Sequential asymmetric dihydroxylation and sulfoxidation of homoallylic sulfides. Stereochemical aspects of the preparation of new trifunctional chiral building blocks

Article abstract of DOI:10.1016/S0957-4166(02)00123-4

Products with three new stereogenic centers were generated via sequential asymmetric dihydroxylation and sulfoxidation of homoallylic sulfides. The non-racemic homoallylic sulfoxides were prepared using chiral, vanadyl-based catalytic system with e.e. of

Full text of DOI:10.1016/S0957-4166(02)00123-4

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 369–375
Sequential asymmetric dihydroxylation and sulfoxidation of
homoallylic sulfides. Stereochemical aspects of the preparation of
new trifunctional chiral building blocks
Jacek Skarz; ;
ewski,a,* Elzbieta Wojaczyn´skaa and Ilona Turowska-Tyrkb
aInstitute of Organic Chemistry, Biochemistry and Biotechnology, Wrocław University of Technology, 50-370 Wrocław, Poland
bInstitute of Physical and Theoretical Chemistry, Wrocław University of Technology, 50-370 Wrocław, Poland
Received 15 January 2002; accepted 7 March 2002
Abstract—Products with three new stereogenic centers were generated via sequential asymmetric dihydroxylation and sulfoxida-
tion of homoallylic sulfides. The non-racemic homoallylic sulfoxides were prepared using chiral, vanadyl-based catalytic system
with e.e. of up to 85%. Subsequently, these compounds were dihydroxylated with AD-mix system and gave products of low d.e.s
(up to 40%). Recrystallization of l-diastereomers furnished both enantiomerically pure 1-phenyl-4-phenylsulfinylbutane-1,2-diols
(X-ray), which are new and useful chiral building blocks. Further oxidation at sulfur produced the corresponding enantiomers of
1-phenyl-4-phenylsulfonylbutane-1,2-diol. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
the vic-diol with modest enantioselectivity only.7 More-
over, there is no report on the stereoselective sulfoxida-
tion of homoallylic and dihydroxy sulfides.
Osmium-catalyzed asymmetric dihydroxylation (AD)
using the Sharpless catalytic system is one of the most
useful synthetic tools for the preparation of optically
active compounds.1 Catalytic asymmetric oxidation of
sulfides allows access to enantiomerically enriched sul-
foxides—the most widely used chiral auxiliaries and
building blocks.2 In both cases the stereochemical out-
come of the individual oxidative transformation can be
predicted. Under these circumstances it seems interest-
ing to examine the mutual interplay of both chiral
catalytic oxidations in the preparation of chiral non-
racemic dihydroxysulfoxides, which are interesting chi-
ral building blocks.
We describe herein the results of stereoselective sulfoxi-
dations of homoallylic sulfides and enantioenriched 3,4-
dihydroxysulfides. We also report the outcomes of the
AD reactions of homoallylic sulfides and sulfones, and
the dihydroxylation of the double bond of chiral (E)-
homoallylic sulfoxides (Scheme 1).
2. Results and discussion
With our optimized version 7a8c,d of the Bolm catalytic
system (30% H2O2/VO(acac)2-chiral ligand 7, cat.)8 we
oxidized homoallylic sulfides 1 to afford the enantio-
enriched sulfoxides 2 with the absolute configuration at
sulfur corresponding to that of the ligand.8 It is note-
worthy that other chiral oxidizing systems investigated
were ineffective in these reactions (Table 1).
The OsO4-catalyzed dihydroxylation of the double
bonds separated from chiral sulfinyl group by two or
three carbon atoms, additionally with one of them
being stereogenic, has already been reported.3–5 While
high degrees of 1,5-stereoinduction was observed for
diastereoselective dihydroxylation,3 for the 1,4-cases the
respective stereoselectivities were less pronounced and
the influence of the additional stereogenic center was
demonstrated.5 The homoallylic sulfide was chemo- and
enantioselectively dihydroxylated by the Sharpless
reagent,6 but the reaction of the analogous sulfone gave
* Corresponding author.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00123-4

370
J. Skarz; ewski et al. / Tetrahedron: Asymmetry 13 (2002) 369–375
Scheme 1. (i) VO(acac)2, H2O2, ligand 7 or TEMPO, NaOCl; (ii) AD-mix a or AD-mix b or K2OsO4/quinuclidine, K3[Fe(CN)6];
(iii) Oxone®.
Table 1. Asymmetric sulfoxidation of sulfides 1 to sulfoxides 2
E.e.(%)b
a
Sulfide
Oxidant
Yield of 2 (%)
[h]D
1a
VO(acac)2/H2O2, (S)-7a
VO(acac)2/H2O2, (R)-7a
VO(acac)2/H2O2, (S)-7b
Ti(O-iPr)4, CHP, (+)-DETc
VO(acac)2/H2O2, (S)-7a
VO(acac)2/H2O2, (S)-7c
Ti(O-iPr)4, TBHP, (R)-Binold
VO(acac)2/H2O2, (S)-7a
60
77
60
52
65
92
10
90
−48
+47
−43
(−)-(S) 67
(+)-(R) 66
(−)-(S) 60
rac
(−)-(S) 70
(−)-(S) 48
(+)-(R) 25
(−)-(S) 85
1b
1c
−131
−90
+47
−118
a In CH2Cl2, c=1.0, 25°C.
b Enantiomeric excess was determined by 1H NMR measurement with Eu(hfc)3 in CCl4.
c See Ref. 9.
d See Ref. 10.
dihydroxylating agent is not an asymmetric one, this
outcome proved undoubtedly the remote stereoinduc-
tion from the stereogenic sulfur atom to the prochiral
double bond. Moreover, the sign of specific rotation for
the enantioenriched 6a suggested that the major
diastereomer of 5a was that of like (l) configurations
and the corresponding sign of 6b indicated that for 5b
an unlike (u) diastereomer was in excess (vide infra).
The configurational stability of these chiral sulfoxides
was limited and for neat 2a at 20°C the e.e. value was
half that of the original value after 20 days. All data
given in Table 1 refer to the values obtained 3–4 days
after the oxidation was performed. The highest enan-
tioselectivity for 2a (84% e.e. using 7a) was recorded
when the sample was analyzed immediately after the
oxidation.
The thus obtained optically active sulfoxides 2a and 2b
were dihydroxylated with potassium ferricyanide using
OsO4/quinuclidine as a catalyst.11 The resulting product
5a was obtained as a mixture of two diastereomers in
ca. 6:4 d.r. The major diastereomer showed the high
field 1H NMR signals for the aliphatic part being
shifted downfield versus the signals for the minor one
(Dl ca. 0.08 ppm). In the case of 5b an opposite
diastereomer slightly dominated. After further sulfur
oxidation 5a and 5b gave enantioenriched sulfones 6a
and 6b in over 90% yield. Their enantiomeric excesses
were markedly reduced as compared to that for the
starting sulfoxides 2 (Table 2). Nevertheless, since the
Table 2. Dihydroxylation of enantioenriched sulfoxide 2
to 5, and its oxidation to sulfone 6
Sulfoxide
(E.e., %)
Yield of 5 (%)
D.e. (%)
Sulfone 6
(S)-(−)-2a (35)
(R)-(+)-2a (59)
(S)-(−)-2b (70)
75
35
40
24 (l)
16 (l)
10 (u)
(−)-(3S,4S)a
(+)-(3R,4R)b
(+)-(3R)c
a After several recrystallizations pure l-diastereomer of 5a was
obtained. Its oxidation gave sulfone (−)-6a in 58% e.e.
b (+)-6a, 21% e.e.
c (+)-6b, 10% e.e.

J. Skarz
;
ewski et al. / Tetrahedron: Asymmetry 13 (2002) 369–375
371
Table 3. AD of enantioenriched sulfoxide 2a to 5a, and its oxidation to sulfone 6a
Sulfoxide 2a (E.e., %)
Oxidant
5a
6a
Yield (%)
D.e. (%)
Yield (%)
E.e. (%)
(S)-(−) (35)
(S)-(−) (35)
(R)-(+) (59)
(R)-(+) (66)
AD-mix a
AD-mix b
AD-mix a
AD-mix b
99
82
60
98
24 (Ss,3S,4S)
36 (Ss,3R,4R)
40 (Rs,3S,4S)
26 (Rs,3R,4R)
92
70
81
99
58 (3S,4S)a
49 (3R,4R)
43 (3S,4S)
87 (3R,4R)b
a In the second step, recrystallized 5a was used ([h]D=−118, 100% d.e.).
b In the second step, recrystallized 5a was used ([h]D=+117, 100% d.e.)
obtained after second oxidation step was of higher e.e.
than the starting dihydroxysulfide 3a (Table 4, entry 4).
The TEMPO-catalyzed sulfoxidation led to higher
yields of l-diastereomers, but the products obtained at
ca. 50% conversion were less enantioenriched than the
starting diols.
Moreover, we observed that pure l-5a can be obtained
by recrystallization and this process leads also to its
enantioenrichment (Table 2, footnote a).
We also examined asymmetric dihydroxylation using
AD-mix a and b.1 These reagents, when applied to 1a
gave 3a in 71% e.e. (S,S) and 76% e.e. (R,R), respec-
tively. Both products were oxidized with Oxone® to the
corresponding sulfones 6a and recrystallization gave
these compounds in over 95% e.e. This reaction
sequence is more selective than the direct AD of sulfone
4a (40% e.e., this work) or 4b (53% e.e., Ref. 7). When
enantioenriched sulfoxides 2a were dihydroxylated with
both AD-mixes, AD-mix a led to the (SC,SC)-isomer
and AD-mix b to the (RC,RC)-isomer, regardless of the
configuration at sulfur. We observed a better match
(higher diastereoselectivity) for the formation of an
unlike diastereomer (u) (Table 3). However, in the
mismatched cases (lower d.e.), (l)-isomers formed as the
main products and could be recrystallized to give pure
(SS,S,S)-5a and (RS,R,R)-5a. We confirmed these
assignments by a single-crystal X-ray analysis for
(SS,S,S)-5a (Fig. 1). Their further oxidation12 with
Oxone® again furnished the enantiomeric sulfones 6a.
3. Conclusions
In conclusion, we have demonstrated direct remote
stereoinduction in the osmium-catalyzed dihydroxyla-
tion of nonracemic homoallylic sulfoxides. The asym-
metric dihydroxylation of these compounds led to the
products of low d.e.s, but for l-diastereomers simple
recrystallization furnished both enantiomeric 1-phenyl-
4-phenylsulfinylbutane-1,2-diols, which are interesting
new chiral building blocks. The chiral and achiral cata-
lytic sulfoxidations of enantioenriched diols resulted in
the additional kinetic resolution of substrate and/or
product.
Additionally, (S)-(−)-2a (84% e.e.) was dihydroxylated
shortly with 0.7 equiv. of AD-mix-b and gave 21% of
(Ss,3R,4R)-5a (88% d.e.) along with 70% of the highly
enantioenriched substrate (92% e.e.). Consequently, the
kinetic resolution of the chiral substrate took place
during the AD reaction.
Finally, we examined the sulfoxidation of chiral diols 3
using VO(acac)2-chiral ligand 7a/30% H2O2 and
TEMPO/NaOCl systems. The last achiral oxidant has
already proved its high chemo- and diastereoselectivity
in sulfoxidation.13 The obtained results (Table 4) sug-
gest that the stereoselectivity of the first reaction is
steered by the configuration of diol substrate, leading to
(u)-5 in ca. 20% d.e. Thus, in spite of the fact that
usually the (RS)-configuration of the sulfoxide is
induced by (R)-7a, in the case of (R,R)-3a the forma-
tion of (SS,R,R)-5a was favored. It seems that the chiral
diol moiety builds into the coordination sphere of the
vanadyl oxidant, thus changing its regular stereochemi-
cal preferences. However, it is interesting to note that at
the some time, kinetic resolution of the enantioenriched
substrate/product took place, so the sulfone 6a
Figure 1. An Ortep view of the molecule 5a.14 Thermal
ellipsoids were drawn on the 25% probability level. Hydrogen
atoms were diminished for clarity.

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J. Skarz; ewski et al. / Tetrahedron: Asymmetry 13 (2002) 369–375
Table 4. Sulfoxidation of enantioenriched diol 3a to sulfoxide 5a, and then to 6a
Entry
Diol 3a (E.e., %)
Oxidant
5a
6a
E.e. (%)
Yield (%)
D.e. (%)
Yield (%)
a
1
2
3
4
5
6
(S,S)-(−) (71)
(R,R)-(+) (60)
(S,S)-(−) (71)
(R,R)-(+) (60)
(S,S)-(−) (53)
(R,R)-(+) (78)
VO(acac)2, (S)-7a, H2O2
VO(acac)2, (S)-7a, H2O2
VO(acac)2, (R)-7a, H2O2
VO(acac)2, (R)-7a, H2O2
TEMPO (cat.)/NaOCl
TEMPO (cat.)/NaOCl
90
73
76
84
40
46
26 (Rs,3S,4S)
20 (Ss,3R,4R)
18 (Rs,3S,4S)
24 (Ss,3R,4R)
62 (Ss,3S,4S)
62 (Rs,3R,4R)
85
76
81
54 (3R,4R)
37 (3S,4S)
82 (3R,4R)
47 (3S,4S)
43 (3R,4R)
84
ca. 100b
a Oxidation to sulfone not performed.
b In the second step recrystallized pure l-5a was used.
−3
,
4. Experimental
4.1. General
all data, S=1.16, zmax=0.28, zmin=−0.28 e A , Flack
absolute structure parameter x=−0.02(13).
Crystallographic data (excluding structure factors) for
the structure in this paper has been deposited with the
Cambridge Crystallographic Data Centre as supple-
mentary publication number CCDC 176272. Copies of
the data can be obtained, free of charge, on application
to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK
[fax: +44(0)-1223-336033 or e-mail: deposit@ccdc.
cam.ac.uk].
Melting points were determined using a Boetius hot-
stage apparatus and are uncorrected. IR spectra were
recorded on a Perkin–Elmer 1600 FT-IR spectrophoto-
1
meter. H and 13C NMR spectra were measured on a
Bruker CPX (1H, 300 MHz) spectrometer using TMS
as an internal standard. Enantioselectivities of the reac-
tion were determined by the NMR discrimination of
appropriate signals using Eu(hfc)3 as a chiral shift
reagent. Observed rotations at 578 nm were measured
using an Optical Activity Ltd. Model AA-5 automatic
polarimeter. GC–MS analyses were determined on a
Hewlett–Packard 5890 II gas chromatograph (25 m
capillary column) with a Hewlett–Packard mass spec-
trometer 5971 A operating in electron impact mode (70
eV). Separations of products by chromatography were
performed on silica gel 60 (230–400 mesh) purchased
from Merck. Thin-layer chromatography analyses were
performed using silica gel 60 precoated plates (Merck).
4.3. Homoallylic sulfides 1
1-Phenyl-4-phenylsulfanylbut-1-ene 1a was prepared
according to the standard procedure15 using thiophenol
and 4-bromo-1-phenylbut-1-ene obtained from cyclo-
propyl phenyl ketone.16 4-Arylsulfanylbut-1-enes 1b–c
were obtained in a similar manner from commercially
available homoallylic bromide (Aldrich) and the appro-
priate thiophenols.
4.3.1. 1-Phenyl-4-phenylsulfanylbut-1-ene 1a. Yield 94%.
1H NMR (CDCl3): l=2.51–2.58 (m, 2H, CH2), 3.02–
3.07 (m, 2H, CH2), 6.18–6.28 (m, 1H, -CHꢀCH-), 6.40–
6.46 (d, 1H, -CHꢀCH-, J=15.9 Hz), 7.15–7.37 ppm (m,
10 H, ArH). 13C NMR (CDCl3): l=32.8, 33.5, 125.8,
126.0, 127.2, 128.0, 128.5, 129.0, 129.4, 131.5, 136.4,
137.3 ppm. IR (KBr): 692, 740, 967, 1091, 1386, 1583,
1679, 2925, 3058 cm−1. Rf=0.83 (t-BuOMe/CHCl3,
3:2). MS (EI, 70 eV): m/z (%)=240 (57) [M+], 123 (100)
4.2. X-Ray crystallographic data
Colorless crystals of 5a suitable for X-ray diffraction
studies were grown by dissolving the compound in an
n-hexane–methylene chloride mixture, and then by the
slow evaporation at room temperature. The crystal was
examined on
a Kuma KM4CCD diffractometer
[M+−C6H5CHꢀCHCH2], 91 (33) [C6H5CH2 ], 77 (22)
+
,
equipped with a CCD camera (u=0.71073 A, qmax
=
+
26°) at 293(2) K. Precise cell constants were determined
by the least-squares method on the ground of the most
of the data collection reflections. The data were cor-
rected for the Lorentz-polarization effect.18 The struc-
ture was solved by direct methods from SHELXS-9719
and refined by SHELXL-97.20 All non-hydrogen atoms
were treated anisotropically. Hydrogen atoms were
found from a DF map and refined without constraints.
[C6H5 ].
4.3.2. 4-(Phenylsulfanyl)but-1-ene 1b. Yield 91%. Char-
acteristics in agreement with the literature data.17
4.3.3. 4-(2-Tolylsulfanyl)but-1-ene 1c. Yield 91%. 1H
NMR (CDCl3): l=2.34–2.42 (m, 5H, CH3, CH2), 2.91–
2.96 (m, 2H, CH2), 5.03–5.12 (m, 2H, ꢀCH2), 5.81–5.90
(m, 1H, ꢀCH-), 7.05–7.25 ppm (m, 5H, ArH). 13C
NMR (CDCl3): l=20.8, 32.7, 33.7, 116.1, 125.5, 126.3,
127.9, 130.0, 135.7, 136.4, 137.5 ppm. IR (film): 743,
916, 1066, 1469, 1589, 1640, 2923, 3062 cm−1. Rf=0.72
(t-BuOMe/CHCl3, 3:2). MS (EI, 70 eV): m/z (%)=178
(77) [M+], 137 (100) [M+−CH2ꢀCHCH2], 91 (27) [M+−
SCH2CH2CHꢀCH2].
Orthorhombic, P212121, a=5.9906(7), b=5.9906(7), c=
−3
3
,
,
30.152(4) A, Dx=1.331 Mg m , V=1449.6(3) A , Z=
4, v=0.228 mm−1, F(000)=616, CCD camera, 7704
reflections collected, 2805 unique reflections, 2515
observed unique reflections, Rint=0.072, R1=0.070 and
wR2=0.110 for I>2|(I), R1=0.084 and wR2=0.115 for

J. Skarz
;
ewski et al. / Tetrahedron: Asymmetry 13 (2002) 369–375
373
4.4. Oxidation of sulfides
mL) and the combined organic phases were washed
with water, brine and dried (Na2SO4). The products
were chromatographed on a silica gel column with
tert-BuOMe/CHCl3 (3:2) and finally purified by recrys-
tallization from CH2Cl2/hexane.
4.4.1. Oxidation with VO(acac)2 and chiral Schiff bases.8
Vanadyl acetylacetonate (5.2 mg, 0.02 mmol) and the
ligand 7 (0.03 mmol) were dissolved in a test tube in
dichloromethane (4 mL), and the solution was stirred
for 5 min at 25°C. After the addition of the sulfide (2
mmol) the solution was cooled to 0°C and 30% H2O2
(0.26 mL, 2.3 mmol) was added dropwise during 10
min. The mixture was stirred for 20 h at 0°C and
extracted with CH2Cl2 (2×5 mL). The combined
organic extracts were washed with H2O, brine and dried
over Na2SO4. The solvent was removed in vacuo and
the crude product was submitted to the chromatogra-
phy on silica gel (t-BuOMe/CHCl3/hexane).
4.5.1. 1-Phenyl-4-phenylsulfinylbut-1-ene (R)-2a. [h]2D0=
+47 (0.50, CH2Cl2, 66% e.e.), (S)-2a: [h]2D0=−48 (0.58,
CH2Cl2, 67% e.e.), [h]2D0=−60 (0.91, CH2Cl2, 84% e.e.),
1
[h]2D0=−66 (0.64, CH2Cl2, 92% e.e.). H NMR (CDCl3):
l=2.45–2.55 (m, 1H, CH2), 2.64–2.76 (m, 1H, CH2),
2.88–2.96 (m, 2H, CH2), 6.09–6.19 (m, 1H, -CHꢀCH-),
6.42–6.47 (d, 1H, -CHꢀCH-, J=15.6 Hz), 7.19–7.29 (m,
5H, ArH), 7.50–7.65 ppm (m, 5H, ArH). Dl=0.100
ppm in the presence of equimolar amount of Eu(hfc)3
in CCl4 (a-CH2). 13C NMR (CDCl3): l=25.5, 56.5,
124.0, 126.0, 126.3, 127.4, 128.5, 129.2, 130.9, 132.3,
136.9, 143.7 ppm. IR (film): 535, 693, 748, 968, 1043,
1087, 1443, 1598, 3026, 3056 cm−1. Rf=0.67 (t-BuOMe/
CHCl3, 3:2).
4.4.2. Other oxidation methods. Hydroperoxide asym-
metric oxidation was performed according to two liter-
ature procedures A9 and B.10
Method A.9 (+)-(R,R)-DET (4 mmol, 0.7 mL) was
dissolved in dichloromethane (20 mL) under an argon
atmosphere. Ti(O-i-Pr)4 (2 mmol, 0.6 mL) and H2O (2
mmol, 0.04 mL) were introduced to the solution by
means of syringe. The mixture was stirred for 20 min,
and then sulfide (2 mmol) was added. After 0.5 h of
mixing at 0°C, cumyl hydroperoxide (2 mmol, 0.42 mL
of 70% solution in cumene) was introduced, and the
mixture was stirred for 24 h at 0°C. Water (0.8 mL) was
added, and the stirring was maintained for 1 h at room
temperature. After filtration over Celite the solution
was stirred with aqueous NaOH (5%) and brine for
another hour. The organic phase was separated, dried
(Na2SO4), and concentrated to give the crude product
which was purified on a silica gel column.
4.5.2. 4-(Phenylsulfinyl)but-1-ene (S)-2b. [h]2D0=−131
1
(1.0, CH2Cl2, 70% e.e.). H NMR (CCl4): l=2.45–2.50
(m, 1H, CH2), 2.68–2.73 (m, 1H, CH2), 2.83–2.98 (m,
2H, CH2), 5.20–5.31 (m, 2H, ꢀCH2), 5.90–6.04 (m, 1H,
ꢀCH-), 7.55–7.75 ppm (m, 5H, ArH). Dl=0.118 ppm
in the presence of equimolar amount of Eu(hfc)3 in
CCl4 (a-CH2). 13C NMR (CDCl3): l=26.3, 56.2, 117.0,
124.1, 129.0, 130.4, 135.4 ppm. IR (film): 535, 693, 748,
1043, 1087, 1444, 1478, 1641, 2916, 3059 cm−1. Rf=0.6
(t-BuOMe/CHCl3/hexane, 3:2:0,8).
4.5.3. 4-(2-Tolylsulfinyl)but-1-ene (S)-2c. [h]2D0=−118
1
(1.0, CH2Cl2, 85% e.e.). H NMR (CCl4): l=1.58 (m,
4H, CH2, CH3), 1.80–1.86 (m, 2H, CH2), 1.98–2.02 (m,
1H, CH2), 4.25–4.37 (m, 2H, CH2), 4.96–5.06 (m, 1H,
CH2), 6.33–6.35 (d, 1H, ArH, J=7.3 Hz), 6.50–6.64 (m,
2H, ArH), 7.04–7.06 ppm (d, 1H, ArH, J=7.4 Hz).
Dl=0.201 ppm in the presence of equimolar amount of
Eu(hfc)3 in CCl4 (a-CH2).13C NMR (CDCl3):18.1, 26.3,
54.1, 116.9, 123.8, 127.1, 130.6, 130.6, 134.2, 134.8,
141.8 ppm. IR (film): 757, 1035, 1065, 1446, 1472, 1594,
1641, 2918, 2979, 3065 cm−1. Rf=0.55 (t-BuOMe/
CHCl3, 3:2).
Method B.10 To a solution of (+)-(R)-1,1%-binaphthol
(0.2 mmol, 57 mg) in CCl4 (3 mL) were introduced
Ti(O-i-Pr)4 (0.1 mmol, 0.03 mL) and H2O (2 mmol,
0.04 mL) by means of syringe under an argon atmo-
sphere. The resulting solution was stirred for 1 h at
room temperature, and the sulfide (1 mmol) dissolved
in a small amount of CCl4 was added with a syringe.
After stirring for 0.5 h at 0°C, tert-butyl hydroperoxide
(2 mmol, 0.25 mL of 80% solution in di-tert-butyl
peroxide) was introduced, and the mixture was stirred
for 24 h at 0°C. The reaction mixture was directly
chromatographed on a silica gel column. The sulfoxide
was eluted with tert-BuOMe/CHCl3 (3:2).
4.6. Dihydroxylation
4.6.1. General procedure for OsO4 dihydroxylation.11
A
round-bottomed flask was charged with potassium fer-
ricyanide (3.0 mmol, 0.98 g), potassium carbonate (3.0
mmol, 0.41 g), quinuclidine (0.04 mmol, 4.4 mg), potas-
sium osmate dihydrate (0.01 mmol, 3.7 mg) and
methanesulfonamide (1.0 mmol, 95.1 mg, added only in
the case of 2a) in a two-phase system (5 mL of water
and 5 mL of t-butanol). The mixture was stirred until
all solids had dissolved. The substrate 2 (1 mmol) was
added and the suspension was stirred vigorously for 72
h at 0°C. Anhydrous sodium sulfite (0.01 mol, 1.26 g)
was added and stirring continued for 1 h before the
addition of ethyl acetate (15 mL). The layers were
separated and the aqueous phase was extracted with
ethyl acetate (3×10 mL). The combined organic extracts
were washed with 2 M KOH (3 mL, in the case of 2a
4.5. TEMPO catalyzed oxidation
TEMPO oxidation was performed according to the
described procedure.13 A 50 mL flask was charged with
a solution of sulfide 3a (3 mmol) in 20 mL of CH2Cl2,
TEMPO (0.09 mmol, 14 mg), and a saturated aqueous
NaHCO3 (16 mL) containing KBr (36 mg, 0.3 mmol).
To this cooled (0°C, ice-water bath) and well-stirred
mixture, a solution of NaOCl (0.90 M, 3.6 mL)
together with saturated aqueous NaHCO3 (4 mL) was
added dropwise. The mixture was stirred for 2–5 h at
0°C (monitored by TLC) and the layers were separated.
The aqueous phase was extracted with CH2Cl2 (3×10

374
J. Skarz; ewski et al. / Tetrahedron: Asymmetry 13 (2002) 369–375
substrate), dried (MgSO4) and evaporated under
reduced pressure. The residue was purified by column
chromatography, eluted with tert-BuOMe:CH2Cl2 3:2,
and recrystallized (CH2Cl2–hexane).
4.6.2.3. 4-Phenylsulfinylbutane-1,2-diol 5b. D.m. 1H
NMR (CDCl3): l=1.72–1.95 (m, 2H, CH2), 2.86–3.18
(m, 2H, CH2), 3.27 (s, 2H, 2×OH), 3.44–3.49 (m, 2H),
3.70–3.74 (m, 1H, CH), 7.50–7.91 ppm (m, 5H, ArH).
13C NMR (CDCl3): 21.0, 21.1, 48.2, 48.3, 61.4, 65.5,
65.8, 119.3, 124.5, 126.4, 138.0 ppm. IR (film): 692, 996,
1086, 1405, 1668, 2927, 3364 cm−1. Rf=0.15 (t-BuOMe/
CHCl3, 3:2).
4.6.2. Typical procedure for AD-reactions.6 These reac-
tions were run as follows: The substrate 1, 2 or 4 (1
mmol) was dissolved in 1:1 water/t-BuOH mixture (10
mL) and cooled to 0°C. Then, the commercial (Aldrich)
AD-mix a or AD-mix b (1.4 g) and methanesulfon-
amide (1.0 mmol, 95.1 mg, except for substrates with a
terminal double bond) were added and the mixture was
stirred for 48 h at 0°C. Anhydrous sodium sulfite (0.01
mol, 1.26 g) was introduced and after 1 h stirring
dichloromethane (15 mL) was added. The layers were
separated and the aqueous phase was extracted with
dichloromethane (3×10 mL). The combined organic
extracts were washed with 2 M KOH (3 mL, in the case
of non-terminal substrates), dried (MgSO4) and evapo-
rated under reduced pressure. The residue was purified
by column chromatography, eluted with tert-
BuOMe:CH2Cl2 3:2, and recrystallized (CH2Cl2–
hexane).
1
4.6.2.4. 4-(2-Tolylsulfinyl)butane-1,2-diol 5c. D.m. H
NMR (CDCl3): l=1.81–1.90 (m, 2H, CH2), 2.37 (s,
3H, CH3), 2.82–2.89 (m, 1H, CH2), 3.03–3.10 (m, 1H,
CH2), 3.44–3.50 (m, 1H), 3.59–3.74 (m, 3H, 2×OH,
CH2), 3.60–3.86 (m, 1H, *CH), 7.19–7.21 (d, 1H, ArH,
J=6.8 Hz), 7.36–7.45 (m, 2H, ArH), 7.84–7.86 ppm (d,
1H, ArH, J=6.9 Hz). 13C NMR (CDCl3): 18.2, 18.2,
26.3, 26.3, 51.0, 51.4, 66.4, 66.4, 70.4, 70.7, 123.9, 124.1,
127.2, 127.2, 130.8, 130.8, 130.9, 130.9, 134.4, 134.5,
140.7, 140.9 ppm. IR (film): 758, 1020, 1455, 1472,
1656, 2925, 3369 cm−1. Rf=0.29 (t-BuOMe/CHCl3/
MeOH, 2:1:1).
4.7. Preparation of sulfones12
A solution of sulfoxide 3 (1 mmol) in methanol (20 mL)
was treated with Oxone® (675 mg, 1.1 mmol—in the
case of sulfide 1 oxidation the amount of oxidant was
doubled) in water (10 mL). The reaction mixture was
stirred at room temperature for 2 h. The solution was
extracted with dichloromethane (30 mL), the organic
phase was separated, dried (Na2SO4), and evaporated
under reduced pressure. The products were recrystal-
lized or chromatographed on silica gel.
4.6.2.1. 1-Phenyl-4-phenylsulfanylobutane-1,2-diol 3a.
Mp=56–58°C (petroleum ether/CH2Cl2). (R,R)-(3a):
[h]D20=+49 (0.60, CH2Cl2, 76% e.e.), (S,S)-(3a): [h]2D0=
1
−46 (0.48, CH2Cl2, 71% e.e.). H NMR (CDCl3): l=
1.52–1.77 (m, 2H), 2.63 (s, 2H, 2×OH), 2.88–2.98 (m,
1H), 3.03–3.16 (m, 1H), 3.87–3.94 (m, 1H), 4.42–4.44
(d, 1H, J=6.8 Hz), 7.14–7.36 ppm (m, 10H, ArH).
Dl=0.122 ppm in the presence of Eu(hfc)3 in CCl4
(CH2CHOH). 13C NMR (CDCl3): 30.3, 31.9, 74.6, 77.8,
126.0, 126.8, 128.2, 128.6, 128.8, 129.4, 135.9, 140.7
ppm. IR (KBr): 702, 739, 910, 1052, 1078, 1199, 1439,
1454, 1584, 2971, 3387 cm−1. Rf=0.50 (t-BuOMe/
CHCl3, 3:2). Anal. calcd for: C16H18O2S (M=274.38):
C, 70.05; H, 6.62; S, 11.66; found C, 70.28; H, 6.90; S,
11.46%.
4.7.1. 1-Phenyl-4-phenylsulfonylbut-1-ene 4a. Yield 91%.
1
Mp=68–69.5°C (MeOH). H NMR (CDCl3): l=2.63–
2.70 (m, 2H, CH2), 3.24–3.29 (m, 2H, CH2), 6.02–6.12
(m, 1H, -CHꢀCH-), 6.39–6.45 (d, 1H, -CHꢀCH-, J=
15.8 Hz), 7.25–7.29 ppm (m, 5H, ArH), 7.57–7.68 ppm
(m, 3H, ArH), 7.95–7.98 ppm (d, 2H, ArH, J=7.7 Hz).
13C NMR (CDCl3): l=26.3, 55.7, 125.1, 126.1, 127.5,
128.1, 128.5, 129.3, 132.4, 133.7, 136.6, 139.0 ppm. IR
(KBr): 536, 566, 682, 741, 795, 976, 1086, 1139, 1230,
1282, 1294, 1449, 1480, 1585, 1597, 2919, 3031, 3081
cm−1. Anal. calcd for: C16H16O2S (M=272.36): C,
70.56; H, 5.92; S, 11.75; found C, 70.40; H, 5.74; S,
11.47%.
4.6.2.2. 1-Phenyl-4-phenylsulfinylbutane-1,2-diol 5a.
Isomer l: mp=134–135°C (hexane/CH2Cl2). (R,R,R)-
5a: [h]2D0=+126 (0.40, CH2Cl2, >98% e.e.), (S,S,S)-5a:
[h]2D0=−125 (0.34, CH2Cl2, >98% e.e.). 1H NMR
(CDCl3): l=1.77–1.87 (m, 2H, CH2), 2.84–3.05 (m, 2H,
CH2), 3.13 (s, 2H, 2×OH), 3.78–3.84 (m, 1H, -CH),
4.44–4.46 (d, 1H, -CH, J=6.8 Hz), 7.33–7.37 (m, 5H,
ArH), 7.49–7.57 (m, 5H, ArH); 13C NMR (CDCl3):
l=26.5, 53.6, 74.3, 77.6, 124.0, 126.9, 128.2, 128.6,
129.3, 131.1 ppm. Mixture of l and u: 1H NMR
(CDCl3): l=1.70–1.75 and 1.77–1.87 (two m, 2H,
CH2), 2.84–3.05 (m, 2H, CH2), 3.13 (br. s, 2H, 2×OH),
3.69–3.74 and 3.78–3.84 (two m, 1H, -CH), 4.39–4.42
and 4.44–4.46 (two d, 1H, -CH, J=7.2 Hz and J=6.8
Hz, respectively), 7.32–7.48 (m, 5H, ArH), 7.48–7.57
ppm (m, 5H, ArH). 13C NMR (CDCl3): l=26.5, 26.9,
53.5, 53.6, 74.3, 74.5, 77.6, 77.9, 124.0, 124.2, 125.9,
126.9, 127.0, 128.2, 128.6, 128.6, 129.3, 131.1 ppm. IR
(KBr): 698, 745, 1015, 1044, 1181, 1442, 2911, 3361
cm−1. Rf=0.23 (t-BuOMe/CHCl3, 3:2). Anal. calcd for:
C16H18O3S (M=290.38): C, 66.18; H, 6.25; S, 11.04;
found C, 65.90; H, 6.20; S, 11.30%.
4.7.2.
(R,R)-1-Phenyl-4-phenylsulfonylbutane-1,2-diol
6a. Mp=90–92°C (CH2Cl2/hexane). [h]2D0=+17 (0.30,
CH2Cl2, 89% e.e.). 1H NMR (CDCl3): l=1.78–1.80 (m,
2H), 2.68 (s, 2H, 2×OH), 3.04–3.20 (m, 1H), 3.24–3.34
(m, 1H), 3.82 (s, 1H), 4.42 (s, 1H), 7.27–7.36 (m, 5H,
ArH), 7.49–7.57 (m, 2H, ArH), 7.61–7.66 (m, 1H,
ArH), 7.79–7.82 ppm (m, 2H, ArH). 13C NMR
(CDCl3): 25.9, 52.9, 73.8, 77.6, 126.7, 127.9, 128.5,
128.8, 129.2, 133.7, 138.9, 142.0 ppm. IR (KBr): 527,
736, 913, 1020, 1072, 1087, 1288, 1405, 1445, 1494,
1471, 2892, 3063, 3510 cm−1. Rf=0.41 (t-BuOMe/
CHCl3, 3:2). Anal. calcd for: C16H18O4S (M=306.38):
C, 62.72; H, 5.92; S, 10.46; found C, 63.04; H, 6.10, S,
10.73%.

J. Skarz
;
ewski et al. / Tetrahedron: Asymmetry 13 (2002) 369–375
375
4.7.3. 4-Phenylsulfonylbutane-1,2-diol 6b. Mp=76–
78°C. [h]2D0=+2.5 (0.42, CH2Cl2, 10% e.e.), [h]2D0=+2.7
(1.48, EtOH, ca. 10% e.e.), lit.7 [h]D20=+23.2 (1.4,
4. Solladie´, G.; Fre´chou, C.; Demailly, G. Tetrahedron Lett.
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5. Solladie´, G.; Fre´chou, C.; Hutt, J.; Demailly, G. Bull.
1
EtOH, 94% e.e.). H NMR (CDCl3): l=1.79–1.91 (m,
Soc. Chim. Fr. 1987, 827–836.
2H, CH2), 2.27 (br s, 2H, 2×OH), 3.24–3.35 (m, 2H,
CH2), 3.42–3.48 (m, 1H, CH2), 3.61–3.68 (dd, 1H,
J1=3.3 Hz, J2=11.2 Hz, CH), 3.79–3.85 (m, 1H, CH),
7.56–7.70 (m, 3H, ArH), 7.90–7.93 ppm (m, 2H, ArH).
IR (KBr): 539, 689, 737, 1040, 1086, 1143, 1305, 1447,
2931, 3388 cm−1. Rf=0.38 (t-BuOMe/CHCl3/MeOH,
2:1:1). Anal. calcd for: C10H14O4S (M=230.212): C,
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Acknowledgements
10. Komatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S. J.
Org. Chem. 1993, 58, 4529–4533.
The authors thank the Polish Committee for Scientific
Research for financial support (KBN Grant 7 T09A
109 21). The support of the Foundation for Polish
Science for the purchase of the CCD camera is grate-
fully acknowledged.
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