An Economic Approach to Chiral Thiosulfinates by Enantioselective Oxidation with Hydroperoxide

Article abstract of DOI:10.1081/SCC-120027290

Some novel chiral ligands and VO(acac)₂ were utilized to catalytic asymmetric oxidation of disulfides. The optically active thiosulfinates were obtained.

Full text of DOI:10.1081/SCC-120027290

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An Economic Approach to Chiral Thiosulfinates by
Enantioselective Oxidation with Hydroperoxide
a
a
a
a
a
Yudao Ma , Xiaomei Wang , Yong Wang , Yu Feng & Yunfu Zang
a
School of Chemistry and Chemical Engineering , Shandong University , Shanda South
Road #27, Jinan, 250100, P.R. China
Published online: 16 Aug 2006.
To cite this article: Yudao Ma , Xiaomei Wang , Yong Wang , Yu Feng & Yunfu Zang (2004) An Economic Approach to Chiral
Thiosulfinates by Enantioselective Oxidation with Hydroperoxide, Synthetic Communications: An International Journal for
Rapid Communication of Synthetic Organic Chemistry, 34:3, 501-507, DOI: 10.1081/SCC-120027290
To link to this article: http://dx.doi.org/10.1081/SCC-120027290
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w
SYNTHETIC COMMUNICATIONS
Vol. 34, No. 3, pp. 501–507, 2004
An Economic Approach to Chiral
Thiosulfinates by Enantioselective
Oxidation with Hydroperoxide
*
Yudao Ma, Xiaomei Wang, Yong Wang, Yu Feng,
and Yunfu Zang
School of Chemistry and Chemical Engineering, Shandong University,
Jinan, P.R. China
ABSTRACT
2
Some novel chiral ligands and VO(acac) were utilized to catalytic
asymmetric oxidation of disulfides. The optically active thiosulfinates
were obtained.
Key Words: Asymmetric catalysis; Chiral thiosulfinates; Enantioselec-
tive oxidation; Hydroperoxide.
There have been numerous reports in which the sulfinyl group has acted
as a removable source of diastereoselection in asymmetric synthesis. While
*
Correspondence: Yudao Ma, School of Chemistry and Chemical Engineering,
Shandong University, Shanda South Road #27, Jinan 250100, P.R. China; E-mail:
ydma@sdu.edu.cn.
5
01
DOI: 10.1081/SCC-120027290
0039-7911 (Print); 1532-2432 (Online)
www.dekker.com
Copyright # 2004 by Marcel Dekker, Inc.

ORDER
REPRINTS
5
02
Ma et al.
Scheme 1.
tert-butanesulfinimines were new chiral nitrogen intermediates for preparation
[2–5]
[
1]
of a range of chiral amines, including a-branched amines,
[
tertiary
1,2- and 1,3-amino
2,6–8]
[9–11,12–14]
carbinamines,
[
a-and b-amino acid,
alcohol, a-trifluoromethyl amines.
and coworkers described a method
15–19]
[20,21]
As shown in Scheme 1. Ellman
for preparing enantiomerically
[22,23]
enriched tert-butyl tert-butanethiosulfinate 2 in the first example of an
asymmetric catalytic oxidation upon tert-butyl disulfide 1. Reaction of LiNH2
with 2 provided the sulfinamide 3 in high yield with absolute stereospecificity,
3
condensed with aldehydes or ketones to provide tert-butanesulfinimine 4.
But the chiral ligand was prepared by the condensation of 3,5-di-tert-
butylsalicylaldehyde and (S)-tert-leucinol, which is expensive and difficult to
synthesize.
Now, we wish to report the results of the catalytic asymmetric oxidation of
tert-butyl disulfide in the presence of cheap and easily available chiral ligands
(
di-tert-butylsalicylaldehyde and amino alcohols, which are from reduction of
Figure 1) 5a–i, 6a–c, 7a–b. Ligand 5 was formed from condensation of 3,5-
[
24]
natural L-amino acids,
from amino acid esters. Reduction of Schiff base ligands provided ligand 7.
except ligand 5f. While ligand 6 was synthesized
[25]
We investigated the effects of R in ligand 5a–i on the e.e.% of tert-
1
butanethiosulfinate 2, the results are summerized in Table 1. Compared with
entry 1–6, we found that the bulkiness of R in ligand 5a–i do affect the
1
enantioselectivity of 2. The larger R is, the higher enantioselectivity the
1
catalyst shows. Because another hydroxyl group at opposite position of R can
1
also cooperate with VO(IV), the e.e.% of 2 in entry 9 is very low. The opposite
cooperation is also affect e.e.% of 2 in entry 7 and 8.
Figure 1. Chiral ligands 5, 6 and 7.

ORDER
REPRINTS
Chiral Thiosulfinates
Table 1. Asymmetric oxidation of tert-butyl disulfide with ligand.
a–i
503
5
a,b
d
Entry
Ligand 5
R1
Yield (%)
e.e. (%)
1
2
3
4
5
6
7
8
9
5a
5b
5c
5d
5e
5f
Me
49.8
92.8
87.6
80.8
53.3
63.4
30.2
45.7
41.2
49.0
62.1
65.5
65.9
67.3
88.3
29.6
44.2
Bn
i-Bu
s-Bu
i-Pr
c
t-Bu
5g
5h
5i
4-OH-Bn
1-indolyl-methylene
1-OH-Et
4.24
a
Isolated yield.
1
Product was confirmed by HNMR and elemental analysis.
b
c
Determined by HPLC analysis using chiral column (DAICEL CHIRALPAK AS,
hexanes/2-propanole ¼ 97/3).
d
Estimated from the specific rotation.
Ligand 6a in Table 2 can seldom catalyze the oxidation of tert-butyl
disulfide, because ester group can not cooperate with VO(IV). For containing
hydroxyl group in R , ligand 6b and 6c can lightly catalyze the reaction. with
2
enantioselectivity.
In Table 3, reduced Schiff base ligands can also catalytically oxide tert-
butyl disulfide, but the enantioselectivity is almost lost, and nearly racemic
products are obtained. Probably because ligand 7a and 7b do not contain the
conjugated construction of C 55 N double bond and aromatic ring, and no
appropriate complexes can be formed during the reaction.
Table 2. Asymmetric oxidation of tert-butyl disulfide with ligand.
6
a–c
a
Entry
Ligand 6
R2
R3
Yield (%)
e.e. (%)
1
2
3
6a
6b
6c
Me
Et
Et
5.6
15.5
13.7
4.24
12.1
14.7
HO–CH
HO–CH2
2
i-amyl
a
Isolated yield.

ORDER
REPRINTS
5
04
Ma et al.
Table 3. Asymmetric oxidation of tert-butyl disulfide with ligand.
a–b
R4
7
a
Entry
Ligand 7
Yield (%)
e.e. (%)
1
2
7a
7b
HO–CH2
COOH
25.8
32.6
6.05
4.84
a
Isolated yield.
In order to compare the efficiency of this oxidation between alkyl
disulfides and aryl disulfides, we make a further study of asymmetric oxidation
of p-tolyl disulfide in Sch. 2 with ligand 5b–f listed in Table 4. Because of
lower density of electron cloud of sulfur, yield and e.e.% of p-tolyl p-
toluenethiosulfinate is lower.
EXPERIMENTAL
General Procedure
2
4
1
.50 Â 10 mol (0.50 mol%) VO(acac) dissolved in 2.5 mL anhydrous
2
chloroform under nitrogen in a 50 mL tube, followed by the addition of
2
4
1
.56 Â 10 mol (0.52 mol%) chiral ligand (5a–i, 6b, 6c, 7a–b) and 12 mL
chloroform, The resulting solution was stirred 20 min. before 5.78 mL
Table 4. Asymmetric oxidation of p-tolyl disulfide with ligand.
5
b–f
d
a,b
c
Entry
Ligand 5
R1
Yield (%)
e.e. (%)
1
2
3
4
5
5b
5c
5d
5e
5f
Bn
41.3
35.4
46.5
35.7
48.0
35.0
38.5
32.7
36.9
34.5
i-Bu
s-Bu
i-Pr
t-Bu
a
Isolated yield.
1
Product was confirmed by H NMR and elemental analysis.
b
c
Determined by HPLC analysis using chiral column (DAICEL
CHIRALPAK AS, hexanes/2-propanole ¼ 90/10).
d
All reactions were performed at 258C with 2.6 mol % ligand.

ORDER
REPRINTS
Chiral Thiosulfinates
505
Scheme 2.
(
0.03 mol) tert-butyl disulfide was added, followed by 4.5 mL 30% H O in
2 2
a slow steady steam. The cooling bath temperature was maintained at
5 ꢀ 208C. After 4 days the organic phase was separated, washed with
saturated brine, dried with Na SO and concerntrated. Column chramato-
1
2
4
graphy on silica gel (200–300 mesh) using petroluem/ethyl acetate ¼ 15 : 1
as elutant furnished 2 as a white crystalline solid with main configuration of
R. The results are shown in Tables 1, 2, and 3, with different chiral ligands.
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2
3
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Received in Japan June 9, 2003

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