but a poor 1,3-induction is achieved,19–23
which determines an efficient control of the stereogenic center next to the sulfinyl sulfur but a
less efficient control of the hydroxylic stereogenic center.
On the basis of this assumption we reasoned that the use of a combined effect of the sulfinyl
group at the electrophilic ketone and at the nucleophile would allow the simultaneous control
of both stereogenic centers formed in reactions with prochiral carbanions. We have checked the
efficiency of this combination in reactions involving N-sulfinylimines.24 In this paper we report
on the asymmetric addition of a-lithiated alkyl aryl sulfides, sulfoxides, and sulfones to the
[(S)R]-2-(p-tolylsulfinyl)cyclohexanones 1 and some useful transformations of the obtained
tertiary carbinols allowing their configurational assignment.
2. Results and discussion
Reactions with a-sulfinylcarbanions derived from enantiomerically pure [(S)R]-alkyl p-tolyl
sulfoxide are especially significant because the double stereoselection allows the simultaneous
control of three contiguous stereogenic centers. The stereochemical study is completed with the
reactions of sulfide and sulfone carbanions. These reactions are a valuable reference to those of
sulfoxide anions, besides the synthetic properties of the obtained adducts by themselves. The
synthesis of the starting sulfinylcyclohexanone 1, as a 75:25 mixture of epimers at C-2, was
performed by sulfinylation of the cyclohexanone N-phenylimine, according to a previously
reported method.25 The results obtained in the reactions of this epimeric mixture with a-thiocarb-
anions 2–4 are collected in Table 1. In all cases the reactions were carried out by slow addition
at −78°C of the epimeric mixture to a solution of the lithium anions (3.5 equiv.) derived from
[(S)R]-methyl p-tolyl sulfoxide 2 or its corresponding thioether 3‡ or sulfone 4, which were
prepared by deprotonation with LDA at the same temperature in THF.
The reaction of the sulfinylcarbanion 2 takes place with complete stereoselectivity affording
hydroxy bis-sulfoxide 5A as the only diastereoisomer in 84% yield. The reactions with carban-
ions derived from sulfone 3 and sulfide 4 were less stereoselective, a mixture of two diastereoiso-
mers having been isolated (Table 1). A dynamic resolution of the C-2 stereogenic center is
observed in all cases determining the exclusive formation of compounds which exhibit the (S)
configuration at such a center. This suggests a much quicker evolution of [(S)R,2S]-1a and the
easy epimerization of C-2 in the presence of the strongly basic thiocarbanions. The chemical
‡ The reaction with the sulfide anion required 6 molar equiv. and the use of n-BuLi as the base.

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4387
Table 1
Addition of a-thiocarbanions 2–4 to ketosulfoxides 1
Entry
Nucleophile
Adduct
A:B
Yield (%)a
1
2
3
2
3
4
[(S)R]-SOTol
SO2Ph
STol
5
6
7
100:0
96:4
85:15
84
65b
51c
a Isolated yield of the major compounds A.
b 15% of 1 (as a 75:25 epimeric mixture) was recovered.
c 40% of 1 (75:25) was recovered.
correlation of the major compounds 5A and 7A was carried out by their oxidation into the same
1
bis-sulfone 9A. The H NMR spectrum of 8A, obtained by oxidation of 6A, is almost identical
to that of 9A (they only differ in the aromatic residue of the acyclic sulfone) thus suggesting that
both sulfones must have the same stereochemistry. The [1S,2S,(S)R)] configuration was tenta-
tively assigned to the major adducts 5A–7A taking into account previous results obtained with
sulfinylcyclohexanone 1 and lithium ester enolates.13 The same criteria were applied to assign the
minor compounds 6B and 7B (they could not be isolated in their diastereomerically pure form),
as indicated in Table 1.
As a second stage of this research we investigated the reaction with prochiral a-thiocarban-
ions. The obtained results are collected in Table 2. Starting from ethyl p-tolyl sulfoxide
[(S)R]-10, compound 13A was obtained exclusively in 88% yield (no other diastereoisomer could
1
be detected by H NMR of the reaction crude). By contrast, the reaction with the sulfonylcarb-
anion 11 afforded a 55:45 diastereoisomeric mixture of two sulfinyl-sulfones 14A and 14A%, and
sulfenylcarbanion 12 did not react.§ The comparison between these results and those obtained
from reactions of 1 with ester enolates13 suggests that these exhibit a behavior similar to
carbanions derived from sulfones. In both cases a quite efficient control of the configuration at
the endocyclic stereogenic carbon but a quite poor control of that of the exocyclic one are
observed. It allows us to assign tentatively the configurations depicted in Table 2 for compounds
14A and 14A%, which were confirmed by X-ray diffraction analysis for compound 14A (Fig. 1).
The formation of only one diastereoisomer in reactions of 1 with 10 suggests that the sulfur
configuration at the carbanion is responsible for the control of the stereoselective formation of
the exocyclic stereogenic carbon. In order to verify this point we treated compound 1 with a
carbanion derived from racemic ( )-10. The reaction afforded an almost equimolar mixture
§ The strong basic character of the sulfenylcarbanion could enolizate the substrate, thus precluding its reaction with
nucleophiles.

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Table 2
Addition of a-thiocarbanions 10–12 to ketosulfoxides 1
Entry
Nucleophile
Adduct
A:A%a
Yield (%)b
1
2
3
10
11
12
[(S)R]-SOTol
SO2Ph
STol
13
14
100:0
55:45
88
A (38):A% (28)
–
No reactionc
1
a From the H NMR spectra of the reaction crudes.
b Isolated yield.
c Unaltered 1 were recovered.
of two diastereoisomers, 13AR and 13A% , which must exhibit a different configuration at the
S
exocyclic sulfinyl group. The chemical correlation of this mixture with the previously described
[1S,2S,(S)R]-2-(p-tolylsulfinyl)-1-vinylcyclohexanol 16A7 by pyrolytic elimination of the exo-
Figure 1. X-Ray structure for compound 14A

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4389
cyclic sulfinyl group allowed us to state that 13AR and 13A% have an identical configuration at
S
the two stereogenic carbons of the cyclohexane ring. Additionally, the oxidation of the mixture
of 13AR and 13A% yielded a mixture of diastereomeric sulfones, 15A and 15A%, which must differ
S
in the configurations at the exocyclic stereogenic carbon. All these reactions (Scheme 2) allowed
us to assign unequivocally the configurations of the bis-sulfoxides 13AR and 13A% and, therefore,
S
to confirm the simultaneous control exerted by the sulfinyl groups at nucleophiles and elec-
trophiles on the exocyclic and endocyclic new stereogenic carbons, respectively. Finally, the
relative configuration assigned to 14A and 14A% is based on the fact that the MCPBA oxidation
of a 55:45 mixture of both afforded a similar mixture of bis-sulfones 17A and 17A% with identical
1H NMR spectra (except in the aromatic signals) to the mixture of 15A and 15A%.
Scheme 2.
Therefore, the stereochemical course of the reaction should explain the following experimental
facts: (a) the (R) configuration at sulfur in starting ketosulfoxide 1 induces the (S) configuration
at hydroxylic carbon; (b) the reactivity of the [(S)R,2S]-1 epimer is higher than that of the
[(S)R,2R]-1 one (kinetic resolution is observed); (c) the configuration of the sulfinyl group in the
nucleophile controls the configuration of the exocyclic stereogenic carbon, but has no significant
influence in that of the endocyclic hydroxylic carbon.
Taking into account the preference of nucleophiles for the equatorial attack on cyclohex-
anones to avoid steric interactions with the axial hydrogens at C-3 and C-5,7,13 both the control
of the sulfinyl group at 1 and the kinetic resolution observed in reactions with 2 are easily
explained. As we can see in Scheme 3 the equatorial approach of the carbanions on [(S)R,2S]-1
must be sterically favored with respect to a similar approach to [(S)R,2R]-1.
In order to rationalize the control of the sulfinyl group at nucleophiles on the configuration
of the exocyclic stereogenic carbon it is necessary to assume that a-sulfinyl carbanions must be
stabilized by the sulfinyl oxygen. In the case of compound 10 intermediates exhibiting p-tolyl
and methyl groups in a trans arrangement in the four-membered ring will be clearly favored with
respect to their cis-isomers (Scheme 4). If we assume that the nucleophilic attack takes place

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Scheme 3.
Scheme 4.
with retention of the configuration of the stabilized carbanion, the experimental results (identical
configuration at the above-mentioned sulfur and carbon atoms are favored) are easily explained.
The contribution of the sulfinyl oxygen to the stabilization of the lithium could explain the
higher reactivity and selectivity of these carbanions.
As a conclusion, we have demonstrated in this paper that the reactions of a-thiocarbanions
with sulfinyl cyclohexanones take place with a total control of the stereoselectivity at the
hydroxylic carbon. The best results are obtained with sulfinyl carbanions, which are also able to
control the stereoselectivity of the exocyclic stereogenic carbons obtained from prochiral
carbanions. We are currently interested in the synthetic transformations of the obtained
products, mainly those with bis-sulfoxide structures, in order to obtain spiro-epoxides.
3. Experimental
Diastereoisomeric ratios were established by integration (1H NMR) of well-separated signals
of the diastereoisomers in the crude reaction mixtures. All reactions were monitored by TLC,
which was performed on precoated sheets of silica gel 60 (F254), and flash chromatography was
effected with silica gel 60 (230–400 mesh). The vessels for inert atmospheric experiments were
flame-dried in a stream of dry argon. THF was distilled from sodium/benzophenone under
argon. Diisopropylamine was distilled from potassium hydroxide. n-Butyllithium (2.5 M solu-
tion in hexanes) was purchased from Aldrich.

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4391
The X-ray structure was refined by full-matrix least-squares (Sheldrick, G. M., SHELXL96,
Program for Crystal Structure Refinement; University of Go¨ttingen: Go¨ttingen, 1996) on F2.
All non-hydrogen atoms were refined anisotropically.
3.1. Condensation of lithium alkyl aryl sulfoxides and keto sulfoxide 1. General procedure
A solution of butyllithium (5.9 mL of a 2.5 M solution in hexanes, 14.9 mmol) was added
dropwise to a cooled (−78°C) solution of diisopropylamine (2.2 mL, 15.7 mmol). After 20
min of stirring, a solution of the corresponding sulfoxide (14.9 mmol) in 5 mL of THF at rt
was added via cannula. The mixture was maintained for 30 min at the same temperature and
a solution of 2-(p-tolylsulfinyl)cyclohexanone (1, 1.01 g, 4.3 mmol) in 25 mL of THF was
added via cannula. After 20 min at −78°C the reaction was quenched with a saturated
solution of NH4Cl (40 mL) and extracted with ethyl acetate (2×40 mL). The organic extracts
were washed with brine (2×20 mL) and dried (MgSO4). The solvent was removed under
vacuum and the crude product purified by flash chromatography to afford the corresponding
hydroxy sulfoxide.
3.1.1. [(S%)R,1S,2S,(S)R]-1-[(p-Tolylsulfinyl)methyl]-2-(p-tolylsulfinyl)cyclohexanol 5A
Compound 5A was obtained as the sole diastereomer following the general procedure from
(R)-methyl p-tolyl sulfoxide 2. Column chromatography on silica gel (hexane–acetone, 3:1)
and subsequent recrystallization (hexane–CHCl3) afforded 3.46 g of pure 5A (84%) as a white
1
solid. [h]2D5 +195 (c 1, CHCl3), mp 182–184°C (acetone). H NMR l 7.6 and 7.3 (8H, AA%BB%
system), 4.59 (1H, d, J1,3=1 Hz), 3.47 and 3.38 (2H, AB system, JAB=13.6 Hz), 3.42 (1H,
dd, J=13.6 and 3.3 Hz), 2.44 (3H, s), 2.43 (3H, s), 2.20–1.00 (8H, bm). 13C NMR l 141.9,
141.5, 140.7, 136.6, 130.2 (2C), 130.1 (2C), 130.0 (2C), 124.3 (2C), 73.9, 68.4, 65.4, 38.7, 24.5,
21.4 (2C), 20.4, 16.7. IR (CHCl3) 3390, 1705, 1170, 1020, 1010, 800. Anal. calcd for
C21H26O3S2: C, 64.58; H, 6.71; S, 16.42. Found: C, 64.23; H, 6.82; S, 16.19.
3.1.2. [(S%)R,1%R,1S,2S,(S)R]-1-[1%-(p-Tolylsulfinyl)ethyl]-2-p-tolylsulfinylcyclohexanol 13A
Compound 13A was obtained as a sole diastereomer from (R)-ethyl p-tolyl sulfoxide 10
following the general procedure. Purification was effected by crystallization (CHCl3–hexane).
1
Yield 88%. [h]2D5 +111 (c 1, CHCl3), mp 193–195°C. H NMR l 7.52 and 7.32 (4H, AA%BB%
system), 7.44 and 7.36 (4H, AA%BB% system), 4.28 (1H, d, J=1.3 Hz), 3.62 (1H, q, J=6.9
Hz), 3.37 (1H, dd, J=12.0 and 2.8 Hz,), 2.44 (3H, s) and 2.41 (3H, s), 2.3–1.0 (8H, m), 1.17
(3H, d, J=6.9 Hz). 13C NMR l 141.7, 141.1, 138.8, 135.5, 130.1 (2C), 129.9 (2C), 124.3 (2C),
124.0 (2C), 76.1, 66.5, 63.7, 33.0, 24.8, 21.4, 21.3, 20.1, 17.2, 2.0. Anal. calcd for C22H28O3S2:
C, 65.31; H, 6.98; S, 15.85. Found: C, 65.12; H, 6.67; S, 15.72.
A 59:41 mixture of C-1% epimers 13AR:13A% was obtained from racemic ethyl p-tolyl
S
sulfoxide ( )-10. Purification and separation of both epimers was effected by crystallization
(CHCl3–hexane) and subsequent column chromatography on silica gel (hexane–acetone, 3:1).
1
[(S%)S,1%S,1S,2S,(S)R]-13A%S: H NMR l 7.70 and 7.30 (8H, m), 4.71 (1H, d, J=1.8 Hz),
3.94 (1H, q, J=6.9 Hz), 2.58 (1H, dd, J=11.8 and 3.1 Hz), 2.44 (3H, s), 2.41 (3H, s),
2.30–1.00 (8H, m), 1.21 (3H, d, J=6.9 Hz).

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3.2. Condensation of lithium alkyl aryl thioether or sulfone and i-keto sulfoxides. General
procedure
A solution of n-butyllithium (5.9 mL of a 2.5 M solution in hexanes, 14.9 mmol) was added
dropwise to a cooled (−78°C) solution of the corresponding sulfur compound (14.9 mmol) in 5
mL of THF. The mixture was stirred for 30 min (at 0°C for sulfones and −20°C for thioethers)
and then cooled at −78°C before the addition via cannula of a solution of 2-(p-tolylsul-
finyl)cyclohexanone (1, 1.01 g, 4.3 mmol) in 25 mL of THF. After 5 min at −78°C, the reaction
mixture was quenched with a saturated solution of NH4Cl (40 mL) and extracted with ethyl
acetate (2×40 mL). The organic extracts were washed with brine (2×20 mL) and dried (MgSO4).
The solvent was removed under vacuum and the crude product was purified by flash chromatog-
raphy to afford the corresponding adducts.
3.2.1. 1-(Phenylsulfonyl methyl)-2-p-tolylsulfinylcyclohexanol 6
Compound 6 was obtained following the general procedure from methyl phenyl sulfone 3 as
a 96:4 mixture of C-1 epimers, 6A:6B. Column chromatography on silica gel (CH2Cl2–acetone,
10:1) afforded pure 6A (65%) as a white solid.
1
[1S,2S,(S)R]-6A: [h]2D5 +4 (c 1, CHCl3), mp 100–102°C (hexane–ether). H NMR l 8.10 and
7.30 (9H), 4.74 (1H, d, J1,3=1.7 Hz), 4.20 and 3.47 (2H, AB system, JAB=14.2 Hz), 3.39 (1H,
dd, J=12.5 and 3.5 Hz), 2.42 (3H, s), 2.40–0.70 (8H, m). 13C NMR l 141.4, 140.9, 135.9, 133.9,
129.9 (2C), 129.5 (2C), 127.5 (2C), 124.4 (2C), 74.7, 64.7, 63.9, 38.5, 24.4, 21.4, 20.3, 16.2. Anal.
calcd for C20H24O4S2: C, 61.20; H, 6.16; S, 16.34. Found: C, 60.91; H, 6.25; S, 16.28.
3.2.2. 1-(p-Tolylthio)methyl-2-p-tolylsulfinylcyclohexanol 7
Compound 7 was obtained following the general procedure from methyl p-tolyl sulfide 4 as
an 85:15 mixture of C-1 epimers, 7A:7B (global yield 67%). Column chromatography on silica
gel (hexane–ethyl acetate, 4:1) of the mixture afforded 7A which was further purified by
crystallization (hexane–ethyl acetate) to yield the pure compound as a white solid (51%).
Isolation of diastereomer 7B has not been accomplished.
1
[1S,2S,(S)R]-7A: [h]2D5 −10 (c 1, CHCl3). H NMR l 7.39 and 7.33 (4H, AA%BB% system), 7.29
and 7.16 (4H, AA%BB% system), 4.59 (1H, s,), 3.86 and 3.36 (2H, AB system, JAB=13.5 Hz), 2.76
(1H, dd, J=12.7 and 3.8 Hz), 2.40 (3H, s), 2.30 (3H, s), 2.2–0.7 (8H, m). 13C NMR l 141.1,
136.7, 136.4, 132.5, 130.5 (2C), 129.8 (2C), 129.7 (2C), 124.2 (2C), 75.4, 63.0, 45.7, 37.1, 24.7,
21.3, 20.9, 20.4, 16.5. Anal. calcd for C21H26O2S2: C, 67.34; H, 7.00; S, 17.12. Found: C, 67.13;
H, 6.85; S, 17.40.
3.2.3. 1-[1%-(Phenylsulfonyl)ethyl]-2-(p-tolylsulfinyl)cyclohexanol 14
Compound 14 was obtained following the general procedure from ethyl phenyl sulfone 11 as
a 55:45 mixture of C-1% epimers, 14A:14A% (global yield: 75%). Purification and separation of
both epimers was effected by column chromatography on silica gel (hexane–CH2Cl2–acetone,
5:1:1).
1
[1%R,1R,2S,(S)R]-14A: [h]2D5 −22 (c 1, CHCl3). H NMR l 8.10–7.30 (9H, m), 4.55 (1H, d,
J=2.1), 4.29 (1H, q, J=6.9 Hz), 3.85 (1H, dd, J=12.7 and 3.6 Hz), 2.43 (3H, s), 2.2–0.8 (8H,
bm), 1.38 (3H, d, J=6.9 Hz). 13C NMR l 141.3, 139.3, 135.7, 133.7, 130.0 (2C), 129.2 (2C),
128.2 (2C), 124.4 (2C), 76.7, 64.9, 64.5, 32.8, 24.6, 21.4, 20.2, 16.8, 16.8, 10.6. Anal. calcd for
C21H26O4S2: C, 62.04; H, 6.45; S, 15.77. Found: C, 61.73; H, 6.41; S, 15.38.

J. L. Garc´ıa Ruano et al. / Tetrahedron: Asymmetry 11 (2000) 4385–4395
4393
1
[1%S,1R,2S,(S)R]-14A%: [h]2D5 +30 (c 1, CHCl3). H NMR l 8.10–7.30 (9H, m), 4.70 (1H, d,
J=1.3), 4.02 (1H, q, J=6.9 Hz), 2.67 (1H, dd, J=12.0 and 3.5 Hz), 2.43 (3H, s), 2.30–1.00 (8H,
bm), 1.50 (3H, d, J=6.9 Hz). 13C NMR l 139.7, 138.1, 137.0, 132.6, 128.6 (2C), 128.0 (2C),
127.3 (2C), 123.0 (2C), 76.9, 67.8, 66.3, 35.7, 25.6, 22.6, 21.6, 17.5, 13.4.
3.3. Sulfinyl group pyrolysis. General procedure
A 25 mL two-necked round bottomed flask, equipped with a stirrer and a reflux condenser
and containing sodium bicarbonate (3.5 g, 40.6 mmol), was flame-dried in an N2 stream. A
solution of the corresponding hydroxysulfoxide (1.06 mmol) in o-xylene (10 mL) was added via
cannula and the mixture was stirred vigorously and heated in an oil bath at the temperature
indicated in each case. The mixture was cooled to room temperature and the crude was filtered
over Celite® and washed with a saturated solution of NH4Cl (20 mL). The organic layer was
separated and the aqueous one was extracted with ethyl acetate (2×20 mL). The combined
organic layers were finally washed with brine and dried (MgSO4). To prevent any reaction
product from evaporating, ethyl acetate was eliminated under reduced pressure without heating.
Alkene isolation was effected by flash chromatography using successively hexane (to remove
remaining o-xylene) and the eluent indicated in each case.
3.3.1. [1S,2S,(S)R]-2-(p-Tolylsulfinyl)-1-vinylcyclohexanol 16A
Compound 16A was obtained from a 55:45 mixture of 13AR:13A% diastereomers by heating
S
the mixture for 4 h at 110°C. Chromatographic purification (ethyl acetate–hexane, 1:5) affords
compound 16A (68%) as a white solid. [h]D25 +23 (c 1, CHCl3), mp 92–93°C (acetone–hexane). 1H
NMR l 7.34 (4H, m), 6.16 (1H, dd, J=17.1 and 10.4 Hz), 5.71 (1H, dd, J=17.1 and 1.5 Hz),
5.65 (1H, dd, J=10.4 and 1.5 Hz), 4.00 (1H, d, J=2.2 Hz, OH), 2.43 (3H, s), 2.20–0.80 (8H, m).
13C NMR l 143.8, 141.1, 136.7, 129.8, (2C), 124.3 (2C), 115.0, 74.7, 65.2, 39.2, 24.8, 21.3, 20.2,
16.5. Anal. calcd for C15H20SO2: C, 68.15; H, 7.62; S, 12.13. Found: C, 68.05; H, 7.71; S, 12.10.
3.4. MCPBA oxidation of hydroxy sulfoxides. General procedure
A CDCl3 solution of the corresponding hydroxy sulfoxides was added to an NMR tube
containing a previously dried (MgSO4) MCPBA solution in the same solvent. The bis-sulfones
ratios and NMR signals were evaluated from the crude mixtures.
3.4.1. [1%R,1S,2S]-1-[1%-(p-Tolylsulfonyl)ethyl]-2-(p-tolylsulfonyl)cyclohexanol 15A
1
Compound 15A was obtained from 13A by MCPBA oxidation (5 molar equiv.). H NMR l
8.10–7.30 (8H), 4.96 (1H, q, J=6.90 Hz), 4.59 (1H, dd, J=13.2 and 2.6 Hz), 2.50 (3H, s), 2.48
(3H, s), 2.20–0.80 (8H, m), 1.36 (3H, d, J=7.0 Hz). 13C NMR l 145.4, 139.4, 135.2, 133.1, 129.8
(2C), 129.3 (2C), 128.9 (2C), 128.7 (2C), 75.7, 66.9, 64.2, 33.0, 25.2, 24.6 (2C), 21.5, 19.8, 10.2.
3.4.2. 1-[1%-(Phenylsulfonyl)ethyl]-2-(p-tolylsulfonyl)cyclohexanol 17
Compound 17 was obtained as a 75:25 diastereoisomeric mixture of 17A and 17A% by
MCPBA oxidation (3 molar equiv.) of a 75:25 mixture of 14A and 14A%.
1
[1%R,1S,2S]-17A: H NMR l 8.10–7.30 (9H), 4.97 (1H, c, J=6.90 Hz), 4.63 (1H, dd, J=13.2
and 2.5 Hz), 2.50 (3H, s, CH3-Ar), 2.2–0.8 (8H, m), 1.37 (3H, d, J=6.9 Hz, CH3CH). 13C NMR
l 145.2, 139.8, 134.9, 133.4, 129.8 (2C), 129.3 (2C), 128.9 (2C), 128.7 (2C), 75.3, 66.3, 63.8, 33.1,
25.2, 24.6, 21.7, 19.8, 10.4.

4394
J. L. Garc´ıa Ruano et al. / Tetrahedron: Asymmetry 11 (2000) 4385–4395
1
[1%S,1S,2S]-17A%: H NMR l 8.10–7.30 (7H), 4.83 (1H, c, J=7.1 Hz), 3.17 (1H, dd, J=10.2
and 3.0 Hz), 2.48 (3H, s), 2.2–0.8 (8H, m), 1.51 (3H, d, J=7.0 Hz). 13C NMR l 144.5, 139.6,
135.8, 133.8, 129.5 (2C), 129.2 (2C), 128.5 (2C), 128.3 (2C), 76.8, 68.1, 65.2, 33.8, 25.0, 24.7,
21.7, 19.9, 12.2.
3.4.3. (1S,2S)-1-(p-Tolylsulfonylmethyl)-2-(p-tolylsulfonyl)cyclohexanol 9A
Compound 9A was obtained from 5A or 7A by MCPBA oxidation (5 molar equiv. for 5A and
1
3 molar equiv. for 7A) following the general procedure. H NMR l 8.40–7.30 (8H), 4.35–3.38
(2H, AB system, J=15 Hz), 3.56 (1H, dd, J=12.1 and 2.7 Hz), 2.42 (3H, s), 2.20–1.00 (8H)
Acknowledgements
The authors would like to thank the Direccio´n General de Investigacio´n Cient´ıfica y Te´cnica
for financial support (PB 98-0102).
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