Application of a novel 1,3-diol with a benzyl backbone as chiral ligand for asymmetric oxidation of sulfides to sulfoxides

Article abstract of DOI:10.1016/j.tetlet.2012.03.077

A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides to sulfoxides. Moderate to good yields and enantioselectivity (upto 87% ee) have been observed.

Full text of DOI:10.1016/j.tetlet.2012.03.077

Tetrahedron Letters 53 (2012) 2726–2729
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Tetrahedron Letters
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Application of a novel 1,3-diol with a benzyl backbone as chiral ligand for
asymmetric oxidation of sulfides to sulfoxides
Paramartha Gogoi, Trimurthulu Kotipalli, Kiran Indukuri, Somasekhar Bondalapati, Pipas Saha,
⇑
Anil K. Saikia
Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati 781039, Assam, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A chiral 1,3-diol with a benzyl backbone has been used for the asymmetric oxidation of sulfides to sulf-
oxides. Moderate to good yields and enantioselectivity (upto 87% ee) have been observed.
Ó 2012 Elsevier Ltd. All rights reserved.
Received 16 February 2012
Revised 19 March 2012
Accepted 21 March 2012
Available online 28 March 2012
Keywords:
Titanium tetraisopropoxide
Chiral ligand
Chiral sulfoxide
Oxidation
Chiral catalyst
Optically active sulfoxides are not only important in organic
synthesis as chiral auxiliaries1 but also important chiral ligands
in asymmetric synthesis.2 Chiral sulfoxides are also found in many
natural products and pharmaceuticals.3 There are two different
types of chemical approaches namely direct and indirect methods
for their syntheses. The indirect method consists of the synthesis of
a sulfinylating agent with an electrophilic sulfur of known config-
uration, followed by reaction with an organometallic reagent.4 On
the other hand, in the direct method chiral sulfoxides are obtained
from the reaction of prochiral sulfides with chiral chemical re-
agent5 or enzymes.6 Over the years many approaches have been
developed for the synthesis of chiral sulfoxides using metal com-
plexes including initial reports of Kagan7 and Modena.8 Different
types of chiral ligands such as DEAT,7,8 BINOL,9 salen10 have been
used for this type of oxidation. Titanium peroxo complexes bearing
C2-symmetric ligands (DEAT, BINOL) have been used for the asym-
metric sulfoxidation.7–9 Titanium peroxo complexes having
C3-symmetry have also been reported in the literature.11 Although
chiral 1,2-diols have been used extensively as chiral ligands, the
use of chiral 1,3-diols as chiral ligand is limited.12 Recently, Van
der Eyken and co-workers have reported the use of C2-symmetric
1,3-bisphosphane ligand with a chiral cyclopropane backbone for
the catalytic asymmetric 1,4-addition of arylboronic acids.13 Here
we report the use of 1,3-diol with a benzylic backbone as a chiral
ligand for asymmetric oxidation of sulfides to sulfoxides assuming
that the benzylic backbone will provide some rigidity to the ligand
for better asymmetric induction.
The chiral 1,3-diols were synthesized as shown in Scheme 1.
Diketones 3 were synthesized by the reaction of 1,3-diketone 1
with bromides 2 in the presence of K2CO3/NaI in acetone. The
resulting diketones 3 were converted to 1,3-diols ( )-4 according
to Barluenga method.14 Out of four probable isomers 4
a
and 4b
were obtained as major isolated products (75–90%). The isomers
4a , 4b , 4c , and 4d
were detected by 1H NMR in minor
amounts 3%, 3%, 6%, and 4%, respectively.14 On the other hand
the isomers 4d were not detected by 1H NMR. The diols ( )-4
were then resolved to its chiral components 4 and 4b by convert-
ing them to their diastereomeric esters 6 and 6b using N-car-
c
c
c
c
a
b
a
a
bethoxy-L-proline derivative 5, and subsequent hydrolysis by
methanolic solution of potassium hydroxide.15 The absolute con-
figuration of the diols was determined by X-ray crystallographic
analysis.16 The absolute stereochemistry of (+)-4a
be (S,S).
a was found to
The utility of these chiral 1,3-diols for the enantioselective
oxidation of sulfides to sulfoxides was examined using methyl
(p-tolyl)sulfane (Scheme 2). Thus the reaction of methyl
(p-tolyl)sulfane with titanium isopropoxide and tertiary butyl
hydroperoxide in presence of chiral 1,3-diols 4aa and 4ab gave chi-
ral methyl-4-(methylsulfinyl)benzene 8g(R) and 9g(S), respectively
with 87% ee each (Table 1).17 On the other hand chiral 1,3-diol hav-
ing a butyl backbone is found to be not effective in the enantiose-
lective oxidation of sulfide to sulfoxide under the same reaction
⇑
Corresponding author.
E-mail address: asaikia@iitg.ernet.in (A.K. Saikia).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.077

P. Gogoi et al. / Tetrahedron Letters 53 (2012) 2726–2729
2727
R'
Br
O
O
2
K2CO3/ NaI
LiAlH(O-tBu)3
O
O
Ph
Ph
THF, 0 oC - rt
Ph
Ph
R'
Acetone
reflux
1
3a: R' = Ph, 91%
3b: R' = C3H7, 81%
3c: R' = 4-MeO-C6H4, 77%
3d: R' = 4-Cl-C6H4, 70%
OH OH
Ph
OH OH
Ph
OH OH
Ph
OH OH
+
Ph
+
Ph
+
Ph
Ph
Ph
δ
β
α
γ
R'
R'
R'
R'
4aγ: R' = Ph, 3%
4aδ: R' = Ph, 0%
4aα + 4aβ: R' = Ph, 90%
4bγ: R' = C3H7, 3%
4bδ: R' = C3H7, 0%
4bα + 4bβ: R' = C3H7, 81%
4cγ: R' = 4-MeO-C6H4,6%
4dγ: R' = 4-Cl-C6H4, 4%
4cδ: R' = 4-MeO-C6H4,0%
4dδ: R' = 4-Cl-C6H4, 0%
4cα + 4cβ: R' = 4-MeO-C6H4, 84%
4dα + 4dβ: R' = 4-Cl-C6H4, 75%
COCl
OR OR
OR OR
OH OH
Ph
N
CO2Et
5
+
Ph
Ph
Ph
Ph
Ph
Py /CH2Cl2
R'
R'
R'
0 o
C
6aα: R' = Ph, 46%
4aαβ: R' = Ph
6aβ: R' = Ph, 47%
6bα: R' = C3H7, 38%
4bαβ: R' = C3H7
6bβ: R' = C3H7, 40%
6cα: R' = 4-MeO-C6H4, 35%
6dα: R' = 4-Cl-C6H4, 32%
4cαβ: R' = 4-MeO-C6H4
4dαβ: R' = 4-Cl-C6H4
6cβ: R' = 4-MeO-C6H4, 37%
6dβ: R' = 4-Cl-C6H4, 37%
CO-
where R =
KOH/MeOH
reflux
KOH/MeOH
reflux
N
CO2Et
OH OH
Ph
OH OH
Ph
Ph
Ph
R'
R'
4aβ: R' = Ph, 89%
4aα: R' = Ph,86%
4bβ: R' = C3H7, 89%
4bα: R' = C3H7, 88%
4cβ: R' = 4-MeO-C6H4, 84%
4dβ: R' = 4-Cl-C6H4, 87%
4cα: R' = 4-MeO-C6H4,78%
4dα: R' = 4-Cl-C6H4, 84%
Scheme 1. Synthesis of chiral 1,3-diol.
O
O
and steric effects of the benzylic groups. Chiral diols with 4-meth-
oxy- and 4-chloro-benzyl backbone gave sulfoxide 8g(R) with 37%
and 71% ee, respectively. This implies that both the rigidity and
electronic effects of the benzyl group are crucial in high enantiose-
lectivity. Both electron-donating and electron-withdrawing sub-
stituents on the aromatic ring of the benzyl group decrease the
enantioselectivity in comparison to the simple benzylic group.
Ti(O- iPr)4 / toluene
S
S
S
°
t-BuOOH / -20 C
o
7g
8g (R)
Ligand 4
MS 4A /
9g (S)
36 h
Scheme 2. Enantioselective oxidation of sulfides to sulfoxide.
The chiral 1,3-ligands 4a
found to be the best ligands for enantioselectivity.
The utility of chiral 1,3-diol 4a was extended to various sub-
a and 4ab having benzyl backbones are
a
Table 1
Enatioselective oxidation of sulfides with chiral 1,3-diols
strates as shown in Table 2. It was observed from the Table 2 that
the nature of alkyl group and electronic factor of the aryl substitu-
ents do not have a straightforward effect on enantioselection. In
the case of simple phenyl alkyl sulfides the increase in the length
of side chain increases the enantioselectivity (entries a–c), but
for 4-methyl-, 4-bromo-phenyl, and naphthyl alkyl sulfides (en-
tries g–n) the trend is reverse. Branching in a side chain increases
the enantioselection (entry d). Presence of olefinic and aromatic
rings (entries e,f) in the alkyl side chain does not improve the
enantioselectivity. They are comparable to methyl(phenyl)sulfane
(entry a).
Entry
1,3-Diol
4a
4c
4d
4ab
4bb
Yield (%)
% ee
Products
1
2
3
4
5
a
a
a
60
59
57
58
45
87
37
71
87
24
8g(R)
8g(R)
8g(R)
9g(S)
9g(S)
conditions. The oxidation of methyl(p-tolyl)sulfane using chiral
1,3-diol 4bb gave only 24% ee of corresponding S-isomer 9g(S).
Chiral 1,3-diols with 4-methoxy benzylic 4c
In conclusion we have investigated a new chiral ligand, 1,3-diol
for the oxidation of prochiral sulfide using titanium peroxo com-
a and 4-chloro ben-
zylic 4d groups were also synthesized to determine the electronic
a

2728
P. Gogoi et al. / Tetrahedron Letters 53 (2012) 2726–2729
Table 2
Synthesis of chiral sulfoxide from sulfides
Ligand 4aα
OH OH
Ph
Ti(O-iPr)4 /
O
toluene
Ph
S
Ar
R
S
°
Ar
R
t-BuOOH /-20 C
MS 4Å
Ph
7
8
4aα
Entry
a
Substrate 7
Time (h)
36
Product 8
Yielda (%)
59
eeb (%) 8/Abs. Conf.c
52 (R)
S
8a
S
b
c
d
e
f
40
40
40
24
36
36
40
8b
8c
8d
8e
8f
65
60
61
59
70
60
65
72 (R)
75 (R)
80 (R)
50 (R)
54 (R)
87 (R)
78 (R)
S
S
S
S
C6H5
S
g
h
8g
8h
S
S
i
j
40
36
8i
8j
69
64
45 (R)
43 (R)
S
S
Br
k
l
48
36
8k
8l
60
55
41 (R)
39 (R)
Br
S
MeO
S
S
m
n
48
48
8m
8n
52
52
72 (R)
67 (R)
a
b
c
Yield refers to isolated yield of sulfoxides, the remaining is isolated as sulfone.
Determined by HPLC using Chiralcel OD and OD-H columns.
Determined by comparison of its sign of specific rotation with the literature data.
plex as oxidant. The use of this chiral ligand for other asymmetric
synthesis is under investigation in our laboratory.
for his chiralcel OD-H column. Authors are also grateful to review-
ers for their valuable comments and suggestions.
Acknowledgments
Supplementary data
Authors are grateful to the Department of Science and Technol-
ogy (DST), New Delhi, for financial support (Grant No. SR/S1/OC-
33/2007). We thank Dr. Prodeep Phukan of the Gauhati University
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.03.
077.

P. Gogoi et al. / Tetrahedron Letters 53 (2012) 2726–2729
2729
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0
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Ti(O-iPr)4 (7.4
lL, 0.025 mmol) in toluene (1 mL). The mixture was stirred for
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2 h at rt and then methyl(p-tolyl)sulfane (68
l
L, 0.5 mmol) was added. The
mixture was cooled to ꢀ20 °C and t-butylhydroperoxide (0.16 mL, 0.8 mmol)18
was added. After stirring for 36 h at the same temperature, the reaction was
quenched with 10% aqueous solution of sodium sulfite. The aqueous layer was
extracted with ethyl acetate (3 ꢁ 15 mL) and organic layer was dried (Na2SO4).
The solvent was evaporated under reduced pressure to leave the crude
product, which was separated by preparative TLC (3:2; hexane/ethyl acetate)
to give 8g (46 mg, 60%). The product was characterised by spectroscopic
analysis and the analyses were consistent with the literature. Enantiomeric
excess was determined by chiral HPLC on a Chiralcel OD-H (250 ꢁ 4.6 mm)
column eluting with
a
hexane/isopropanol (9:1) mixture (1 mL/min,
k = 250 nm). ½a 2D5
ꢂ
+127 (C 0.2, CH2Cl2), lit.19
½ ꢂ
a 2D5
+132 (C 2, CHCl3) for 91%
ee (R).
18. The optimum concentration of t-butylhydroperoxide was found to be
1.6 equiv. The reaction of 7g with one equivalent of t-butylhydroperoxide
yielded 8g with 75% yield and 32% ee (please see Supplementary data). The
enantioselectivity decreased from 87% ee to 32% ee.
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