Efficient asymmetric oxidation of sulfides and kinetic resolution of sulfoxides catalyzed by a vanadium-salan system

Article abstract of DOI:10.1021/jo040221d

The asymmetric oxidation of sulfides to chiral sulfoxides with hydrogen peroxide in good yield and high enantioselectivity has been catalyzed very effectively by chiral vanadium-salan [N,N′-alkyl bis(salicylamine)] complex. The salan ligand shows results superior in terms of reactivity and enantioselectivity to those of salen [N,N′-alkylene bis(salicylideneimine) ] analogue, and provides the sulfoxide with opposite configuration. The high enantioselectivity of this reaction is the direct result of the asymmetric oxidation. The efficient kinetic resolution of racemic sulfoxides catalyzed by the vanadium-salan system is also described.

Full text of DOI:10.1021/jo040221d

alkyl peroxide was used as the oxidant, was reported by
Fujita.7a Subsequently, Bolm reported a highly selective
and promising catalyst system in which a combination
of the amino alcohol-derived Schiff base with vanadium
was employed, and the oxidation proceeded in up to 85%
enantiomeric excess, with very low catalyst loading and
with hydrogen peroxide as a nontoxic and inexpensive
stoichiometric oxidant.7b Employing this catalyst system,
Ellman has successfully and extensively studied the
catalytic asymmetric oxidation of tert-butyl disulfide.8
Very recently, Bolm reported the iron-catalyzed version
of this system for the asymmetric sulfide oxidation.7d An
oxidation catalyst system for the sulfoxidation of sulfide
that combines high catalytic efficiency and excellent
enantioselectivity remains an important goal.
Nitrogen-containing ligands are one of the most com-
mon types of chiral ligands, which are becoming applic-
able for catalytic asymmetric synthesis.9 It has been re-
ported that the chiral ligands containing a secondary
amino group (sp3-hybridized nitrogen atom) are superior
in terms of reactivity and enantioselectivity to imino ana-
logues (sp2-hybridized nitrogen atom).10 Herein, we wish
to report a catalytic asymmetric oxidation of sulfides to
sulfoxides with excellent enantioselectivity by means of
a facile and efficient procedure using chiral vanadium-
salan complexes as the catalysts. Kinetic resolution of
racemic sulfoxides catalyzed by an identical system is
also described.
Efficient Asymmetric Oxidation of Sulfides
and Kinetic Resolution of Sulfoxides
Catalyzed by a Vanadium-Salan System
Jiangtao Sun,† Chengjian Zhu,*,†,‡ Zhenya Dai,†
Minghua Yang,† Yi Pan,† and Hongwen Hu†
School of Chemistry and Chemical Engineering, State Key
Laboratory of Coordination Chemistry, Nanjing University,
Nanjing 210093, China, and State Key Laboratory of
Organometallic Chemistry, Shanghai Institute of Organic
Chemistry, Chinese Academy of Sciences,
Shanghai 200032, China
cjzhu@netra.nju.edu.cn
Received June 25, 2004
Abstract: The asymmetric oxidation of sulfides to chiral
sulfoxides with hydrogen peroxide in good yield and high
enantioselectivity has been catalyzed very effectively by chi-
ral vanadium-salan [N,N′-alkyl bis(salicylamine)] complex.
The salan ligand shows results superior in terms of reactiv-
ity and enantioselectivity to those of salen [N,N′-alkylene
bis(salicylideneimine)] analogue, and provides the sulfoxide
with opposite configuration. The high enantioselectivity of
this reaction is the direct result of the asymmetric oxidation.
The efficient kinetic resolution of racemic sulfoxides cata-
lyzed by the vanadium-salan system is also described.
Enantiopure sulfoxides constitute a class of the most
efficient and versatile chiral controllers and useful syn-
thons in asymmetric synthesis, and they are of great
interest in the pharmaceutical industry as biologically
significant compounds.1 The synthesis of chiral nonra-
cemic sulfoxides with high enantiomeric purity has been
a subject of constant interest over the past two decades.
The following two types of procedures have been most
commonly employed for the preparation of chiral sulfox-
ides: (1) an approach that consists of the synthesis of a
sulfinylating agent with an electrophilic sulfur of known
configuration, followed by the reaction with an organo-
metallic regent,2 and (2) the direct asymmetric oxidation
of the easily available prochiral sulfides.3 In the latter
procedure, catalytic asymmetric oxidation of sulfides with
chiral metal complexes or enzymes is undoubtedly the
most attractive and economical method because of its
simplicity. Following the initial reports by Kagan4 and
Modena5 on the use of a modified Sharpless reagent, most
of the metal-catalyzed enantioselective oxidation of sul-
fides are based on the use of chiral titanium or manga-
nese complexes.6 In contrast, vanadium catalysts have
been less extensively investigated.7 The first example of
vanadium-catalyzed asymmetric sulfoxidation, in which
The readily obtainable tetradentate salan ligands 1
and 2, which are based on the (R,R)-1,2-diaminocyclo-
(3) (a) Crich, D.; Mataka, J.; Sun, S.; Lam, K. C.; Rheingold, A. L.;
Wink, D. Chem. Commun. 1998, 2763. (b) Ozaki, S.; Matsui, T.;
Watanabe, Y. J. Am. Chem. Soc. 1997, 119, 6666. (c) Kagan, H. B.;
Rebiere, F. Synlett 1990, 643. (d) Schultz, P. G.; Lerner, R. A. Science
1995, 269, 1835. (e) Bethel, D.; Page, P. B.; Vahedi, H. J. Org. Chem.
2000, 65, 6756. (f) Adam, W.; Korb, M. N.; Roschmann, K. J.; Saha-
Moller, C. R. J. Org. Chem. 1998, 63, 3424. (g) Schenk, W. A.; Durr,
M. Chem.sEur. J. 1997, 3, 713. (h) Kadnikova, E.; Kostic, N. M. J.
Org. Chem. 2003, 68, 2600.
(4) (a) Kagan, H. B.; Dunach, E.; Nemecek, C.; Pitchen, P.; Samuel,
O.; Zhao, S. H. Pure Appl. Chem. 1985, 57, 1911. (b) Zhao, S. H.;
Samuel, O.; Kagan, H. B. Tetrahedron 1987, 43, 5135. (c) Puchot, C.;
Samuel, O.; Dunach, E.; Zhao, S.; Agami, C.; Kagan, H. B. J. Am.
Chem. Soc. 1986, 108, 2353. (d) Luukas, T. O.; Girard, C.; Fenwick,
D. R.; Kagan, H. B. J. Am. Chem. Soc. 1999, 121, 9299.
(5) (a) Di Furia, F.; Modena, G.; Seraglia, R. Synthesis 1984, 325.
(b) Bortolini, O.; Di Furia, F.; Licini, G.; Modena.; Rossi, M. Tetrahe-
dron Lett. 1986, 27, 6257.
(6) (a) Brunel, J. M.; Kagan, H. B. Synlett 1996, 404. (b) Bonchio,
M.; Licini, G.; Modena G.; Bartolini, O.; Moro, S.; Nugent, W. J. Am.
Chem. Soc. 1999, 121, 6258. (c) Chen, Y.; Yekta, S.; Martyn, J. P.;
Zheng, J.; Yudin, A. K. Org. Lett. 2002, 2, 3433. (d) Noda, K.; Hosoya,
N.; Irie, R.; Yamashita, Y.; Katsuki, T. Tetrahedron 1994, 50, 9609.
(7) (a) Nakajima, K.; Kojima, M.; Fujita, J. Chem. Lett. 1986, 1483.
(b) Bolm, C.; Bienewald, F. Angew. Chem., Int. Ed. Engl. 1995, 34,
2640. (c) Liu, G.; Cogan, D. A.; Ellman, J. A. J. Am. Chem. Soc. 1997,
119, 9913. (d) Vetter, A.; Berkessel, A. Tetrahedron Lett. 1998, 39, 1741.
(e) Legros, J.; Bolm, C. Angew. Chem., Int. Ed. 2003, 42, 5487.
(8) (a) Liu, G.; Cogan, D.; Ellman, J. A. J. Am. Chem. Soc. 1997,
119, 9913. (b) Cogan, D.; Liu, G.; Kim, K.; Backes, B. J.; Ellman, J. A.
J. Am. Chem. Soc. 1998, 120, 8011.
(9) For reviews see: (a) France, S.; Guerin, D. J.; Miller, S. J.;
Lectka, T. Chem. Rev. 2003, 103, 2985. (b) Bennani, Y. L.; Hanessian,
S. Chem. Rev. 1997, 97, 3161. (c) Canali, L.; Sherrington, D. C. Chem.
Soc. Rev. 1999, 28, 85.
(10) (a) Gao, J. X.; Ikariya, T.; Noyori, R. Organometallics 1996, 15,
1087. (b) Ward, C. V.; Jiang, M. L.; Kee, T. Tetrahedron Lett. 2000,
41, 6181. (c) Duxbury, J. P.; Cawley, A.; Thornton-Pett, M.; Wantz,
L.; Warne, J. N. D.; Greatrex, R.; Brown, D.; Kee, T. Tetrahedron Lett.
1999, 40, 4403.
† Nanjing University.
‡ Chinese Academy of Sciences.
(1) (a) Fernandez, I.; Khiar, N. Chem. Rev. 2003, 103, 3651 and
references therein. (b) Garcia Ruano, J. L.; Cid, B. Top. Curr. Chem.
1999, 204, 103. (c) Renaud, P.; Gerster, M. Angew. Chem., Int. Ed.
1998, 37, 2562. (d) Blum S. A.; Bergman R. G.; Ellman J. A. J. Org.
Chem. 2003, 68, 150. (e) Carlsson, E.; Lindberg, P.; von Unge, S. Chem.
Br. 2002, May, 42. (f) Renfrey, S.; Featherstne, J. Nat. Rev. Drug.
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Senanayake, C. H. J. Am. Chem. Soc. 2002, 124, 7880. (b) Whitesell
J. K.; Wong, M. S. J. Org. Chem. 1994, 59, 597. (c) Oppolzer, W.;
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10.1021/jo040221d CCC: $27.50 © 2004 American Chemical Society
Published on Web 10/28/2004
8500
J. Org. Chem. 2004, 69, 8500-8503

TABLE 1. Catalyzed Asymmetric Oxidation of Methyl
Phenyl Sulfide Using Various Ligands under Different
Conditionsa
time VO(acac)2: yield ee configura-
entry ligand solvent (h)
ligand
(%)b (%)c
tiond
1
1
1
1
1
1
1
1
1
1
1
1
2
2
3
4
5
5
6
7
CH2Cl2
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CHCl3
CCl4
12
16
16
16
16
16
16
20
6
14
18
20
18
16
16
20
20
16
16
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.2
1:1
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
1:1.5
84
81
80
78
67
80
78
71
91
83
70
82
78
76
75
82
83
37
42
70
95
62
95
93
94
91
45
37
66
22
63
51
31
22
21
37
5
R
R
R
R
R
R
R
R
R
R
R
R
R
S
S
R
R
S
S
2
3e
4f
5g
6
7
8
9
CH3CN
THF
10
11
12
13
14
15
16
17
18
19
toluene
CCl4
CHCl3
CHCl3
CHCl3
CHCl3
CH2Cl2
CHCl3
CHCl3
FIGURE 1. Structures of ligands used in this study.
hexane backbone, ligands 3 and 4, which are derived from
(S,S)-1,2-diamino-1,2-diphenylethane, and ligand 5, in
which there are two tertiary nitrogen atoms, were chosen
as chiral auxiliaries (Figure 1). Ligands 1-4 were
prepared by the reduction of their corresponding Schiff
base salen precursor with sodium borohydride in absolute
methanol in very high yields,11 while ligand 5 was
synthesized by the treatment of 1 in THF with n-
butyllithium and iodomethane successively. These salan
ligands have been employed in the formation and char-
acterization of different metal complexes,12 while, to the
best of our knowledge, only one example of their chem-
istry in asymmetric catalysis has been reported.10b
Following Bolm’s protocol,7b in which the catalyst was
formed in situ from the reaction of VO(acac)2 and chiral
ligand, where hydrogen peroxide was used as an oxidant,
we studied the reactivity and enantioselectivity of the
oxidation of sulfide using methyl phenyl sulfide as a
model substrate. The influence of parameters such as the
nature of the ligand and the metal/ligand ratio, together
with the effects of the temperature and the solvent, has
been examined. The results were collected in Table 1.
All of the catalysts bearing amine ligands showed good
catalytic reactivity, with the yields ranging from 71 to
91%, but with different selectivity in the range between
21 and 95% ee. Ligands (1 and 2) with a cyclohexane
backbone showed better selectivity than those with a 1,2-
diphenylethane backbone (3 and 4). The secondary amine
ligand 1 gave the best result (entry 2) in terms of
selectivity, but when 1 was methylated to tertiary amine
5, the selectivity decreased to only 21% and 37% ee in
CHCl3 and CH2Cl2 (entries 16 and 17), respectively.
Surprisingly, in contrast with other systems,13 the steri-
cally demanding substituents such as the t-Bu group in
the salicyl component induced a negative effect in the
enantioselectivity of the reaction in our system.
10
a Unless otherwise noted, all reactions were carried out at 0 °C
with VO(acac)2 loading of 2 mol % and 1.5 mmol of H2O2 (30%).
b Isolated yields; amount of sulfone < 5%. c Ee values were deter-
mined by HPLC with a Daicel Chiralcel OD-H column. d Absolute
configuration was assigned by comparison of optical rotation re-
ported in the literature.14 e Reaction performed at 25 °C. f Reaction
performed at -20 °C. g Performed with a 5% H2O2 solution.
For comparison, the imine salen ligands 6 and 7
(Figure 1) were also examined in this oxidation system
(entries 18 and 19). The reactivity and especially the
selectivity are very poor, which is consistent with the
results obtained for a VO/salen/CHP system.7a It is
noteworthy that the products resulting from amine
ligands 1 and 2 are of R configuration, which is the
reverse of that of corresponding salen ligands 6 and 7
(the major product is of S configuration). This may be
due to the electronic difference and the stereogenic
character of nitrogen atoms in salan ligands, which
resulted from the coordination of nitrogen atoms to the
central metal. The influence of the chirality of the
nitrogen atom in the ligand on the catalytic selectivity
deserves more investigation.
The nature of the solvent was revealed to have a
remarkable effect upon the enantioselectivity and chemi-
cal yield. Of the six solvents we investigated, CHCl3 gave
the highest enantioselectivity and good chemical yield
using 1 as the chiral ligand. When CH2Cl2 and THF were
used as solvents, moderate ee values were obtained
(entries 1 and 10). CH3CN gave the highest chemical
yield but lower ee values (entry 9). Thus, CHCl3 proved
to be the best solvent in terms of selectivity. A variation
of the reaction temperature from 0 to 25 °C caused a
sharp decrease in the ee value to 62% (entry 3), but there
was no significant change when the reaction was carried
out at -20 °C (entry 4). Moreover, there was a slight
decrease when the metal/ligand ratio changed from 1:1.5
to 1:1.1 (entries 2, 5, and 7). The use of dilute hydrogen
peroxide (5%) caused a slight decrease in chemical yield
but no significant change in selectivity (entry 5).
(11) (a) Atwood, D. A.; Benson, J.; Jegier, J. A.; Lindholm, N. F.;
Martin, K. J.; Pitura, R. J. Rutherford, D. Main Group Met. Chem.
1995, 1, 99. (b) Garcia-Zarracino, R.; Ramos-Quinones, J.; Hopfl, H.
J. Organomet. Chem. 2002, 664, 188.
(12) (a) Ellas, H.; Stock, F.; Rohr, C. Acta Crystallogr. 1997, C53,
862. (b) Garcia-Zarracino, R.; Ramos-Quinones, J.; Hopfl, H. J.
Organomet. Chem. 2002, 604, 188. (c) Balsells, J.; Carroll, P. J.; Walsh,
P. J. Inorg. Chem. 2001, 40, 5568.
We thus used 1 as the chiral ligand for enantioselective
oxidation of a variety of sulfides using VO(acac)2 as a cat-
(13) Jacobsen, E. J. Acc. Chem. Res. 2000, 33, 373.
J. Org. Chem, Vol. 69, No. 24, 2004 8501

TABLE 2. Vanadium-Catalyzed Enantioselective
Oxidation of Sulfides Using Chiral Ligand 1a
sulfoxide
(%)b
ee
entry
R
R′
(%)c configurationd
1
2
Ph
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
81
78
80
83
86
71
80
72
62
82
83
78
84
83
76
83
95
66
85
92
83
58
51
60
64
81
75
72
66
76
63
72
R
R
R
R
R
R
R
R
S
R
R
R
R
/
p-CH3C6H4
p-iPrC6H4
m-BrC6H4
o-BrC6H4
p-ClC6H4
3
4
5
6
7
p-FC6H4
8
o-NO2C6H4
m-NO2C6H4
9
10
11
12
13
14
15
16
m-CH3OC6H4 CH3
p-CH3OC6H4
Ph
CH3
CH2Ph
CH2Ph
CH3
p-CH3C6H4
t-Bu
FIGURE 2. Time profile of the enantioselectivity (% ee of
methyl phenyl sulfoxide) in the oxidation of methyl phenyl
sulfide in entry 1 of Table 2.
t-Bu
t-Bu
i-Pr
n-Bu
/
/
a All reactions were carried out in CHCl3 at 0 °C for 16-20 h.
Molar ratio: substrate/H2O2/VO(acac)2/1 ) 1:1.5:0.02:0.03. b Iso-
lated yields. c Ee values of entries 1-13 were determined by HPLC
with a Daicel Chiralcel OB-H or OD-H column, while those of
entries 14-16 were determined by 1H NMR analysis. d Absolute
configuration was assigned by comparison of optical rotation
reported in the literature.14
SCHEME 1. Proposed Mechanism for the
Asymmetric Sulfide Oxidation
alyst precursor. The reactions were carried out at 0 °C
in CHCl3 under air with 1.5 equiv of H2O2 as an oxidant.
The results are summarized in Table 2. Good chemical
yields of isolated products, in the range of 62-86%, were
obtained for all cases, with these being almost indepen-
dent of the structure of the sulfides. All the products of
aryl alkyl sulfides obtained were of R configuration except
for entry 9. The enantioselectivity varied from 51 to 95%
depending on the nature of the sulfide. The change of
the aryl group in the methyl sulfide to probe electronic
effects displayed no regular trends in the enantioselec-
tivity. The highest ee value was observed for the phenyl
group, but lower enantioselectivities were obtained both
for the electron-donating and electron-accepting groups
attached to the phenyl ring. Moreover, good enantiose-
lectivities were also achieved even for the dialkyl sulfide
(entries 14-16). The method appears to be fairly general
for the enantioselective oxidation of sulfide.
In most cases, the high ee values of the sulfoxides were
caused by two independent stereoselective processes, i.e.,
the asymmetric oxidation producing sulfoxide and its
subsequent kinetic resolution via further oxidation to
sulfone.15 To our delight, sulfones were formed only in
very low quantities (<5%) in the reaction processes using
the catalytic system described here. From the time profile
of the oxidation of methyl phenyl sulfide (Figure 2), it
can be seen that the ee of sulfoxide does not change
significantly during the reaction process. On the basis
of these studies, it is deduced that the high ee values of
the sulfoxides do not arise from a selectivity enhancement
caused by kinetic resolution of the chiral sulfoxide but
are the direct result of the enantioselective oxidation. On
the other hand, a nonlinear effect was not observed in
our catalytic system; this is presumably because the
catalytic species contains only one ligand in the config-
uration-determining step.
A proposed mechanism for the catalytic asymmetric
oxidation of sulfide is shown in Scheme 4. The reaction
of salan ligand with VO(acac)2 gave a salan-oxovana-
dium complex A as a catalyst species.7a As no Hammett
correlations were found in this reaction, the process of
oxygen transfer might not involve the formation of
discrete intermediate sulfur radicals or cations but, most
(14) (a) Pitchen, P.; Dunach, E.; Deshmukh, M. N.; Kagan, H. B. J.
Am. Chem. Soc. 1984, 106, 8188. (b) Capozzi, M. A. M.; Cardellicchio,
C.; Naso, F.; Tortorella, P. J. Org. Chem. 2000, 65, 2843. (c) Palucki,
M.; Hanson, P.; Jacobsen, E. N. Tetrahedron Lett. 1992, 33, 7111. (d)
Donnoli, M. I.; Superchi, S.; Rosini, C. J. Org. Chem. 1998, 63, 9392.
(e)Kokubo, C.; Katsuki, T. Tetrahedron 1996, 52, 13895.
(15) (a) Kamatsu, N.; Hashizume, M.; Sugita, T.; Uemura, S. J. Org.
Chem. 1993, 58, 4529. (b) Furia, F. D.; Licini, G.; Modena, G.; Motterle,
R.; Nugent, W. A. J. Org. Chem. 1996, 61, 5175.
8502 J. Org. Chem., Vol. 69, No. 24, 2004

TABLE 3. Kinetic Resolution of Racemic Sulfoxides
In summary, the asymmetric oxidation of sulfides as
well as the kinetic resolution of sulfoxides with hydrogen
peroxide under air catalyzed by a salan-vanadium
catalyst provides an efficient procedure for the prepara-
tion of chiral sulfoxides in both good chemical yields and
excellent enantiomeric purity. An important character-
istic of the new catalytic system is that it provided chiral
sulfoxides in higher ee values and with opposite enan-
tioselection as compared with that of the corresponding
salen system. Moreover, the high enantioselectivity of the
asymmetric oxidation of sulfides did not arise from a
selectivity enhancement caused by kinetic resolution of
the chiral sulfoxide but was the direct result of the
enantioselective oxidation. The R and S forms of sulfox-
ides can be obtained by the enantioselective oxidation of
sulfides or the kinetic resolution of sulfoxides, respec-
tively, catalyzed by the identical salan-vanadium cata-
lyst system. Investigations are currently underway to
understand the oxidation mechanism.
Catalyzed by Vanadium-Salan Systema
entry
R
R′
sulfoxide (%)b ee (%)c configurationd
1
2
3
4
5
6
7
8
Ph
CH3
32
29
28
30
26
30
26
27
92
98
87
78
93
86
93
91
S
S
S
S
S
S
S
S
p-CH3C6H4 CH3
p-iPrC6H4
m-BrC6H4 CH3
CH3
o-BrC6H4
p-ClC6H4
Ph
CH3
CH3
CH2Ph
p-CH3C6H4 CH2Ph
a All reactions were carried out in CHCl3 at 25 °C for 20-24 h.
Molar ratio: substrate/H2O2/VO(acac)2/1 ) 1:2:0.05:0.075. b Iso-
lated yields. c Ee values were determined by HPLC with a Daicel
Chiralcel OB-H or OD-H column. d Absolute configuration was
assigned by comparison of optical rotation reported in the litera-
ture.14
likely, proceeds by a concerted mechanism.16 Nucleophilic
attack of sulfur on the oxygen atom, which could be
regarded as a remote nucleophilic attack on the metal,
formed intermediate B. Reaction of intermediate C with
hydrogen peroxide gave the chiral sulfoxide and regener-
ated species A.
Experimental Section
General Procedure for the Asymmetric Oxidation of
Sulfides. VO(acac)2 (5.2 mg, 0.02 mmol) and the ligand (0.03
mol) were dissolved in a reaction tube in CHCl3 (4 mL), and the
solution was stirred for 1 h, with the color of the solution turning
gradually from blue to deep brown. The sulfide (1 mmol) was
added into the tube after the system was cooled to 0 °C. After
the solution was stirred for another 10 min, the hydrogen
peroxide (30%, 1.5 mmol) was added dropwise. The mixture was
stirred for 16 h at 0 °C. Then, 10 mL of H2O was added into the
mixture. The aqueous layer was separated and extracted with
CH2Cl2. The combined organic layer was dried over anhydrous
Na2SO4, and the solvent was removed in vacuo. The crude
product was purified by chromatography on silica gel (petroleum
ether/ethyl acetate ) 1.5/1). The fractions of sulfoxide were
mixed.18 The enantioselectivities were determined by chiral
HPLC (Daicel UV detector (254 nm), flow rate 0.5 mL/min). The
reaction can be scaled up to 10 mmol without significant change
of chemical yield and ee value.
Kinetic resolution of racemic sulfoxides has also emerged
as a promising method for obtaining optically pure
sulfoxides, as racemic sulfoxides are readily prepared by
direct oxidative methods. Although several examples
have been reported, only a few examples of kinetic
resolutions have been effective for obtaining sulfoxides
of high ee.17 It is of interest to study the kinetic resolution
of racemic sulfoxides with the vanadium-salan catalyst.
After optimization studies, combination of VO(acac)2
(5 mol %), chiral ligand 1 (7.5 mol %), and H2O2 (2 equiv)
in CHCl3 at 25 °C proved to be the best reaction
conditions for the asymmetric kinetic resolution of race-
mic sulfoxides. The kinetic resolutions of different race-
mic sulfoxides were accomplished under the above con-
ditions, and the results are presented in Table 3. From
the results, it can be seen that kinetic resolution of race-
mic sulfoxides could be also achieved by catalysis with
chiral vanadium-salan complex 1 to give the sulfoxides
in moderate chemical yields and good to excellent ee
values, with the methyl p-tolyl sulfoxide providing the
best result of up to 98% ee (entry 2). The stereoselectivity
factor krel is 7.3 for the resolution of methyl phenyl
sulfoxide (entry 1).4d It is clear that the chiral vanadium-
salan complex recognizes (R)- and (S)-sulfoxides and
catalyzes predominantly the oxidation of (R)-sulfoxide.
Once again, it strongly supported that the high ee values
of the catalytic oxidation of sulfides were not the result
of kinetic resolution. We would like to mention that both
R and S forms of optical active sulfoxides can be obtained
with the same salan-vanadium catalyst system through
the oxidation of sulfides and the kinetic resolution of
racemic sulfoxides, respectively.
General Procedure for the Kinetic Resolution. VO(acac)2
(0.05 mmol) and the ligand (0.075 mol) were dissolved in a
reaction tube in CHCl3 (4 mL), and the solution was stirred for
1 h, with the color turning gradually from blue to deep brown.
After the addition of the racemic sulfoxide (1 mmol) and the
dropwise addition of 30% H2O2 (2.0 mmol), the resulting mixture
was stirred for 20 h at ambient temperature. Then, 10 mL of
H2O was added into the reaction mixture. The aqueous layer
was separated and extracted with CH2Cl2, and the combined
organic layer was dried over anhydrous Na2SO4. After the
solvent was removed, the crude product was purified by chro-
matography on silica gel (petroleum ether/ethyl acetate ) 1.5/
1).
Acknowledgment. We gratefully acknowledge the
National Natural Science Foundation of China for
financial support (20102002, 20332050).
Supporting Information Available: Characterization
data for ligands 1-5 and the sulfoxides. This material is
available free of charge via the Internet at http://pubs.acs.org.
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