Vanadium-catalyzed enantioselective sulfoxidation of methyl aryl sulfides with hydrogen peroxide as terminal oxidant

Article abstract of DOI:10.1055/s-2002-19361

Chiral vanadium complex prepared in situ from VO(acac)₂ and Schiff base 9 was found to be an efficient catalyst for oxidation of various methyl aryl sulfides with hydrogen peroxide as terminal oxidant. For example, oxidation of methyl 2-naphthyl sulfide using a VO(acac)₂, 9, and hydrogen peroxide system proceeded with high enantioselectivity of 93% ee as well as acceptable chemical yield.

Full text of DOI:10.1055/s-2002-19361

LETTER
161
Vanadium-catalyzed Enantioselective Sulfoxidation of Methyl Aryl Sulfides
with Hydrogen Peroxide as Terminal Oxidant
V
anadium-cataly
h
ze
d
E
nantios
i
electiv
s
e
Sulfoxid
a
ation of
M
ethyl
A
O
ryl Sulfides hta, Hideki Shimizu, Akiko Kondo, Tsutomu Katsuki*
Department of Chemistry, Faculty of Science, Graduate School, Kyushu University 33, Hakozaki, Higashi-ku, Fukuoka 812-8581, Japan
Fax +81(92)6422607; E-mail: katsuscc@mbox.nc.kyushu-u.ac.jp
Received 5 November 2001
VO(acac)2 (1 mol%)-ligand
Ph
Abstract: Chiral vanadium complex prepared in situ from
VO(acac)2 and Schiff base 9 was found to be an efficient catalyst for
oxidation of various methyl aryl sulfides with hydrogen peroxide as
terminal oxidant. For example, oxidation of methyl 2-naphthyl sul-
fide using a VO(acac)2, 9, and hydrogen peroxide system proceeded
with high enantioselectivity of 93% ee as well as acceptable chem-
ical yield.
Ph
S+
O-
S
aq. H2O2, CH2Cl2
1: 70% ee, 94% (at rt)
2: 78% ee, 92% (at 0 °C)
NO2
OH
Bu-t
N
OH
t-Bu
OH
Key words: asymmetric catalysis, chiral vanadium complex,
Schiff base, enantioselective sulfoxidation, hydrogen peroxide
S
N
Bu-t
HO
1
2
Optically active sulfoxides serve as useful chiral auxilia-
ries in various asymmetric reactions, and much effort has
been directed toward metal-mediated enantioselective ox-
idation of sulfides.1 In 1984, Kagan et al. reported a highly
enantioselective oxidation of sulfides by using titanium-
tartrate complex modified with water as the catalyst.2 In
the same year, Modena et al. also reported enantioselec-
tive sulfoxidation using a combination of Ti(i-PrO)4-di-
ethyl tartrate (1:4).3 Although these reactions are
stoichiometric ones, it was later found that the latter reac-
tion could be carried out in a catalytic manner, when iso-
propyl alcohol was added to the reaction medium.4,5 On
the other hand, Fujita et al. reported V(salen)-catalyzed
asymmetric sulfoxidation using alkyl hydroperoxide as
the oxidant.6 Jacobsen et al. further reported Mn(salen)-
catalyzed sulfoxidation that used hydrogen peroxide as
the oxidant,7 but its enantioselectivity was moderate. We
also reported that asymmetric sulfoxidation using the
Mn(salen) bearing a 1,1’-binaphthyl unit as the catalyst
showed high enantioselectivity (up to 95% ee). However,
the reaction needed low atom-economic iodosylbenzene
as the oxidant.8 We further found that di- -oxo Ti(salen)
bearing 1,1’-binaphthyl unit was an excellent catalyst for
asymmetric sulfoxidation with urea hydrogen peroxide
adduct as the oxidant (up to 99% ee).9 In 1995, Bolm et al.
reported that vanadium-chiral Schiff base 1 complex cat-
alyzed asymmetric sulfoxidation using aqueous hydrogen
peroxide as the oxidant with good enantioselectivity
(Scheme).10 Berkessel et al. improved the Bolm’s proto-
col by using chiral Schiff base ligand 2 possessing 1,1'-bi-
naphthyl unit.11 Since we had found that Schiff base
(salen) ligands possessing various 1,1'-binaphthyl units
are efficient chiral auxiliaries,12 we also tried to improve
Scheme
the Bolm’s protocol with new Schiff base tridentate
ligands.
We synthesized various new Schiff base ligands from
amino alcohols [(1S,2R)-1-amino-2-indanol 3, (R)-2-ami-
no-3,3-diphenyl-1-propanol 4, and (S)-t-leucinol 5] and
aldehydes [(S)-2-formyl-1,1'-binaphthyl derivatives (6
and 7) and (S)- and (R)-3-formyl-2-hydroxy-1-[(2-phe-
nyl)phenyl]naphthalenes 813] (Figure) and examined the
oxidation of methyl phenyl sulfide. Although 5 was better
amino alcohol moiety in the most cases examined than the
other two amino alcohols 3 and 4 (vide infra), it was found
that 3 served as an efficient amino alcohol moiety when it
was combined with (S)-3-formyl-2-hydroxy-1-[(2-phe-
nyl)phenyl]naphthalene (S)-8 (Schiff base 9, Table 1, en-
try 1). Schiff base 10 prepared from 3 and (R)-8 was a less
efficient chiral auxiliary (entry 2). Schiff base 11 prepared
from 5 and (S)-8 also induced a good but slightly inferior
enantioselection to 9 (entries 13–15). Thus, we scruti-
nized the oxidation of methyl aryl sulfides with 9 as the
chiral auxiliary.
We first examined effect of solvent on the enantioselectiv-
ity. Among the solvents (CH2Cl2, CHCl3, acetone, aceto-
nitrile, chlorobenzene, ether, toluene) examined, CH2Cl2
was found to be the solvent of choice. Use of CHCl3 also
gave a relatively good result (entry 8). Use of polar or ar-
omatic solvent such as acetone and toluene, however, de-
creased enantioselectivity to a considerable extent.
Temperature effect was next examined. The best enantio-
selectivity of 86% ee was obtained at 0 °C (entry 4) but
further lowering the temperature to –20 °C decreased the
enantioselectivity (entry 6).
Synlett 2002, No. 1, 28 12 2001. Article Identifier:
1437-2096,E;2002,0,01,0161,0163,ftx,en;Y22201ST.pdf.
© Georg Thieme Verlag Stuttgart · New York
ISSN 0936-5214
The 51V-NMR analysis of a mixture of vanadium-Schiff
base complex and aqueous hydrogen peroxide have dis-

162
C. Ohta et al.
LETTER
Table 1 Asymmetric Oxidation of Methyl Phenyl Sulfide by using
a VO(acac)2, Schiff Base Ligand (9, 10, and 11) and aqueous H2O2
System
Ph
Ph
Bu-t
H2N
H2N
H2N
VO(acac)2 (1 mol%)-ligand (1.5mol%)
OH
Ph
Ph
S+
S
OH
OH
3
5
4
aq. H2O2 (1.1 eq), CH2Cl2
O-
CHO
CHO
OH
CHO
Entry
Ligand Additive Solvent Temp % eea
(°C)
Yield
(%)b,c
OH
Ph
OH
Ph
S
S
S
1
2
9
10
9
–
–
CH2Cl2
CH2Cl2
r.t.
r.t.
r.t.
0
77
32
78
86
88
68
83
65
73
80
87
78
71
74
83
88
77
84
83
81
81
54
66
76
74
75
82
72
72
71
(S)-8
(S)-6
(S)-7
3
MeOHd CH2Cl2
CH2Cl2
MeOHd CH2Cl2
4
9
–
N
N
5
9
0
OH
OH
OH
OH
Ph
Bu-t
R
6
9
–
CH2Cl2
–20
–20
r.t.
r.t.
0
S
Ph
N
7
9
MeOHd CH2Cl2
OH
OH
Ph
9
10
S
8
9
–
CHCl3
CHCl3
CHCl3
CHCl3
9
9
MeOHd
–
11
10
11
12
13
14
15
9
Figure
9
MeOHd
0
2
MeOHd CH2Cl2
0
Oxidation of some other methyl aryl sulfides was also ex-
amined under the optimized conditions (Table 2). Most of
the oxidation showed high enantioselectivity greater than
80%, except for the ortho-substituted substrates that
showed only moderate enantioselectivity (entries 3 and 4).
The highest enantioselectivity (93% ee) was observed in
the oxidation of methyl 2-naphthyl sulfide (entry 7). Oxi-
dation of the resulting sulfoxides were slow and only a
trace amount of the sulfones were formed under the con-
ditions, except for the oxidation of methyl p-nitrophenyl
sulfide in which the corresponding sulfone was obtained
in 10% yield (entry 5). Methyl 2-naphthyl sulfoxide is
also oxidized to sulfone in the presence of excess amount
of H2O2 and stoichiometric H2O2 was used for the oxida-
tion of methyl 2-naphthyl sulfide (entry 7). Oxidation of
racemic methyl p-nitrophenyl sulfoxide with 9 as the
chiral ligand showed modest s-values (the relative reac-
tion ratio of the enantiomeric sulfoxides = 4). Thus, in or-
der to measure genuine enantioselectivity in the oxidation
of methyl p-nitrophenyl sulfide, the oxidation was
stopped before the formation of sulfone was detected and
enantiomeric excess of the corresponding sulfoxide was
determined to be 71% ee. This suggested that enantiomer-
ic excess of methyl p-nitrophenyl sulfoxide was enhanced
through its oxidation (entry 5).
11
11
11
–
–
CH2Cl2
CH2Cl2
r.t.
0
MeOHd CH2Cl2
0
a Determined by HPLC using Daicel Chiralcel OD-H, (hexane–i-
PrOH = 9:1).
b Isolated yield after column chromatography (silica gel, hexane–
EtOAc).
c Absolute configuration of the product was determined to be S, by
comparison of the elution order in HPLC with the authentic sample.
d The reaction was carried out in the presence of 10 L of MeOH (see
the typical experimental procedure).
closed that the mixture includes several peroxo vanadium
species which are equilibrated under the reaction condi-
tions.10,16 Thus, we expected that addition of a donor
ligand such as alcohol would affect the equilibration and
might improve the enantioselectivity. We examined addi-
tive effect of various alcohols and found that the addition
of a small amount of methanol (10 L) slightly improved
the enantioselectivity (up to 88% ee) (entry 5). The addi-
tion of excess amount of methanol (20 L), however, de-
creased enantioselectivity to 74% ee. The same additive
effect was observed in the reactions using chloroform as
the solvent (entries 10 and 11). Based on this result, we
also examined the oxidations with Berkessel’s ligand 2
and with ligand 11 in the presence of a small amount of
methanol (entry 12 and entries 14 and 15). Although some
improvement was observed in the reaction with 11, enan-
tioselection by 11 was again a little smaller than that by 9
(cf. entries 5 and 15).
Typical experimental procedure is exemplified with the
oxidation of methyl phenyl sulfide with 9 as the chiral
ligand: The ligand 9 (1.3 mg, 3.0 mol) and VO(acac)2
(0.50 mg, 2.0 mol) were dissolved in dichloromethane
(0.50 mL) and the solution was stirred for 30 minutes. Af-
ter addition of methanol (10 L) and methyl phenyl sul-
fide (24 L, 0.20 mmol), the mixture was stirred for
Synlett 2002, No. 1, 161–163 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Vanadium-catalyzed Enantioselective Sulfoxidation of Methyl Aryl Sulfides
163
Table 2 Asymmetric Oxidation of Methyl Aryl Sulfides by using a
VO(acac)2, Schiff Base Ligand (9) and aqueous H2O2 System
References
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Chemistry; Katsuki, T., Ed.; Oxford University Press:
Oxford, 2001, Chap. 4.1.
VO(acac)2 (1 mol%)-9 (1.5 mol%)
Ar
*
Ar
S+
S
aq. H2O2 (1.1 eq), MeOH (10 µL)
O-
solvent, 0 °C
(2) Pitchen, P.; Dunach, E.; Deshmukh, M. N.; Kagan, H. B. J.
Am. Chem. Soc. 1984, 106, 8188.
Entry Sulfide (Ar) Solvent
Time (h) % ee
Yield (%)a
92 (trace)
83 (trace)
92 (trace)
98 (trace)
83 (10)
1
2
3
4
5
6
7g
p-ClC6H4
p-ClC6H4
o-BrC6H4
o-O2NC6H4
p-O2NC6H4
CH2Cl2
CHCl3
CH2Cl2
CH2Cl2
CHCl3
14
16
15
18
16
16
7
84b
88b
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65b,c
36b
81d
p-MeOC6H4 CHCl3
2-naphthyl CH2Cl2
80e,f
93h,i
92 (trace)
94 (trace)
a Isolated yield after column chromatography (silica gel, hexane/
EtOAc). The number in the parentheses corresponds to the yield of
sulfone.
b Determined by HPLC using Daicel Chiralcel OB-H, (hexane–i-
PrOH, 4:1).
c The absolute configuration of the product was determined to be S,
by chiroptical comparison (ref.11).
d Determined by HPLC using Daicel Chiralcel OJ-H, (hexane–i-
PrOH, 7:3).
e Determined by HPLC using Daicel Chiralcel OB-H, (hexane–i-
PrOH, 1:1).
f The absolute configuration of the product was determined to be S,
by chiroptical comparison (ref.8b).
g The reaction was carried out with 1 equiv of aq H2O2.
h Determined by HPLC using Daicel Chiralcel OD-H, (hexane–i-
PrOH, 9:1).
i The absolute configuration of the product was determined to be S,
by chiroptical comparison (ref.17).
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(13) Although we synthesized compound 8 according to the
reported procedure (ref.14), it can be prepared
another 30 minutes and cooled to 0 °C. To the mixture
was added aqueous H2O2 (30%, 0.22 mmol) at 0 °C. The
whole mixture was stirred for 12 hours at the temperature.
The mixture was directly chromatographed on silica gel to
give (S)-methyl phenyl sulfoxide of 88% ee in 81% yield.
enantioselectively in a short step by using Yamamoto
procedure (ref.15).
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In summary, we were able to achieve high enantioselec-
tivity in the oxidation of methyl aryl sulfides with modi-
fied Bolm’s protocol using the new Schiff base ligand 9.
Further investigation is in progress in our laboratory.
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Acknowledgement
This research was partially supported by Banyu Pharmaceutical Inc.
to which the authors are grateful.
Synlett 2002, No. 1, 161–163 ISSN 0936-5214 © Thieme Stuttgart · New York