Novel method for efficient aerobic oxidation of silyl ethers to carbonyl compounds catalyzed with N-hydroxyphthalimide (NHPI) and lipophilic Co(II) complexes

Article abstract of DOI:10.1021/ol049294+

(Equation Presented) In this work, a new method for highly efficient and selective oxidative deprotection of a variety of structurally diverse trimethylsilyl (TMS) and tert-butyldimethylsilyl (TBS) ethers using molecular oxygen in the presence of N-hydroxyphthalimide (NHPI) and various types of Co(II) complexes is reported. As a result of the relatively neutral reaction medium, acid-sensitive functional groups such as phenolic TBS ethers survived intact under the presented reaction conditions.

Full text of DOI:10.1021/ol049294+

ORGANIC
LETTERS
2004
Vol. 6, No. 17
2841-2844
Novel Method for Efficient Aerobic
Oxidation of Silyl Ethers to Carbonyl
Compounds Catalyzed with
N-Hydroxyphthalimide (NHPI) and
Lipophilic Co(II) Complexes
Babak Karimi*,†,‡ and Jamshid Rajabi†
Department of Chemistry, Institute for AdVanced Studies in Basic Sciences (IASBS),
P.O. Box 45195-159, GaVa Zang, Zanjan, Iran, and Institute for Fundamental
Research (IPM), Farmanieh, P.O. Box 19395-5531, Tehran, Iran
karimi@iasbs.ac.ir
Received April 17, 2004
ABSTRACT
In this work, a new method for highly efficient and selective oxidative deprotection of a variety of structurally diverse trimethylsilyl (TMS) and
tert-butyldimethylsilyl (TBS) ethers using molecular oxygen in the presence of N-hydroxyphthalimide (NHPI) and various types of Co(II) complexes
is reported. As a result of the relatively neutral reaction medium, acid-sensitive functional groups such as phenolic TBS ethers survived intact
under the presented reaction conditions.
The protection of hydroxyl functions as silyl ethers consti-
tutes a very useful tool in synthetic reactions of reasonable
complexity.1 Although the major goal of such a protection
is usually to prevent their oxidation, in many cases it is
necessary or convenient to achieve the direct transformation
of silyl ethers to the corresponding carbonyl compounds.2
However, in contrast to the oxidation of alcohols, which is
easily accomplished under a wide variety of reaction condi-
tions, the oxidation of silyl ethers is often difficult because
of the exceedingly low reactivity of the latter. Practically,
this transformation can be carried out by either a direct
method or in a two-step procedure, deprotection followed
by oxidation of the free alcohol. The use of a direct method
to establish such a transformation will increase the overall
efficiency. However, methods allowing the direct oxidation
of silyl ethers to the corresponding carbonyl compounds often
require stoichiometric reagents,2,3 heating,4 ultraviolet ir-
radiation,5 highly acidic medium,6 or prolonged reaction
times. Moreover, most of these oxidations bring about a large
quantity of noxious byproducts, and the yields of the
corresponding carbonyl compounds are not always satisfac-
tory. Some rare examples based on the use of cleaner
oxidants such as t-BuOOH in the presence of a catalytic
amounts of chromium(VI) catalysts were also developed for
this purpose.7 However, these methods also have drawbacks
such as the use of molar excess of t-BuOOH and prolonged
reaction times. Furthermore, the latter methods are not
(3) (a) Baker, R.; Rao, V. B.; Ravenscroft, P. D.; Swain, C. J. Synthesis
1983, 572. (b) Pinnick, H. W.; Lajis, N. H. J. Org. Chem. 1978, 43, 371.
(c) Olah, G. A.; Ho, T. L. Synthesis 1976, 609. (d) Hart, T. W.; Metcalfe,
D. A.; Scheinmann, F. J. Chem. Soc., Chem. Commun. 1979, 156. (e)
Chandrasekhar, S.; Mohanthy, P. K.; Takhi, M. J. Org. Chem. 1997, 62,
2628. (f) Park, S. T.; Ko, K. Y. Bull. Korean Chem. Soc. 2002, 23, 367.
(4) Marko, I. E.; Mekhalfia, A.; Ollis, W. D. Synlett 1990, 345.
(5) Piva, O.; Amoungay, A.; Pete, J. P. Tetrahedron Lett. 1991, 32, 3993.
(6) Afonso, C. M.; Barros, M. T.; Maycock, C. D. J. Chem. Soc., Perkin
Trans. 1 1987, 1221.
† IASBS.
‡ IPM.
(1) (a) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis, 3rd ed.; Wiley: New York, 1999, (b) Kocienski, P. J. ProtectiVe
Groups; Thieme, New York, 1994.
(2) For a review on oxidative deprotection of silyl ethers, see: Muzart,
J. Synthesis 1993, 11.
(7) (a) Muzart, J.; N’ait Ajjou, A. Synlett 1991, 497. (b) Muzart, J.; N’ait
Ajjou, A. Synth. Commun. 1992, 22, 1993.
10.1021/ol049294+ CCC: $27.50 © 2004 American Chemical Society
Published on Web 07/21/2004

suitable for the oxidative deprotection of TBS ethers at all
and afforded the corresponding carbonyl compounds in low
yields. From the standpoint of the so-called green and
sustainable chemistry, another approach to construct cleaner
catalytic systems for oxidation reactions using molecular
oxygen (O2) as final oxidant has been becoming increasingly
attractive in recent years.8 Although there have been many
catalytic methods for the aerobic oxidation of alcohols to
the corresponding carbonyl compounds,8-10 despite the
importance and attractiveness of this issue, to the best of
our knowledge there is no report for the direct aerobic
oxidation of silyl ethers to the corresponding carbonyl
compounds.
be able to convert the silyl ethers to the corresponding
oxygenated products through the intermediacy of an R-siloxy
radical (Scheme 1).
Scheme 1
The efficient aerobic oxidation of various types of organic
compounds has been carried out using N-hydroxyphthalimide
(NHPI) as a key radical generator in recent years.11 It is
believed that the phthalimide N-oxyl (PINO) radical gener-
ated insitu from the reaction of O2 and NHPI, abstracts the
hydrogen atom from the sp3 (saturated) carbons, forming the
corresponding alkyl radicals. Under aerobic conditions, these
radicals subsequently react with O2, which lies predominately
in its triplet state to give various types of oxygen-containing
compounds such as alcohols, ketones, etc. We hypothesized
that PINO radical under aerobic conditions might similarly
This led us to become interested in the use of this relatively
general reaction pathway for the aerobic oxidation of silyl
ethers.
More recently, Ishii and co-workers showed that the use
of lipophilic NHPI instead of NHPI itself has an extraordi-
nary effect on both selectivity and total yields of the air
oxidation of alkanes.12 They also found that the use of
lipophilic NHPI as catalyst is superior to NHPI from the
standpoint of both the turnover number of the catalyst and
rate of oxidation of hydrocarbons. However, to our knowl-
edge there is no systematic investigation on the effect of
lipophilization of Co(II) ions on the oxidation reaction in
the presence of NHPI. In a preceding paper, we have
developed a novel method for the selective oxidation of a
variety of structurally diverse acetals with molecular oxygen
using NHPI combined with Co(OAc)2 under mild reaction
conditions.13 In these investigations, we found that although
TBS ethers survived through the oxidation of acetals using
a NHPI/Co(OAc)2/O2 system, the situation is considerably
altered in the absence of the acetals. In continuation of this
study, we wish herein to disclose our recent finding on the
aerobic oxidation of various types of silyl ethers using NHPI
as radical generator combined with lipophilic Co(II) com-
plexes (Scheme 2).
(8) (a) Sheldon, R. A. Dioxygem ActiVation and Homogeneous Catalytic
Oxidation; Simandi, L. L. Ed.; Elsevier: Amsterdam, 1991; p 573. (b)
James, B. R. Dioxygen ActiVation and Homogeneous Catalytic Oxidation;
Simandi, L. L. Ed.; Elsevier: Amsterdam, 1991; p 195.
(9) Ruthenium catalyst: (a) Tang, R.; Diamond, S. E.; Neary, N.; Mares,
F. J. Chem. Soc., Chem. Commun. 1978, 562. (b) Matsumoto, M.; Watanabe,
N. J. Org. Chem. 1984, 49, 3435. (c) Bilgrien, C.; Davis, S.; Drago, R. S.
J. Am. Chem. Soc. 1987, 109, 3786. (d) Backvall, J.-E.; Chowdhury, R. L.;
Karlsson, U. J. Chem. Soc., Chem. Commun. 1991, 473. (e) Murahashi,
S.-I.; Naota, T.; Hirai, J. J. Org. Chem. 1993, 58, 7318. (f) Wang, G. Z.;
Andreasson, U.; Backvall, J.-E. J. Chem. Soc., Chem. Commun. 1994, 1037.
(g) Inokuchi, T.; Nakagawa, K.; Torii, S. Tetrahedron Lett. 1995, 36, 3223.
(h) Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut, M. I.; Urch,
C. J.; Brown, S. M. J. Am. Chem. Soc. 1997, 1199, 12661. (i) Lenz, R.;
Ley, S. V. J. Chem. Soc., Perkin Trans. 1 1997, 3291. (j) Hanyu, A.;
Takezawa, E.; Sakaguchi, S.; Ishii, Y. Tetrahedron Lett. 1998, 39, 5557.
(k) Kaneda, K.; Ya-mashita, T.; Matsushita, T.; Ebitani, K. J. Org. Chem.
1941, 63, 1750. (l) Marko, I. E.; Giles, P. R.; Tsukazaki, M.; Chelle-Regnaut,
M. I.; Urch, C. J.; Brown, S. M. J. Org. Chem. 1941, 63, 7576. Cobalt
catalysts: (m) Yamada, T.; Mukaiyama, T. Chem. Lett. 1989, 519. (n)
Mandal, A. K.; Iqbal, J. Tetrahedron Lett. 1997, 53, 7641. (o) Iwahama,
T.; Yoshino, Y.; Keitoku, T.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2000,
65, 6502. (p) Iwahama, T.; Sakaguchi, S.; Nishiyama, Y.; Ishii, Y.
Tetrahedron Lett. 1995, 36, 6923. Other metals: (q) Semmelhack, M. F.;
Schmidt, C. R.; Cortes, D. A.; Chou, C. S. J. Am. Chem. Soc. 1984, 106,
3374. (r) Coleman, K. S.; Coppe, M.; Thomas, C.; Osborn, J. A. Tetrahedron
Lett. 1999, 40, 3723.
(10) For examples of Pd(II)-catalyzed aerobic oxidations, see: (a)
Schultz, M. J.; Park, C.; Sigman, M. Chem. Commun. 2002, 3034. (b) Ten
Brink, G. J.; Arends, I. W. C. E.; Sheldon, R. A. AdV. Synth. Catal. 2002,
344, 355. (c) Kakiuchi, N.; Maeda, Y.; Nishimura, T.; Uemura, S. J. Org.
Chem. 2001, 66, 6620. (d) Ten Brink, G. J.; Arends, I. W. C. E.; Sheldon,
R. A. Science 2000, 287, 1636. (e) Nishimura, T.; Onoue, T.; Ohe, K.;
Uemura, S. Tetrahedron Lett. 1998, 39, 6011. (f) Yamaguchi, K.; Mizuno,
N. Angew. Chem., Int. Ed. 2002, 41, 4538. (g) Blackburn, T. F.; Schwartz,
J. J. Chem. Soc., Chem. Commun. 1977, 158. (h) Kaneda, K.; Fujie, Y.;
Ebitani, K. Tetrahedron Lett. 1997, 38, 9023. (i) Peterson, K. P.; Larock,
R. C. J. Org. Chem. 1941, 63, 3185. (j) For related examples of oxidative
kinetic resolutions, see: (k) Ferreira, E. M.; Stoltz, B. M. J. Am. Chem.
Soc. 2001, 123, 7725. (l) Bagdanoff, J. T.; Ferreira, E. M.; Stoltz, B. M.
Org. Lett. 2003, 5, 835. (m) Mandal, S. K.; Jensen, D. R.; Pugsley, J. S.;
Sigman, M. S. J. Org. Chem. 2003, 68, 4600. For an example of
Pd-catalyzed oxidation of alcohols using dichloroethane (DCE), see: (n)
Rothenberg, G.; Humbel, S.; Muzart, J. J. Chem. Soc., Perkin Trans. 2
2001, 1998. (o) Muzart, J. Tetrahedron 2003, 59, 5789.
Scheme 2
a ∑ ) Me3Si, t-BuMe2Si; L ) CH3CO2 (1a), CH3(CH2)4CO2
(1b), C6H5CO2 (1c), CH3(CH2)8CO2 (1d), CH3(CH2)16CO2 (1e);
solvent ) CH3CN.
The cobalt complexes that we used in our studies were
cobalt acetate (1a), cobalt hexanoate (1b), cobalt benzoate
(1c), cobalt decanoate (1d), and cobalt stearate (1e). We first
investigated the oxidation of benzyl trimethylsilyl ether (2)
as a model substrate using O2 (1 atm) in the presence of
NHPI (10 mol %) and different types of the indicated cobalt
carboxylate (1a-e, 0.5 mol %) in CH3CN at room temper-
(12) Savatari, N.; Yokota, T.; Sakaguchi, S.; Ishii, Y. J. Org. Chem.
2001, 66, 7889.
(13) Karimi, B.; Rajabi, J. Synthesis 2003, 2373.
(11) Ishii, Y.; Sakaguchi, S.; Iwahama, T. AdV. Synth. Catal. 2001, 343,
393.
2842
Org. Lett., Vol. 6, No. 17, 2004

ature. In this study, we found that among the cobalt
complexes, 1c and 1d exert better effect on total conversion.
Table 1 shows the representative results. As can be seen,
Table 2. Aerobix Oxidative Deprotection of Silyl Ethers Using
NHPI Combined with Cobalt Benzoate (1c)
time
yielda,b
(%)
entry
R1
R2
Σ
(min/[h])
Table 1. NHPI-Catalyzed Aerobic Oxidation of Benzyl
Trimethylsilyl Ether (1)a
1
2
3
4
5
6
7
8
Ph
Ph
H
H
H
H
H
H
H
H
H
H
H
H
TMS
TBS
TMS
TBS
TMS
TBS
TMS
TBS
TMS
TBS
TMS
TMS
TMS
TBS
TMS
TBS
TMS
TBS
TMS
TBS
TMS
TBS
TMS
TMS
TMS
TBS
20
45
[3]
[5]
20
30
20
40
[10]
[12]
[12]
[15]
60
[2]
60
[2]
[3]
[5]
60
[2]
[10]
[12]
[10]
[15]
[10]
[12]
[7]
92
90
86
91
95
95
89
90
86c
91c
90c
86c
92
87
91
93
85
90
94
95
92
89
88
86
89
82
93
93
product distribution (%)c
4-(NO2)C6H4
4-(NO2)C6H4
4-(MeO)C6H4
4-(MeO)C6H4
4-(i-Pr)C6H4
4-(i-Pr)C6H4
PhCH2CH2
PhCH2CH2
PhCH2CH2CH2
PhCH2CH2CH2
Ph
time
benzaldehyde benzoic conversion
entry catalystb (min)
(3)
acid (4)
(%)
1
2
3
4
5
6
5 h
30
30
20
30
30
<5
75
85
100
100
74
1a
1b
1c
1d
1e
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
99
89
tr
11
CH3
CH3
Et
a Benzyl trimethylsilyl ether (1 mmol)/NHPI/cobalt salts ratios were 1:0.1:
0.005 in 5 mL of CH3CN. b The cobalt complexes 1a-e are defined in the
text. c GC yields.
Ph
Ph
Ph
Et
4-(Ph)C6H4
4-(Ph)C6H4
Ph
CH3
CH3
Ph
however, 1c is better suited as cocatalyst considering both
conversion and selectivity.
Ph
Ph
The oxidation of various types of substituted primary
benzylic TMS and TBS ethers with O2 using a NHPI/1c
catalytic system at room temperature was selectively achieved,
giving the corresponding substituted benzaldehydes in good
to excellent yields (Table 2, entries 1-8). These results are
similar to those obtained very recently by Minisci’s group
for the aerobic oxidation of primary benzylic alcohols using
NHPI/Co(OAc)2/m-chlorobenzoic acid.14 Under the same
reaction conditions, however, primary aliphatic silyl ethers
gave the corresponding carboxylic acid in high yields (Table
2, entries 9-12). To show the generality of our new protocol,
various types of structurally diverse benzylic and aliphatic
secondary silyl ethers including cyclic ones were allowed
to react in the presence of a catalytic amount of NHPI (10
mol %) and 1c (0.5 mol %) under O2 (1 atm) in CH3CN at
room temperature. As can be seen, the oxidation of both TMS
and TBS ethers in all cases furnished the corresponding
ketone in excellent yields (Table 2, entries 13-28).
Interestingly, we have also observed that phenolic TBS
ethers survived intact under the described reaction conditions
(Scheme 3).
4-tert-butylcylcohexyl
4-tert-butylcylcohexyl
(-)-bornyl
(-)-bornyl
cycloheptyl
cycloheptyl
Ph
PhCO TMS
PhCO TBS
Ph
[9]
oxidation of silyl ethers. However, at this time there are two
plausible explanations that seem to be in accord with our
evidence. We found that the solubility of cobalt salts in CH3-
CN increased significantly with an increase in the carboxylate
ligand’s size to reach a maximum in 1b and 1c and the
reaction solution became clear under the operated reaction
conditions, whereas in the reactions involving 1a, 1d, and
1e the solutions remained turbid under the same reaction
conditions. Although this observation indicates an incomplete
Scheme 3
It is also noteworthy that using this method, the oxidation
of silyl ethers is much faster than the oxidation of the
corresponding alcohols.9°,14 This observation is presumably
because the oxidation of alcohols produces water as a
byproduct, which deactivates the Co(II) species via com-
plexation. On the other hand, in our reaction, the silyl ethers
are oxidized to the corresponding carbonyl compounds with
concomitant formation of either hexamethyldisiloxane or di-
tert-butyl terramethyl disiloxane (in the case of TBS ethers),
which apparently do not affect the catalyst’s proficiency.
It is rather difficult to explain exactly the effect of
lipophilic carboxylate (benzoate) ligands on overall aerobic
(14) Minisci, F.; Punta, C.; Recuporo, F.; Fontana, F.; Pedulli, G. F.
Chem. Commun. 2002, 688.
Org. Lett., Vol. 6, No. 17, 2004
2843

solubility of these reagents in the reaction medium, it may
not be the whole story of the ligand’s effect.
In conclusion, we have developed a remarkably mild and
catalytic protocol for the aerobic oxidative deprotection of
a relatively wide range of both TMS and TBS ethers. To
the best of our knowledge this protocol is the first example
of clean oxidative conversion of silyl ethers to the corre-
sponding carbonyl compounds using molecular oxygen. The
reaction times are reasonable, and yields are in most cases
excellent. Further application of this catalytic system for
oxidative deprotection of other types of protecting groups is
currently ongoing in our laboratories.
The effect of benzoic acids such as m-chlorobenzoic acid
(MCBA) on the rate enhancement of the oxidation of
alcohols has already been demonstrated by Ishii and co-
workers.9° They found experimentally that the complex C
[Co-NHPI], formed in situ from the reaction of 1a and
NHPI, probably decreased the overall rate of reaction. They
further showed that addition of MCBA to the catalyst mixture
of NHPI/1a decomposed the complex C, which in turn
facilitated the rate of aerobic oxidation of alcohols. Based
on this observation, the superior catalytic activity of the
NHPI/1c system in comparison with NHPI/1a is presumably
due to the fact that in the former system benzoate ligands
(similar to MCBA in Ishii’s procedure) strongly prevent the
formation of C and thus accelerate the overall rate of the
aerobic oxidation process (Scheme 4). However, further
studies are currently underway to clarify this issue.
Acknowledgment. The authors appreciate Institute for
Advanced Studies in Basic Sciences (IASBS) and Institute
for Fundamental Research (IPM) Research Council for
support of this work. We also thank D. Zareyee and Dr. E.
Shams for their help.
Supporting Information Available: Experimental pro-
cedures and 1H and 13C NMR spectral data for new products.
This material is available free of charge via the Internet at
http://pubs.acs.org.
Scheme 4
OL049294+
2844
Org. Lett., Vol. 6, No. 17, 2004