Substituent effects and mechanism elucidation of enantioselective sulfoxidation catalyzed by vanadium Schiff base complexes

Article abstract of DOI:10.1039/b505237h

The effects of substituents of the Schiff base ligands on oxovanadium-catalyzed enantioselective sulfoxidation were first systematically studied, and a rational mechanism of enantioselective sulfoxidation based on our experimental data and the reported da

Full text of DOI:10.1039/b505237h

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L E T T E R
Substituent effects and mechanism elucidation of enantioselective
sulfoxidation catalyzed by vanadium Schiff base complexes
a
a
b
b
a
a
Qingle Zeng,* Heqing Wang, Wen Weng, Wenshi Lin, Yuxing Gao, Xiantong Huang
and Yufen Zhao*a
a
Key Laboratory for Chemical Biology of Fujian Province, Department of Chemistry, Xiamen
University, Xiamen, 361005, China. E-mail: qlzeng@xmu.edu.cn; yfzhao@xmu.edu.cn;
Fax: þ86-592-2185780; Tel: þ86-592-2185780
b
Department of Chemistry, Zhangzhou Teachers College, Zhangzhou, 363000, China
Received (in Durham, UK) 15th April 2005, Accepted 12th July 2005
First published as an Advance Article on the web 21st July 2005
The effects of substituents of the Schiff base ligands on oxo-
vanadium-catalyzed enantioselective sulfoxidation were first
systematically studied, and a rational mechanism of enantiose-
lective sulfoxidation based on our experimental data and the
reported data is proposed.
substituents of Schiff base ligands on enantioselective sulfox-
idation have not been systematically studied, and there is no
appropriate mechanism of vanadium-catalyzed enantioselec-
tive sulfoxidation. Here we evaluate the effects of substituents
of Schiff base ligands on enantioselective sulfoxidation.
Furthermore, based on our experimental results and the re-
ported data, a rational mechanism for vanadium-catalyzed
enantioselective sulfoxidation is proposed.
Introduction
Results and discussion
Chiral sulfoxides are widely used as chiral auxiliaries and as
1
chiral drugs. For example, the important intermediates thio-
sulfinate 1 and sulfinamide 2 have extensive application in
Chiral Schiff base ligands 8 were prepared from salicylaldehyde
analogues 6 and chiral amino alcohols 7, as shown in Scheme 3,
and were fully characterized by H NMR, C NMR, IR and
ESI-MS. The preformed vanadium complexes 9 were charac-
terized with IR. There existed all characteristic absorbing
1a
1
13
organic synthesis; esomeprazole 3 (the S form of omeprazole)
has a much better curative effect for stomach ulcers than the R
1d,2
form and racemic omeprazole (Scheme 1).
Recently, enantioselective oxidation of sulfides catalyzed by
ꢀ
1
peaks of C N (about 1625 cm ), and V O (987–995
Q Q
3
chiral complexes of transition metals, such as titanium, vana-
ꢀ1
cm ) for vanadium complexes 9. In addition, 9e was also
further characterized by FAB-HRMS. The FAB-FT-ICRMS
spectrum of 9e demonstrated a predominant peak at 336.0440
4
5
6
dium, iron, or manganese, has been extensively researched.
In particular, Bolm found that 30% H is an effective and
environmentally friendly oxidant for sulfoxidation catalyzed
2 2
O
ꢀ
([M ꢀ H] , C H NO V, calculated: 336.0446), which accords
1
6
15
4
by the in situ vanadium Schiff base complexes derived from
with the structure 9e as shown in Scheme 3. Thus, the
preformed vanadium complexes 9 probably have the general
structure as shown in Scheme 3.
4a
chiral amino alcohols (Scheme 2). Bolm found that the Schiff
base ligand derived from 3-tert-butyl-5-nitrosalicylaldehyde
with high steric hindrance gave higher ee values than that
The vanadium complexes 9 were applied to the asymmetric
7
sulfoxidation of thioanisole 4a, as shown in Scheme 2. The re-
4
a
derived from 5-nitrosalicylaldehyde. In a preliminary study,
we surprisingly discovered that some ligands derived from 3,5-
di-tert-butylsalicylaldehyde gave even lower enantioselectivity
than those derived from less sterically hindered salicylalde-
hyde. Furthermore, to our best knowledge, the effects of
sults of enantioselective sulfoxidation catalyzed by vanadium–
Schiff base complexes are listed in Table 1. For all of the
catalysts 9, the configurations of the products are all S form
(entries 1–13), which suggests all of the reactions had a similar
transitional state.
Surprisingly, for the tested complexes 9, when the hydrogen
atom on the 2,4-salicylaldehyde moieties was replaced by a
tert-butyl slightly lower ee values resulted, except for the ligand
derived from phenylglycinol (entries 1 vs. 2, 3 vs. 4, 5 vs. 6, 7 vs.
8
). The catalysts derived from valinol, isoleucinol and phenyl-
alaninol gave similar ee values (entries 1, 3, 5 or entries 2, 4, 6).
It is easy to understand that a low ee value was obtained when
the smaller alaninol derived catalyst 9i was adopted (entry 9).
Scheme 1 Some applications of sulfoxides.
Furthermore, there exists a certain relation between the R
and the ee values, that is, a small R group will cooperate
with a larger R , and a large R will cooperate with a smaller
. When R is bulky tert-butyl, bulky R groups, for example
-exo-bornyl, 2-phenylethyl, decreased the enantioselectivity.
It seems that there exists a bulky group on Berkessel’s Schiff
1
and
R
2
1
2
1
R
2
2
1
2
4b
base 10 (Scheme 4). But in fact, its stereo structure is like that
of 11, and the two naphthyl groups form a dihedral angle of a
certain degree. Thus, the naphthyl groups construct a shield,
Scheme 2 Vanadium-catalyzed enantioselective oxidation of sulfides
with aqueous H O .
2 2
T h i s j o u r n a l i s & T h e R o y a l S o c i e t y o f C h e m i s t r y a n d t h e
C e n t r e N a t i o n a l d e l a R e c h e r c h e S c i e n t i f i q u e 2 0 0 5
N e w J . C h e m . , 2 0 0 5 , 2 9 , 1 1 2 5 – 1 1 2 7
1125

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Scheme 3 Synthesis of Schiff base ligands 8 and vanadium–Schiff base complexes 9.
which limits the orientation of attack of anisole and thus
4c
4e
improves the enantioselectivity (11). Katsuki’s and Ahn’s
Schiff bases have similar stereo structures and demonstrate
better enantioselectivity in asymmetric sulfoxidation.
R
3
and R
tion (entries 8 and 10). In particular, when R
4
also affected the enantioselectivity of sulfoxida-
and R are both
3
4
bulky phenyls, a very low ee value was obtained. This is
because the symmetric bulky groups decrease the asymmetry
of the surroundings, and suggests that the V–O bond of the
amino alcohol moiety never breaks down during the sulfoxida-
tion. If V–O bond is easily broken during the reaction, little
influence on enantioselectivity is expected. The facts seem not
Scheme 4 Berkessel’s Schiff base (10) and its stereo structure.
8
to coincide with Bryliakov’s conclusion.
Then an electron pair from thioanisole coordinates with the
vanadium of the complex (13), which is the rate-determining
step. Due to steric repulsion, the other lone pair of electrons on
thioanisole will point to the amino alcohol moiety and the
bulky phenyl will locate between the R group and V(O H)
The complexes 9a, 9c and 9e were used in sulfoxidation of
p-chlorophenyl methyl sulfide 4b, and enantioselectivity of up
to 68.1% ee was achieved (entries 11–13).
9
10
Although Fujita’s and Ellman’s oxovanadium Schiff base
complexes contain oxovanadium alkoxide VO(OR) fragments,
a VO(OH) fragment exists in the structures of the algal bromo/
3
2
(13), which will determine the absolute configuration of the
product sulfoxide. The coordinated thioanisole will show a
partial positive charge, and the hydroperoxyl shows some
negative charge; and S–V–O is in a space-favorable triangle
(13). Therefore, the oxygen atom of hydroperoxyl attacks the
sulfur atom of sulfide (to produce the S form of the sulfoxide)
and an electron pair of the S–V bond moves to vanadium (14).
Sequentially, the electrons of the V–O(–O–H) bond will turn to
the S–O bond, which triggers the breaking of the O–O bond of
hydroperoxyl and then the hydroxyl of hydroperoxyl and the
vanadium form V–OH (14). Thus the S-sulfoxide is released
from the cycle and the five-coordinate oxovanadium complex
12 is recovered. A new catalytic cycle will occur.
1
1
iodoperoxidases and the fungal chloroperoxidase, which
suggests that the VO(OR) in Fujita’s and Ellman’s single
crystals will be converted into VO(OH) in the presence of
water. The FAB-FT-ICRMS spectrum of vanadium–Schiff
base complex 9e extracted from water verified the existence
of a VO(OH) fragment. Based on those facts, we deduced a
mechanism of enantioselective sulfoxidation as shown in
Scheme 5.
Five-coordinate oxovanadium Schiff base complex 12 is the
start of the catalytic cycle. The hydroxyl of the oxovanadium
complex 12 is in exchange with hydroperoxide to release H O.
2
a
Table 1 Enantioselective sulfoxidation catalyzed by chiral vanadium–Schiff base complexes (in italics when R
1
¼ t-Bu)
b
c
Entry
Complex
Substrate
Yield (%)
Ee (%)
1
2
3
4
5
6
7
8
9
9a
9b
9c
9d
9e
9f
4a
4a
4a
4a
4a
4a
4a
4a
4a
4a
4b
4b
4b
78.1
82.6
86.3
63.0
76.0
93.5
67.4
88.7
51.6
75.4
74.4
68.2
71.9
55.9
51.4
55.7
48.6
59.2
45.3
48.4
45.1
6.7
9g
9h
9i
d
10
11
12
13
a
9j
2.9 (3.6)
68.1
9a
9c
9e
57.5
60.1
2 2 2 2
Reaction conditions: vanadium Schiff base complexes (0.01 mmol), sulfide (1 mmol) and aqueous H O (30%; 1.1 mmol) in CH Cl (2 ml) in an
b
c
ice–water bath (about 4 1C) for 4 h, unless otherwise mentioned. Isolated yield after column chromatography. The ee values were measured on
the isolated product and determined by HPLC analysis on a Daicel chiralcel OD-H column. The absolute configurations were assigned by
d
comparing optical rotations and/or HPLC elution order with known literature data. All configurations of sulfoxides are S form. The datum was
obtained using an ice–salt bath for 5 h.
1
126
N e w J . C h e m . , 2 0 0 5 , 2 9 , 1 1 2 5 – 1 1 2 7

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Scheme 5 Proposed mechanism for enantioselective sulfoxidation catalyzed by vanadium–Schiff base complexes.
The oxygen atoms of the product sulfoxide and the hydroxyl
in the oxovanadium complex all are from H , which agrees
with Ellman’s observation.
4
5
(a) C. Bolm and F. Bienewald, Angew. Chem., Int. Ed. Engl., 1995,
4, 2640–2642; (b) H. Vetter and A. Berkessel, Tetrahedron Lett.,
3
2 2
O
1
0
1998, 39, 1741–1744; (c) C. Ohta, H. Shimizu, A. Kondo and T.
Katsuki, Synlett, 2002, 161–163; (d) R. Pelotier, M. S. Anson, I. B.
Campbell, S. J. F. Macdonald, G. Priem and R. F. W. Jackson,
Synlett, 2002, 1055; (e) Y. C. Jeong, S. Choi, Y. D. Hwang and
K. H. Ahn, Tetrahedron Lett., 2004, 45, 9249–9252.
(a) J. Legros and C. Bolm, Angew. Chem., Int. Ed., 2003, 42,
5487–5489; (b) J. Legros and C. Bolm, Angew. Chem., Int.
Ed., 2004, 43, 4225–4228; (c) Y. Mekmouche, H. Hummel,
R. Y. N. Ho, L. Que, Jr., V. Schunemann, F. Thomas, A. X.
Trautwein, C. Lebrun, K. Gorgy, J. C. Lepretre, M. N. Collomb,
A. Deronzier, M. Fontecave and S. Menage, Chem. Eur. J., 2002,
Conclusion
The effects of substituents of Schiff base ligands on enantio-
selective sulfoxidation were systematically examined. Some inter-
esting results were obtained. Based on the experimental data
and the reported facts, a reasonable mechanism of enantio-
selective sulfoxidation was proposed.
8
, 1196–1204.
(a) M. Palucki, P. Hanson and E. N. Jacobsen, Tetrahedron Lett.,
992, 33, 7111–7114; (b) K. Noda, N. Hosoya, K. Yanai, R. Irie
6
7
Acknowledgements
1
The authors would like to thank National Foundation Science
and Technology (No. 20132020), Fujian Foundation of Science
and Technology (No. 2001F008) and Fujian Key Foundation
of Science and Technology (No. 2002H011) for supporting
this work.
and T. Katsuki, Tetrahedron Lett., 1994, 35, 1887; (c) H. Sasaki,
R. Irie, Y. Ito and T. Katsuki, Synlett, 1994, 356.
The general procedure for the sulfoxidation reactions is as follows.
Vanadium–Schiff base complex (0.01 mmol) and 1 mmol sulfide
were dissolved in CH
mixture, 30% H (0.13 mL, 1.1 mmol) was added dropwise. The
mixture was stirred for 2 to 16 h in an ice–water bath. The
resulting solution was diluted with CH Cl and washed with water
and then with saturated NaCl solution. The organic layer was
dried over anhydrous MgSO , filtered and concentrated under
2 2
Cl (2 mL) with an ice–water bath. To the
2
O
2
2
2
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