S-Oxidation products of (+)-thiomicamine-derived oxazolines - Promising substrates in the synthesis of alkyl methyl sulfoxides

Article abstract of DOI:10.1016/j.tetasy.2005.01.027

Highly stereoselective oxidation of the 4-methylthio substituent in oxazolines 2-4, derived from (+)-thiomicamine 1, performed using the Kagan procedure and with the vanadium/chiral salen catalytic system, afforded R _S and S_S diaster

Full text of DOI:10.1016/j.tetasy.2005.01.027

Tetrahedron:
Asymmetry
Tetrahedron: Asymmetry 16 (2005) 953–958
S-Oxidation products of (+)-thiomicamine-derived
oxazolines—promising substrates in the synthesis
of alkyl methyl sulfoxides
*
´ ´ ´
Danuta Brozda, Agata Głuszynska, Agnieszka Kosciołowicz and Maria D. Rozwadowska
´
Faculty of Chemistry, A. Mickiewicz University, ul. Grunwaldzka 6, 60-780 Poznan, Poland
Received 19 October 2004; revised 7 January 2005; accepted 21 January 2005
Abstract—Highly stereoselective oxidation of the 4-methylthio substituent in oxazolines 2–4, derived from (+)-thiomicamine 1, per-
formed using the Kagan procedure and with the vanadium/chiral salen catalytic system, afforded RS and SS diastereomeric sulfox-
ides 5–7, respectively. The reaction of sulfoxide RS-6 with n-butyl- and tert-butyllithium reagents produced the corresponding butyl
methyl sulfoxides in high enantiomeric excess and with an (S) absolute configuration, albeit in moderate yields.
Ó 2005 Elsevier Ltd. All rights reserved.
1. Introduction
2. Results and discussion
Preparation of enantiomerically pure sulfoxides, a class
of compounds gaining increasing importance in asym-
metric synthesis,1 has usually been performed via two
general methodologies: enantioselective oxidation of
prochiral sulfides2 and stereoselective nucleophilic dis-
placement of ligands at the stereogenic sulfur in chiral
sulfinyl derivatives.3 The latter method, based upon
the classical Andersen procedure, has been extended to
various sulfinyl derivatives, in which nitrogen-, oxygen-
and sulfur-containing anionic species are the leaving
groups. Substitution of carbanionic leaving groups in
chiral nonracemic sulfoxides by organometallic reagents
is another modification of this method, recently in-
tensely studied by Naso et al.4 Their work has encour-
aged us to reveal the results of our experiments on the
stereoselective oxidation of sulfur of the 4-methylthio
substituent in (+)-thiomicamine 1 derived oxazolines
2–4, and application of the so obtained S-oxides 5–7
as chiral methylsulfinyl group transfer agents in the syn-
thesis of butyl methyl sulfoxides with high enantiomeric
purity.
In connection with our interest in the application of (+)-
thiomicamine 1, an industrial waste product in asym-
metric transformations,5 we envisaged that the S-methyl
substituent, after S-oxidation, might be useful as a
source of chiral methylsulfinyl group.
To approach this problem, we have undertaken experi-
ments in which (4S,5S) oxazolines 2,6 37 and 4,8 pre-
pared from (+)-thiomicamine 1 to protect the two
functionalities (–OH and –NH2), have been chosen as
the starting compounds, while the primary hydroxyl
was transformed into O-methyl ether in 3 and O-tosyl
ester in 4 (Scheme 1).
Since the synthetic validity of the ꢀcarbon-for-carbon
displacementꢁ strategy4 strongly depends upon the avail-
ability of the starting sulfoxide of high enantiomeric
purity, our attention has been focused on finding an effi-
cient and selective oxidation system for compounds 2–4.
It seemed at first that because of the two stereogenic
centres present in oxazolines 2–4, the oxidation with
achiral oxidizing agents would give sulfoxides with an
acceptable degree of diastereoselectivity. Williams
et al.9 have reported mCPBA oxidation of oxazoline 8,
prepared from (1S,2S)-2-amino-1-phenyl-1,3-propano-
diol, the analogue of (+)-thiomicamine 1, to proceed
with high diastereoselectivity. However, in our experi-
ments with the commonly used sulfoxidation reagents:
*
Corresponding author. Tel.: +48 61 8291322; fax: +48 61 8658008;
e-mail: mdroz@amu.edu.pl
0957-4166/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2005.01.027

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D. Brozda et al. / Tetrahedron: Asymmetry 16 (2005) 953–958
954
Ph
N
Ph
O
O
OH OH
NH2
N
[O]
lit.6,7
H3C
H3C
H3C
OR
OR
S
S
S
O
1
2 R = H
5 R = H
3 R = CH3
4 R = Ts
6 R = CH3
7 R = Ts
Scheme 1.
NaOCl/TEMPO,10 bromine/H2O/NaHCO3,11 mCPBA9
the diastereoselectivities were disappointingly low (0.6–
10% de) apparently because of a too distant 1,8-asym-
metric induction.
>99% de, respectively, in satisfactory yields (Table 1, en-
tries 1, 4 and 5). Their (RS) absolute configuration was
later inferred from the (S)-configuration of the sulfox-
ides produced in the reaction with n-butyllithium and
tert-butyllithium (Table 3) on the basis of the assump-
tion that the nucleophilic substitution at the sulfinyl sul-
fur occurs with inversion of configuration.
In this context, the well known Sharpless oxidation
methodology, mediated by D- or L-diethyl tartrate
(DET)/titanium(IV) complexes, adapted for the enantio-
selective oxidation of prochiral sulfides by Kagan et al.12
was applied. Keeping a constant ratio of the reagents
Ti(O-i-Pr)4/L-(+)-DET/H2O (1:2:0.5),13 using methylene
chloride as the solvent and cumylhydroperoxide (CHP),
(1.3 equiv), as the stoichiometric oxidant, we were able
to prepare sulfoxides 5, 6 and 7 with 95%, 96% and
On the other hand, the catalytic asymmetric oxidation
of prochiral sulfides using vanadium/chiral salen com-
plexes and aqueous hydrogen peroxide as the oxidant,
applied by Bolm and Bienewald,14 and further modified
by others15,16 appeared to be a more rewarding
approach.
Table 1. Oxidation of sulfides 2–4 using the Kagan methodologya
Reaction conditions
Product
Entry
Sulfide
Oxidant (equiv)
Solvent
Temperature (°C)
Sulfoxide
Y (%)
De (%)b/c
1
2
3
4
5
2
3
3
3
4
CHP (1.3)
t-BuOOH (1.2)
CHP (1.3)
CHP (1.3)
CHP (1.3)
CH2Cl2
CH2Cl2
CCl4
ꢀ23
5
6
6
6
7
70
98
35
98
66
96
51
ꢀ23
ꢀ18 ! ꢀ22
ꢀ23
71
95
CH2Cl2
CH2Cl2
ꢀ23
>99
a Reagent ratio: L-(+)-DET–Ti(O-i-Pr)4–H2O = 1:2:0.5.12,13
b Determined by HPLC (Chiralcel OD-H column).
c (RS)-configuration inferred from the (S)-configuration of n-butyl methyl and tert-butyl methyl sulfoxides prepared (see Table 3).
Table 2. Catalytic oxidation of sulfides 2–4 using VO(acac)2/Schiff base/30% H2O2 oxidation systema,b
Entry
Sulfide
Reaction conditions
H2O2 (equiv)
Sulfoxides
Dec (%)
Schiff base
Time (h)
No.
Y (%)
Conf.c,d at sulfur
1
2e
3
3
3
3
3
3
3
4
4
4
9
9
10
48
24
2.5
24
48
48
23
23
4
5
6
6
6
6
6
6
6
7
7
7
10
73
70
58
38
43
45
67
55
63
74
14
52
55
22
0
2
1.15
1.4
1.5
6.5
3.9
1.4
1.4
1.4
1.2
1.5
(R)
(S)
(R)
3
13
10
11
12
14
15
13
15f
15g
4
5
6
30
41
62
63
82
99
(S)
(S)
(S)
7
8
9
10
11
25
33
(S)
(S)
a Reagent ratio: VO(acac)2–Schiff base–CH2Cl2 = 1 mol %:1.5 mol %:4 mL.
b At 0 °C.
c Determined by HPLC (Chiralcel OD-H column).
d Configuration at sulfur of the major diastereomer.
e At 0 °C ! rt due to solubility problems.
f 0.8 mol %.
g 1.3 mol %.

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D. Brozda et al. / Tetrahedron: Asymmetry 16 (2005) 953–958
955
Table 3. Reaction of sulfoxide (RS)-6 with butyllithium reagentsa
Entry
Butyllithium
Butyl methyl sulfoxides
Yb (%)
Eec (%)
½aꢁ2D0/conf.
1
2
3
n-BuLi
t-BuLi
sec-BuLi
n-Bu–S(O)–CH3
t-Bu–S(O)–CH3
sec-Bu–S(O)–CH3
52
47
50
92
99
99
+95.1 (S) (c 0.65, acetone)
+17.3 (S) (c 0.33, MeOH)
—
d
a Reaction conditions: 6–BuLi = 1:3, THF, ꢀ76 °C.
b Yield of isolated product.
c Determined by 1H NMR with DNBA as the chiral solvating agent.
d Diastereomeric ratio 1:1.
Thus, several chiral Schiff bases, 9–1515,17,18 (Fig. 1)
were synthesized, using readily available chiral aminoal-
cohols, and screened in vanadium-catalyzed oxidation
of sulfides 2–4 with hydrogen peroxide (Table 2).
products, in which 4-methyloxazole (ca. 30%), formed
apparently by the elimination–aromatization process,
could be detected (1H NMR). Satisfying results were ob-
tained with sulfoxide (RS)-6, whose reaction with each of
the reagents: n-butyl-, tert-butyl- and sec-butyllithium,
produced the corresponding butyl methyl sulfoxides
with practically no loss of enantiomeric purity, yet in
moderate yield (Table 3). In the reaction in which sec-
butyllithium was used two enantiopure diastereomers
in a 1:1 ratio were formed. The enantiomeric purity of
the butyl methyl sulfoxides prepared, was determined
by 1H MNR spectra, recorded in the presence of the chi-
ral solvating agent, (R)-(ꢀ)-N-(3,5-dinitrobenzoyl)(1-
phenylethyl)amine (DNBA). The absolute (S)-configu-
ration of both n-butyl methyl sulfoxide and tert-butyl
methyl sulfoxide was assigned on the basis of the posi-
tive sign of the specific rotation.20,21
The complex prepared in situ by reacting VO(acac)2
with Schiff base 15,15 prepared from 3,5-diiodosalicylal-
dehyde and (S)-tert-leucinol was found to be the most
efficient catalytic system (Table 2, entries 8, 10, 11), lead-
ing to diastereomers with the (SS)-configuration oppo-
site to that produced according to the Kagan et al.12
procedure. In this way (SS) sulfoxides 6 and 7 were pre-
pared with 62% and >99% de, respectively, yet in mod-
erate yield because of overoxidation to sulfones 16 and
17 often taking place before sulfoxidation was com-
pleted. Therefore, the reaction was quenched when
either the sulfide was consumed or when no more sulfox-
ide was produced after the addition of another aliquot
of H2O2 and/or over oxidation to sulfones 16 and 17
became a dominating process.
The synthesis of n-butyl methyl sulfoxides by exchang-
ing carbanionic groups at sulfur in chiral sulfoxides
had been performed earlier. Johnson et al.20 obtained
(R)-(ꢀ)-n-butyl methyl sulfoxide and its (S)-(+)-enantio-
mer in satisfactory yield (ca. 80%) from (S)-(ꢀ)-methyl
phenyl sulfoxide and (R)-(+)-methyl p-tolyl sulfoxide,
respectively, on treatment with n-butyllithium. How-
ever, Naso et al.21 by treating methyl phenyl sulfoxide
with Grignard reagents obtained a mixture of products,
while at the same time, under the action of long-chain
Sulfoxides (R)S-6, (R)S-7 and (S)S-7, obtained in pure
form by chromatographic separation, were then sub-
jected to the reaction with excess (3 equiv)19 butyl-
lithium reagents in THF solution or in suspension.
Unfortunately, both diastereomeric sulfoxides 7, ob-
tained with the highest enantiomeric purity and in the
crystalline form, afforded nonseparable mixtures of
R
Ph
O
N
O
Ph
R
O
S
N
R1
R2
Tol
OR
OH
N
S
H3C
O
HO
HO
R3
8
R
H
I
R1
R2
H
R3
H
16 R = CH3
17 R = Ts
917
Bn
Bn
H
H
10
1117
tBu Bn
H
H
H
H
H
I
H
H
CH3
H
12
1317
1418
1515
H
Bn
H
tBu
tBu
H
H
H
Figure 1.

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D. Brozda et al. / Tetrahedron: Asymmetry 16 (2005) 953–958
956
alkyl Grignard reagents, methoxy- and halo-phenyl
methyl sulfoxides gave exchange products in satisfactory
yield and with high enantioselectivity.
alaninol (0.45 g, 3 mmol) in methanol (3 mL) was heated
under reflux for 1 h. After evaporation of the solvent,
the residue was digested with n-hexane to give a yellow
crystalline solid (0.73 g, 48%); mp 61–64 °C,
[a]D = +217.5 (c 0.50, CH2Cl2). IR (KBr), m (cmꢀ1):
1633. 1H NMR (CDCl3/D2O): d 2.84 (dd, J = 8.7,
13.7 Hz, 1H, PhCHH), 3.00 (dd, J = 4.8, 13.7 Hz, 1H,
PhCHH), 3.56–3.64 (m, 1H, C@NCH), 3.72 (dd,
J = 7.9, 11.3 Hz, 1H, CHHOH), 3.86 (dd, J = 3.6,
11.3 Hz, 1H, CHHOH), 7.10–7.33 (m, 6H, ArH), 7.78
(s, 1H, N@CH), 7.99 (d, J = 2.0 Hz, 1H, ArH). 13C
NMR (CDCl3): d 38.59 (CH2), 65.43 (CH2), 71.38
(CH), 77.94 (C), 89.55 (C), 118.50 (C), 126.75 (CH),
128.60 (2CH), 129.20 (2CH), 136.82 (C), 140.12 (CH),
148.98 (CH), 162.83 (C), 163.83 (CH). EI MS m/z (%):
508 (M++1, 26), 507 (M+, 100), 416 (86), 359 (54), 91
(53), 77 (10), 65 (14). HRMS (M+) calcd for
C16H15I2NO2: 506.91922. Found: 506.91775.
(R)-(ꢀ)-tert-Butyl methyl sulfoxide of high enantiomeric
purity was prepared by Naso et al.22 by exchanging the
methylphosphonate substituent in (R)-(+)-dimethyl-
(methylsulfinyl)methylphosphonate with a tert-butyl
group.
The absolute (SS)-configuration of the levorotatory dia-
stereomeric sulfoxide 7, can be postulated on the basis
of the negative sign of the specific rotation of small sam-
ples of n-butyl- and tert-butyl methyl sulfoxides isolated
by fractional extraction (methylene chloride) from the
product mixture of reactions in which the levorotatory
diastereomer 7 was treated with n-butyl- and tert-butyl-
lithium reagents, respectively.
4.2.2.
(R)-2-Hydroxybenzylidene-2-hydroxy-1-propyl-
3. Conclusion
amine 12. A mixture of salicylaldehyde (0.5 mL,
5 mmol) and (R)-1-amino-2-propanol (0.39 mL,
5 mmol) in toluene (50 mL) were heated under reflux
for 2.5 h using a Dean–Stark water trap. The solution
was then concentrated and the yellow oil was separated
and digested with n-hexane to give a yellow solid; mp
83–86 °C, [a]D = ꢀ31.3 (c 0.51, CH2Cl2). IR (KBr), m
Enantiomerically pure sulfoxides 5–7 have been pre-
pared from (+)-thiomicamine 1, an industrial waste
product, via oxazolines 2–4. Stereoselective oxidation
of 2–4 by the Kagan procedure with L-(+)-DET/Ti(O-
i-Pr)4/H2O/CHP (1:2:0.5:1.3)13,14 afforded (RS)-isomers
while the catalytic asymmetric oxidation with vana-
dium/chiral salen complexes (VO(acac)2/15/H2O2)17 led
to the (SS)-sulfoxides. The ability of sulfoxide (RS)-6
to act as a chiral methylsulfinyl group transfer agent
was tested in the reaction with butyllithium reagents
involving exchange of carbanionic group at stereogenic
sulfur. In this way n-butyl methyl, tert-butyl methyl
and diastereomeric sec-butyl methyl sulfoxides were pre-
pared in high ee and moderate yield in a short synthesis
involving simple procedures and commercially available
substrates. Herein we present another example of useful-
ness of the ꢀcarbanionic leaving groupꢁ strategy4 for the
synthesis of chiral nonracemic dialkyl sulfoxides.
(cmꢀ1): 1642. H NMR (CDCl3): d 1.13 (d, J = 6.3 Hz,
1
3H, CH3), 3.49 (ddd, J = 1.1, 7.1, 12.1 Hz, 1H,
C@NCHH), 3.73 (ddd, J = 1.4, 3.8, 12.1 Hz, 1H,
C@NCHH), 4.13 (m, 1H, CHOH), 6.86–6.98 (m, 2H,
ArH), 7.26–7.35 (m, 2H, ArH), 8.38 (s, 1H, N@CH).
13C NMR (CDCl3): d 20.20 (CH3), 67.08 (CH2), 67.33
(CH), 116.95 (CH), 118.56 (C), 118.59 (CH), 131.35
(CH), 132.36 (CH), 160.96 (C), 166.69 (CH). EI MS
m/z (%): 179 (M+, 61), 134 (100), 107 (71), 77 (16).
HRMS (M+) calcd for C10H13NO2: 179.09464. Found:
179.09379.
4.3. Oxidation of sulfides 2–4 using the Kagan et al.12,13
oxidizing system
4. Experimental
4.1. General
4.3.1. General procedure. Titanium(IV) isopropoxide
(1 mmol) and (R)-(+)-DET (2 mmol) in methylene chlo-
ride (5 mL) were stirred for 2 min at rt and then water
(0.5 mmol) was added. After stirring for 20 min at rt
and for 30 min at ꢀ23 °C, the sulfide (1 mmol) in meth-
ylene chloride (10 mL) was added followed by CHP
(1.3 mmol) and stirring continued for 24 h at ꢀ23 °C.
Water (ca. 25 mL) was then added, the mixture filtered
through a pad of CeliteÒ then the phases were separated.
The organic phase was washed twice with brine,
dried and the solvent evaporated. The crude reaction
product was purified by column chromatography over
silica gel.
Melting points were determined on a Koffler block and
are not corrected. IR spectra: Perkin–Elmer 180 in KBr
pellets. NMR spectra: Varian Gemini 300, with TMS as
internal standard. Mass spectra (EI): Joel D-100, 75 eV,
and FAB, m-nitrobenzylalcohol as the matrix. Optical
rotations: Perkin–Elmer polarimeter 243B at 20 °C.
Analytical HPLC: Waters HPLC system with Mallink-
rodt–Baker Chiralcel OD-H column. Merck DC-Alufo-
lien Kieselgel 60254 were used for TLC. (+)-
Thiomicamine was purchased from the Aldrich Chemi-
cal Co and used as received.
4.3.2. (4S,5S,RS)-4-Hydroxymethyl-5-(4-methylsulfinyl-
phenyl)-2-phenyl-4,5-dihydro-1,3-oxazole
4.2. Synthesis of Schiff bases
5. Yield:
70% (64% after crystallization from methanol); mp
203–205 °C; de: 96%; [a]D = +173.1 (c 0.60, CH2Cl2);
[a]D = +196.3 (c 0.40, methanol); IR (KBr), m (cmꢀ1):
1650, 1056. 1H NMR (CDCl3): d 2.13 (s, 1H, disappears
4.2.1.
(R)-[(3,5-Diiodo)-2-hydroxybenzylidene]-1-hydr-
oxy-3-phenylisopropylamine 10. A mixture of 3,5-di-
iodosalicylaldehyde (1.12 g, 3 mmol) and (R)-phenyl-

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D. Brozda et al. / Tetrahedron: Asymmetry 16 (2005) 953–958
957
on treatment with D2O, OH), 2.74 (s, 3H, SCH3), 3.94
4.4. Catalytic asymmetric oxidation of sulfides 2–4
(dABq, J = 4.1, 11.5 Hz, 2H, CH2OH), 4.26 (td,
J = 4.1, 8.0 Hz, 1H, CHN), 5.60 (d, J = 7.4 Hz, 1H,
ArCH), 7.46–7.69 (m, 7H, ArH), 8.02 (d, J = 7.1 Hz,
2H, ArH). 13C NMR (CDCl3): d 44.01 (CH3S), 63.53
(CH2OH), 76.93 (CHN), 82.06 (ArCH), 124.03,
126.49, 128.34, 131.76 (CH), 126.68, 143.81, 145.61
(C), 164.55 (C@N). EI MS m/z (%): 315 (M+, 7), 284
(100), 181 (20), 147 (24), 130 (28), 105 (28), 77 (27).
HRMS (M+) calcd for C17H17NO3S: 315.09293. Found:
315.09160.
4.4.1. General procedure. A solution of the Schiff base
(0.015 mmol) and VO-(acac)2 (2.6 mg, 0.01 mmol) in
methylene chloride (2 mL) was stirred at rt for 30 min,
then the sulfide (1 mmol) in methylene chloride (2 mL)
was introduced and the mixture stirred at rt for another
30 min. The mixture was cooled to 0 °C and 30% hydro-
gen peroxide (in amounts specified in the Table 2) was
added dropwise and stirring continued at 0 °C until no
more starting material was present or no more sulfoxide
could be produced (TLC, 2.5–48 h, Table 2). Water was
then added and the phases separated, the aqueous one
was extracted additionally with methylene chloride.
The combined organic extracts were washed with brine,
dried and the solvent evaporated. The yield and enantio-
meric purity was evaluated by HPLC of the crude reac-
tion product (Table 2), using Chiralcel OD-H column
and 20% v/v isopropanol in hexane, flow 0.5 mL/min,
224 nm; retention time: 26 min for (RS) diastereomer,
28 min for (SS) diastereomer and 40 min for sulfone 17.
4.3.3. (4S,5S,RS)-4-Methoxymethyl-5-(4-methylsulfinyl-
phenyl)-2-phenyl-4,5-dihydro-1,3-oxazole
6. Yield:
98%; Oil; De 95%; [a]D = +145.9 (c 1.05, CH2Cl2). IR
1
(KBr), m (cmꢀ1): 1650, 1058. H NMR (CDCl3): d 2.73
(s, 3H, SCH3), 3.46 (s, 3H, OCH3), 3.60 (dd, J = 7.1,
9.6 Hz, 1H, CHHO), 3.80 (dd, J = 4.4, 9.6 Hz, 1H,
CHHO), 4.32 (ddd, J = 4.4, 6.9, 7.1 Hz, 1H, CHN),
5.57 (d, J = 6.9 Hz, 1H, ArCH), 7.43–7.55 (m, 5H,
ArH), 7.67 (d, J = 8.2 Hz, 2H, ArH), 8.05 (d,
J = 8.5 Hz, 2H, ArH). 13C NMR (CDCl3): d 43.97
(CH3S), 59.38 (CH3O), 74.36 (CH2O), 75.05 (CHN),
83.08 (CHAr), 123.98, 126.40, 128.44, 128.46, 131.75
(CH), 127.17, 144.32, (C), 163.99 (C@N). EI MS m/z
(%): 329 (M+, 7), 284 (100), 181 (48), 130 (58), 105
(46), 77 (53). HRMS (M+) calcd for C18H19NO3S:
329.10855. Found: 329.10745.
4.4.2. (4S,5S,SS)-4-Tosyloxymethyl-5-(4-methylsulfinyl-
phenyl)-2-phenyl-4,5-dihydro-1,3-oxazole (SS)-7. Yield:
74%; mp 77–80 °C (from 96% ethanol) after column
chromatography separation; [a]D = ꢀ280.0 (c 0.79,
CH2Cl2). IR (KBr), m (cmꢀ1): 1646, 1059. 1H NMR
(CDCl3): d 2.45 (s, 3H, CH3Ts), 2.73 (s, 3H, SCH3),
4.15–4.23 (m, 1H, CHN), 4.32–4.41 (m, 2H, CH2OTs),
5.59 (d, J = 6.3 Hz, 1H, CHAr), 7.31–7.34 (m, 2H,
ArH), 7.43–7.49 (m, 4H, ArH), 7.53–7.58 (m, 1H,
ArH), 7.64–7.68 (m, 2H, ArH), 7.77–7.81 (m, 2H,
ArH), 7.95–7.98 (m, 2H, ArH). 13C NMR (CDCl3): d
21.65 (CH3Ar) 43.92 (CH3S), 70.18 (CH2OTs), 73.72
(CHN), 82.46 (CHAr), 124.17, 126.37, 127.96, 128.52,
128.53, 129.97, 132.17 (CH), 126.52, 132.38, 143.09,
145.24, 145.94 (C), 165.17 (C@N). EI MS m/z (%):
469 (M+, 0.2), 453 (1), 297 (79), 284 (9) 282 (100),
172 (46), 130 (6), 105 (48), 91 (34), 77 (20). Anal. Calcd
for C24H23NO5S2H2O: C, 59.12; H, 5.17; N, 2.87; S,
13.12. Found: C, 59.42; H, 5.06; N, 2.86; S, 13.56.
4.3.4. (4S,5S)-4-Methoxymethyl-5-(4-methylsulfonylphen-
yl)-2-phenyl-4,5-dihydro-1,3-oxazole 16. Yield: vari-
ous; Oil. [a]D = +118.8 (c 0.89, CH2Cl2). IR (KBr), m
(cmꢀ1): 1652. 1H NMR (CDCl3): d 3.05 (s, 3H,
SCH3), 3.46 (s, 3H, OCH3), 3.58 (dd, J = 7.4, 9.3 Hz,
1H, CHHO), 3.81 (dd, J = 4.3, 9.6 Hz, 1H, CHHO),
4.30 (ddd, J = 4.4, 6.8, 7.4 Hz, 1H, CHN), 5.61 (d,
J = 6.6 Hz, 1H, ArCH), 7.43–7.59 (m, 5H, ArH), 7.95
(d, J = 8.5 Hz, 2H, ArH), 8.04 (d, J = 8.5 Hz,
2H, ArH). EI MS m/z (%): 345 (M+, 3), 300 (100),
130 (38), 118 (35), 105 (43), 77 (42). Anal. Calcd
for C18H19NO4SÆ1/3H2O: C, 61.52; H, 5.45; N,
3.99; S, 9.12. Found: C, 61.46; H, 5.46; N, 3.96; S,
9.14.
4.4.3. (4S,5S)-4-Tosyloxymethyl-5-(4-methylsulfonylphen-
yl)-2-phenyl-4,5-dihydro-1,3-oxazole 17. Yield: 29%;
mp 111–114 °C; (from 96% ethanol) after column chro-
matography separation [a]D1= +423.9 (c 1.1, CH2Cl2).
IR (KBr), m (cmꢀ1): 1650. H NMR (CDCl3): d 2.45
(s, 3H, ArCH3), 3.06 (s, 3H, ArSO2CH3), 4.18 (dd,
J = 9.9, 7.1 Hz, CHHOTs), 4.30–4.36 (m, 1H, CHN),
4.40 (dd, J = 9.9, 3.8 Hz, CHHOTs), 5.63 (d,
J = 6.3 Hz, 1H, ArCH), 7.33 (d, J = 8.00 Hz, 2H,
ArH), 7.43–9.98 (3m, 11H, ArH). EI MS m/z (%): 485
(M+, 0.2), 313 (100), 299 (50), 284 (2), 130 (42), 105
(91), 91 (34), 77 (22). Anal. Calcd for C24H23NO6S2Æ1/
2H2O: C, 58.28; H, 4.89; N, 2.83; S, 12.94. Found: C,
57.96; H, 4.76; N, 2.82; S, 13.27.
4.3.5. (4S,5S,RS)-4-Tosyloxymethyl-5-(4-methylsulfinyl-
phenyl)-2-phenyl-4,5-dihydro-1,3-oxazole (RS)-7. Yield:
66%; mp 100–102 °C; [a]D = +127.4 (c 0.79, CH2Cl2). IR
1
(KBr), m (cmꢀ1): 1646, 1059. H NMR (CDCl3): d 2.45
(s, 3H, CH3Ar), 2.73 (s, 3H, SCH3), 4.15–4.23 (m, 1H,
CHN), 4.31–4.41 (m, 2H, CH2OTs), 5.58 (d,
J = 6.0 Hz, 1H, CHAr), 7.31–7.34 (m, 2H, ArH), 7.42–
7.49 (m, 4H, ArH), 7.52–7.58 (m, 1H, ArH), 7.64–7.68
(m, 2H, ArH), 7.77–7.80 (m, 2H, ArH), 7.94–7.98 (m,
2H, ArH). 13C NMR (CDCl3): d 21.74 (CH3Ar) 43.99
(CH3S), 70.20 (CH2OTs), 73.76 (CHN), 82.49 (CHAr),
124.09, 126.32, 127.87, 128.44, 129.87, 132.06 (CH),
126.47, 132.34, 142.99, 145.109, 145.90 (C), 164.99
(C@N). EI MS m/z (%): 469 (M+, 0.2), 453 (1), 297
(79), 284 (9) 282 (100), 172 (46), 130 (6), 105 (48), 91
(34), 77 (20). Anal. Calcd for C24H23NO5S2ÆH2O: C,
59.12; H, 5.17; N, 2.87; S, 13.12. Found: C, 59.42; H,
5.06; N, 2.86; S, 13.56.
4.5. Reaction of sulfoxides 6 and 7 with butyllithium
reagents
4.5.1. General procedure. Sulfoxide (RS)-6 (1 mmol) in
freshly distilled THF was cooled to ꢀ70 °C under an
argon atmosphere. Butyllithium reagent (n-butyllithium:

´
D. Brozda et al. / Tetrahedron: Asymmetry 16 (2005) 953–958
958
´
5. For representative publications, see: (a) Brozda, D.;
Koroniak, Ł.; Rozwadowska, M. D. Tetrahedron: Asym-
1.6 mol in hexane, t-butyllithium: 1.7 mol in pentane
and sec-butyllithium: 1.4 mol in cyclohexane) (3 mmol)
was then added and the mixture stirred at ꢀ70 °C
for 1.5 h; during that time the initially formed
green colour of the solution turned red brown. The
reaction was quenched by addition of 20% NH4Cl
(25 mL) and the phases separated. The aqueous phase
was extracted with ethyl ether and then three times
with methylene chloride. The combined ethereal ex-
tracts were shown (HPLC) to contain mainly unreacted
starting material and desulfinylated oxazoline, while in
methylene chloride the sulfoxide synthesized was
present.
´
´
metry 2000, 11, 3017–3025; (b) Głuszynska, A.; Mack-
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6. Rozwadowska, M. D. Tetrahedron: Asymmetry 1998, 9,
1615–1618.
´
7. Głuszynska, A.; Rozwadowska, M. D. Tetrahedron:
Asymmetry 2000, 11, 2359–2366.
´
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8. Brozda, D.; Chrzanowska, M.; Głuszynska, A.; Rozwa-
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Acknowledgements
This work was supported by a research grant from the
State Committee for Scientific Research in the year
2003–2006 (KBN Grant no. 4T09A 07824).
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