Enantioselective oxidation of sulfides with hydrogen peroxide catalyzed by vanadium complex of sterically hindered chiral Schiff bases

Article abstract of DOI:10.1016/j.tetlet.2004.10.070

Sterically hindered chiral Schiff base ligands 4a-d were prepared from an aldehyde derived from BINOL. The vanadium complexes of the ligands catalyze an efficient, enantioselective H₂O₂-promoted sulfoxidation of alkyl aryl sulfides, and enantioselectivities as high as 98-99% ee are observed in the sulfoxidation of benzyl aryl sulfides.

Full text of DOI:10.1016/j.tetlet.2004.10.070

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 9249–9252
Enantioselective oxidation of sulfides with hydrogen peroxide
catalyzed by vanadium complex of sterically hindered chiral
Schiff bases
Yong-Chul Jeong, Soojin Choi, Yao Dong Hwang and Kwang-Hyun Ahn*
College of Environment and Applied Chemistry, Institute of Natural Science, Kyung Hee University, Yongin City 449-701, South Korea
Received 9 September 2004; revised 11 October 2004; accepted 13 October 2004
Abstract—Sterically hindered chiral Schiff base ligands 4a–d were prepared from an aldehyde derived from BINOL. The vanadium
complexes of the ligands catalyze an efficient, enantioselective H O -promoted sulfoxidation of alkyl aryl sulfides, and enantioselec-
2 2
tivities as high as 98–99% ee are observed in the sulfoxidation of benzyl aryl sulfides.
Ó 2004 Elsevier Ltd. All rights reserved.
Chiral sulfoxides are an important class of compounds
as chiral auxiliaries in asymmetric carbon–carbon bond
sulfoxides. Especially, the catalytic system of a chiral
7
vanadium-tridentate ligand 1 reported by Bolm
b
1
forming reactions and as bioactive ingredients in the
2
has received a great attention recently because of its
simplicity and high activity using hydrogen peroxide,
an environmentally benign oxidant (Scheme 1). The
enantioselectivity of the reaction has been further im-
pharmaceutical industry. As part of our research for
3
the synthesis of lansoprazole, a drug used to heal and
relieve symptoms of gastric or duodenal ulcers, we have
been interested in the synthesis of chiral sulfoxides, par-
ticularly using an asymmetric oxidation of sulfides. The
enantioselective oxidation of sulfides catalyzed by chiral
7
d
7e
proved by Berkessel and Katsuki employing ligands
derived from a chiral binaphthalene (2) and a chiral
biphenyl (3), respectively.
4
complexes of transition metals such as titanium, man-
5
6
7
ganese, iron or vanadium has been extensively studied
in recent years for the synthesis of optically active
We were particularly interested in Berkesselꢀs ligand
because the catalytic system might be improved by
O-
S
VO(acac)2/ ligand
S
+
Ph
Me
H2O2, CH2Cl2
Ph
Me
(
S)
o
RmT or 0 C
t-Bu
t-Bu
R1
N
OH
N
OH
N
OH
R2
OH
t-Bu
OH
OH
Ph
2
3
1
Scheme 1.
Keywords: Enantioselective sulfoxidation; Chiral sulfoxide; Hydrogen peroxide.
*
Corresponding author. Tel.: +82 312012447; fax: +82 312027337; e-mail: khahn@khu.ac.kr
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.10.070

9250
Y.-C. Jeong et al. / Tetrahedron Letters 45 (2004) 9249–9252
9
8
introducing a substituent onto the binaphthyl subunit
such as ligand 4 (Scheme 2). It had been reported that
the steric effect of the substituent, R of ligand 1 is
1
base (R,S)-4a, prepared from the aldehyde (R)-5a de-
rived from (R)-BINOL and (S)-t-leucinol, was applied
to the asymmetric sulfoxidation of thioanisole at room
1
0
important to get a high enantioselectivity in the vana-
h
temperature. The reaction produced (S)-methyl phenyl
sulfoxide in 86% yield with an enantioselectivity of 82%
ee (Table 1, entry 1), which is better than the reported
result obtained with 2 (71% ee). Since the ligand 4a
showed a good enantioselectivity at room temperature,
we decided to study the asymmetric sulfoxidation in
detail. At first, we ran the reaction at 0°C to see the
temperature effect with thioanisole and obtained the
enantioselectivity of 86% ee (entry 2). The result is better
7
dium catalyzed asymmetric oxidation of sulfides. We
thought that R as well as R of the ligand 4 might also
2
1
provide an improvement in the enantioselectivity as had
been observed in the asymmetric epoxidation of olefins
8
catalyzed by a chiral manganese salen complex. Thus,
here we want to report the enantioselective sulfoxidation
of aryl sulfides catalyzed by chiral vanadium complexes
derived from the chiral Schiff base 4.
7
d
than the Berkesselꢀs result (78% ee) studied with ligand
7
e
Initially, we expected that the ligand 4a, which contains
sterically hindered t-butyl group at R and t-butyl ester
2 at 0°C, and similar to the results reported by Katsuki
and Anson. Interestingly, (S,S)-4a whose binaphthyl
subunit is in S-configuration also gave the same (S)-iso-
mer of methyl phenyl sulfoxide as the major enantiomer,
7f
1
at R might give a good enantioselectivity in the vana-
2
dium catalyzed oxidation of sulfide. Thus, the Schiff-
R1
N
OH
O
R1
OH
R2
OH
+
R2
H N
OH
2
4
5
6
(
(
(
(
R,S)-4a, R1 = t-Bu, R2 = -OOC-t-Bu
R,S)-4b, R1 = t-Bu, R2 = -OOC-CH3
R,S)-4c, R1 = t-Bu, R2 = -O-SiPh2(t-Bu)
R)-4d, R = H, R = -OOC-t-Bu
5
5
5
a, R2 = -OOC-t-Bu
b, R = -OOC-CH
2
3
c, R2 = -O-SiPh2(t-Bu)
1
2
Scheme 2.
Table 1. Asymmetric sulfoxidation of methyl aryl sulfide
O-
S
S
+
CH3
VO(acac)2 (1mol%)/ Ligand (1.5mol%)
CH3
o
H2O2 (1.1 eq.), CH2Cl2, 0 C
X
X
a
Yield (%)
b
Ee (%)
c
Entry
Sulfide
–S–CH
Schiff base
Config.
d
1
2
3
4
5
6
7
8
9
C
6
H
5
3
(R,S)-4a
(R,S)-4a
(S,S)-4a
(R,S)-4b
(R,S)-4c
(R,S)-4a
(R,S)-4a
(R,S)-4a
(R,S)-4a
(R,S)-4a
(S,S)-4a
(R,S)-4b
(R)-4d
86
90
95
95
66
82
86
77
76
78
89
79
46
82
S
S
S
S
S
S
S
S
S
S
S
S
86
72
78
45
77
87
p-MeO–C
p-Me–C
p-Br–C
p-NO –C
o-Br–C
6
H
4
–S–CH
–S–CH
–S–CH
–S–CH
–S–CH
3
6
H
4
3
e
6
H
4
3
73
f
2
6
H
4
3
68
10
11
12
13
6
H
4
3
31
42
40
d
C
6
H
5
–S–CH
3
0
a
b
c
d
e
f
Isolated yield.
Determined by HPLC with a Daicel Chiralcel OD column.
Absolute configuration of the major product was determined by comparison of its sign of optical rotation with literature data.
Room temperature reaction.
1
Determined by H NMR (400MHz) analysis using (R)-(+)-2,2 -dihydroxy-1,1 -binaphthyl as a shift reagent.
0
0
1
Determined by H NMR (400MHz) analysis using (R)-(ꢀ)-2,2,2-trifluoro-1-(9-anthryl)ethanol as a shift reagent.

Y.-C. Jeong et al. / Tetrahedron Letters 45 (2004) 9249–9252
9251
however, with an inferior enantioselectivity (72% ee,
entry 3). As shown in entry 13, the ligand without a chiral
center at the imine subunit such as 4d did not give any
enantioselectivity in the reaction. Thus, the configura-
tion of sulfoxide must be greatly affected by the config-
uration of aminoalcohol used in the ligand synthesis. To
improve the enantioselectivity, a sterically hindered sub-
with the benzyl group of incoming aryl benzyl sulfides
under the catalytic condition to give the high face selec-
tion in the sulfide oxidation.
In summary, we were able to optimize the Berkesselꢀs
catalytic system for the asymmetric oxidation of alkyl
aryl sulfides. The Schiff base ligand 4a showed an excel-
lent enantioselectivity reaching 99% ee in the oxidation
of benzyl aryl sulfide.
stituent R such as tert-butyldiphenylsilyloxy group was
2
introduced (ligand 4c). However, the selectivity obtained
with 4c was low (entry 5) and even worse than the enan-
tioselectivity obtained with 4b (entry 4) containing ace-
tyl group at R , indicating that a proper steric
2
Acknowledgements
hindrance has to be introduced at R . Thus, ligand 4a
2
showed the best enantioselectivity in the oxidation of
thioanisole among the ligands that we prepared.
This work was supported by the Basic Research Pro-
gram of the Korea Science & Engineering Foundation
(
R01–2003–000–10187–0).
Oxidations of various alkyl substituted-aryl sulfides
were also examined with ligand 4a (entry 6–11). Most
of the reactions showed good enantioselectivities reach-
ing 87% ee (entry 7) except ortho-substituted substrates
References and notes
. (a) Carreno, M. C. Chem. Rev. 1995, 95, 1717; (b)
Colobert, F.; Tito, A.; Khiar, N.; Denni, D.; Media, M.
A.; Martin-Lomas, M.; Ruano, J.-L.; Solladie, G. J. Org.
Chem. 1998, 63, 8918; (c) Carreno, M. C.; Ribagorda, M.;
Posner, G. H. Angew. Chem., Int. Ed. 2002, 41, 2753; (d)
Marino, J. P.; Mcclure, M. S.; Holub, D. P.; Comasseto, J.
V.; Tucci, F. C. J. Am. Chem. Soc. 2002, 124, 1664.
. (a) Tanaka, M.; Yamazaki, H.; Hakusui, H.; Nakamichi,
N.; Sekino, H. Chirality 1997, 9, 17; (b) Hutton, C. A.;
White, J. M. Tetrahedron Lett. 1997, 38, 1643; (c) Holland,
H. L.; Brown, F. M. Tetrahedron: Asymmetry 1998, 9, 535;
(
entries 10–12). Sulfones expecting from an oxidation
1
2
of the corresponding sulfoxides were formed only to a
minor extent (less than 3%). Interestingly, (S,S)-4a was
shown to be the better catalyst compared to (R,S)-4a
in the oxidation of methyl o-bromophenyl sulfide (en-
tries 10 and 11). The result contrasts with the oxidation
of thioanisole (entries 2 and 3).
We also examined the oxidation of benzyl 4-substituted
phenyl sulfides with ligand 4a (Table 2). Surprisingly,
the reaction proceeded with an excellent enantioselectiv-
ity. In the sulfoxidation of benzyl phenyl sulfide, (S)-
benzyl phenyl sulfoxide was obtained in 99% ee (entry
(
d) Cotton, H.; Elebring, T.; Larsson, M.; Li, L.;
Sorensen, H.; von Unge, S. Tetrahedron: Asymmetry
2000, 11, 3819.
3. Ahn, K.-H.; Kim, H.; Kim, J. R.; Jeong, S. C.; Kang, T.
1
). This is the best record that has been observed in
S.; Shin, H. T.; Lim, G. J. Bull. Korean Chem. Soc. 2002,
2
the sulfoxidation of benzyl phenyl sulfide with a
vanadium catalyst. Further, in the oxidation of benzyl
3, 626.
4
. (a) Pitchen, P.; Deshmukh, M. N.; Duach, E.; Kagan, H.
B. J. Am. Chem. Soc. 1984, 106, 8188; (b) Di Furia, F.;
Modena, G.; Seraglia, R. Synthesis 1984, 325; (c) Kagan,
H. B.; Rebiere, F. Synlett 1990, 643; (d) Komatsu, N.;
Nishibayashi, Y.; Sugita, T.; Uemura, S. Tetrahedron Lett.
4
oxide, a versatile intermediate for the syntheses of vari-
-bromophenyl sulfide, (S)-benzyl 4-bromophenyl sulf-
4
l
ous chiral sulfoxides using a substitution reaction was
also obtained in 98% ee (entry 3). These results demon-
strate the potential of our catalytic system. It is difficult
to provide a reasonable explanation for the high enan-
tioselectivities observed with our catalytic system at
the present stage. However, the low enantioselectivity
obtained with (R,S)-4b (entry 5) suggests that the piva-
loyl group of (R,S)-4a-vanadium catalyst may interact
1
992, 33, 5391; (e) Komatsu, N.; Hashizume, M.; Sugita,
T.; Uemura, S. J. Org. Chem. 1993, 58, 4529; (f) Brunel,
J.-M.; Luukas, T. O.; Kagan, H. B. Tetrahedron: Asym-
metry 1998, 9, 1941; (g) Donnoli, M. I.; Superchi, S.;
Rosini, C. J. Org. Chem. 1998, 63, 9392; (h) Bonchio, M.;
Licini, G.; Modena, G.; Bortolini, O.; Moro, S.; Nugent,
W. A. J. Am. Chem. Soc. 1999, 121, 6258; (i) Saito, B.;
Katsuki, T. Tetrahedron Lett. 2001, 42, 3873; (j) Saito, B.;
Katsuki, T. Tetrahedron Lett. 2001, 42, 8333; (k) Massa,
A.; Siniscalchi, F. R.; Bugatti, V.; Lattanzi, A.; Scettri, A.
Tetrahedron: Asymmetry 2002, 13, 1277; (l) Capozzi, M.
A. M.; Cardellicchio, C.; Naso, F.; Rosito, V. J. Org.
Chem. 2002, 67, 7289; (m) Tanaka, T.; Saito, B.; Katsuki,
T. Tetrahedron Lett. 2002, 43, 3259.
Table 2. Asymmetric sulfoxidation of aryl benzyl sulfide
O-
S
S
Ph VO(acac)2 (2 mol%)/ Ligand (3 mol%)
+
Ar
Ph
o
Ar
H2O2 (1.1 eq.), CH2Cl2, 0 C
a
Yield (%) Ee (%) Config.
b
c
Entry Ligand
Ar
5. (a) Palucki, M.; Hanson, P.; Jacobsen, E. N. Tetrahedron
Lett. 1992, 33, 7111; (b) Noda, K.; Hosoya, N.; Irie, R.;
Yamashita, Y.; Katsuki, T. Tetrahedron 1994, 50, 9609; (c)
Chellamani, A.; Kylanthaipandi, P.; Rajagopal, S. J. Org.
Chem. 1999, 64, 2232.
1
2
3
4
5
(R,S)-4a Ph
78
90
85
81
67
99
94
98
67
69
S
S
S
S
S
6 4
(R,S)-4a p-MeC H
6 4
(R,S)-4a p-BrC H
(R,S)-4a p-MeOC
6 4
H
6
. (a) Legros, J.; Bolm, C. Angew. Chem., Int. Ed. 2003, 42,
487; (b) Legros, J.; Bolm, C. Angew. Chem., Int. Ed. 2004,
43, 4225.
(R,S)-4b Ph
5
a
Isolated yield.
Determined by HPLC using Daicel Chiralcel OJ column.
b
c
7. (a) Nakajima, K.; Kojima, K.; Fujita, J. J. Chem. Lett.
1986, 1483; (b) Bolm, C.; Binewald, F. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 2640; (c) Cogan, A. D.; Liu, G.;
Absolute configuration of the major product was determined by
comparison of its sign of optical rotation with literature data.

9252
Y.-C. Jeong et al. / Tetrahedron Letters 45 (2004) 9249–9252
1
3
Kim, K.; Backes, B. J.; Ellman, J. A. J. Am. Chem. Soc.
998, 120, 8011; (d) Vetter, A. H.; Berkessel, A. Tetra-
2.73Hz, 1H), 1.63 (s, 2H), 0.97 (s, 9H), 0.78 (s, 9H);
C
1
NMR (CDCl , 100MHz) d 176.2, 165.7, 154.5, 146.9,
3
hedron Lett. 1998, 39, 1741; (e) Ohta, C.; Shimizu, H.;
Kondo, A.; Katsuki, T. Synlett 2002, 161; (f) Pelotier, B.;
Anson, M. S.; Campbell, I. B.; Macdonald, S. J. F.; Priem,
G. Synlett 2002, 1055; (g) Bolm, C. Coord. Chem. Rev.
135.0, 133.6, 133.4, 131.7, 129.0, 128.3, 128.2, 128.1, 127.1,
126.3, 126.1, 125.3, 125.0, 124.4, 123.4, 122.0, 120.2, 115.6,
81.7, 62.4, 38.6, 33.3, 27.1, 26.5. Anal. Calcd for
32 4 2
C H35NO ÆH O: C, 74.54; H, 7.23; N, 2.72. Found C,
2003, 237, 245; (h) Skarzewski, J.; Ostrycharz, E.; Sied-
lecka, R. Tetrahedron: Asymmetry 1999, 10, 3457.
. Ahn, K.-H.; Park, S. W.; Choi, S.; Kim, H.-J.; Moon, C. J.
Tetrahedron Lett. 2001, 42, 2485.
74.76; H, 6.85; N, 2.63%.
10. The general procedure used for the sulfoxidation reactions
is as follows: Vanadyl acetylacetonate (5.3mg, 0.02mmol),
and a ligand (0.03mmol) were dissolved in CH Cl (3mL),
8
2
2
9
. A solution of 5a (100mg, 0.25mmol) and (S)-t-leucinol
(
and stirred 10min at room temperature. After the addition
of a sulfide (1.0mmol), 30% H (0.13mL, 1.1mmol) was
added. The mixture was stirred for 24h at room temper-
35mg, 0.30mmol) in ethanol (6mL) was stirred at room
temperature. After 3h, the solution was concentrated
under reduced pressure. Flash column chromatography of
2 2
O
ature or 0°C and quenched with satd Na SO solution.
2
3
2
D
2
the residue provided 4a (115mg, 92%): mp 97–98°C; ½aꢁ
2 2
The resulting solution was extracted with CH Cl . The
1
); H NMR (CDCl
+
17 (c 0.5, CHCl , 400MHz) d 8.61 (s,
H), 8.01–7.94 (m, 3H), 7.86–7.84 (m, 1H), 7.48–7.40 (m,
3
3
4
organic layer was briefly dried over anhydrous MgSO ,
1
3
1
filtered and concentrated under reduced pressure. The
crude product was purified by flash column chromato-
graphy.
H), 7.34–7.26 (m, 3H), 7.12–7.11 (m, 1H), 3.97–3.91 (m,
1 2
H), 3.74–3.70 (m, 1H), 3.03 (dd, J = 9.44Hz, J =