Asymmetric oxidation of dithioacetals and dithioketals catalyzed by a chiral vanadium complex

Article abstract of DOI:10.1055/s-1998-1948

Vanadium-catalyzed enantioselective oxidations of dithioacetals and dithioketals with 30% aqueous H₂O₂ give the corresponding monosulfoxides with enantioselectivities of up to 85% ee. The scope of this asymmetric catalysis has been i

Full text of DOI:10.1055/s-1998-1948

December 1998
SYNLETT
1327
Asymmetric Oxidation of Dithioacetals and Dithioketals Catalyzed by a Chiral Vanadium
1
Complex
Carsten Bolm*, Frank Bienewald
Institut für Organische Chemie der RWTH Aachen, Professor Pirlet-Str. 1, D-52056 Aachen, Germany.
Fax: +49 241 8888 391; e-mail Carsten.Bolm@RWTH-Aachen.de
Received 1 September 1998
Abstract: Vanadium-catalyzed enantioselective oxidations of dithio-
acetals and dithioketals with 30% aqueous H O give the corresponding
a two-phase solvent system with CH Cl as the organic component.
2 2
Table 1 summarizes the most significant results.
2
2
monosulfoxides with enantioselectivities of up to 85% ee. The scope of
this asymmetric catalysis has been investigated.
Sulfoxides have widely been used as chiral auxiliaries in asymmetric
2
synthesis. More recently, they have been introduced as ligands in
3,4
enantioselective metal catalysis and as bioactive substances for drugs
5
and plant protection. A number of methods are available for the
6
synthesis of optically active sulfoxides. The most common ones are
7
based on stereoselective transformations involving chiral auxiliaries
and asymmetric oxidations of sulfides with a modified Sharpless
8,9
reagent. In 1995, we introduced a chiral vanadium catalyst for
10
enantioselective sulfide oxidations. A number of groups have since
11
used this system for various asymmetric sulfur oxidations. Interesting
features of this system are: 1) the use of 30% aqueous H O as terminal
2
2
oxidant, 2) the simplicity of the reaction conditions, 3) its catalytic
efficiency (0.01 - 1 mol% of catalyst), 4) the use of simple ligands
derived from amino alcohols and salicylaldehydes, and 5) the ligand
12
acceleration of the catalysis. The oxidation of a variety of compounds
was studied, and the highest enantioselectivities have been achieved
with a combination of [VO(acac) ] and ligands (S)-3.
2
Various 1,3-dithianes were efficiently oxidized to give the
corresponding monosulfoxides in good yields. The enantiomeric
excesses were moderate to good depending on the substituents at the 2-
position. 1,3-Dithianes prepared from aromatic aldehydes (entries 1-7)
afforded products with higher asymmetric induction than those obtained
from compounds with branched aliphatic substituents (entries 8 and 9).
Only trans sulfoxides were formed from dithioacetals. Dithioketals
(entries 10 and 11) gave cis/trans mixtures with the former as the major
16
isomer.
The enantiomeric excesses of the cis sulfoxides were
significantly higher than those of the trans ones. Vanadium-catalyzed
oxidation of 2-phenyl-1,3-dithiolane (4) resulted in the formation of the
corresponding trans monosulfoxide (+)-5 (acetone) in 81% yield with
an enantioselectivity of 33% ee.
Whereas simple alkyl aryl sulfides were oxidized to the corresponding
sulfoxides with enantioselectivities in the range of 50-76% ee,
dithioacetal 1a afforded trans-sulfoxide (1R,2R)-2a with 85% ee. This
result is particularly noteworthy because the synthetic value of optically
active oxides derived from dithioacetals and dithioketones has been
13,14
described in a number of reports.
In order to investigate whether
this asymmetric vanadium catalysis could be generalized and with the
intention to expand the scope of the process we decided to study sulfur
15
oxidations of various substrates of type 1.
An early catalyst screening had revealed that ligand (S)-3a having a tert-
butyl substituent in the 4-position gave a higher asymmetric induction in
the oxidation of 1a than nitro-substituted (S)-3b. This behavior was in
contrast to oxidations of most alkyl aryl sulfides where catalysts with
(S)-3b as ligand gave higher ee-values. In further studies we therefore
Previously, we had demonstrated that even catalyst loadings of 0.01
mol% of the vanadium complex catalyzed the formation of optically
active sulfoxides. In a scale-up experiment we now oxidized 100
mmol of 1a using one tenth of the usual catalyst amount. With 0.1 mol%
of a catalyst prepared from (S)-3a, sulfoxide (1R,2R)-2a was obtained in
91% yield with an ee of 84%. Thus, compared to the 1 mmol test
reaction (Table 1, entry 2) the chemical yield was increased without
significantly lowering the enantiomeric excess (85 versus 84% ee).
10
employed in situ catalysts prepared from 1 mol% of [VO(acac) ] and
2
1.5 mol% of ligand (S)-3a. The reactions were performed at room
temperature on a 1 mmol scale using 1.1 equiv. of 30% aqueous H O in
2
2

1328
LETTERS
SYNLETT
Attempts to improve the enantioselectivity of the vanadium catalysis by
York, 1993; p 203. Kagan, H. B.; Luukas, T. In Transition Metals
for Organic Synthesis, Vol. 2; Beller, M.; Bolm, C., Eds.; Wiley-
VCH: Weinheim, 1998; p 361.
17
modifying the oxidant remained unsuccessful. H O is crucial for
2
2
high catalyst activity and good asymmetric induction. These results
51
together with those obtained from
V-NMR investigations and
(7) Andersen, K. K. Tetrahedron Lett. 1962, 93. Andersen, K. K. J.
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10
asymmetric amplification studies let us assume that vanadium(V)
species such as 6 having oxoperoxo groups could be involved in the
18
catalysis. The two orientations of the oxo moiety with respect to the
substituent R would then lead to diastereomeric arrangements 6a and
19
6b.
(8) Pitchen, P.; Duñach, E.; Deshmukh, M. N.; Kagan, H. B. J. Am.
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(9) Enzymes and microorganisms have also been employed for
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Allenmark, S. G.; Andersson, M. A. Tetrahedron: Asymmetry
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Based on this hypothesis our current efforts are directed towards a
refinement of the ligand structure to increase the enantioselectivity of
the oxygen transfer. In addition, we investigate whether complexes
20
bearing ligands of type 3 could also be used in other oxidations.
Acknowledgment. We are grateful to the Fonds der Chemischen
Industrie and the DFG for financial support of this work (SFB 260,
Graduiertenkolleg and Schwerpunktprogramm: Sauerstofftransfer-
Peroxidchemie) which was performed at the University of Marburg. We
thank the BASF for a doctoral fellowship for F. B. and the Degussa for
the donation of chemicals. We are indebted to Professor Pasta, Milano,
Italy, for providing chromatographic data for 2.
(10) Bolm, C.; Bienewald, F. Angew. Chem. 1995, 107, 2883; Angew.
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(15) The experimental procedure was identical to the one described in
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(16) Both isomers were separated by column chromatography. They
13
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2
2
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2
2
2 2
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<10% yield; H O -urea complex: 80% yield, 3% ee; H O -
NaOH: 0% yield.
2
2
2 2
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