Efficient preparation of enantiomerically pure (E)-γ-hydroxy-α,β- unsaturated p-tolylsulfoxides using lipase-mediated acylations

Article abstract of DOI:10.1016/S0957-4166(00)00257-3

(E)-γ-Hydroxy-α,β-unsaturated p-tolylsulfoxides 1 have been efficiently resolved via irreversible enzymatic acylation with lipase PS (Pseudonomas cepacia) and vinyl acetate. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0957-4166(00)00257-3

Tetrahedron: Asymmetry 11 (2000) 2991±3001
Ecient preparation of enantiomerically pure (E)-g-hydroxy-
a,b-unsaturated p-tolylsulfoxides using lipase-mediated
acylations
Victor Guerrero de la Rosa,a Mario Ordonezb and Jose Manuel Lleraa,*
a
Â
Dpto de Quõmica Organica y Farmaceutica, Facultad de Farmacia, Universidad de Sevilla, E-41071 Seville, Spain
Â
Centro de Investigaciones Quõmicas, U. Autonoma del Estado de Morelos, Av. Universidad No. 1001,
Â
b
Â
Â
62210 Cuernavaca, Mor. Mexico
Â
Received 31 May 2000; accepted 29 June 2000
Abstract
(E)-g-Hydroxy-a,b-unsaturated p-tolylsulfoxides 1 have been eciently resolved via irreversible
enzymatic acylation with lipase PS (Pseudonomas cepacia) and vinyl acetate. # 2000 Elsevier Science Ltd.
All rights reserved.
1. Introduction
The sulfoxide group has emerged as an ecient chiral auxiliary in numerous asymmetric
syntheses.1 In particular, enantiomerically pure a,b-unsaturated sulfoxides have been successfully
used as chiral dienophiles,2 dienes,3 dipolarophiles,4 and Michael acceptors5 mainly due to the
potential of the sulfoxide moiety as a stereocontrolling element.6 Related reactions have also been
reported for the corresponding sulfones,7 for which it has been additionally shown that substitution
at the g-position have a strong in¯uence on the facial selectivity for addition reactions to the
carbon±carbon double bond.8 However, g-hydroxy-a,b-unsaturated sulfoxides have been scarcely
investigated in this context, in spite of being intriguing substrates for stereochemical studies due
to the presence of two stereocontrolling elements, the sulfoxide group and the alcohol (or its equiv-
alent).9 Therefore, methods for the preparation of enantiomerically pure g-hydroxy-a,b-unsaturated
sulfoxides are of great importance in asymmetric synthesis. At present the base-catalyzed elimination
of diastereomerically pure 2,3-epoxy sulfoxides10 and the reduction of g-keto-a,b-unsaturated
sulfoxides11 are the main methods described in the literature for the preparation of this type of
sulfoxide.
Recently, we reported a practical one-step procedure for the synthesis of (E)-g-hydroxy-a,b-
unsaturated p-tolylsulfoxides 1 by SPAC condensation of enantiomerically pure (S,S)-bis-p-
* Corresponding author. Fax: 95 423 37 65; e-mail: llera@fafar.us.es
0957-4166/00/$ - see front matter # 2000 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(00)00257-3

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tolylsul®nylmethane 2 with enolizable aldehydes (Scheme 1).12 The process involves a Knoevenagel
type condensation between the aldehyde and the methylene active bis-sulfoxide in tandem with an
allylic sulfoxide±sulfenate rearrangement. Unfortunately, the corresponding (E)-g-hydroxy-a,b-
unsaturated sulfoxides 1 were obtained as an 1:1 mixture of the two possible epimers at the
carbinol center that resulted as being inseparable in our hands. Recently, we have been using
several types of bis-sulfoxides di€erently substituted at sulfur with the aim of improving
diastereoselectivity in the allylic sulfoxide±sulfenate rearrangement, without any relevant success.13
Scheme 1.
At the present there is a notable interest in the use of lipases as catalysts for the resolution of
racemic alcohols.14,15 Some of the reasons for the popularity of these enzymes are the following:
they are readily available and relatively inexpensive; require no expensive cofactors; often exhibit
high stereoselectivities with a wide range of substrates; and ®nally, allow the production of
multigram quantities of optically enriched alcohols in a facile laboratory procedure. Herein, we
report the results obtained in the lipase-mediated acylation of several (E)-g-hydroxy-a,b-unsaturated
sulfoxides 1.
2. Results
2.1. Kinetic resolution of (E)-ꢀ-hydroxy-ꢁ,ꢂ-unsaturated sulfoxides 1
The kinetic resolution of 1 by lipase-catalyzed transesteri®cation in organic media was
examined. Initially, we explored the resolution of the ethyl derivative 1b using di€erent enzymes
and vinyl acetate at room temperature in the presence of molecular sieves16 as illustrated in Table 1.
Table 1
Biocatalytic resolution of (E)-1-(p-tolylsul®nyl)-1-penten-3-ol 1b

V. Guerrero de la Rosa et al. / Tetrahedron: Asymmetry 11 (2000) 2991±3001
2993
Among the enzymes used, lipase PS (from Pseudomonas cepacia, Amano) was the most e€ective
for the resolution of (E)-g-hydroxy-a,b-unsaturated sulfoxide 1b, yielding the acetate 3b and
unreacted alcohol with very high diastereoselectivity (entry 4). To isolate the products, the
reaction was stopped at ca. 50% conversion, which was determined by NMR analysis (selectivity
factors17 E >50). The resulting acetate 3b was then separated from unreacted g-hydroxysulf-
oxides 1b by column chromatography. The diastereomeric excesses for 1b and 3b were determined
1
by H NMR and con®rmed by HPLC analysis using a reverse-phase column Lichrocart C-18.
The con®guration at the carbinol center for both derivatives was assigned by chemical correlation
with the known (E)-g-hydroxy and g-acetoxy-a,b-unsaturated sulphones18 (see Section 2.2).
In order to explore the scope of the kinetic resolution of (E)-g-hydroxy-a,b-unsaturated
sulfoxides mediated by lipase PS, the optimized enzymatic acylation conditions for 1b were
applied to a wide variety of substrates (Table 2).
Table 2
Biocatalytic resolution of (E)-g-hydroxy-a,b-unsaturated Sulfoxides 1a±f
From the results summarized in Table 2, it should be pointed out that the diastereoselectivity
of the enzymatic acetylation of (E)-g-hydroxy-a,b-unsaturated sulfoxides 1 is almost independent
of the increasing length or size of the R group. Except for the bulkiest derivative 1f (entry 6), the
lipase PS mediated acetylations were very ecient, taking place at very high values of selectivity
factors (E >50). In all cases the acetylation reaction was extremely slow with conversions near
50%, the (Rs,Rc)-diastereomer being the most reactive.
The results obtained with (E)-g-hydroxy-a,b-unsaturated sulfoxides 1a (R=Me), 1e (R=iPr)
and 1f (R=tBu) show the e€ect of the increasing size of the R alkyl group in the reactivity and
diastereoselectivity of this enzymatic reaction. Thus, despite the large steric requirement of the iPr
group, g-hydroxy sulfoxide 1e (entry 5) was diastereoselectively acetylated (E >50), although the
rate was about 20 times slower than that of g-hydroxy sulfoxide 1a (entry 1). By contrast, after 12
days the reaction of g-hydroxy sulfoxide 1f (entry 6) took place with poor selectivity factor
(E=25) and only 7% of conversion was observed in the acetylation.19

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2.2. Assignment of the relative con®guration for (E)-ꢀ-hydroxy-ꢁ,ꢂ-unsaturated sulfoxides 1
The con®guration at the hydroxylic carbon atom for unreacted g-hydroxysulfoxides 1 was deter-
mined by chemical correlation with the known g-hydroxy-a,b-unsaturated sulfones 4. Thus, g-
hydroxysulfoxides 1c and 1d were oxidated using the conditions developed by Trost20 to
a€ord g-hydroxy-a,b-unsaturated sulfones 4c and 4d with high chemical yields (Table 3).
Table 3
Preparation of (E)-g-hydroxy-a,b-unsaturated sulfones 4
At this point, speci®c rotations, melting points, and the 1H and 13C NMR spectra of 4c and 4d
were essentially identical to those described in the literature.18 This chemical correlation allows
the assignment of the relative con®guration (S) for the hydroxylic carbon in the unreacted (E)-g-
hydroxy-a,b-unsaturated sulfoxides 1c and 1d, while the opposite (R) con®guration at C3 can be
assumed for (E)-g-acetyl-a,b-unsaturated sulfoxides 3 and 3d. The con®guration for the g-
acetylsulfoxides 3c and 3d was further con®rmed by chemical correlation. Thus, compounds 3c
and 3d were ®rst transformed into the g-acetylsulfones 5c and 5d by oxidation. The latter were
hydrolyzed using Et3N in MeOH±H2O to give the (E)-g-hydroxy-a,b-unsaturated sulfones 6c and
6d in 98% and 95% yields, respectively (Table 4). The speci®c rotations for compounds 6c and 6d
were opposite to that described for sulfones 4c and 4d, con®rming the (R) con®guration for C3 in
(E)-g-acetyl-a,b-unsaturated sulfoxides 3.
Table 4
Preparation of (E)-g-hydroxy-a,b-unsaturated sulfones 6c and 6d

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2995
Since all the studied compounds are closely related, and lipase PS gave normally highly
stereoselective resolutions of several types of alcohols always being acylated the same isomer.14 16
It seems reasonable to assume that the absolute con®guration for C3 in unreacted (E)-g-hydroxy-
a,b-unsaturated sulfoxides 1 is (S) and that for the corresponding (E)-g-acetyl-a,b-unsaturated
sulfoxides 3 it is (R) in all cases.
In summary, the ready access to (E)-g-hydroxy-a,b-unsaturated sulfoxides 1, via one-pot SPAC
condensation between aldehydes and bis-sulfoxides, coupled with the ecient enzymatic
resolution described in this paper make this experimental operation a good and simple method to
obtain enantiomerically pure (E)-g-hydroxy and (E)-g-acetyl-a,b-unsaturated sulfoxides which
are dicult to prepare by other means. The use of the allylic acetate moiety in these substrates is
being currently investigated in palladium-catalyzed allylic substitution reactions and the results
will be reported in due course.
3. Experimental
Melting points were determined in open capillary tubes on a Gallenkamp apparatus and are
uncorrected. 1H NMR spectra were registered on a Bruker AC-200 (200 MHz) or AMX-500 (500
MHz) instrument and 13C NMR on an AC-200 (50.3 MHz) or AMX-500 (125.72 MHz)
spectrometer. All spectra were obtained using CDCl3 as solvent and TMS as internal standard.
Chemical shifts are reported in ppm, and coupling constants in hertz. Optical rotations were
taken on a Perkin±Elmer 241-MC polarimeter in a 1 dm tube; concentrations are given in g/100
mL. High resolution mass measurements were performed on a Kratos MS-80-RFA spectrometer.
HPLC analysis was carried out on a Waters, Millipore 600A model using a Chiral OD (Diacel)
column or reverse phase column Lichrocart C-18. Routine monitoring of reactions was
performed using Merck 60 F 254 silica gel, aluminium supported TLC plates. For the ¯ash
chromatography,21 silica gel 60 (230±400 mesh ASTM, Merck) was used.
Flasks, stirrings bars, and hypodermic needles used for the generation of organometallic
compounds were dried for ca. 12 h at 120ꢀC and allowed to cool in a dessicator over anhydrous
calcium sulfate. Anhydrous solvents (ethers) were obtained by distillation from benzophenone
ketyl.22 The n-BuLi employed was titrated according to the method described by Juaristi et al.23
3.1. (S,S)-Bis-p-tolylsu®nylmethane 2
A solution of i-Pr2NH 1.99 mL (14.3 mmol) in 15 mL of anhydrous THF was cooled to ^78ꢀC
before the slow addition of 8.9 mL (14.3 mmol) of n-BuLi in hexane (1.6 M). The resulting
solution was stirred at ^78ꢀC for 30 min and then treated with 1.0 g (6.5 mmol) of (+)-(R)-methyl
p-tolyl sulfoxide24 in 10 mL of THF. The yellow solution formed was stirred at ^78ꢀC for 1 h
before the addition of the 1,2:5,6-di-O-isopropylidene-a-d-glucofuranosyl (^)-(S)-p-toluene-
sul®nate24 in 10 mL of THF. The reaction mixture was stirred at this temperature for 1 h and at
room temperature for 10 min. The mixture was then treated with 5 mL of saturated ammonium
chloride solution. The aqueous phase was extracted with CH2Cl2 (50 mL). The combined extracts
were dried (Na2SO4), ®ltered, evaporated under reduced pressure and the crude product was
puri®ed by recrystallization from hot hexane to yield enantiomerically pure (S,S)-bis-p-
tolylsu®nylmethane (1.55 g, 82% yield) as a white solid, m.p.=136±137ꢀC, [ꢁ]D=+317 (c 1,
acetone), lit.25 m.p.=137.5ꢀC and [ꢁ]D=+318 (c 1, acetone).

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3.2. (E)-ꢀ-Hydroxy-ꢁ,ꢂ-unsaturated sulfoxides 1a±f
The procedure described by Llera et al. was followed.12
3.2.1. General procedure for the lipase-mediated acylation of compounds 1a±f
To a solution (50 mM) of the two isomers of (E)-g-hydroxy-a,b-unsaturated sulfoxides 1a±f in
isopropyl ether was added sequentially 50 mg/mL of powdered molecular sieves (4 A), (25 mg/mL)
of enzyme and 5 equivalents of vinyl acetate. The resulting suspension was vigorously shaken at
1
room temperature and monitored by TLC and H NMR for the conversion. When 50%
conversion was reached, the enzyme and the molecular sieves were ®ltered o€ and the solvent was
evaporated to give a mixture of unreacted alcohol 1 and acetylated product 3.
3.2.2. (Rs,Sc)-(E)-1-(p-Tolylsul®nyl)-1-buten-3-ol (Rs,Sc)-1a and (Rs,Rc)-(E)-3-acetoxy-1-(p-
tolylsul®nyl)-1-butene (Rs,Rc)-3a
The general procedure was followed for the acylation of 220 mg (1.05 mmol) of 1a for 12 h.
Puri®cation of the mixture by ¯ash chromatography (ethyl acetate:hexane, 3:1) a€orded 108 mg
(49% yield) of (Rs,Sc)-1a as a viscous oil, and 140 mg (50% yield) of (Rs,Rc)-3a as a viscous oil.
Compound (Rs,Sc)-1a: d.e. 98%. [ꢁ]D=+239.6 (c 4.3, CHCl3). 1H NMR (500 MHz, CDCl3) ꢃ 1.35
(d, J=6.6 Hz, 3H, CH3-), 1.74 (br, 1H, OH), 2.42 (s, 3H, CH3-Ar), 4.56 (m, 1H, CH(OH)), 6.46 (dd,
Janti=15.0 Hz, J1,3=1.6 Hz, 1H, ˆCH-S(O)), 6.63 (dd, Janti=15.0 Hz, J2,3=4.4 Hz, 1H, CHˆ), 7.32±
7.51 (AA0BB0 system, 4H, aromatics). 13C NMR (125.72 MHz, CDCl3) ꢃ 21.4, 23.0, 67.2, 124.8, 130.1,
133.7, 140.3, 141.6, 141.7. HRMS calcd m/z for C11H14O2S: 210.0731. Found: 210.0714.
1
Compound (Rs,Rc) 3a: d.e. 96%. [ꢁ]D=+178 (c 7.6, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
1.35 (d, J=6.6 Hz, 3H, CH3), 2.03 (s, 3H, CH3CO), 2.39 (s, 3H, CH3-Ar), 5.48 (m, 1H, CH-
(OCOCH3), 6.39 (dd, Janti=15.1 Hz, J1,3=1.4 Hz, 1H, ˆCH-S(O)), 6.53 (dd, Janti=15.1 Hz,
J2,3=5.2 Hz, 1H, CHˆ), 7.31±7.49 (AA0BB0 system, 4H, aromatics). 13C NMR (125.72 MHz,
CDCl3) ꢃ 19.7, 20.9, 21.2, 68.7, 124.7, 130.0, 135.5, 136.3, 139.8, 141.8, 169.7. HRMS calcd m/z
for C13H16O3S: 252.1632. Found: 252.1677.
3.2.3. (Rs,Sc)-(E)-1-(p-Tolylsul®nyl)-1-penten-3-ol (Rs,Sc)-1b and (Rs,Rc)-(E)-3-acetoxy-1-(p-
tolylsul®nyl)-1-pentene (Rs,Rc)-3b
The general procedure was followed for the acylation of 473 mg (2.11 mmol) of 1b for 48 h.
Puri®cation of the mixture by ¯ash chromatography (ethyl acetate:hexane, 3:1) a€orded 236 mg
(49.9% yield) of (Rs,Sc)-1b, and 280 mg (49.6% yield) of (Rs,Rc)-3b as viscous oils.
1
Compound (Rs,Sc)-1b: d.e. 96%. [ꢁ]D=+251 (c 2.7, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
0.91 (t, J=7.4 Hz, 3H, CH3), 1.58 (m, 2H, -CH2-), 2.37 (s, 3H, CH3Ar), 3.38 (br, 1H, OH), 4.20
(m, 1H, CH(OH)), 6.41 (dd, Janti=15.0 Hz, J1,3=0.9 Hz, 1H, ˆCH-S(O)), 6.56 (dd, Janti=15.0
Hz, J2,3=4.7 Hz, 1H, CHˆ), 7.26±7.46 (AA0BB0 system, 4H, aromatics). 13C NMR (125.72 MHz,
CDCl3) ꢃ 9.4, 21.3, 29.6, 71.9, 124.8, 129.7, 130.2, 133.8, 141.5, 141.6. HRMS calcd m/z for
C12H16O2S: 224.0876. Found: 224.0870.
1
Compound (Rs,Rc)-3b: d.e. 98%. [ꢁ]D=+226.6 (c 3, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
0.87 (t, J=7.4 Hz, 3H, CH3), 1.68 (m, 2H, -CH2-), 2.02 (s, 3H, CH3CO), 2.37 (s, 3H, CH3-Ar),
5.34 (m, 1H, CH(OCOCH3)), 6.37 (dd, Janti=15.0 Hz, J1,3=0.8 Hz, 1H, ˆCH-S(O)), 6.48 (dd,
Janti=15.0 Hz, J2,3=5.7 Hz, 1H, CHˆ), 7.28±7.46 (AA0BB0 system, 4H, aromatics). 13C NMR
(125.72 MHz, CDCl3) ꢃ 9.0, 20.8, 21.4, 26.9, 73.4, 124.8, 130.0, 135.1, 136.2, 140.1, 141.8, 169.9.

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2997
HRMS calcd m/z for C14H18O3S: 266.0971. Found: 266.0991. Anal. calcd for C14H18O3S: C,
63.13; H, 6.81. Found: C, 62.92; H, 6.60.
3.2.4. (Rs,Sc)-(E)-1-(p-Tolylsul®nyl)-1-hexen-3-ol (Rs,Sc)-1c and (Rs,Rc)-(E)-3-acetoxy-1-(p-
tolylsul®nyl)-1-hexene (Rs,Rc)-3c
The general procedure was followed for the acylation of 392 mg (1.65 mmol) of 1c for 24 h.
Puri®cation of the mixture by ¯ash chromatography (ethyl acetate:hexane, 2:1) a€orded 194 mg
(49.5% yield) of (Rs,Sc)-1c, and 227 mg (49.3% yield) of (Rs,Rc)-3c as viscous oils.
1
Compound (Rs,Sc)-1c: d.e. 98%. [ꢁ]D=+236 (c 2.6, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
0.88 (t, J=7.3 Hz, 3H, CH3), 1.31±1.40 (m, 2H, -CH2-, 1.52 (m, 2H, -CH2-), 2.36 (s, 3H, CH3Ar),
3.43 (br, 1H, OH), 4.25 (m, 1H, CH(OH)), 6.38 (dd, Janti=15.0 Hz, J1,3=1.4 Hz, 1H, ˆCH-S(O)),
6.56 (dd, Janti=15.0 Hz, J2,3=4.6 Hz, 1H, CHˆ), 7.25±7.44 (AA0BB0 system, 4H, aromatics). 13
C
NMR (125.72 MHz, CDCl3) ꢃ 13.7, 18.4, 21.2, 38.6, 70.3, 124.7, 129.9, 133.1, 139.9, 141.6, 142.3.
HRMS calcd m/z for C13H18O2S: 238.1041. Found: 238.1027.
1
Compound (Rs,Rc)-3c: d.e. 98%. [ꢁ]D=+154.8 (c 6.3, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
0.87 (t, J=7.4 Hz, 3H, CH3), 1.28±1.34 (m, 2H, -CH2-), 1.59±1.66 (m, 2H, -CH2-), 2.01 (s, 3H,
CH3CO), 2.37 (s, 3H, CH3Ar), 5.40 (m, 1H, CH(OCOCH3)), 6.35 (dd, Janti=15.1 Hz, J1,3=1.2
Hz, 1H, ˆCH-S(O)), 6.48 (dd, Janti=15.1 Hz, J2,3=5.7 Hz, 1H, CHˆ), 7.26±7.45 (AA0BB0 sys-
tem, 4H, aromatics). 13C NMR (125.72 MHz, CDCl3) ꢃ 13.4, 17.8, 20.6, 21.7, 35.7, 71.9, 124.6,
129.8, 135.1, 135.6, 139.8, 141.5, 169.6. HRMS calcd m/z for C15H20O3S: 280.1115. Found:
280.1056. Anal. calcd for C15H20O3S: C, 64.25; H, 7.19. Found: C, 64.56; H, 7.23.
3.2.5. (Rs,Sc)-(E)-1-(p-Tolylsul®nyl)-1-octen-3-ol (Rs,Sc)-1d and (Rs,Rc)-(E)-3-acetoxy-1-(p-
tolylsul®nyl)-1-octene (Rs,Rc)-3d
The general procedure was followed for the acylation of 685 mg (2.57 mmol) of 1d for 3 h.
Puri®cation of the mixture by ¯ash chromatography (ethyl acetate:hexane, 2:1) a€orded 336 mg
(49.0% yield) of (Rs,Sc)-1d, and 390 mg (49.2% yield) of (Rs,Rc)-3d as viscous oils.
1
Compound (Rs,Sc)-1d: d.e. 96%. [ꢁ]D=+294 (c 2.8, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
0.88 (t, J=7.9 Hz, 3H, CH3), 1.26±1.42 (m, 6H, (CH2)3), 1.61 (m, 2H, -CH2-), 2.23 (br, 1H, OH),
2.40 (s, 3H, CH3Ar), 4.33 (m, 1H, CH(OH)), 6.44 (dd, Janti=15.0 Hz, J1,3=1.6 Hz, 1H, ˆCH-
S(O)), 6.60 (dd, Janti=15.0 Hz, J2,3=4.6 Hz, 1H, CHˆ), 7.30±7.49 (AA0BB0 system, 4H, aro-
matics). 13C NMR (125.72 MHz, CDCl3) ꢃ 13.8, 21.4, 22.54, 24.88, 31.5, 36.2, 70.8, 124.6, 129.9,
133.5, 140.3, 141.4, 141.9. HRMS calcd m/z for C15H22O2S: 266.1361. Found: 266.1340.
1
Compound (Rs,Rc)-3d: d.e. 98%. [ꢁ]D=+223 (c 3.1, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
0.86 (t, J=7.4 Hz, 3H, CH3), 1.19±1.38 (m, 6H, (CH2)3), 1.63±1.69 (m, 2H, ±CH2±), 2.05 (s, 3H,
CH3CO), 2.40 (s, 3H, CH3Ar), 5.40 (m, 1H, CH(OCOCH3)), 6.37 (dd, Janti=15.1 Hz, J1,3=1.2
Hz, 1H, ˆCH-S(O)), 6.51 (dd, Janti=15.1 Hz, J2,3=5.7 Hz, 1H, CHˆ), 7.30±7.48 (AA0BB0 sys-
tem, 4H, aromatics). 13C NMR (125.72 MHz, CDCl3) ꢃ 13.8, 21.1, 21.3, 22.3, 24.4, 31.3, 33.8,
72.4, 124.9, 130.1, 135.4, 135.9, 140.0, 141.9, 169.9. HRMS calcd m/z for C17H24O3S: 308.1446.
Found: 308.1446. Anal. calcd for C17H24O3S: C, 66.20; H, 7.84. Found: C, 65.96; H, 7.71.
3.2.6. (Rs,Sc)-(E)-4-Methyl-1-(p-tolylsul®nyl)-1-penten-3-ol (Rs,Sc)-1e and (Rs,Rc)-(E)-3-
acetoxy-4-methyl-1-(p-tolylsul®nyl)-1-pentene (Rs,Rc)-3e
The general procedure was followed for the acylation of 304 mg (1.27 mmol) of 1e for 10 days.
Puri®cation of the mixture by ¯ash chromatography (ethyl acetate:hexane:ether, 6:3:1) a€orded 147
mg (48.4% yield) of (Rs,Sc)-1e as a viscous oil, and 175 mg (49.2% yield) of (Rs,Rc)-3e as a viscous oil.

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1
Compound (Rs,Sc)-1e: d.e. 96%. [ꢁ]D=+225 (c 4.7, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
0.91 (d, J=6.7 Hz, 6H, (CH3)2), 1.25 (s, 1H, OH), 1.83 (oct, J=6.7 Hz, 1H, CH), 2.39 (s, 3H,
CH3Ar), 4.12 (m, 1H, CH(OH)), 6.44 (dd, Janti=15.0 Hz, J1,3=1.5 Hz, 1H, ˆCH-S(O)), 6.60 (dd,
Janti=15.0 Hz, J2,3=4.8 Hz, 1H, CHˆ), 7.29±7.49 (AA0BB0 system, 4H, aromatics). 13C NMR
(125.72 MHz, CDCl3) ꢃ 17.7, 18.2, 21.3, 33.5, 75.9, 124.5, 130.2, 134.7, 139.9, 141.3, 141.8.
HRMS calcd m/z for C13H18O2S: 238.1028. Found: 238.1027.
1
Compound (Rs,Rc)-3e: d.e. 98%. [ꢁ]D=+195 (c 4.1, CHCl3). H NMR (500 MHz, CDCl3) ꢃ
0.88 (d, J=6.8 Hz, 6H, (CH3)2), 1.95 (m, 1H, CH), 2.04 (s, 3H, CH3CO), 2.38 (s, 3H, CH3Ar),
5.24 (m, 1H, CH(OCOCH3)), 6.37 (dd, Janti=15.1 Hz, J1,3=1.2 Hz, 1H, ˆCH±(O)), 6.50 (dd,
Janti=15.1 Hz, J2,3=5.8 Hz, 1H, CHˆ), 7.29±7.47 (AA0BB0 system, 4H, aromatics). 13C NMR
(125.72 MHz, CDCl3) ꢃ 17.6, 17.8, 20.8, 21.3, 31.9, 76.7, 124.9, 130.0, 134.0, 136.4, 139.7, 141.9,
169.9. HRMS calcd m/z for C15H20O3S: 280.1116. Found: 280.1176. Anal. calcd for C15H20O3S:
C, 64.25; H, 7.19. Found: C, 63.77; H, 6.97.
3.2.7. (Rs,Rc)-(E)-3-Acetoxy-4,4-dimethyl-1-(p-tolylsul®nyl)-1-pentene (Rs,Rc)-3f
The general procedure was followed for the acylation of 330 mg (1.19 mmol) of 1f for 12 days.
Puri®cation of mixture by ¯ash chromatography (ethyl acetate:hexane, 3:2) a€orded 13 mg (7.4%
yield) of (Rs,Rc)-3f as a viscous oil.
1
Compound (Rs,Rc)-3f: d.e. 98%. [ꢁ]D=+118 (c 1, CHCl3). H NMR (500 MHz, CDCl3) ꢃ 0.9
(s, 9H, (CH3)3), 2.02 (s, 3H, CH3CO), 2.37 (s, 3H, CH3Ar), 5.14 (dd, J2,3=6.1 Hz, J1,3=1.1 Hz,
1H, CH(OCOCH3)), 6.31 (dd, Janti=15.1 Hz, J1,3=1.1 Hz, 1H, ˆCH-S(O)), 6.55 (dd, Janti=15.1
Hz, J2,3=6.1 Hz, 1H, CHˆ), 7.27±7.45 (AA0BB0 system, 4H, aromatics). 13C NMR (125.72 MHz,
CDCl3) ꢃ 20.9, 21.4, 25.7, 34.9, 79.3, 125.0, 130.1, 133.3, 137.3, 140.0, 141.9, 170.0. HRMS calcd
m/z for C16H22O3S: 294.1289. Found: 294.1345.
3.3. (S)-(+)-(E)-3-Hydroxy-1-(p-tolylsulfones) (4c and 4d)
Derivatives 4c and 4d were prepared by oxidation of optically pure sulfoxides (Rs,Sc)-1c and
(Rs,Sc)-1d according to the procedure described by Trost et al.20
3.4. (R)-(+)-(E)-3-Acetoxy-1-(p-tolylsulfonyl)-1-hexenene 5c
A solution of (Rs,Rc)-3c (42 mg, 0.38 mmol) in 4 mL of methanol was treated with 93 mg (0.15
mmol) of Oxone1 in 2 mL of water. The reaction mixture was stirred at room temperature for 3
h. The aqueous phase was extracted with CH2Cl2 (15 mL). The combined extracts were dried
(Na2SO4), ®ltered, and evaporated under reduced pressure to a€ord 44 mg (98% yield) of (R)-5c
1
as a viscous oil; e.e. 98%. [ꢁ]D=+12.8 (c 4.4, CHCl3). H NMR (500 MHz, CDCl3) ꢃ 0.84 (t,
J=7.1 Hz, 3H, CH3), 1.18±1.33 (m, 2H, -CH2-), 1.53±1.65 (m, 2H, -CH2-, 1.99 (s, 3H, CH3CO),
2.37 (s, 3H, CH3Ar), 5.38 (m, 1H, CH(OCOCH3)), 6.37 (dd, Janti=15.1 Hz, J1,3=1.6 Hz, 1H,
ˆCH-SO2), 6.81 (dd, Janti=15.1 Hz, J2,3=4.6 Hz, 1H, CHˆ), 7.27±7.68 (AA0BB0 system, 4H,
aromatics). 13C NMR (125.72 MHz, CDCl3) ꢃ 13.6, 18.0, 21.5, 22.6, 35.6, 71.2, 127.7, 129.9,
130.8, 136.9, 143.0, 144.5, 169.7. HRMS calcd m/z for C15H20O4S: 296.1081. Found: 296.1085.
3.5. (R)-(+)-(E)-3-Acetoxy-1-(p-tolylsulfonyl)-1-octenene 5d
A solution of (Rs,Rc)-3d (50 mg, 0.16 mmol) in 5 mL of methanol was treated with 100 mg
(0.16 mmol) of Oxone1 in 3 mL of water. The reaction mixture was stirred at room temperature

V. Guerrero de la Rosa et al. / Tetrahedron: Asymmetry 11 (2000) 2991±3001
2999
for 3 h. The aqueous phase was extracted with CH2Cl2 (15 mL). The combined extracts were
dried (Na2SO4), ®ltered, and evaporated under reduced pressure to a€ord 51 mg (95% yield) of
1
(R)-5d as a viscous oil; e.e. 98%. [ꢁ]D=+7.8 (c 1.6, CHCl3). H NMR (500 MHz, CDCl3) ꢃ 0.75
(t, J=6.2 Hz, 3H, CH3), 1.12±1.23 (m, 6H, (CH2)3), 1.51±1.62 (m, 2H, -CH2-), 1.95 (s, 3H,
CH3CO), 2.32 (s, 3H, CH3Ar), 5.30±5.40 (m, 1H, CH(OCOCH3)), 6.36 (dd, Janti=15.1 Hz,
J1,3=1.6 Hz, 1H, ˆCH-SO2), 6.79 (dd, Janti=15.1 Hz, J2,3=4.6 Hz, 1H, CHˆ), 7.23±7.65
(AA0BB0 system, 4H, aromatic). 13C NMR (125.72 MHz, CDCl3) ꢃ 13.6, 20.6, 21.3, 22.1, 24.1,
31.0, 33.2, 71.1, 127.4, 129.7, 130.7, 136.8, 142.9, 144.3, 169.5. HRMS calcd m/z for C17H24O4S:
324.1393. Found: 324.1397.
3.6. (R)-(^)-(E)-1-(p-Tolylsulfonyl)-1-hexen-3-ol 6c
A solution of 5c (26 mg, 0.08 mmol) in 4.5 mL of methanol:H2O:Et3N (1:1:1) was stirred at
room temperature for 8 h. The reaction was quenched by the addition of 10% hydrochloric acid
(5 mL), and the aqueous phase was extracted with CH2Cl2 (15 mL). The combined extracts were
washed successively with saturated aqueous NaHCO3 solution (5 mL) and saturated aqueous
NaCl solution (5 mL) and dried over Na2SO4. The solvent was evaporated under reduced
pressure to a€ord 19 mg (86.4% yield) of (R)-6c as a white solid; m.p. 89±90ꢀC. [ꢁ]D=^43.6 (c
1.8, CHCl3); e.e. 98%. 1H NMR (500 MHz, CDCl3) ꢃ 0.86 (t, J=7.1 Hz, 3H, CH3), 1.56±1.28 (m,
4H, (CH2)2), 2.38 (s, 3H, CH3Ar), 2.48 (br, 1H, OH), 4.27±4.32 (m, 1H, CH(OH)), 6.52 (dd,
Janti=14.9 Hz, J1,3=1.8 Hz, 1H, ˆCH-SO2), 6.89 (dd, Janti=14.9 Hz, J2,3=3.8 Hz, 1H, CHˆ),
7.28±7.69 (AA0BB0 system, 4H, aromatics). 13C NMR (125.72 MHz, CDCl3) ꢃ 13.7, 18.3, 21.5,
38.2, 69.8, 127.5, 129.8, 137.1, 144.3, 148.0. HRMS calcd m/z for C13H18O3S: 254.0982. Found:
254.0963.
3.7. (R)-(^)-(E)-1-(p-Tolylsulfonyl)-1-octen-3-ol 6d
A solution of 5d (46 mg, 0.14 mmol) in 9 mL of methanol:H2O:Et3N (1:1:1) was stirred at
room temperature for 8 h. The reaction was quenched by addition of 10% hydrochloric acid
(10 mL), and the aqueous phase was extracted with CH2Cl2 (25 mL). The combined extracts were
washed successively with a saturated aqueous NaHCO3 solution (10 mL) and saturated aqueous
NaCl solution (10 mL) and dried over Na2SO4. The solvent was evaporated under reduced
pressure to a€ord 35 mg (87.5% yield) of (R)-6d as a white solid; m.p. 103±105ꢀC. [ꢁ]D=^39.5 (c
2.4, CHCl3); e.e. 98%. 1H NMR (500 MHz, CDCl3) ꢃ 0.78 (t, J=7.1 Hz, 3H, CH3), 1.17±1.41 (m,
6H, (CH2)3), 1.40±1.48 (m, 2H, -CH2-), 2.34 (s, 3H, CH3Ar), 3.02 (br, 1H, OH), 4.23 (m, 1H,
CH(OH)), 6.48 (dd, Janti=14.9 Hz, J1,3=1.7 Hz, 1H, ˆCH-SO2), 6.85 (dd, Janti=14.9 Hz,
J2,3=3.8 Hz, 1H, CHˆ), 7.23±7.65 (AA0BB0 system, 4H, aromatics). 13C NMR (125.72 MHz,
CDCl3) ꢃ 13.7, 21.3, 22.2, 24.6, 31.3, 36.0, 69.8, 127.3, 129.7, 137.0, 144.2, 148.2. HRMS calcd
m/z for C15H22O3S: 282,1290. Found: 282,1274.
Acknowledgements
We wish to thank the Spanish DIGICYT (Project PB94-1431), the Junta de Andalucõa and the
CONACYT (Project 28762-E) for ®nancial support.

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