Manganese-catalyzed oxidative transformation of silyl ethers to ketones: Enantioselective synthesis of optically active β- and γ-siloxyketones

Article abstract of DOI:10.1055/s-2004-829577

(Salen)manganese(III)-catalyzed oxidation of silyl ethers with iodosylbenzene gave the corresponding carbonyl compounds. The enantioselective oxidation of symmetrical 1,3- and 1,4-disilyl ethers gave the corresponding optically active β- and γ-siloxyketones, respectively (up to 93% ee).

Full text of DOI:10.1055/s-2004-829577

LETTER
1739
Manganese-Catalyzed Oxidative Transformation of Silyl Ethers to Ketones:
Enantioselective Synthesis of Optically Active b- and g-Siloxyketones
E
a
nantioselecti
h
u
of
O
ptically
n
Active
b
-
an
-
d
g
-Silox
I
yketone
c
s
hi Murahashi,*a,b Satoru Noji,b Tatsuo Hirabayashi,b Naruyoshi Komiyab
Department of Applied Chemistry, Faculty of Engineering, Okayama University of Science, 1-1, Ridai-cho, Okayama,
Okayama 700-0005, Japan
Fax +81(86)2564292; E-mail: murahashi@high.ous.ac.jp
b
Department of Chemistry, Graduate School of Engineering Science, Osaka University, 1-3, Machikaneyama, Toyonaka,
Osaka 560-8531, Japan
Received 2 May 2004
OSiR3
R2
O
1 (cat.)
H
R1
Abstract: (Salen)manganese(III)-catalyzed oxidation of silyl
ethers with iodosylbenzene gave the corresponding carbonyl com-
pounds. The enantioselective oxidation of symmetrical 1,3- and 1,4-
disilyl ethers gave the corresponding optically active b- and g-sil-
oxyketones, respectively (up to 93% ee).
(1)
(2)
R1
R2
PhIO
2 (cat.)
R3SiO
R1
OSiR3
O
OSiR3
R1
R1
R1
( ) n
( ) n
PhIO
Key words: asymmetric oxidation, silyl ethers, manganese cata-
lyst, iodosylbenzene, siloxyketones
n = 1, 2
R3
R3
N
O
N
Mn
O
R4
R4
The direct catalytic oxidative transformation of silyl
ethers to carbonyl compounds is highly useful, because
the conversion of silyl ethers to the corresponding carbo-
nyl compounds is often used for organic synthesis and is
usually carried out by two steps, that is, deprotection of si-
lyl group and oxidation.1 Although numerous stoichio-
metric methods have been reported,2 the catalytic method
reported is the chromiun-catalyzed oxidation of silyl
ethers with t-BuOOH.3 This method can be used only for
less hindered substrates.3 To develop a method for direct
oxidation of silyl ethers, it is necessary to oxidize an a-C-
H bond of silyl ether. We reported that non-activated C-H
bonds of alkanes can be oxidized with catalytic systems4
such as RuCl2(PPh3)3/t-BuOOH,5 Ru-C/CH3CO3H,5a,6
Cl
R4
1: R3 = R4 = H
2: R3 = (R,R)-(CH2)4-; R4 = t-Bu
R4
Scheme 1
siloxyketones, which are important intermediates for the
synthesis of biologically active compounds.13 Oxidative
desymmetrization reactions of symmetrical substrates are
highly useful, and hence enantioselective, catalytic oxida-
tions of symmetrical alkanes,14 meso-tetrahydrofuran,15
meso-pyrrolidine,16 and meso-diols17 have been reported.
RuCl3·nH2O/RCHO/O2,7
Fe/RCHO/O2,7
Cu(OH)2/
We found that (salen)Mn(III) is an efficient catalyst for
the oxidation of silyl ethers. Treatment of benzylic silyl
ethers with iodosylbenzene in the presence of achiral
(salen)Mn(III) complex 1 in MeCN at 25 °C under argon
gave the corresponding ketones efficiently. The represen-
tative results of the oxidation of silyl ethers using 1 are
shown in Table 1. The trimethylsilyl (TMS) ether of 1-
phenyl ethanol is readily oxidized to acetophenone (entry
1). Importantly, the oxidation of the hindered tert-bu-
tyldimethylsilyl (TBDMS) ether also proceeds with high
conversion (entry 2), while the chromium-catalyzed oxi-
dation is not effective for the oxidation of the TBDMS
ether.3 The oxidations of the substituted benzylic silyl
ethers (p-methyl, p-methoxy, p-chloro) gave the corre-
sponding ketones in high yields (entries 3–5). Diphenyl-
methyl silyl ether can be converted to benzophenone
efficiently (entry 6). The minor products of the reaction
mixture could not be identified because of a small amount.
CH3CHO/O2,8 CuCl2–crown ether/CH3CHO/O2,9 Ru-,
Mn-, and Co-porphyrin/CH3CHO/O210 and Fe-phthalocy-
anine/CH3CHO/O2.11 We have also reported the oxidative
transformation of cyclic acetals of aldehydes to the corre-
sponding carboxylic acid esters.12
We wish to report here a new catalytic method for oxida-
tion of silyl ethers to the corresponding ketones using a
(salen)Mn(III) complex catalyst [Scheme 1, (1)]. We also
wish to report that the catalytic oxidation of silyl ethers
can be applied to the enantioselective desymmetrization
of disilyl ethers. Using chiral (salen)Mn(III) catalysts,
enantioselective oxidation of symmetrical 1,3- and 1,4-
disilyl ethers occurs efficiently to give the corresponding
optically active b- and g-siloxyketones, respectively
[Scheme 1, (2)]. This is, to the best of our knowledge,
the first report on the direct, catalytic enantioselective
transformation of disilyl ethers to optically active b- or g-
We next examined the enantioselective oxidation of sym-
metrical disilyl ethers using a chiral (salen)Mn catalyst.
Asymmetric oxidative desymmetrization of cis-1,3-disil-
oxyindane (3) bearing two silyl ethers using a chiral
SYNLETT 2004, No. 10, pp 1739–1742
0
9
.0
8
.2
0
0
4
Advanced online publication: 15.07.2004
DOI: 10.1055/s-2004-829577; Art ID: U12704ST
© Georg Thieme Verlag Stuttgart · New York

1740
S.-I. Murahashi et al.
LETTER
Table 1 Catalytic Oxidation of Silyl Ethers Using (salen)Mn(III) (1)a
Entry
Substrate
Product
Conv. (%)b
Yield (%)c
OR4
O
H
1
2
R4 = SiMe3
84
80
81
81
R4 = SiMe2t-Bu
OSiMe2-t-Bu
O
H
X
X
3
4
5
6
X = OMe
X = Me
X = Cl
H
91
87
78
83
71
61
85
91
OSiMe2-t-Bu
O
a A mixture of substrate (0.10 mmol), (salen)Mn(III) 1 (0.015 mmol), PhIO (0.40 mmol), and MeCN (1.0 mL) was stirred at r.t. for 6 h.
b Determined by GLC analysis based on the starting substrate using an internal standard.
c Determined by GLC analysis based on the converted substrate.
(salen)Mn complex catalyst gives the corresponding opti- symmetrization of other substrates also proceeds with
cally active 3-siloxy-1-indanone (4). The representative high enantioselectivity (Scheme 2).
results of the enantioselective oxidation of 3 are shown in
Table 2.
The oxidation of cis-1,3-di(tert-butyldimethylsiloxy)-2,2-
dimethylindane (5) at –20 °C gave the siloxyketone 6 with
The oxidation of cis-1,3-di(tert-butyldimethylsiloxy)in- 81% ee (S, conversion 5%).20 Furthermore, the oxidation
dane (3a) with iodosylbenzene in the presence of (R,R)- of cis-1,4-di(tert-butyldimethylsiloxy)tetraline (7) gave 8
218 catalyst gave siloxyketone 4a with 57% ee (R, entry 1). with 93% ee (R, 15%).21 The chiral 3-siloxyindanone 6
The absolute configuration of 4a was assigned in compar- and 4-siloxytetralone 8 obtained can be readily converted
ison with the reported optical rotation value after convert- to the corresponding chiral 3-hydroxyindanone and 4-hy-
ing to 3-hydroxy-1-indanone.13 The addition of 4- droxytetralone, respectively. The chiral 3-hydroxyin-
phenylpyridine N-oxide as an axial ligand of the catalyst danone unit is found in the natural product such as
improved both the conversion and the enantioselectivity indatraline,22 while the chiral 4-hydroxytetralone unit is
(entry 2).19 When the reactions were carried out at lower present in biologically active compounds such as cat-
temperatures such as 0 °C and –20 °C, the enantioselec- alponol,23 isoshinanolone,24 and palmarumycin CP4.25
tivities of 4a were improved to 78% ee and 89% ee, re-
spectively (entries 3–5). The effect of the silyl group is
O
OSiMe2-t-Bu
(R,R)-2
remarkable. The asymmetric oxidation of less hindered
trimethylsilyl (TMS) derivative 3b gave the product 4b
with lower enantioselectivity (49% ee, entry 6). On the
other hand, the oxidations of the substrates bearing steri-
cally bulky triisopropylsilyl (TIPS) and tert-butyldiphe-
nylsilyl (TBDPS) groups are not effective. The oxidation
of non-protected cis-1,3-indandiol (3c) was examined us-
ing (R,R)-2 catalyst at 0 °C (entry 7). The enantioselectiv-
ity of 3-hydroxyindane-1-one (4c) was 51% ee, which is
lower than (78% ee) that of 4a (entry 4).
(10 mol%)
PhIO (2 equiv)
4-phenylpyridine N-oxide
OSiMe2-t-Bu
OSiMe2-t-Bu
(0.5 equiv)
CH2Cl2, –20 °C
5
6
81% ee (S)
OSiMe2-t-Bu
O
(R,R)-2
(10 mol%)
PhIO (2 equiv)
4-phenylpyridine N-oxide
OSiMe2-t-Bu
OSiMe2-t-Bu
(0.5 equiv)
CH2Cl2, –20 °C
The siloxy groups and their size have considerable influ-
ence for the improvement of the enantioselectivity, and
tert-butyldimethylsiloxy group is the most suitable for the
present asymmetric oxidation reaction. The oxidative de-
8
7
93% ee (R)
Scheme 2
Synlett 2004, No. 10, 1739–1742 © Thieme Stuttgart · New York

LETTER
Enantioselective Synthesis of Optically Active b- and g-Siloxyketones
1741
Table 2 Enantioselective Oxidation of 1,3-Disiloxyindanes Using
(R,R)-2 Catalysta
comparison with the authentic sample. The siloxy group
plays an important role to improve the enantioselectivity
by enhancing the steric effect between the siloxy group of
the substrates and (salen)Mn catalysts.
O
OR
(R,R)-2
(10 mol%)
PhIO (2 equiv)
4-phenylpyridine N-oxide
In conclusion we developed a new method for direct oxi-
dation of silyl ethers to the corresponding ketones using
(salen)Mn(III) catalysts. The catalytic system can be ap-
plied to the enantioselective oxidative transformation of
1,3- and 1,4-disilyl ethers to the corresponding optically
active b- and g-siloxy ketones, respectively, with high
enantioselectivity (up to 93% ee).
OR
OR
(0.5 equiv)
CH2Cl2, 0 °C, 12 h
R = SiMe2-t-Bu (3a)
= SiMe3 (3b)
= H (3c)
4a–c
Entry
Substrate Additiveb Temp (°C) Conv. (%)c Ee (%)d
1
3a
3a
3a
3a
3a
3b
3c
None
25
25
0
13
24
5
57 (R)
66 (R)
78 (R)
78 (R)
89 (R)
49f (R)
51g (R)
Acknowledgment
2
4-PPN
4-PPN
4-PPN
4-PPN
4-PPN
4-PPN
This work was supported by the Research for the Future Program,
The Japan Society for the Promotion of Science, and a Grant-in-Aid
for Scientific Research, the Ministry of Education, Science, Sports,
and Culture, Japan.
3
4e
5e
6
0
17
8
–20
0
30
19
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LETTER
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