Asymmetric oxidation catalysis by a chiral Al(salalen) complex: Highly enantioselective oxidation of sulfides with aqueous hydrogen peroxide

Article abstract of DOI:10.1002/anie.200700792

(Chemical Equation Presented) Not afraid to get wet: Aluminum(salalen) complexes were found to be water compatible and therefore suitable catalysts for asymmetric oxidation with aqueous hydrogen peroxide. A variety of sulfides underwent the title reaction in the presence of the aluminum(salalen) complex shown to the give the desired sulfoxides with high to excellent enantioselectivity (see scheme; Bn = benzyl).

Full text of DOI:10.1002/anie.200700792

Angewandte
Chemie
DOI: 10.1002/anie.200700792
Asymmetric Catalysis
Asymmetric Oxidation Catalysis by a Chiral Al(salalen) Complex:
Highly Enantioselective Oxidation of Sulfides with Aqueous Hydrogen
Peroxide**
Tetsufumi Yamaguchi, Kazuhiro Matsumoto, Bunnai Saito, and Tsutomu Katsuki*
Chiral aluminum complexes have become established as
promising Lewis acid catalysts for a wide variety of asym-
metric reactions.[1,2] In contrast, asymmetric oxidation catal-
ysis by aluminum complexes has scarcely been developed. As
a rare example, Bolm and co-workers reported an Al-
catalyzed asymmetric Baeyer–Villiger oxidation with an
alkyl hydroperoxide as the oxidant. High enantioselectivity
was observed in the reaction, which required anhydrous
conditions.[3] To the best of our knowledge, no chiral
aluminum catalyst has been reported for a highly enantiose-
lective oxidation with aqueous hydrogen peroxide as the
oxidant.[4] Herein, we describe the development of an
asymmetric oxidation of sulfides with aqueous hydrogen
peroxide in the presence of a chiral Al(salalen) complex.[5–12]
Recently, we reported the first synthesis of the chiral
Al(salalen) complex 1 and its asymmetric catalysis of hydro-
the complex to further explore new catalysis of Al(salalen)
complexes. During the course of this investigation, we found
that the treatment of an Al(salalen) complex with water
provided
a new water-compatible Al(salalen) complex.
Although the complex could not be isolated, it occurred to
us that Al(salalen) complexes should serve as catalysts under
aqueous conditions. Thus, we investigated the use of the
complexes as catalysts for asymmetric oxidation with aqueous
hydrogen peroxide as the oxidant.
First, we examined the asymmetric oxidation of thioani-
sole with 30% hydrogen peroxide (1.1 equiv) in the presence
of Al(salalen) complexes (2 mol%) and found that the
structure and configuration of the complexes affected signifi-
cantly their catalytic and asymmetry-inducing abilities
(Table 1). The reaction with complex 1 was only modestly
selective and poorly reproducible. In contrast, complexes 2–5,
which contain a binol-based salalen ligand (binol = 1,1’-
binaphthalene-2,2’-diol), showed higher catalytic activity
with good reproducibility in the presence of a phosphate
buffer. The reproducibility of the reaction with 1 was not
improved by the addition of the phosphate buffer. Asym-
metric induction by the (aR,R,R) complexes 2 and 3 was
modest; however, much higher levels of asymmetric induction
Table 1: Al(salalen)-catalyzed asymmetric oxidation of thioanisole.
phosphonylation.[13] Reactions with both aldehydes and
imines furnished the corresponding products with high to
excellent enantioselectivities. We decided to modify and tune
Entry Cat. Solvent Conv. [%][a]
Yield [%][b]
sulfoxide sulfone
ee [%][c,d]
1
2
3
4
5
6
7
8
9
1
2
3
4
5
5
5
5
5
5
5
MeOH 40–60
MeOH 70
MeOH 55
MeOH 86
MeOH 99
40–60
64
2–10 20–60 (S)
6
4
46 (S)
10 (R)
89 (S)
98 (S)
98 (S)
97 (S)
98 (S)
99 (S)
99 (S)
94 (S)
[*] T. Yamaguchi, K. Matsumoto, Dr. B. Saito,[+] Prof. T. Katsuki
Department of Chemistry, Faculty of Science
Graduate School, Kyushu University
51
78
90
78
68
66
78
59
8
9
EtOH
AcOEt
THF
92
85
85
81
14
17
18
13
25
<1
Hakozaki, Higashi-ku, Fukuoka 812-8581 (Japan)
Fax: (+81)92-642-2607
E-mail: katsuscc@mbox.nc.kyushu-u.ac.jp
[+] Current address:
CH2Cl2
10
toluene 84
MeOH 33
Department of Chemistry
Massachusetts Institute of Technology
Cambridge, MA 02139-4307 (USA)
11[e]
32
1
[a] The conversion was determined by H NMR spectroscopic analysis
(400 MHz). [b] Yields were determined by 1H NMR spectroscopic
analysis (400 MHz). [c] The ee value was determined by HPLC analysis
on a chiral phase (Daicel Chiralcel OB-H). [d] The absolute configuration
was determined by HPLC analysis by comparison of the elution order of
the enantiomers with that of an authentic sample. [e] Reaction time: 1 h.
[**] Financial support (Specially Promoted Research18002011) through
a Grant-in-Aid for Scientific Researchfrom the Ministry of
Education, Science, and Culture, Japan is gratefully acknowledged.
K.M. and B.S. are grateful for JSPS ResearchFellowships for Young
Scientists. Salalen refers to a hybrid salan/salen tetradentate ligand.
Angew. Chem. Int. Ed. 2007, 46, 4729 –4731
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4729

Communications
were observed with the (aR,S,S) complexes 4 and 5.[14] In
particular, the reaction with complex 5 proceeded smoothly
with high enantioselectivity to give the product with 98% ee.
Although excellent enantioselectivity was observed regard-
less of the solvent used (Table 1, entries 5–10), the reaction in
methanol gave the desired sulfoxide in the highest yield
accompanied by the smallest amount of the sulfone over-
oxidation product (entry 5). Although the production of the
sulfone was suppressed when the reaction time was
decreased, the sulfoxide was then formed in lower yield
with a somewhat lower ee value (Table 1, entry 11).
Scheme 1. Asymmetric oxidation of sulfides withthe Al(salalen) com-
plex 5.
The scope of the reaction with respect to the sulfide
substrate was investigated with complex 5 under the opti-
mized conditions (Table 2). All aryl methyl sulfides under-
of racemic methyl phenyl sulfoxide (Scheme 2) and found
that the R sulfoxide was oxidized preferentially to the sulfone
with a relative ratio of 4.6. As the S enantiomer was produced
Table 2: Asymmetric oxidation of various aryl methyl sulfides with the
Al(salalen) complex 5.[a]
Entry
Ar
Yield [%]
sulfoxide[b]
ee [%][d]
sulfone[c]
1
2
3
4
C6H5
p-ClC6H4
86
83
82
82
82
91
84
81
9
9
9
8
1
<1
2
10
98 (S)[e]
97 (S)[e]
98 (S)[e]
97 (S)[e]
99 (S)[e]
99 (S)[e]
99 (S)[g]
99 (S)[e]
Scheme 2. Kinetic resolution of racemic methyl phenyl sulfoxide.
p-MeC6H4
p-MeOC6H4
o-MeOC6H4
o-MeOC6H4
o-NO2C6H4
m-BrC6H4
5
6[f]
7
selectively in the oxidation of thioanisole, this result explains
the gradual increase in the ee value of the sulfoxide as the
reaction proceeds: The synergistic combination of the initial
highly enantioselective oxidation of the sulfide with the
following oxidative kinetic resolution process is responsible
for the high ee values observed for the sulfoxides.[6e,f,15]
In conclusion, we have introduced the concept of water-
compatible aluminum(salalen) complexes and developed a
highly enantioselective oxidation of sulfides with aqueous
hydrogen peroxide. A variety of sulfides were converted
smoothly into the corresponding sulfoxides with good to
excellent enantioselectivity. The elucidation of the reaction
mechanism and further investigation of the oxidation catalysis
of Al(salalen) complexes are in progress.
8
[a] The reaction was carried out on a 0.20-mmol scale, unless otherwise
noted. [b] Yield of the isolated sulfoxide. [c] The yield of the sulfone was
determined by 1H NMR spectroscopic analysis (400 MHz). [d] The
absolute configuration was determined by HPLC analysis by comparison
of the elution order of the enantiomers with that of an authentic sample.
[e] The ee value was determined by HPLC analysis on a chiral phase
(Daicel Chiralcel OB-H). [f] The reaction was carried out on a 10.0-mmol
scale. [g] The ee value was determined by HPLC analysis on a chiral
phase (Daicel Chiralcel OD-H).
went the reaction to give the desired products in high yield
with excellent enantioselectivity, irrespective of the position
of the substituent on the aromatic ring and the electronic
nature of the aryl substituent. The best ee value was observed
for the oxidation of methyl ortho-methoxyphenyl sulfide,
methyl ortho-nitrophenyl sulfide, and methyl meta-bromo-
phenyl sulfide (Table 2, entries 5–8). In the oxidation of
ortho-substituted aryl methyl sulfides, the formation of the
corresponding sulfone was inhibited significantly (Table 2,
entries 5–7). The oxidation could be carried out on a scale as
large as 10.0 mmol (Table 2, entry 6). The reaction of ethyl
phenyl sulfide also proceeded with high enantioselectivity
(Scheme 1), and the oxidation of benzyl methyl sulfide was
high yielding, although a slight decrease in enantioselectivity
was observed.
Experimental Section
5: Diethylaluminum chloride (0.92m in hexane, 100 mL) was added to
a solution of the corresponding salalen ligand (84.5 mg, 0.10 mmol) in
dry toluene (1.0 mL) at room temperature. The mixture was stirred at
room temperature for 3 h, then the resulting red solution was
suspended in hexane. The suspension was filtered through a glass
sinter funnel, and the yellow precipitate collected was washed with n-
hexane to give 5 (79.5 mg, 87%) as a yellow solid, which was used
without further purification. C,H,N analysis (%) calcd for
C61H48N2O2AlCl·0.5H2O: C 79.20, H 5.49, N 3.03; found: C 79.10,
H 5.36, N 3.03.
Typical oxidation procedure: Thioanisole (24.8 mg, 0.20 mmol),
phosphate buffer (20.0 mL, pH 7.4, 67 mmolLÀ1), and 30% aqueous
hydrogen peroxide (25.0 mg, 0.22 mmol) were added sequentially to a
solution of 5 (3.6 mg, 4.0 mmol) in methanol (2.0 mL), and the
resulting solution was stirred at room temperature for 24 h. The
mixture was then concentrated in vacuo, and the residue was purified
As already noted, further oxidation of the sulfoxide
products was observed in this Al-catalyzed sulfide oxidation.
We investigated enantiomer differentiation in the oxidation
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Angewandte
Chemie
by chromatography on silica gel (n-hexane/acetone 4:1–1:1) to give
methyl phenyl sulfoxide (24.1 mg, 86%). The enantiomeric purity of
the sulfoxide (98% ee) was determined by HPLC analysis with a
Daicel Chiralcel OB-H column (n-hexane/iPrOH 4:1).
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Saito, T. Katsuki, Tetrahedron Lett. 2002, 43, 3259 – 3262; f) B.
Saito, T. Katsuki, Chirality 2003, 15, 24 – 27.
Received: February 21, 2007
Published online: May 11, 2007
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Keywords: aluminum · asymmetric catalysis ·
hydrogen peroxide · oxidation · sulfides
.
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