Nb(salen)-catalyzed sulfoxidation

Article abstract of DOI:10.1055/s-2003-39321

Niobium(salen) complex was found to be an effective catalyst for asymmetric oxidation of various sulfides using urea-hydrogen peroxide as terminal oxidant.

Full text of DOI:10.1055/s-2003-39321

1046
LETTER
Nb(salen)-Catalyzed Sulfoxidation
N
b(salen)-Catal
a
yze
d
Sulfo
k
xidation anori Miyazaki, Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, CREST, Japan Science and Technology (JST),
Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Fax +81(92)6422607; E-mail: katsuscc@mbox.nc.kyushu-u.ac.jp
Received 27 March 2003
Table 1 Asymmetric Oxidation of Methyl Phenyl Sulfide with
Various Niobium Complexes as Catalyst
Abstract: Niobium(salen) complex was found to be an effective
catalyst for asymmetric oxidation of various sulfides using urea·hy-
drogen peroxide as terminal oxidant.
O–
S+
S
Key words: niobium, asymmetric catalysis, sulfoxidation, niobi-
um(salen) complex
NbCl3(dme) (5 mol%), ligand (5 mol%)
UHP, CH2Cl2 , MS 4 Å, r.t., 1 d
Entry
Ligand
% eea
Yield (%)
Confignb
Asymmetric catalysis has been a main topics of synthetic
organic chemistry in the last three decades, and catalysis
of chiral complexes of various metal ions has been exten-
sively studied. As the results, a wide variety of highly
enantioselective reactions have been realized.1 Neverthe-
less, asymmetric catalysis of some metal complexes is
still underdeveloped. One of such metals is niobium.
Some niobium complexes are known to show catalytic
performances such as Lewis acid and oxidizing catalysts.2
However, niobium-catalyzed asymmetric reactions are
limited to a few examples (Diels–Alder reaction3 and
epoxidation4), in which moderate enantioselectivity has
been achieved.
1
1
2
3
4
5
4
4
48
57
50
59
33
S
S
S
S
R
2
3
2
4
68
38
5c
a Determined by HPLC analysis using chiral stationary phase column
(Daicel Chiralcel OD-H, hexane–i-PrOH = 9:1).
b Determined by comparison of the elution order in the HPLC analysis
with that of the authentic sample.
c The reaction was carried out at 0 °C.
In order to explore asymmetric catalysis of niobium com-
plexes, we examined oxidation of sulfides using chiral
niobium complexes as catalyst. As niobium ion has been
reported to make complexes with dinitrogen, salen,3 and
porphyrin2a ligands, we prepared chiral niobium-Schiff
base and niobium(salen) complexes in situ by only mixing
equimolar amounts of NbCl3(dme) and Schiff base 1 or
salen ligands (2–5), and examined asymmetric sulfoxida-
tion using them as catalyst (Figure 1).5
Ph
N
Ph
(R)
N
(R)
Cl
N
N
Cl
t-Bu
OH HO
t-Bu
Cl Cl
t-Bu t-Bu
2
1
(R)
N
N
t-Bu
OH HO
t-Bu
We first examined oxidation of methyl phenyl sulfide us-
ing the niobium complexes as catalyst in the presence of
urea·hydrogen peroxide adduct (UHP) (Table 1).6 Com-
plexes bearing ligands 1–3 showed poor enantioselectivi-
ty, but complexes bearing 4 and 5 showed moderate
enantioselectivity. It is noteworthy that the sense of asym-
metric induction of these complexes is dictated by the
chirality of their diamine unit7 and the chirality at the bi-
naphthyl unit has a crucial influence on the magnitude of
the asymmetric induction. These results suggested that the
salen ligands (2–5) served as h4 ligands (vide infra).
t-Bu t-Bu
3
(S)
(R)
N
N
N
N
OH HO
Ar
OH HO
Ar
Ph
Ph
(aR)
(aS)
Ar=3,5-dimethylphenyl
5
4
Thus, we next examined the oxidation using niobium-
chiral ligands (6–8) complexes as catalyst (Table 2).
(aS,R)-4 and (aR,S)-7 are superior to (aR,R)-6 and (aR,R)-
Figure 1
8 (Figure 2) in terms of asymmetric induction, respective-
ly. This is sharp contrast to asymmetric sulfoxidation us-
ing Ti(salen) and Mn(salen) catalysts, in which (aR,R)
type of complexes are superior to the corresponding
Synlett 2003, No. 7, Print: 02 06 2003.
Art Id.1437-2096,E;2003,0,07,1046,1048,ftx,en;U05603ST.pdf.
© Georg Thieme Verlag Stuttgart · New York

LETTER
Nb(salen)-Catalyzed Sulfoxidation
1047
(aR,S) type of complexes.7 Again, the sense of asymme- action, especially at low catalyst concentration and ii) the
tric induction was dictated by the chirality of the diamine complex was equilibrated with its oligomer(s). In order to
unit.
avoid the participation of a niobium complex bearing no
chiral ligand, complexes were prepared in the presence of
excess amounts of ligand 4 and used for the oxidation. As
expected, maximum enantioselectivity was attained when
the complexes prepared with 1.5 or more equivalents of
ligands were used as the catalyst (Table 4).
Table 2 Asymmetric Oxidation of Methyl Phenyl Sulfide with
Niobium(salen) Complexes (6–8) as Catalysta
Entry
Ligand
% ee
27
Yield (%)
Confign
1
2
3
6
7
8
36
55
48
S
R
S
Table 4 Effect of the Ratio of NbCl3(dme) and 4 on Enantioselec-
tivity
59
O–
17
S+
S
a Reactions were carried out at room temperature in the presence of
MS 4 Å for 24 h.
NbCl3(dme) (8 mol%), 4, UHP
CH2Cl2 , MS 4 Å, –10 °C, 2 d
Entry
NbCl3(dme) : 4
1: 1
% ee
82
Yield (%)
Ph
N
Ph
(S or R)
(R)
1
2
3
4
81
93
88
94
N
N
N
1: 1.2
83
OH
Ph Ph
OH
HO
HO
Ph Ph
1: 1.5
86
(aR)
1: 2.0
86
(aS or aR)
4: (aS,R)
6: (aR,R)
We also explored the relationship between ee of the cata-
lyst and ee of the product, and observed a positive non-lin-
ear relationship (Figure 3). This suggested that NbCl3-4
complex existed in a equilibrium mixture of monomer and
oligomer(s), possibly dimmer.8–10
7: (aR,S)
8: (aR,R)
Figure 2
The reaction was next examined by using the niobium-4
complex in other solvents such as toluene, tetrahydro-
furan, and acetone, but the use of these solvents reduced
enantioselectivity.
The reaction was also carried out at various temperatures
in dichloromethane. Enantioselectivity increased as the
reaction temperature decreased, and the maximum enan-
tioselectivity was observed at –10 °C (Table 3). Further
lowering the temperature reduced not only enantioselec-
tivity but also chemical yield.
Table 3 Asymmetric Oxidation of Methyl Phenyl Sulfide with 4 as
Catalyst at Various Temperatures
Entry
Temp. ( °C) Time (h)
% ee
68
Yield (%)
1
2
3
4
25
0
24
48
48
72
59
52
58
21
69
–10
–20
79
Figure 3 Non-linear relationship between ees of product and of 4
(Reactions were carried out at room temperature).
75
Effect of catalyst-loading on enantioselectivity was also
examined. Enantioselectivity was improved until the
amount of the catalyst reached 8 mol% [19% ee with 2
mol% of the complex, 69% ee with 5 mol%, 76% ee with
8 mol%, 76% ee with 10 mol%; the reactions were carried
out at 0 °C in the presence of MS 4 Å]. The above results
suggested the following catalyst behaviors: i) the salen
ligand partly dissociated from niobium ion during the re-
Under the optimized conditions, we examined oxidation
of several other sulfides. It is noteworthy that the oxida-
tion not only of aryl alkyl sulfides but also of benzyl me-
thyl sulfide showed good level of enantioselectivity,
ranging from 77% to 86% ee (Table 5).11
Based on the FABMS analysis using m-nitrobenzyl alco-
hol as the matrix, we studied about the structure of the
Synlett 2003, No. 7, 1046–1048 ISSN 1234-567-89 © Thieme Stuttgart · New York

1048
T. Miyazaki, T. Katsuki
LETTER
Table 5 Asymmetric Oxidation of Various Sulfides with a Combi-
nation of NbCl3(dme)-4 as Catalyst
References
(1) (a) Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.;
Wiley-VCH: New York, 2000. (b) Comprehensive
Asymmetric Catalysis; Jacobsen, E. N.; Pfaltz, A.;
O–
S+
NbCl3(dme) (8 mol%), 4 (12 mol%)
S
R1
R2
R1
R2
UHP, CH2Cl2 , MS 4 Å, –10 °C, 2 d
Yamamoto, H., Eds.; Springer: Berlin, 2000.
(2) (a) Matsuda, Y.; Sakamoto, S.; Koshima, H.; Murakami, Y.
J. Am. Chem. Soc. 1985, 107, 6415. (b) Ushikubo, T. Cat.
Today 2000, 57, 331. Chen, H.; Dai, W.-L.; Jiang, A.-R.;
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Ji, M.; Choi, H.; Kee, M.; Ahn, K.-H.; Byeon, S.-H.; Baik,
W.; Koo, S. J. Org. Chem. 2001, 66, 8192. (d) Kapoor, M.
P.; Raj, A. Studies in Surface Science and Catalysis 2000,
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Kozhevnikov, I. V. J. Mol. Cat. A: Chem. 2000, 153, 103.
(3) Howarth, J.; Gillespie, K. Molecules 2000, 5, 993;
http://www.mdpi.org/molecules/papers/50800993.pdf.
(4) Colletti, S. L.; Halterman, R. L. J. Orgmet. Chem. 1993, 455,
99.
(5) Metallosalen complexes are usually prepared by mixing the
corresponding metal ion (usually in the form of metal halide
or metal alkoxide) and salen ligand under basic conditions or
by mixing metal ion and a salen ligand pretreated with NaH.
However, the niobium complex prepared from NbCl3(dme)
and salen ligand in these ways showed inferior catalytic
activity in terms of enantioselectivity (for examples, the
oxidation of methyl phenyl sulfides with these Nb-4
complexes at room temperature showed 12–46% ee).
(6) For the recent reviews on asymmetric sulfoxidation, see:
(a) Bolm, C.; Muniz, K.; Hildebrand, J. P. In Comprehen-
sive Asymmetric Catalysis, Vol. II; Jacobsen, E. N.; Pfaltz,
A.; Yamamoto, H., Eds.; Springer: Berlin, 1999, Chap. 19.
(b) Kagan, H. B. In Catalytic Asymmetric Synthesis, 2nd ed.;
Ojima, I., Ed.; Wiley-VCH: New York, 2000, Chap. 6C.
(7) Katsuki, T. Synlett 2003, 281.
Entry R1
R2
% ee
81b
77c
83d
84d
83d
86e
80d
Yield (%) Configna
1
2
3
4
5
6
7
p-MeOC6H4
Me
Me
Me
Me
Me
Et
94
93
94
92
65
58
61
S
S
S
S
S
S
S
p-O2NC6H4
p-BrC6H4
p-ClC6H4
o-BrC6H4
C6H5
C6H5CH2
Me
a Determined by comparison of the elution order in the HPLC analysis
with that of the respective authentic sample.
b Determined by HPLC analysis using chiral stationary phase column
(Daicel Chiralcel OB-H, hexane–i-PrOH = 2:1).
c Determined by HPLC analysis using chiral stationary phase column
(Daicel Chiralcel OJ-H, hexane–i-PrOH = 7:3).
d Determined by HPLC analysis using chiral stationary phase column
(Daicel Chiralcel OB-H, hexane–i-PrOH = 4:1).
e Determined by HPLC analysis using chiral stationary phase column
(Daicel Chiralcel OD-H, hexane-i-PrOH = 9:1).
complex generated in situ from NbCl3(dme) and 4. The
two peaks corresponding to 9 (FABMS, found: m/z =
933.42, calcd for [C60H44N2O3Nb]+: m/z = 933.24) and to
(8) (a) Puchot, C.; Samuel, O.; Dunach, E.; Zhao, S.; Agami, C.;
Kagan, H. B. J. Am. Chem. Soc. 1986, 108, 2353.
10 (FABMS, found: m/z
=
1221.49, calcd for
[C74H56N4O8Nb]+: m/z
=
1221.32) were detected
(b) Kagan, H. B. Adv. Synth. Cat. 2001, 343, 227.
(9) For examples of positive non-linear effect, see: (a) Oguni,
N.; Matsuda, Y.; Kaneko, T. J. Am. Chem. Soc. 1988, 110,
7877. (b) Kitamura, M.; Okada, S.; Suga, S.; Noyori, R. J.
Am. Chem. Soc. 1989, 111, 4028. (c) Mikami, K.; Terada,
M.; Nakai, T. J. Am. Chem. Soc. 1990, 112, 3949. (d) Soai,
K.; Niwa, S.; Hori, H. J. Chem. Soc., Chem. Commun. 1990,
982. (e) Soai, K.; Shibata, T. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; Wiley-VCH: New York, 2000,
699. (f) Furuno, H.; Hanamoto, T.; Sugimoto, Y.; Inanaga, J.
Org.Lett. 2000, 2, 49.
(Figure 4). This result demonstrated that niobium ion and
ligand 4 made a 1:1 complex and the niobium(III) ion was
oxidized to Nb(V) ion during the complex formation or
handling of the complex for MS measurement. This anal-
ysis agreed with the above-described experimental sug-
gestion that 4 was a h4 ligand.
+
+
(10) For the example of non-linear effect in metallosalen-
catalyzed oxidation, see: Saito, B.; Katsuki, T. Tetrahedron
Lett. 2001, 42, 8333.
O
NO2
O
N
O
N
O
N
O
N
O
Nb
Nb
(11) Typical experiment procedure is exemplified with
asymmetric oxidation of methyl phenyl sulfide with 4 as the
chiral ligand: ligand 4 (10 mg, 12 mmol) and NbCl3(dme)
(2.3 mg, 8.0 mmol) were dissolved in dichloromethane (2
mL) in a glovebox, and the solution was stirred for 2 h at
room temperature. After addition of MS 4 Å (ca. 20 mg), the
mixture was stirred for another 30 min. The mixture was
taken out of the glovebox and cooled to –10 °C under
nitrogen. To this mixture were added methyl phenyl sulfide
(12.0 mL, 0.10 mmol) and urea·hydrogen peroxide adduct
(UHP) (10.5 mg, 0.11 mmol) successively, and the mixture
was stirred for 2 days at the temperature. The mixture was
directly chromatographed on silica gel (hexane–ethyl acetate
= 1:1–1:19) to give methyl phenyl sulfoxide (12.4 mg, 88%).
The enantiomeric excess of the sulfoxide was determined to
be 86% ee by HPLC analysis using chiral stationary phase
column (Daicel Chiralcel OD-H, hexane–i-PrOH = 9:1).
Ph
Ph Ph
Ph
O
9
NO2
10
Figure 4
In conclusion, we were able to demonstrate that Nb(salen)
complex serves as the catalyst for asymmetric oxidation.
Further study on asymmetric catalysis of niobium com-
plexes is under way in our laboratory
Synlett 2003, No. 7, 1046–1048 ISSN 1234-567-89 © Thieme Stuttgart · New York