Highly enantioselective sulfoxidation with vanadium catalysts of Schiff bases derived from bromo- and iodo-functionalized hydroxynaphthaldehydes

Article abstract of DOI:10.1016/j.jcat.2010.05.013

Two series of chiral Schiff bases, 4a-e and 5a-e, prepared from the condensation of the mono-, di-, tribromohydroxynaphthaldehyde or monoiodohydroxynaphthaldehyde with chiral amino alcohols, were used in combination with VO(acac)₂ for the asymmetric oxidation of aryl methyl sulfides using H₂O₂ as terminal oxidant. Among these Schiff bases, dibromo-functionalized 4d and iodo-functionalized 5e gave high yields (91-93%) with good enantioselectivities (80-82% ee) for the oxidation of thioanisole in dichloromethane. The asymmetric oxidation of thioanisole in toluene using these Schiff bases gave methyl phenyl sulfoxide in satisfactory isolated yields (48-62%) with high enantioselectivities (91-94% ee), which were further improved by a modified procedure with the ee value up to 98% in 62% yield. The oxidations of other aryl methyl sulfides in toluene with dibromo- and iodo-functionalized Schiff bases 5d and 5e as ligands using the modified procedure afforded the corresponding sulfoxides in 55-67% isolated yields with 95-99% ee.

Full text of DOI:10.1016/j.jcat.2010.05.013

Journal of Catalysis 273 (2010) 177–181
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Journal of Catalysis
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Highly enantioselective sulfoxidation with vanadium catalysts of Schiff bases
derived from bromo- and iodo-functionalized hydroxynaphthaldehydes
a
a
a
a,b,
Ying Wang a, Mei Wang a, , Yu Wang , Xiuna Wang , Lin Wang , Licheng Sun
*
**
a State Key Laboratory of Fine Chemicals, DUT-KTH Joint Education and Research Center on Molecular Devices, Dalian University of Technology (DUT), Dalian 116012,
People’s Republic of China
b Department of Chemistry, Royal Institute of Technology (KTH), 10044 Stockholm, Sweden
a r t i c l e i n f o
a b s t r a c t
Article history:
Two series of chiral Schiff bases, 4aÀe and 5aÀe, prepared from the condensation of the mono-, di-, trib-
romohydroxynaphthaldehyde or monoiodohydroxynaphthaldehyde with chiral amino alcohols, were
used in combination with VO(acac)2 for the asymmetric oxidation of aryl methyl sulfides using H2O2
as terminal oxidant. Among these Schiff bases, dibromo-functionalized 4d and iodo-functionalized 5e
gave high yields (91–93%) with good enantioselectivities (80–82% ee) for the oxidation of thioanisole
in dichloromethane. The asymmetric oxidation of thioanisole in toluene using these Schiff bases gave
methyl phenyl sulfoxide in satisfactory isolated yields (48–62%) with high enantioselectivities (91–94%
ee), which were further improved by a modified procedure with the ee value up to 98% in 62% yield.
The oxidations of other aryl methyl sulfides in toluene with dibromo- and iodo-functionalized Schiff bases
5d and 5e as ligands using the modified procedure afforded the corresponding sulfoxides in 55–67% iso-
lated yields with 95–99% ee.
Received 8 March 2010
Revised 20 May 2010
Accepted 20 May 2010
Available online 22 June 2010
Keywords:
Asymmetric sulfoxidation
Chiral Schiff bases
Chiral sulfoxides
Sulfides
Vanadium
Ó 2010 Elsevier Inc. All rights reserved.
1. Introduction
(H2O2), and the facile reaction conditions and easy workup.
Investigations on this catalyst system have mainly focused on
Asymmetric oxidation of prochiral sulfides has attracted exten-
sive attention for decades as enantiopure sulfoxides are important
chiral auxiliaries and synthons used in asymmetric synthesis [1–4].
The special biological property of the chiral drugs containing a sul-
finyl group with a defined configuration is another reason for the
current interest in efficient synthesis of enantiopure sulfoxides
[5–8]. Since the pioneer work on the asymmetric oxidation of sul-
fides using Ti(O-i-Pr)4/chiral tartrate systems was reported by
Kagan, Modena and their co-workers [9,10], asymmetric oxidations
of prochiral sulfides catalyzed by chiral transition metal complexes
[1–4,11–14] or chiral organic compounds [15–22] have been
extensively investigated.
In the past decades, Bolm’s catalysts, namely, VO(acac)2/ and
Fe(acac)3/Schiff base systems [12,23–25] have received consider-
able attention. The advantages of this catalyst system include
good-to-high activity and enantioselectivity, the convenient prep-
aration and easy modification of chiral Schiff base ligands, the
utilization of cheap and environmentally benign terminal oxidant
structural modification of chiral Schiff bases, especially the sub-
stituents in the salicylidenyl moiety of the Schiff base, to enhance
the enantioselectivity of the reaction. Different substituents, such
as tert-butyl [23,26], nitro [23,27], aryl [28], bromo [29], iodo
[30–32], and even the substituent with an additional chiral
element [32–35], have been introduced to the amino alcohol
moiety and the 3- and/or 5-position of the salicylidenyl moiety
of the Schiff base, and their influences on the asymmetric oxida-
tion of sulfides have been reported. It was found that the
vanadium-based catalysts of 3,5-dibromo- and 3,5-diiodo-func-
tionalized chiral Schiff bases displayed considerably improved
enantioselectivity in the asymmetric oxidation of sulfides when
compared to other analogous Schiff bases [29–32]. For example,
the oxidation of thioanisole in dichloromethane at 0 °C with
3,5-diiodo (S)-1 as ligand (Fig. 1) in a PhSMe:VO(acac)2:ligand:-
H2O2 molar ratio of 100:1:1.5:120 gave 90% ee and 81% yield
of methyl phenyl sulfoxide [32], and with 3,5-diiodo (R)-1 as li-
gand (Fig. 1) in chloroform at 0 °C, the enantioselectivity of the
reaction is up to 96.7% ee with 70% yield [30]. The ligand (R,S)-
3 containing an axially chiral binaphthyl or biphenyl moiety
(Fig. 1) in combination with VO(acac)2 afforded the enantioselec-
tivity up to 86% ee with 90% yield for the oxidation of thioanisole
in dichloromethane at 0 °C [34]. However, for all reported VO-
(acac)2/ and Fe(acac)3/Schiff base catalyst systems, the high
enantioselectivity could be obtained only when the oxidation of
* Corresponding author. Address: Zhongshan Road 158-46, Dalian 116012,
People’s Republic of China. Fax: +86 411 83702185 (O).
** Corresponding author. Address: Zhongshan Road 158-46 Dalian 116012,
People’s Republic of China. Fax: +86 411 83702185 (O).
E-mail addresses: symbueno@dlut.edu.cn (M. Wang), lichengs@kth.edu.se (L.
Sun).
0021-9517/$ - see front matter Ó 2010 Elsevier Inc. All rights reserved.
doi:10.1016/j.jcat.2010.05.013

178
Y. Wang et al. / Journal of Catalysis 273 (2010) 177–181
(Shanghai) Ltd., respectively. 2-Naphthol, 1-naphthaldehyde, and
other starting compounds of reagent grade were obtained from lo-
cal suppliers and used as received. Schiff bases 4f and 5f were pre-
pared according to literature procedures [39–41]. The others, 4a–e
and 5a–e, are new Schiff bases and their preparation and charac-
terization will be described elsewhere [38].
Conversions of sulfides were obtained by GC analysis using HP 5
column with chlorobenzene as internal standard. Enantiomeric ex-
cesses (ee) of sulfoxides were determined by HPLC analysis using
chiral columns (Daicel Chiracel OD-H, 25 cm  0.46 cm i.d. and
Daicel Chiracel OB-H, 25 cm  0.46 cm i.d.).
Fig. 1. Structures of some effective chiral Schiff bases for Bolm’s catalyst system.
sulfides was carried out in dichloromethane or chloroform at 0 °C
[23–37]. This limit of applicable solvents to toxic small haloalk-
anes makes the vanadium-based catalyst systems less environ-
mental benign and decreases their industrial application value.
Therefore, it is necessary to explore new high-performance chiral
Schiff bases that, in combination with VO(acac)2, can catalyze the
asymmetric oxidation of sulfides in a less-toxic solvent to afford
chiral sulfoxides with high enantioselectivity and yields.
We recently prepared two series of chiral Schiff bases, 4aÀe and
5aÀe (Fig. 2), from the condensation reactions of mono-, di-, trib-
romohydroxynaphthaldehyde or monoiodohydroxynaphthalde-
hyde with chiral amino alcohols, either (S)-valinol or (S)-tert-
leucinol [38]. There is only one report on the catalytic behavior
of the vanadium-based catalyst in combination with the halo-
hydroxynaphthaldehyde-derived Schiff base (5g, Fig. 2) for the oxi-
dation of ethyl phenyl sulfide and methyl 2-naphthyl sulfide [32].
We screened the catalytic behaviors of 4aÀe and 5aÀe in combina-
tion with VO(acac)2 for the asymmetric oxidation of prochiral sul-
fides using H2O2 as terminal oxidant in dichloromethane and
toluene. The catalytic performances of the reference Schiff bases
4f and 5f without halo substituent was also explored to see the
effect of the halo group of the ligand on the asymmetric sulfoxida-
tion by comparison. High-to-excellent enantioselectivities with
satisfactory yields of sulfoxides were achieved for the asymmetric
oxidations of aryl methyl sulfides in toluene with vanadium cata-
lysts of the Schiff bases derived from bromo- and iodo-functional-
ized hydroxynaphthaldehydes.
2.2. A general procedure for the asymmetric oxidation of thioanisole
Compound VO(acac)2 (2.7 mg, 0.01 mmol) and a Schiff base li-
gand (0.015 mmol) were dissolved in solvent (1 mL). The mixture
was stirred at room temperature until it turned brown (ca.
30 min). A solution of the sulfide (1.0 mmol) in solvent (1.0 mL)
was then added, followed by dropwise addition (ca. 30 min) of
aqueous H2O2 (30%, 1.2 mmol) at 0 °C. After the mixture was stir-
red at 0 °C for a certain time, the resulting solution was extracted
with dichloromethane. The organic layer was washed with brine
and dried over Na2SO4. Filtration and evaporation gave a residue,
which was purified by flash chromatography on silica gel with
petroleum ether/ethyl acetate (3:2, V/V) and then ethyl acetate as
eluents. The pure sulfoxide was obtained after removal of the sol-
vent by rotary evaporation. The enantiomeric excess of the sulfox-
ide was determined by HPLC analysis.
2.3. A modified procedure for asymmetric oxidation of aryl methyl
sulfides in toluene
The toluene solution (1 mL) of VO(acac)2 (2.7 mg, 0.01 mmol)
and a Schiff base ligand (0.015 mmol) was stirred at room temper-
ature until it turned brown (ca. 30 min). A solution of the sulfide
(1.0 mmol) in toluene (1.0 mL) was then added, followed by drop-
wise addition (ca. 30 min) of aqueous H2O2 (30%, 1.2 mmol) at 0 °C.
The mixture was stirred at 0 °C for ca. 4 h. When the reaction
reached its equilibrium (monitored by GC analysis), the additional
aqueous H2O2 (30%, 0.3 mmol) was dropwise added at 0 °C and the
solution was stirred for another 4 h. The following workup was
identical with the general procedure described in Section 2.2.
2. Experimental
2.1. Materials and methods
Compound VO(acac)2 was purchased from Alfa Aesar. All aryl
methyl sulfides were purchased from Aldrich and chiral amino
acids (S)-tert-leucine and (S)-valine from Aldrich and GL Biochem
3. Results and discussion
3.1. Influences of Schiff bases 4a–f and 5a–f on the asymmetric
oxidation of thioanisole
In initial studies, the influence of the structures of the Schiff
bases, 4a–f and 5a–f, on the activity and enantioselectivity was
studied using thioanisole as a probe substrate. Considering the
optimal conditions previously reported for the VO(acac)2/Schiff
base catalyst systems [28,32,34], the reactions were carried out
in a molar ratio of 100:1:1.5:120 for sulfide:VO(acac)2:ligand:H2O2
in dichloromethane at 0 °C for a direct comparison of the catalytic
results obtained from the present work to those reported for anal-
ogous vanadium-based catalysts. The catalytic results are given in
Table 1. Each catalytic reaction was repeated at least two times.
The control experiment for the oxidation of thioanisole was car-
ried out with 1% mol of VO(acac)2 and 1.2 equiv of H2O2 in the ab-
sence of Schiff base ligand in CH2Cl2 at 0 °C for 6 h, methyl phenyl
sulfoxide was obtained in a high yield (>80%) [42]. With VO(acac)2/
4a as catalyst system, the reaction was close to end in 4 h under
the same conditions, monitored by the on-line GC analysis
(Fig. S1), and the HPLC analysis shows that the enantioselectivity
Fig. 2. The chiral Schiff bases used in the present work.

Y. Wang et al. / Journal of Catalysis 273 (2010) 177–181
179
Table 1
moderate-to-good enantioselectivities (67À82% ee). Such a high
yield of methyl phenyl sulfoxide indicates that under the condition
adopted, only a small amount of the corresponding sulfone is
formed, which is supported by the GC analysis of the resulting
solution. It is consistent with the previous reports that the good
enantioselectivity is a direct result of the asymmetric oxidation
of thioanisole in CH2Cl2 at 0 °C instead of a kinetic resolution by
overoxidation of the initially formed sulfoxide [30,32]. Considering
the two aspects of the yield and the enantioselectivity, the result
obtained from VO(acac)2/4d system (82% ee and 93% yield) is com-
parable to the best results reported so far for the asymmetric oxi-
dation of thioanisole catalyzed by VO(acac)2 in combination with
the Schiff base (R,S)-3 (78% ee and 92% yield) [33] and with the
diiodo-functionalized Schiff base (S)-1 (87% ee and 80% yield) un-
der similar conditions [31].
Effect of chiral Schiff base ligands on the vanadium-catalyzed asymmetric oxidation
of thioanisole with H2O2 as terminal oxidant in dichloromethane at 0 °C.a
.
Entry Ligand Halo group
R
Yieldb (%) eec,d (%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
4a
4b
4c
4d
4e
4f
5a
5b
5c
5d
5e
5f
1-Br
iPr
iPr
iPr
tBu 93
tBu 91
iPr
iPr
iPr
iPr
tBu 84
tBu 91
93
91
89
76
80
71
1,6-Br2
1,5,6-Br3
1,6-Br2
1-I
No halo group
1-Br
1,5-Br2
1,5,8-Br3
1,5-Br2
1-I
No halo group
3,5-I2
82
75
84
79
81
91
67
67
78
70
79
80
3.2. Asymmetric oxidation of thioanisole in toluene
iPr
85
60
In all reported cases for asymmetric oxidation catalyzed by
VO(acac)2/ and Fe(acac)3/Schiff base systems with H2O2 as termi-
nal oxidant, dichloromethane and chloroform proved to be opti-
mum solvents [23–37]. In addition to our previous paper [28],
only one report describing the asymmetric oxidation of prochiral
sulfides and kinetic resolution of racemic sulfoxides in toluene
was found in the literature [43]. Using (R)-1 as ligand and with
H2O2 as terminal oxidant in toluene at 0 °C, the oxidation of thio-
anisole gave methyl phenyl sulfoxide with modest enantioselectiv-
ity (53% ee in toluene cf. 97% ee in chloroform). As toluene is
preferred to small haloalkane solvents for reactions on an indus-
trial scale [44], we screened the activity and enantioselectivity of
VO(acac)2/4a–e and 5a–e catalyst systems for the asymmetric oxi-
dation of thioanisole in a molar ratio of 100:1:1.5:120 for sul-
fide:VO(acac)2:ligand:H2O2 in toluene at 0 °C. The results are
given in Table 2. The influences of other common organic solvents
were also studied with 4a as ligand. We found that solvents have
an apparent effect on the enantioselectivity and the yield of asym-
metric sulfoxidation reactions. The oxidation of thioanisole in THF,
acetonitrile, acetone, ethyl acetate, and chloroform gave low-to-
moderate enantioselectivities (14À64% ee and 61À96% yields).
To our delight, the oxidation of thioanisole in toluene gave sig-
nificantly higher enantioselectivities (91À94% ee) when compared
(S)-1
tBu 80 (81)
87 (90)e
78f
(R,S)-3 Axially chiral 1,1-binaphthyl tBu 92
a
Reaction conditions: VO(acac)2 (0.01 mmol), ligand (0.015 mmol), thioanisole
(1.0 mmol), aqueous H2O2 (30%, 1.2 mmol), 0 °C, 6 h, CH2Cl2 (2 mL).
b
Isolated yield.
c
Determined by HPLC with Daicel Chiralcel OD-H column V(hexane)/
V(i-PrOH) = 9:1.
d
The absolute configuration was assigned by comparing optical rotations and
HPLC elution orders with literature data. All of the major enantiomers are in the S
configuration.
e
Data cited from Ref. [31]. The data in the brackets were obtained by using 27%
H2O2 [32].
f
Data cited from Ref. [33].
almost remains constant during the reaction (6 h) [25], with the ee
values of 70–76%. Entries 1À3 and 6 for 4aÀc and 4f, respectively,
show that the enantioselectivities are considerably improved by
introduction of one or two bromo groups to the naphthyl ring.
Schiff base 4b with two bromine atoms at the 1,6-positions of
the naphthyl ring gives a better enantioselectivity (80% ee) when
compared to 4a with one bromine atom at 1-position and 4c with
three bromine atoms at the 1,5,6-positions (entry 2 vs. entries 1
and 3). The order of the enantioselectivities obtained is
4b > 4a > 4c > 4f. Introduction of the first bromine atom to the
para-position of the naphthol OH group of 5f also display a positive
effect on the enantioselectivity of the sulfoxide (entry 7 vs. 12). The
secondly introduced bromine atom, being close to the naphthol OH
group ready for chelating the vanadium unit, results in apparent
improvement of the enantioselectivity (entry 8 vs. entries 7 and
12), while introduction of the third bromine atom to the naphthyl
ring results in decrease of the enantioselectivity (entry 9 vs. 8) in a
similar trend observed in the 4a–c set. Presumably, the electron-
withdrawing effect of the multi-bromine atoms abates the coordi-
nation ability of the ligand, leading to an easier disassociation of
the Schiff base ligand from the vanadium centre. The catalyst of
VO(acac)2/iodo-functionalized Schiff base 5e gives methyl phenyl
sulfoxide in 91% yield and 80% ee (entry 11). These results indicate
that both the position and the number of the bromo or iodo substi-
tuent in the naphthyl ring of the Schiff base ligand can apparently
influence the enantioselectivity. When the R group in the amino
alcohol moiety of 4b is changed from iPr to tBu, the enantioselec-
tivity is slightly increased to 82% ee with 93% yield of sulfoxide
(entry 2 vs. 4).
Table 2
Vanadium-catalyzed asymmetric oxidation of thioanisole with H2O2 as terminal
oxidant in toluene at 0 °C.a
.
Entry
Ligand
Yieldb (%)
eec,d (%)
15
16
17
18
19
20
21
22
23
24
25
4a
4b
4d
4f
5a
5b
5d
5e
54
53
48
39
61
61
57
62
91
92
92
44
91
92
94
93
69
87
53e
5f
(S)-2
(R)-1
63
33
Not reported
a
Reaction conditions: VO(acac)2 (0.01 mmol), ligand (0.015 mmol), thioanisole
In general, the results given in Table 1 show that the Schiff
bases 4a–e and 5a–e derived from bromo- and iodo-functionalized
hydroxynaphthaldehydes and amino alcohols are good chiral
inducers for the asymmetric thioanisole oxidation, to give good-
to-high yields (79À93%) of chiral methyl phenyl sulfoxide with
(1.0 mmol), aqueous H2O2 (30%, 1.2 mmol), 0 °C, 4 h, toluene (2 mL).
b
See footnotes in Table 1.
See footnotes in Table 1.
See footnotes in Table 1.
Data cited from Ref. [43].
c
d
e

180
Y. Wang et al. / Journal of Catalysis 273 (2010) 177–181
to the results (67–82% ee, Table 1) obtained from the same reaction
in dichloromethane under the same condition. In contrast, using
Schiff bases 4f and 5f without halo substituent as ligands, the
enantioselectivities are drastically decreased to 44% ee and 69%
ee, respectively (entry 18 vs. entries 15–17 and entry 23 vs. entries
19–22). The results show that the stereoelectronic effect of the bro-
mo and iodo group in the naphthyl moiety of Schiff bases signifi-
cantly influences the enantioselectivity of the sulfoxidation. The
similar effect of the bromo and iodo substituent has been discov-
ered for Schiff bases derived from salicylaldehyde [29–32]. When
the Schiff bases 5b and 5e containing a dibromo- and iodo-func-
tionalized hydroxynaphthol moiety were used as chiral inducers
(entries 20 and 22), the oxidation of thioanisole affords methyl
phenyl sulfoxide with high enantioselectivities (92–93% ee) and
satisfactory yields (61–62%). In contrast, with the corresponding
Schiff bases (S)-2 and (R)-1 (Fig. 1) containing a dibromo- and diio-
do-functionalized hydroxyphenyl moiety as ligands (entries 24 and
25), the oxidation of thioanisole gave methyl phenyl sulfoxide with
modest-to-good enantioselectivities (87% ee for (S)-2 and 53% ee
for (R)-1) and a low yield (33% for (S)-2). A comparison of the cat-
alytic results obtained with 5b, 5e, (S)-2, and (R)-1 indicates that
the enantioselectivity and activity of the vanadium-based catalysts
for the oxidation of thioanisole in toluene can be considerably im-
proved by adjusting the structure of the Schiff base with a bromo-
and iodo-functionalized hydroxynaphthylmethyl unit in place of
the corresponding salicyl moiety.
mixture of CH2Cl2 and toluene as solvent. The GC analysis of the
resulting solution indicates that initially formed sulfoxide can be
overoxidized to sulfone in toluene even at 0 °C. Only slight enanti-
oselectivity (selectivity factor S ꢀ 3) was observed for the kinetic
resolution of racemic methyl phenyl sulfoxide in toluene at 0 °C
using 4a or 5b as ligand in a molar ratio of 100:1:1.5:80 for sulfox-
ide:VO(acac)2:ligand:H2O2. These results are consistent with the
previous report on the low enantioselectivity for oxidation of race-
mic methyl phenyl sulfoxide in toluene with VO(acac)2/(R)-1 as
catalyst and H2O2 as terminal oxidant [43]. Therefore, we can con-
clude that the high enantioselectivities, listed in Table 2, obtained
from the oxidation of thioanisole in toluene dominantly result
from the asymmetric oxidation of sulfide and the overoxidation
of the in-situ generated sulfoxide give only a small contribution
to the enantioselectivity of the sulfoxide finally obtained.
To further improve the enantioselectivity of sulfide oxidation in
toluene, we explored the influences of the loading amount and the
added mode of oxidant H2O2 on the reaction. The GC analysis
shows the resulting solution, from the oxidation of thioanisole
with VO(acac)2/5b, /5d, and /5e as catalysts using 1.2 equiv of
H2O2 (added at once) in toluene at 0 °C for 4 h, contains the methyl
phenyl sulfoxide, sulfone, and unreacted thioanisole with an
approximate ratio of 5:3:2. The fact that some thioanisole left in
the resulting solution means that 1.2 equiv of H2O2 is not enough
for the complete conversion of the starting sulfide because the fur-
ther oxidation of the in-situ formed sulfoxide inevitably, although
slowly, occurs in toluene even at 0 °C. When we raised the loading
amount of H2O2 from 1.2 to 1.3, 1.4, and 1.5 equiv and added it at
once in the beginning of the reaction, both the enantioselectivity
and the yield were apparently decreased with increase in the con-
centration of H2O2 [26,42]. Therefore, a modified procedure with
addition of H2O2 at twice was adopted. A 1.2 equiv of H2O2 was
dropped at 0 °C in the beginning of the reaction, and after the mix-
ture was stirred for 4 h the additional 0.3 equiv of H2O2 was added
3.3. A modified procedure for the enantioselective preparation of aryl
methyl sulfoxides in toluene
The GC monitoring of the thioanisole oxidation shows that the
reaction in toluene levels off after 3 h (Fig. S2). Although about
20% of thioanisole is left in the solution, the conversion could not
be further improved by extending the reaction time or using the
Table 3
A modified procedure for vanadium-catalyzed asymmetric oxidation of aryl methyl sulfides with H2O2 as terminal oxidant in
toluene at 0 °C.a
.
Entry
Ligand
Ar
Yieldb (%)
eec,d (%)
20e
26
21e
27
22e
28
29
30
31
32
33
34
5b
5b
5d
5d
5e
5e
5d
5e
5d
5e
5d
5e
Ph
Ph
Ph
Ph
Ph
Ph
61
59
57
51
62
62
65
58
59
55
67
61
92
97
94
95
93
98
97
96
95
97
98
99
4-BrC6H4
4-BrC6H4
4-MeOC6H4
4-MeOC6H4
2-Naphthyl
2-Naphthyl
a
Reaction conditions: VO(acac)2 (0.01 mmol), ligand (0.015 mmol), aryl methyl (1.0 mmol), aqueous H2O2 (30%,
1.2 + 0.3 mmol, added by two portions), toluene (2 mL).
b
Isolated yield.
c
Determined by HPLC with Daicel Chiralcel OD-H column V(hexane)/V(i-PrOH) = 9:1 for entries 20–22, 26–28, 33 and 34;
Daicel Chiralcel OB-H column V(hexane)/V(i-PrOH) = 8:2 for entries 29 and 30, 5:5 for entries 31 and 32.
d
See the footnote d in Table 1.
e
H2O2 (30%, 1.2 mmol, added at once in the beginning of the reaction). The other conditions are the same as that described
in the footnote a.

Y. Wang et al. / Journal of Catalysis 273 (2010) 177–181
181
to the same reaction vessel. The reaction was extended for another
Acknowledgments
4 h at 0 °C. It is encouraging that excellent enantioselectivities
were obtained by using the modified procedure in toluene. The
combination of the asymmetric oxidation of the left sulfide and
the slightly kinetic resolution of the in-situ formed sulfoxide in
the latter step with an extra 0.3 equiv of H2O2 made an improve-
ment of the enantioselectivity, while only a tolerant drop in the
yield of methyl phenyl sulfoxide was observed. Compared to the
enantioselectivities (92À94% ee) and the yields (57À62% yield)
obtained from the oxidation of thioanisole in toluene with addition
of 1.2 equiv of H2O2 at once, 5b, 5d and 5e display better enanti-
oselectivities (95À98% ee, Fig. S3) in 51À62% yields when the
modified procedure was adopted (entries 20À22 vs. 26À28
respectively).
We are grateful to the National Natural Science Foundation of
China (Grant No. 20973032), the Program for Changjiang Scholars
and Innovative Research Team in University (IRT0711), and the K
& A Wallenberg Foundation of Sweden for financial support of this
work.
Appendix A. Supplementary material
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.jcat.2010.05.013.
With the modified procedure, we performed the asymmetric
oxidation of various aryl methyl sulfides with VO(acac)2/5d and /
5e as catalysts. The catalytic results are given in Table 3. The cor-
responding sulfoxides were obtained in satisfactory isolated yields
(55À65%) with excellent enantioselectivities (95À99% ee, Fig. S4).
In general, ligand 5d gave higher yields of sulfoxides than 5e for
the oxidations of all three tested aryl methyl sulfides, while 5d
and 5e afforded similar enantioselectivities for the oxidation of
each aryl methyl sulfide. To the best of our knowledge, these are
the best results reported so far for the asymmetric oxidation of aryl
methyl sulfides in toluene using vanadium catalysts in combination
with chiral Schiff bases, which are comparable to the best results
obtained from such asymmetric oxidation reactions in dichloro-
methane or chloroform [23–25,30,32].
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4. Conclusions
In conclusion, the Schiff bases 4a–e and 5a–e containing bro-
mo- and iodo-functionalized hydroxynaphthaldehydes are effi-
cient chiral inducers for the vanadium-catalyzed asymmetric
oxidations of various aryl methyl sulfides with H2O2 as terminal
oxidant. A comparison of the catalytic performances of VO(a-
cac)2/Schiff bases 4aÀe and 5aÀe, as well as their analogous Schiff
bases 4f and 5f without halo substituent, in the oxidation of thio-
anisole indicates that the number and the position of the halogen
atom on the naphthyl ring of the Schiff base play significant effects
on the enantioselectivity of the sulfoxides. More interestingly,
using these Schiff bases in combination with VO(acac)2, the asym-
metric oxidation of thioanisole in toluene afforded methyl phenyl
sulfoxide in reasonable yields (48–62%) with relatively high
enantioselectivities (91–94% ee), which are significantly higher
than the catalytic results obtained from the same reaction in tolu-
ene with Schiff bases (S)-2 and (R)-1 containing a dibromo- or diio-
do-functionalized salicyl moiety as ligands. With the modified
procedure by adding 1.5 equiv of H2O2 in two portions, the enanti-
oselectivity for the oxidation of thioanisole in toluene was further
improved up to 98% ee with a satisfactory yield (62%) when iodo-
functionalized 5e was used as ligand. The asymmetric oxidations of
other aryl methyl sulfides in toluene with dibromo-functionalized
5d and iodo-functionalized 5e as ligands, respectively, afforded the
corresponding sulfoxides in satisfactory yields (55À65%) with
excellent enantioselectivities (95À99% ee), which are the best re-
sults ever reported for such sulfide oxidation reactions in toluene
using vanadium-based catalysts. These results are valuable for
the industrial application of these asymmetric sulfoxidation reac-
tions, since as a solvent toluene is preferred over dichloromethane
and chloroform in an environment protection point of view.
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