A new and efficient route to homochiral γ-hydroxysulfoxides and γ-hydroxysulfones

Article abstract of DOI:10.1016/S0957-4166(02)00581-5

Readily available (+)-(R)-1,3-diphenyl-3-phenylsulfanyl-propan-1-one 1 was oxidized to the corresponding sulfone and its reduction gave separable (1R,3R)- and (1S,3R)-1,3-diphenyl-3-phenylsulfonylpropan-1-ols. When 1 was reduced to the mixture of epimeric

Full text of DOI:10.1016/S0957-4166(02)00581-5

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 2105–2111
A new and efficient route to homochiral g-hydroxysulfoxides and
g-hydroxysulfones
Jacek Skarz; ewski,* Renata Siedlecka, Elz; bieta Wojaczyn´ska and Mariola Zielin´ska-Błajet
Institute of Organic Chemistry, Biochemistry and Biotechnology, Wrocław University of Technology, 50-370 Wrocław, Poland
Received 23 July 2002; accepted 23 September 2002
Abstract—Readily available (+)-(R)-1,3-diphenyl-3-phenylsulfanyl-propan-1-one 1 was oxidized to the corresponding sulfone and
its reduction gave separable (1R,3R)- and (1S,3R)-1,3-diphenyl-3-phenylsulfonylpropan-1-ols. When 1 was reduced to the mixture
of epimeric alcohols, subsequent reaction with three different sulfoxidation agents allowed the separation of all four
diastereomeric 1,3-diphenyl-3-phenylsulfinylpropan-1-ols in diastereomerically pure form. The absolute configuration at the newly
created stereogenic carbon was proved by chemical correlation, while the configuration of the sulfur centre of the phenylsulfinyl
group was established by CD spectroscopy. © 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Hydroxysulfoxides constitute an important class of chi-
ral building blocks. Usually, their preparation is based
on the diastereoselective reduction of the corresponding
ketosulfoxides. This method is particularly suitable for
the preparation of b-hydroxysulfoxides of the required
configuration.1 In a few cases the same approach has
also been applied to obtain the respective g-hydroxy
derivatives.2 Recently, we have described a facile and
enantioselective method for the multigram preparation
of the Michael adducts via addition of thiophenols to
chalcones.3 The thus obtained optically active g-keto-
sulfides possess two prostereogenic centers, suitable for
further transformation into hydroxy-, sulfinyl- or sulfo-
nyl functionalities. Since we are interested in the prepa-
ration of stereodifferentiating ligands, we undertook
the elaboration of both prochiral groups into new
chiral derivatives of this type, with divergent
stereochemistry.
Reduction of (+)-(R)-1,3-diphenyl-3-phenylsulfanyl-
propan-1-one 13 with lithium aluminum hydride (LAH)
led to an inseparable mixture of diastereomeric alcohols
2 in excellent yield but with d.r. of ca. 1:1. Application
of other reducing agents, namely DIBAL-H, DIBAL-
H/ZnCl2 or NaBH4 was ineffective. However, when
(R)-1 was oxidized with Oxone® to the corresponding
sulfone (R)-3, its subsequent reduction with LAH also
gave a mixture of diastereomers (24% de). Fortunately,
in this case both products (R,R)- and (R,S)-4 could be
separated completely by crystallization. The pure
diastereomer obtained, (R,S)-4, was desulfonylated to
afford the known (S)-1,3-diphenylpropanol-1 5.4 Alco-
hol (R,S)-4 was mesylated to give (R,S)-6, which
reacted in the presence of potassium tert-butoxide and
a catalytic amount of 18-crown-6 via intramolecular
SN2 reaction5 resulting in homochiral (E)-1,2-diphenyl-
1-phenylsulfonylcyclopropane 7 (Scheme 1). Here, the
stereochemical assignment is based on the fact that a
single optically active diastereomer with cis-located
phenyl groups (see: NOESY correlations, 500 MHz)
was obtained as the only product. Unfortunately,
desulfonylation6 of 7 furnished the mixture of cis- and
trans-1,2-diphenylcyclopropane and no stereoselective
method for this transformation was found.
Herein we report a simple, two-step transformation of
the Michael adduct into g-hydroxysulfoxides and g-
hydroxysulfones, interesting chiral building blocks with
three or two stereogenic centers, respectively. We also
describe their further conversions into enantiomeric
alcohols and cyclopropane derivatives.
In order to exploit the well known stereodirecting prop-
erties of the phenylsulfinyl group,1 we attempted
diastereoselective sulfoxidation of the adduct 1. How-
* Corresponding author. E-mail: skarzewski@kchf.ch.pwr.wroc.pl
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00581-5

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J. Skarz; ewski et al. / Tetrahedron: Asymmetry 13 (2002) 2105–2111
Scheme 1.
ever, the substrate did not react with mild oxidants (see
below) and ultimately the use of MCPBA resulted in
retro-Michael reaction and chalcone was isolated in
46% yield. We therefore attempted sulfoxidation of the
reduced adduct, i.e. diastereomeric mixture of (R)-2.
When a mild chemoselective oxidant (NaIO4)7 was
used, all four possible diastereomeric g-hydroxysulfox-
ides 8 (a,b,g,d) were formed in comparable yields
(Scheme 2). The 1H NMR spectrum for each
diastereomer was different from the others in the reso-
nance pattern for the methine hydrogens (3.5–5.5 ppm).
Recrystallization of the mixture gave
a
single
diastereomerically pure isomer 8a in 21% yield. Further
oxidation of this product with Oxone®8 produced the
Scheme 2.

J. Skarz
;
ewski et al. / Tetrahedron: Asymmetry 13 (2002) 2105–2111
2107
sulfone with identical physical and spectroscopic prop-
erties to (R,S)-4.
absolute configuration of the chromophore.13a Its pri-
mary UV band (s“s*, SꢀO, usually at 235–255 nm,
log m ca. 3.6) is optically active with a CE, Dm of ca. 20.
Additionally, the shorter wavelength absorption (1La,
phenyl ring, ca. 220 nm, log m ca. 4.1) demonstrates a
CE of similar amplitude but of opposite sign. For the
phenylsulfinyl group, a negative CE for the primary
band corresponds to (S)-configuration.9b,13 This corre-
lation has recently been ascribed to the coupling of the
transition dipole moments for both bands, which
defines the chirality.14 We measured the UV and CD
spectra of all our diastereomeric sulfoxides and sul-
fones. The results are shown in Table 1 and Figs. 1 and
2. In the absence of the stereogenic sulfur centre (sul-
fone 4), disregarding the presence of the stereogenic
carbon atoms, the long wavelength UV band disap-
pears, so the CD curve does not show any chirality in
this range (Dm=0 for u>240 nm) (Figs. 1 and 2). Even
in the presence of an additional UV-absorbing group
the CD curves for diastereomers differing in configura-
tion at the stereogenic sulfur were almost mirror
images. We have already observed similar feature for
b-aminosulfoxides.9b The results collected in Table 1
allows unambiguous assignment of configuration at the
newly created sulfur stereocenters. Thus our provisional
assignments were correct, as is confirmed by the data in
Table 1.
The diastereoselective catalytic TEMPO/sodium
hypochlorite system,9 was then applied. Only two
diastereomers of 8 (b and g) were produced, both
different from the previously isolated one. The main
diastereomer 8b (22% de) crystallized readily in pure
form. The second one (8g) was isolated by chromatog-
raphy and recrystallization after stereoselective sulfoxi-
dation (see below). Both the major 8b and minor 8g
were oxidized with Oxone® to (R,R)-4 and (R,S)-4,
respectively. Moreover, on boiling in xylene 8b under-
went thermal elimination furnishing a cis/trans mixture
of the known (+)-(R)-allylic alcohol 9.10 At this point of
the study the absolute configuration at the sulfur atom
in all of the obtained g-hydroxysulfoxides remained
unknown.
In order to solve this problem we used our optimized
version (30% H2O2/VO(acac)2-chiral ligand 10)11 of the
Bolm catalytic sulfoxidizing system.12 The system, when
containing (S)-ligand 10, is known for the preferred
formation of sulfoxides with SS configuration and with
(R)-10, RS configuration.11,12 Thus, when the oxidant
containing ligand (S)-10 was applied, three
1
diastereomers were detected by H NMR, with two of
them (8a and 8d) dominating. Fortunately, again all of
the diastereomers of 8 were separable, one of which was
identical with that previously isolated after oxidation
with NaIO4, i.e. 8a (26% yield). Based on this, we
tentatively assigned the stereochemistry as (R,S,SS)-8.
In the next experiment we used (R)-10 and the main
formed product (8b, 26% yield) was identical with the
major product obtained after oxidation with TEMPO/
NaOCl. On these grounds we assigned it as (R,R,RS)-8.
In the same way we provisionally assigned the absolute
configuration of both remaining sulfoxides; 8d being
(R,R,SS)-8 and 8g being (R,S,RS)-8. In order to verify
our assignments of absolute configuration at the stereo-
genic sulfur centre we studied the CD spectra of the
obtained g-hydroxysulfoxides 8 and, for comparison
their oxidation products (R,R)-4 and (R,S)-4.
It has long been known that the absolute configuration
of sulfoxides correlates with their chiroptical proper-
ties.13 The phenylsulfinyl group was considered by Mis-
low as an inherently chiral chromophore where the sign
of the Cotton effects (CE) is determined solely by the
Figure 1. CD spectra of (1S,3R,RS)-8 (solid line), (1S,3R,SS)-
8 (dotted line) and (1S,3R)-4 (dashed line) in acetonitrile
solution.
Table 1. UV and CD spectraa
Compound
UV absorption properties
Circular dichroism
umax (10−3 m)
u (Dm)
u (0)
u (Dm)
(1R,3R,RS)-8
(1S,3R,SS)-8
(1S,3R,RS)-8
(1R,3R,SS)-8
(1S,3R)-4
216 (16.8), 258 (5.97)
216 (18.0), 256 (5.83)
216 (13.3), 258 (3.50)
216 (19.9), 256 (6.81)
218 (16.4)
226 (−36.6)
225 (25.1)
223 (−16.3)
226 (44.8)
241
243
237
244
258 (20.6)
256 (−9.7)
260 (19.1)
258 (−17.8)
(1R,3R)-4
216 (16.0)
a Spectra were recorded in acetonitrile at the concentration range of 10−4–10−5 M.

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4.2. (R)-1,3-Diphenyl-3-phenylsulfanylpropan-1-one 1
Compound 1 was prepared as described previously.3
4.3. General procedure for reductions with LiAlH4
To a suspension of lithium aluminum hydride (0.34 g, 9
mmol) in absolute ether (250 ml), ketone 1 or 3 (7
mmol) was added gradually. The resulting mixture was
heated under reflux for 3 h. Then, ether saturated with
water (30 ml), H2O (10 ml), and 15% aqueous sodium
hydroxide (ca. 20 ml) were subsequently introduced to
the cooled solution. After 30 min of stirring, the
organic layer was separated from the granulated precip-
itate, and the solid was washed twice with ether (30 ml).
The combined ethereal extract was dried over K2CO3
and evaporated. The products obtained were analyti-
cally pure: 2 (inseparable 1:1 diastereomeric mixture),
and 4 (separated by recrystallization from methylene
dichloride–n-hexane).
Figure 2. CD spectra of (1R,3R,RS)-8 (solid line), (1R,3R,SS)-
8 (dotted line) and (1R,3R)-4 (dashed line) in acetonitrile
solution.
3. Conclusions
4.3.1. (3R)-1,3-Diphenyl-3-phenylsulfanylpropan-1-ol, 2:
(diastereomeric ratio 1:1). Yield 98%; Oil, 1H NMR
(CDCl3): 1.76 (br s, 1H, OH), 2.13–2.24 and 2.25–2.36
(two m, 2H, CH2), 4.15 and 4.33 (t, J=7.4 Hz, dd,
J1=9.8 Hz, J2=5.6 Hz, 1H, S-CH), 4.44 and 4.78 (dd,
J1=9.3 Hz, J2=3.6 Hz, dd, J1=7.6 Hz, J2=5.9 Hz,
1H, CH), 7.08–7.25 (m, 15H, ArH); IR (film): 3410,
3060, 1583, 1493, 1453, 1054, 1025, 747, 699 cm−1; MS
(EI, 70 eV): m/z (%)=320 (1) [M+], 210 (51), 110 (55),
107 (91), 79 (100), 77 (90), 65 (31), 51 (31); [h]2D0=+142
(1.38, CH2Cl2); Rf=0.43 (tert-BuOMe/CHCl3/hexane,
2.0:2.0:7.0). These characteristics are in general agree-
ment with the literature data for the racemic mixture of
diastereomers.15
The readily available adduct of thiophenol to chalcone
allows, after oxidation to the sulfone and subsequent
reduction of the ketone function, easy separation of the
respective diastereomeric alcohols. These derivatives are
suitable for further transformations. Chemo- and
stereoselective sulfoxidations of epimeric g-hydroxy-
sulfides gave, after recrystallization, all four
diastereomeric g-hydroxysulfoxides in diastereomeri-
cally pure form. Thus, sequential reduction and oxida-
tion of the two prochiral groups of the enantiomeric
precursor allows simple preparation of all possible
products with three stereogenic centers.
4.3.2. 1,3-Diphenyl-3-phenylsulfonylpropan-1-ol, 4. Yield
>95%. D.e.=24% (62:38). The diastereomers were sepa-
rated by several recrystallizations from CH2Cl2/hexane;
the major (1S,3R)-4 crystallizes, while the minor
(1R,3R)-4 is retained in the mother liquor.
4. Experimental
4.1. General
4.3.2.1. (+)-(1S,3R)-4. Mp=191–192°C (CH2Cl2/hex-
ane); [h]2D0=+77 (0.20, CH2Cl2, >95% ee); 1H NMR
(CDCl3), l: 1.76 (br s, 1H, OH), 2.35–2.44 (m, 1H,
CH2), 2.67–2.77 (m, 1H, CH2), 4.32 (d, 1H, J=9.0 Hz,
CH), 4.48 (dd, 1H, J1=11.4 Hz, J2=4.5 Hz, CH),
7.09–7.12 (m, 2H, ArH), 7.18–7.32 (m, 10H, ArH),
7.44–7.46 (m, 3H, ArH); 13C NMR (CDCl3), l: 36.8
Melting points were determined using a Boetius hot-
stage apparatus and are uncorrected. IR spectra were
recorded on a Perkin–Elmer 1600 FTIR spectrophoto-
1
meter. H and 13C NMR spectra were measured on a
Bruker CPX (1H, 300 MHz) or a Bruker Avance (1H,
500 MHz) spectrometer using TMS as an internal stan-
dard. UV and CD spectra were recorded for CH3CN
solutions using a Hewlett–Packard 8452 diode array
spectrophotometer and a JASCO J 600 spectropolar-
imeter, respectively. Observed rotations at 589 nm were
measured using an Optical Activity Ltd. Model AA-5
automatic polarimeter. GC–MS analyses were deter-
mined on a Hewlett–Packard 5890 II gas chro-
(CH2), 68.6 (C6 HSO2Ph), 70.8 (C6 HOH), 125.6, 128.0,
128.6, 128.7, 128.9, 129.0, 130.1, 132.0, 133.4, 137.4,
143.7; IR (KBr): 3464, 3058, 1494, 1447; 1289, 1143,
1067, 749, 701, 561 cm−1. Anal. calcd for C21H20SO3
(M=352.391): C, 71.51; H, 5.72; S, 9.08. Found: C,
71.78; H, 5.67; S, 9.07%.
matograph (25
m
capillary column) with
a
4.3.2.2. (+)-(1R,3R)-4. Mp=108–110°C (CH2Cl2/hex-
ane); [h]2D0=+59 (0.96, CH2Cl2, >95% ee); 1H NMR
(CDCl3) l: 2.13 (br s, 1H, OH), 2.54–2.63 (m, 1H,
CH2), 2.81–2.90 (m, 1H, CH2), 4.02–4.06 (m, 1H, CH),
4.77–4.81 (m, 1H, CH), 7.02 (d, 2H, J=7.3 Hz, ArH),
7.21–7.36 (m, 10H, ArH), 7.43–7.55 (m, 3H, ArH); 13C
Hewlett–Packard mass spectrometer 5971 A operating
on the 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).
NMR (CDCl3) l: 37.5 (CH2), 68.1 (C6 HSO2Ph), 72.0

J. Skarz
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2109
(C
6
HOH), 126.1, 128.2, 128.5, 128.6, 128.7, 128.8, 128.9,
4.6.1. (+)-(1S,3R)-(1,3-Diphenyl-3-phenylsulfonylpropyl)
methanesulfonate, 6. Yield 86%, de 100%. Mp=81–
129.0, 129.9, 132.7, 133.5, 142.7; IR (KBr): 3555, 3027,
1492, 1448, 1298, 1290, 1142, 1086, 1053, 701, 692, 594
cm−1.
1
83°C (EtOH); [h]D20=+50 (0.51, CH2Cl2, >95% ee); H
NMR (CDCl3) l: 2.49 (s, 3H, CH3), 2.57–2.58 (m, 1H,
CH2), 3.11–3.15 (m, 1H, CH2), 4.34–4.39 (dd, 1H,
J1=11.6 Hz, J2=2.9 Hz, CH), 5.16–5.19 (dd, 1H, J1=
10.7 Hz, J2=2.2 Hz, CH), 7.11–7.50 (m, 15H, ArH);
13C NMR (CDCl3) l: 35.1 (CH2), 39.2 (CH3), 67.9
4.4. Representative procedure for preparation of
sulfones
A solution of sulfide 1 (1 mmol) in methanol (20 ml)
was treated with Oxone® (2.2 mmol, 1.35 g) in water
(20 ml) (in the case of oxidation of 1 mmol of sulfox-
ides 8, 1.1 mmol of oxidant was used). The reaction
mixture was stirred at room temperature for 2 h. The
solution was extracted with CH2Cl2 (30 ml), the organic
phase was separated, dried over Na2SO4, and evapo-
rated under reduced pressure. The products were
recrystallized or chromatographed on silica gel.
(C6 HSO2Ph), 81.1 (C6 HSO3Me), 126.7, 128.7, 128.8,
129.0, 129.1, 129.3, 129.7, 130.1, 131.0, 133.7, 136.9,
137.3; IR (KBr): 3017, 1448, 1360, 1306, 1172, 1146,
894, 699, 574 cm−1.
4.7. Representative procedure for cyclopropanation
Potassium tert-butoxide (0.04 g, 0.35 mmol), 18-
Crown-6 (7.13 mg, 0.027 mmol), dry toluene (10 ml)
and (1S,3R)-6 (0.12 g, 0.27 mmol) were introduced into
a round-bottomed flask. The resulting solution was
stirred at room temperature for 8 h, then ice-cold water
(15 ml) was added, and the mixture was extracted with
ether (20 ml). The organic layer was separated, washed
with 1 M aqueous HCl (15 ml), water (10 ml), brine (10
ml) and dried over Na2SO4. After solvent evaporation
the crude product (E)-7 was recrystallized from methyl-
ene dichloride/hexane.
4.4.1.
(+)-(R)-1,3-Diphenyl-3-phenylsulfonylpropan-1-
one, 3. Yield >95%. Mp=159–160°C (MeOH); lit.16
(rac) mp=159°C (EtOH), 155.1°C (MeOH); [h]2D0=
+141 (1.13, CH2Cl2, >95% ee); 1H NMR (CDCl3):
l=3.79–3.88 (m, 1H, CH2), 3.99–4.07 (m, 1H, CH2),
4.83 (dd, 1H, J1=9.6 Hz, J2=4.8 Hz, CH), 7.08–7.15
(m, 5H, ArH), 7.25–7.38 (m, 4H, ArH), 7.43–7.50 (m,
4H, ArH), 7.83 (m, 2H, ArH); 13C NMR (CDCl3), l:
37.3 (CH2), 66.9 (C6 HSO2Ph), 128.1, 128.4, 128.7, 128.7,
128.8, 128.9, 129.7, 132.5, 133.7, 133.7, 136.1, 136.9,
194.8 (CꢁO); IR (KBr): 3064, 1687, 1674, 1597, 1448,
1306, 1232, 1145, 1084, 986, 753, 689, 560 cm−1. Anal.
calcd for C12H18O3S (M=350.375): C, 71.98; H, 5.17;
S, 9.13. Found: C, 71.73; H, 5.29; S, 9.16%.
4.7.1. (−)-(1R,2R)-1,2-Diphenyl-1-phenylsulfonylcyclo-
propane, 7. Yield >95%. Mp=181–182.5°C (CH2Cl2/
hexane); lit.18 (rac) mp=211–212°C; [h]2D0=−141 (0.6,
1
CH2Cl2, >95% ee); H NMR (CDCl3) l: 1.82 (dd, 1H,
H3a), 2.38 (dd, 1H, H3b), 3.58 (dd, 1H, H2), 6.76–6.79
(m, 4H, Ph1, Ph2, o-H), 7.00 (t, 2H, Ph1, m-H), 7.06–
7.08 (m, 3H, Ph2, m-H, p-H), 7.14 (t, 1H, Ph1, p-H),
7.38 (t, 2H, PhSO2, m-H), 7.48 (d, 2H, PhSO2, o-H),
7.55 (t, 1H, PhSO2, p-H); 13C NMR (CDCl3, 500 MHz)
l: 18.2 (C2), 28.5 (C3), 54.5 (C1), 127.2 (Ph2, C4%), 128.1,
128.3, 128.4, 128.9; 129.4 (SO2Ph, C2%, C6%), 130.2 (Ph1,
C1%), 133.7 (SO2Ph, C4%), 133.8 (Ph1, C2%, C6%), 135.3 (Ph2,
C1%), 138.3 (SO2Ph, C1%); IR (KBr): 3060, 3027, 1497,
1446, 1309, 1148, 817, 697, 688, 601, 562 cm−1. Anal.
calcd for C21H18O2S (M=334.43): C, 75.41; H, 5.42; S,
9.57. Found: C, 75.28; H, 5.64; S, 9.60%.
4.5. Desulfonylation
The reaction of sulfones (1S,3R)-4 and 7 with 6%
sodium amalgam was run in methanol according to a
standard procedure.17
4.5.1. (−)-(S)-1,3-diphenylpropan-1-ol, 5. Yield 86%.
Mp=44–46°C; [h]2D0=−14.5 (1.0, MeOH, >90% ee);
lit.4a [h]D20=+16.2 (1.17, MeOH, 96% ee) for (R)-5, lit.4b
1
[h]2D0=−14.8 (0.5, MeOH, >99% ee) for (S)-5; H NMR
(CDCl3) l: 1.79 (s, 1H, OH), 2.04–2.16 (m, 2H, CH2),
2.67–2.77 (m, 2H, CH2), 4.69 (dd, 1H, J1=7.4 Hz,
J2=5.7 Hz, CH), 7.19–7.36 (m, 10H, 2×ArH); IR
(KBr): 3395, 3027, 2940, 1603, 1495, 1454, 1058, 747,
699 cm−1. MS (EI, 70 eV): m/z (%)=212 (6) [M+], 194
(38) [212-OH], 107 (100) [PhCHOH+].
4.8. Representative procedures for oxidation of sulfides
4.8.1. Oxidation with sodium periodate. A solution of
NaIO4 (0.206 g, 0.96 mmol) in water (1.5 ml) was
added to hydroxysulfide 2 (0.238 g, 0.74 mmol) dis-
solved in acetone (6 ml). The reaction mixture was
stirred at rt for 2 h and extracted with CH2Cl2 (2×15
ml). The combined organic phase was dried with
Na2SO4, evaporated to dryness, analyzed by NMR and
recrystallized from toluene to give (1S,3R,SS)-8.
4.6. Representative procedure for mesylation
A round-bottomed flask cooled in an ice bath was
charged with alcohol (1S,3R)-4 (0.35 g, 1 mmol), tolu-
ene (30 ml) and triethylamine (0.56 ml, 4 mmol).
Methanesulfonyl chloride (0.10 ml, 1.3 mmol) was then
added with a syringe. The mixture was stirred at 5°C
overnight. The reaction was quenched with water (10
ml), the product was extracted with ether (20 ml), and
the organic layer was subsequently washed with 1 M
aqueous HCl (15 ml), water (10 ml), satd NaHCO3
solution (10 ml), brine (10 ml) and dried with sodium
sulfate. After solvent evaporation the product (1S,3R)-
6 was recrystallized from ethanol.
4.8.2. General procedure for oxidation with NaOCl/
TEMPO. A 50 ml flask was charged with a solution of
sulfide 2 (3 mmol) in CH2Cl2 (20 ml), TEMPO (0.09
mmol, 14 mg), and saturated aqueous solution of
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) in
saturated NaHCO3 (4 ml) was added dropwise. The

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J. Skarz; ewski et al. / Tetrahedron: Asymmetry 13 (2002) 2105–2111
mixture was stirred for 2 h at 0°C (monitored by TLC)
and the layers were separated. The aqueous phase was
extracted with CH2Cl2 (3×10 ml) and the combined
organic phase was washed with water, brine and dried
(Na2SO4). Solvent was evaporated, the crude product
was analyzed by NMR and pure (1R,3R,RS)-8 crystal-
lized from toluene.
2.54–2.63 (m, 1H, CH2), 2.81–2.87 (m, 1H, CH2), 2.91
(s, 1H, OH), 3.72 (t, 1H, J=5.9 Hz, CH-S), 4.86 (t, 1H,
J=4.8 Hz, CH-O), 6.84 (d, 2H, J=6.8 Hz, ArH),
7.12–7.35 (m, 13H, ArH); 13C NMR (CDCl3), l: 39.9,
69.8, 72.1, 125.5, 126.5, 128.2, 128.8, 128.9, 128.9,
129.0, 129.5, 131.6, 134.5, 142.0, 143.6; IR (KBr): 3400,
3059, 3031, 2921, 2890, 1451, 1445, 1055, 1036, 1021,
759, 750, 698 cm−1.
4.8.3. Oxidation with H2O2, VO(acac)2 and chiral Schiff
base. Vanadyl acetylacetonate (5.2 mg, 0.02 mmol) and
ligand 1011b (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 (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 analyzed by NMR was chromatographed on
silica gel (t-BuOMe/CHCl3/hexane) and the collected
fractions were recrystallized from methylene dichloride/
hexane to give in each case three pure diastereomers
(see: Scheme 2).
4.9. Representative procedure for elimination reaction
Hydroxysulfoxide (1R,3R,RS)-8 (70 mg, 0.21 mmol)
was dissolved in xylene (1.5 ml) and anhydrous Na2CO3
was added in excess. The mixture was heated under
reflux for 1 h (monitored by TLC). The solvent was
evaporated. The residue was dissolved in CH2Cl2,
washed with water and brine and dried (Na2SO4).
Product 9 was purified by column chromatography.
4.9.1. (+)-(R)-3-Hydroxy-1,3-diphenylprop-1-ene, 9.
Yield 87%. 6:4 trans/cis mixture; [h]2D0=+20.3 (0.74,
CH2Cl2); lit.10 [h]D20=+28.1 (1, CH2Cl2) for trans-(+)-
1
(R)-9, H NMR (CDCl3), l: 1.86 (br s, 1H, OH), 5.10
(t, 0.4H, J=6.36 Hz CH-O, cis-isomer) 5.38 (d, 0.6H,
J=6.4 Hz, CH-O, trans-isomer), 6.38 (two dd, 1H,
J1=15.9 Hz, J2=6.4 Hz, CH), 6.68 (d, 1H, J=15.9 Hz,
CH), 7.22–7.44 (m, 10H, ArH).
4.8.4. 1,3-Diphenyl-3-phenylsulfinylpropan-1-ol, 8
4.8.4.1. (1R,3R,RS)-8. Mp=130–132°C (toluene).
1
[h]2D0=+126 (0.7, CH2Cl2); H NMR (CDCl3), l: 2.41–
2.50 (m, 1H, CH2), 2.64–2.73 (m, 1H, CH2), 2.74 (s,
1H, OH), 3.88 (t, 1H, J=7.2 Hz, CH-S), 4.97 (t, 1H,
J=6.3 Hz, CH-O), 6.82 (d, 2H, J=7.3 Hz, ArH), 7.06
(d, 2H, J=7.4 Hz, ArH), 7.15–7.40 (m, 11H, ArH); 13C
NMR (CDCl3), l: 37.3, 66.5, 71.6, 125.1, 126.1, 128.0,
128.0, 128.3, 128.4, 128.7, 129.4, 130.9, 132.2, 140.2,
143.4; IR (KBr): 3363, 3085, 3057, 3028, 2909, 1494,
1447, 1024, 1017, 989, 747, 699 cm−1. Anal. calcd for
C21H20O2S (M=336.434): C, 74.96; H, 5.99; S, 9.53.
Found: C, 74.71; H, 6.09; S, 9.40%.
Acknowledgements
The authors thank the Polish Committee for Scientific
Research for financial support (KBN Grant 7 T09A
109 21).
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