Unified oxidation protocol for the synthesis of carbonyl compounds using a manganese catalyst

Article abstract of DOI:10.1055/s-0029-1218809

We have developed a unified protocol for the oxidation of ethers, benzylic compounds, and alcohols to carbonyl compounds. The protocol uses catalytic amounts of manganese(II) chloride tetrahydrate and tri(t-butyl)-2,2':6',2Prime;- terpyridine in combination with a stoichiometric amount of either m-chloroperbenzoic acid (MCPBA) or potassium hydrogen peroxysulfate (KHSO ₅). A reagent system consisting of the Mn catalyst and MCPBA permitted the chemoselective sp³ C-H oxidation of alkyl ethers and benzylic compounds to generate the corresponding ketones. Alternatively, the water-soluble inorganic salt KHSO₅ in combination with the Mn catalyst was used to oxidize alcohols to ketones or carboxylic acids. Importantly, the Mn catalyst/KHSO₅ system eliminates technical difficulties associated with the isolation of carboxylic acid products. All the oxidations presented in this feature article proceed at sup-ambient temperature in an aerobic atmosphere, and can therefore be used in practical syntheses of complex organic molecules. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0029-1218809

FEATURE ARTICLE
2475
Unified Oxidation Protocol for the Synthesis of Carbonyl Compounds Using a
Manganese Catalyst
Synthesis of
C
h
a
rbonyl Com
i
pound
n
s
U
sing
a
Mangane
K
se Catalyst amijo, Yuuki Amaoka, Masayuki Inoue*
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Fax +81(3)58410568; E-mail: inoue@mol.f.u-tokyo.ac.jp
Received 28 April 2010; revised 10 May 2010
of sp3 C–H bonds.4 In principle, such transformation
should increase efficiency in syntheses of structurally
complex and densely functionalized organic compounds
by minimizing the number of functional group manipula-
Abstract: We have developed a unified protocol for the oxidation
of ethers, benzylic compounds, and alcohols to carbonyl com-
pounds. The protocol uses catalytic amounts of manganese(II) chlo-
ride tetrahydrate and 4,4¢,4¢¢-tri(t-butyl)-2,2¢:6¢,2¢¢-terpyridine in
combination with a stoichiometric amount of either m-chloroper- tions, reducing the number of adjustments of oxidation
benzoic acid (MCPBA) or potassium hydrogen peroxysulfate
states, and restricting the need to use protecting groups.
(KHSO5). A reagent system consisting of the Mn catalyst and
Furthermore, the resulting hydroxy and carbonyl groups
MCPBA permitted the chemoselective sp3 C–H oxidation of alkyl
can serve as versatile handles for further elaboration of the
ethers and benzylic compounds to generate the corresponding ke-
carbon framework and for the installation of other func-
tones. Alternatively, the water-soluble inorganic salt KHSO5 in
tionalities.
combination with the Mn catalyst was used to oxidize alcohols to
ketones or carboxylic acids. Importantly, the Mn catalyst/KHSO5
system eliminates technical difficulties associated with the isolation
of carboxylic acid products. All the oxidations presented in this fea-
ture article proceed at sub-ambient temperature in an aerobic atmo-
sphere, and can therefore be used in practical syntheses of complex
organic molecules.
To explore suitable catalysts for sp3 C–H oxidation, we
focused on manganese complexes, because a range of ox-
idative transformations can be effected by using manga-
nese-based reagents, such as potassium permanganate or
manganese dioxide, in stoichiometric amounts.5 In this
feature article, we report a new manganese-catalyzed re-
agent system for the chemoselective oxidation of sp3 C–H
bonds of ethers or benzylic compounds. A combination of
a manganese catalyst composed of manganese(II) chlo-
ride tetrahydrate and 4,4¢,4¢¢-tri(tert-butyl)-2,2¢:6¢,2¢¢-
terpyridine (t-Bu-terpy), in combination with a stoichio-
metric amount of m-chloroperbenzoic acid (MCPBA) was
shown to oxidize alkyl ethers or benzylic compounds
chemoselectively to give the corresponding ketones
(Scheme 1). During the course of this investigation we
found that a similar reaction using the inorganic oxidant,
potassium hydrogen peroxysulfate (KHSO5), instead of
MCPBA gave high yields of ketones or carboxylic acids
from alcohols. The development and the optimization of
these three oxidation reactions are described in detail.
Key words: catalysis, oxidation, ethers, alcohols, ketones, carbox-
ylic acids
Introduction
The oxidation of activated or nonactivated hydrocarbons
to the corresponding carbonyl compounds is a fundamen-
tal transformation in organic synthesis.1 The resulting al-
dehydes, ketones, carboxylic acids, and lactones are
valuable intermediates for further elaboration into com-
plex organic molecules. Excellent methods and a variety
of reagents have been developed to achieve chemoselec-
tive oxidative transformations, but most of these methods
require more than a stoichiometric amount of reagent to
give a high yield of the oxidized product. Consequently,
catalytic methods for various oxidations have been a sub-
ject of recent interest.
OMe
O
The scope and variety of methods for the catalytic oxida-
tion of sp3 C–H bonds in saturated carbon skeletons are
especially limited, despite the prevalence of such bonds in
organic chemistry.2,3 This is mainly because of the high
chemical stability of sp3 C–H bond under a wide array of
conditions. In this context, we initiated our research into
metal-catalyzed chemoselective techniques for the intro-
duction of polar functionalities, such as hydroxy or carbo-
nyl groups, onto carbon skeletons through direct oxidation
1
2
t-Bu
N
ether oxidation
O
Ar
R
Ar
R'
R
t-Bu
t-Bu
3
4
benzylic oxidation
N
N
Mn
+
O
MCPBA or KHSO5 [O]
R' OH
OH
5
6
alcohol oxidation
Scheme 1 Unified oxidation protocol using a manganese catalyst
SYNTHESIS 2010, No. 14, pp 2475–2489
x
x.
x
x
.
2
0
1
0
Advanced online publication: 02.06.2010
DOI: 10.1055/s-0029-1218809; Art ID: E27210SS
© Georg Thieme Verlag Stuttgart · New York

2476
S. Kamijo et al.
FEATURE ARTICLE
tention, mainly because of the harsh acidic conditions that
are required for deprotection.8
Direct Oxidation of Methyl Ethers to Ketones by Us-
ing the Manganese Catalyst/m-Chloroperbenzoic
Acid System6
We envisaged that direct sp3 C–H oxidation could be use-
ful for the chemoselective oxidative cleavage of methyl
ethers, because C–H bonds located in a position a to an
oxygen atom are generally susceptible to oxidation.9 A
number of oxidizing agents bring about one-step oxida-
tion reactions of dialkyl ethers to form the corresponding
carbonyl products. Among these agents, dioxirane10 and
oxaziridine11 are representative nonmetallic stoichiomet-
ric reagents for the oxidation of dialkyl ethers. Several
metal catalysts based on ruthenium, chromium, manga-
nese, or iron have also been reported to effect the oxida-
tion of ethers when used in conjunction with a
stoichiometric amount of a primary oxidant.9,12 However,
the choice of the starting ether is restricted mainly to cy-
clic ethers, and there have been few systematic studies on
metal-catalyzed oxidation of acyclic alkyl ethers.13
Because alkyl ether linkages generally exhibit a high
chemical stability in a wide range of synthetic procedures
under a variety of reaction conditions, such ethers are
widely in protecting hydroxy groups,7 which are present
in many naturally occurring substances of biological and
synthetic interest. In syntheses of polyhydroxy com-
pounds, the judicious choice of protecting groups and the
selection of appropriate methods for their selective intro-
duction and removal are extremely important issues. Ac-
cordingly, a number of ethereal protective groups have
been designed and developed, and various substituted
benzyl ethers have become some of the most frequently
used protecting groups in organic synthesis. On the other
hand, simple robust methyl ethers have received less at-
Biographical Sketches
Shin Kamijo was born in ing two years as a JSPS Masayuki Inoue at the Uni-
1973 in Yamaguchi, Japan. Postdoctoral Fellow with versity of Tokyo as an As-
He received his B.Sc. Professor Gregory B. Dud- sistant Professor in 2007.
(1997) and Ph.D. (2002) de- ley at Florida State Univer- His research interests are fo-
grees from Tohoku Univer- sity (2004–2006) and one cused on the development of
sity under the supervision year as a Postdoctoral Asso- methods involving the acti-
of Professor Yoshinori ciate
with
Professor vation and functionalization
Yamamoto, and was ap- Masakatsu Shibasaki at the of unreactive bonds, and the
pointed as a Research Asso- University of Tokyo (2006– use of these methods in or-
ciate in the same group 2007), he joined the re- ganic synthesis.
(2002–2004). After spend- search group of Professor
Yuuki Amaoka was born in under the guidance of Pro- cused on the development of
1987 in Yokohama, Japan. fessor Masayuki Inoue in reactions that can be applied
He received his bachelor’s the Graduate School of to the synthesis of structur-
degree from the University Pharmaceutical Sciences at ally complex organic mole-
of Tokyo in 2009. He is cur- the same university. His cules.
rently studying for a Ph.D. current researches are fo-
Masayuki Inoue was born of Science at Tohoku Uni- the First Merck–Banyu Lec-
in 1971 in Tokyo, Japan. He versity as an assistant pro- tureship Award (2004), The
received a B.Sc. degree in fessor in the research group Chemical Society of Japan
chemistry from the Univer- of Professor M. Hirama. At Award for Young Chemists
sity of Tokyo in 1993. In Tohoku University, he was (2004), the Thieme Journal
1998, he obtained his Ph.D. promoted to associate pro- Award 2005, the Novartis
from the same university, fessor in 2004 and concur- Lectureship 2008/2009, and
working under the super- rently served as a PRESTO the 5th JSPS Prize (2009).
vision of Professors K. researcher of the Japan Sci- His research interests in-
Tachibana and M. Sasaki. ence and Technology Agen- clude the synthesis, design,
After spending two years cy (2005–2008). In 2007, he and study of biologically
with Professor S. J. moved to the Graduate important molecules, with
Danishefsky at the Sloan– School of Pharmaceutical particular emphasis on the
Kettering Institute for Can- Sciences of the University total synthesis of structural-
cer Research (1998–2000), he of Tokyo as a full professor. ly complex natural prod-
joined the Graduate School He has been honored with ucts.
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Carbonyl Compounds Using a Manganese Catalyst
2477
We found that a catalytic amount of a manganese reagent
and MCPBA efficiently transformed methyl ethers into
the corresponding carbonyl compounds. The reaction
conditions for C–H oxidation were screened and opti-
mized by using cyclododecyl methyl ether (1a)
(Table 1).14,15 Treatment of ether 1a with four equivalents
of reagent-grade MCPBA (70 wt%) in the presence of 0.1
Table 1 Screening of Ligands and Oxidants for the Manganese-
Catalyzed Oxidation of Ether 1a
OMe
O
oxidant (4 equiv)
MnCl2⋅4(H2O) (0.1 mol%)
ligand (0.1 mol%)
H2O (100 µL/mmol)
MeCN (0.1 M)
mol%
of
manganese
dichloride
tetrahydrate
1a
2a
(MnCl2·4H2O) in acetonitrile gave cyclododecanone (2a)
in 32% yield (entry 1), although the reaction was not com-
plete even after twelve hours at room temperature. The at-
tempted oxidation of 1a in acetonitrile by MCPBA in the
absence of the manganese salt resulted in quantitative re-
covery of the starting material. The use of 0.1 mol% of
2,2¢:6¢,2¢¢-terpyridine (terpy, entry 2) as a tridentate nitro-
gen ligand increased the reaction rate, and 2a was isolated
in 50% yield after two hours at room temperature.14 A va-
riety of ligands were examined in attempts to improve the
oxidative power of the catalyst (entries 3–5). Complex-
ation with ligands bearing electron-donating groups, such
as 4,4¢,4¢¢-tri(tert-butyl)-2,2¢:6¢,2¢¢-terpyridine (t-Bu-
terpy; entry 3) or 4,4¢,4¢¢-trimethoxy-2,2¢:6¢,2¢¢-
terpyridine16 (MeO-terpy, entry 4), accelerated the oxida-
tion, whereas the addition of a ligand bearing an electron-
withdrawing group, 4,4¢,4¢¢-trinitro-2,2¢:6¢,2¢¢-terpyridine
(NO2-terpy, entry 5), produced no beneficial effect on the
conversion. Because of its good performance and com-
mercial availability, t-Bu-terpy was selected as the ligand
for further investigation. As a primary oxidant, MCPBA
was found to be far more reactive than magnesium
monoperoxyphthalate (MMPP) or tetrabutylammonium
Oxone (TBA-Oxone)14,17 (entries 6 and 7). Overall, the
optimized conditions (entry 3), which employed
MnCl2·4H2O (0.1 mol%), t-Bu-terpy (0.1 mol%), water
(50 mL), and MCPBA (4 equiv; 70 wt%) in acetonitrile
(0.1 M), resulted in the exclusive formation of 2a in 50%
yield within two hours at 0 °C.18,19
R
R = H: terpy
t-Bu: t-Bu-terpy
MeO: MeO-terpy
NO2: NO2-terpy
R
R
N
N
N
Entry Ligand
Oxidant
Conditionsa
Yield (%)b
1
2
3
4
5
6
7
none
terpy
MCPBAc
MCPBAc
MCPBAc
MCPBAc
MCPBAc
MMPPe
0 °C, 2 h; r.t., 12 h 32 (36)
0 °C, 2 h; r.t., 2 h
0 °C, 2 h
50d
t-Bu-terpy
MeO-terpy
NO2-terpy
t-Bu-terpy
t-Bu-terpy
50d
0 °C, 2 h
41d
0 °C, 2 h; r.t., 2 h
0 °C, 2 h
31 (40)
2.9 (94)
1.4 (90)
TBA-Oxonef 0 °C, 2 h
a Reaction conditions: 1a (0.5 mmol), oxidant (2 mmol), MnCl2·4H2O
(0.5 mmol), ligand (0.5 mmol), H2O (50 mL), MeCN (5 mL).
b Yield calculated by 1H NMR analysis of the crude mixture, unless
otherwise noted. The recovery of the starting material 1a is shown in
parentheses.
c MCPBA (70 wt%) was used.
d Yield of isolated product.
e MMPP (65 wt%) was used.
f TBA-Oxone (30 wt%) was used.
O
R
O
O
R
HO
The procedure developed here is operationally simple. For
instance, the reaction of 1a to 2a took place even under an
aerobic atmosphere by using a stock solution of the man-
ganese complex premixed in acetonitrile containing a
small amount of water.20 The catalytic activity of the pre-
mixed catalyst was retained for at least one month without
any special precautions. It is also important to note that
MCPBA did not promote the Baeyer–Villiger-type oxida-
tion of product 2a under these mild conditions.
[Mn]
R = H, Ar
A
2a
1
R
OH
[Mn]
[Mn]
R = Ar
R
CO2H
[Mn]
6
Scheme 2 shows plausible intermediates for the oxidation
reaction. It has been frequently demonstrated that the re-
activity of sp3 C–H bonds toward C–H bond functional-
ization increases with increasing electron density (R3CH
> R2CH2 > RCH3).21 Therefore, the reaction of methyl
ether 1a probably occurs through insertion of oxygen into
the tertiary C–H bond, which is more prone to oxidation
than the other C–H bond. The ejection of methanol from
the generated hemiacetal A then leads to ketone 2a.
OH
R
O
[Mn]
CHO
O
OH
O
R
R
B
5a
7
Scheme 2 Plausible intermediates for manganese-catalyzed oxida-
tion of ethers 1
To investigate the reactivity of alkyl ethers toward oxida-
tion, a variety of cyclododecanol derivatives were pre-
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

2478
S. Kamijo et al.
FEATURE ARTICLE
Table 2 Manganese-Catalyzed Oxidation Reactions of Cyclodo-
pared and subjected oxidation by the optimized reagent
system (Table 2). The oxidation of cyclododecyl octyl
ether (1b) proceeded in a similar way to that of methyl
ether 1a (entry 1), and the formation of ketone 2a and oc-
tanoic acid (6a) was identified by analysis of the crude re-
action mixture (entry 2). The observation of acid 6a
indicated that octan-1-ol eliminated from A was further
oxidized to give octanoic acid under the reaction condi-
tions (Scheme 2).22 The oxidation of benzyl ethers 1c–e
gave ketone 2a as the major product in 46–55% yield (en- Entry
decanol Derivativea
MCPBA (4 equiv)
OR
O
MnCl2⋅4(H2O) (0.1 mol%)
t-Bu-terpy (0.1 mol%)
H2O (100 µL/mmol)
MeCN (0.1 M)
0 °C, 2 h
1
2a
R
Ether
1a
1b
1c
Yield (%)b
50
tries 3–5). The oxidation of the electron-rich 4-methoxy-
benzyl ether 1d (entry 4) was completed in a shorter
1
Me
2
3
(CH2)7Mec
59d
reaction time (1 h at 0 °C) than that of the other benzyl
ethers, although similar yields of ketone 2a were obtained
irrespective of the electronic properties of the aromatic
ring. In these reactions, cyclododecanol (5a) and ben-
zoates 7 (R = Ph, 4-MeOC6H4, 4-O2NC6H4) were detected
as byproducts. These minor products were probably
formed from hemiacetal B (Scheme 2); oxidation of 1 at
the reactive benzylic position generates hemiacetal B,
which then undergoes either hydrolysis to produce alco-
hol 5a or further oxidation to produce benzoate 7. As a
separate experiment (see above), we found that alcohol 5a
was oxidized to ketone 2a in high yield under these con-
ditions. Thus, the main product 2a in entries 3–5 was po-
tentially delivered by two pathways via intermediates A
and B, respectively. Nevertheless, the isolation of ketone
2a as a major product from benzyl ethers 1c–e represents
a striking difference between the manganese-catalyzed
transformation and its ruthenium tetroxide-catalyzed
counterpart, which generally provides the corresponding
benzoate as the major product.12
Bn
48e
4
4-methoxybenzylf
1d
1e
46g
5
4-nitrobenzyl
i-Pri
55h
6
1f
29
7
t-Bu
1g
1h
1i
trace (32)
0 (49)
trace (73)
0 (49)
8
Bz
9
Ts
10
11
CH2OMe
TBS
1j
j
1k
–
a Reaction conditions: 1 (0.5 mmol), MCPBA (2 mmol, 70 wt%),
MnCl2·4H2O (0.5 mmol), t-Bu-terpy (0.5 mmol), H2O (50 mL), MeCN
(5 mL), 0 °C for 2 h.
b Yield of isolated product. The recovery of the starting material 1 is
shown in parentheses.
c MCPBA (5 equiv) was used and the reaction was further carried out
at r.t. for 2 h.
To assess steric and electronic effects on the oxidation,
various masked cyclododecanol derivatives were treated d Octanoic acid (6a) was observed in the crude reaction mixture [48%
yield (NMR)].
with the manganese catalyst and MCPBA (entries 6–11).
Entries 6 and 7 showed that the transformation is sensitive
e The corresponding benzoate 7c (trace) and cyclododecanol 5a
(12%) were obtained.
to steric hindrance around the ether linkage. In contrast to
the case with the methyl ether (entry 1), the oxidation of
the isopropyl ether 1f was sluggish, affording the desired
ketone 2a in only 29% yield (entry 6), and the oxidation
of the bulkier tert-butyl ether 1g gave only a trace amount
of ketone 2a along with 32% of recovered starting materi-
al 1g (entry 7). Entries 8, 9, and 10 clearly show that the
presence of electron-deficient substituents on the alcohol
retards the oxidation. The benzoylated (entry 8), tosylated
(entry 9), and methoxymethylated (entry 10) cyclodo-
decanols were all resistant to the oxidative conditions, and
the starting materials were recovered exclusively. These
results suggest that benzoyl, tosyl, or methoxymethyl
groups could be used as protecting groups for hydroxy
groups under these oxidative conditions. On the other
hand, the oxidation of the t-butyldimethylsilyl (TBS)
ether 1k led to a complex mixture, presumably because of
its instability under both acidic and oxidative reaction
conditions (entry 11).
f The reaction was completed in 1 h.
g The corresponding benzoate 7d (trace) and 5a (28%) were obtained.
h The corresponding benzoate 7e (7.1%) and 5a (trace) were obtained.
i The reaction was further carried out at r.t. for 1 h.
j A complex mixture was obtained.
Next, we examined the range of substrates that are com-
patible with the direct oxidation of methyl ethers
(Table 3). Entries 1–7 highlight the chemoselectivity of
the present method. The reaction of the cholestanol deriv-
ative 1l, which has reactive tertiary C–H bonds at the C5,
C8, C9, C14, C17, C20, and C25 positions, in addition to
the one at C3, gave (5a)-cholestan-3-one (2b) in 46%
yield in a site-selective manner (entry 1). Oxidation of the
primary methyl ether 1m gave the carboxylic acid 6a (en-
try 2). When differentially protected diol systems were
subjected to the oxidation, methyl ether groups were oxi-
dized preferentially in the presence of electron-deficient
substituents. Thus, oxidation of trans-1-(benzoyloxy)-2-
methoxycyclohexane (1n) and its cis-isomer 1o produced
2-oxocyclohexyl benzoate (2c) in 47 and 30% yield, re-
spectively (entries 3 and 4). On the other hand, the methyl
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Carbonyl Compounds Using a Manganese Catalyst
2479
Table 3 Manganese-Catalyzed Oxidation of Functionalized Methyl Ethersa
Entry
Substrate
Product
Yield (%)b
25
20
17
1c
46
H
H
9
14
8
H
H
H
H
3
5
3
MeO
O
H
H
1l
2b
2d
3f
47e
47
n-C7H15CO2H
n-C7H15
1m
OMe
6a
OMe
OBz
O
OBz
1n
2c
OMe
OBz
O
4f
5f
6f
7f
8
30
66
64
63
80
OBz
2c
1o
MeO
O
OBz
OBz
2d
1p
MeO
O
OBz
OTs
OBz
1q
2d
MeO
O
OTs
2e
1r
CO2Me
CO2Me
OMe
O
O
Ph
Ph
1s
2f
O
O
OMe
9
76
55
Ph
Ph
1t
2g
O
O
OMe
O
10
n-Bu
n-Bu
1u
2h
a Reaction conditions: 1 (0.5 mmol), MCPBA (2 mmol, 70 wt%), MnCl2·4H2O (0.5 mmol), t-Bu-terpy (0.5 mmol), H2O (50 mL), MeCN (5 mL),
0 °C for 2 h then r.t. for 2 h.
b Yield of isolated product unless otherwise noted.
c The reaction was carried out in MeCN–CH2Cl2 (1:1) (0.04 M) at 0 °C for 3 h.
d MCPBA (5 equiv) was used.
e Yield calculated by 1H NMR analysis of the crude mixture.
f Racemic compound.
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

2480
S. Kamijo et al.
FEATURE ARTICLE
ethers 1p and 1q, prepared from the corresponding
monobenzoylated cyclohexane-1,4-diols, gave ketone 2d
in 66 and 64% yields, respectively (entries 5 and 6). The
oxidation of tosylate 1r proceeded selectively at the meth-
yl ether moiety to provide 2e in 63% yield (entry 7). These
experiments confirmed that benzoyl and tosyl groups op-
erate as orthogonal protecting groups to the methyl group
under these conditions. Entries 8–10 show the compatibil-
ity of electron-withdrawing functional groups, such as es-
ters and ketones. The acyclic benzyl methyl ethers 1s and
1t, bearing ester and ketone groups, respectively, gave the
keto ester 2f and diketone 2g in 80 and 76% yield, respec-
tively (entries 8 and 9), whereas the alkyl ether 1u gave
the corresponding diketone 2h in 55% yield (entry 10).
MCPBA (4 equiv)
O
MnCl2⋅4(H2O) (0.1 mol%)
t-Bu-terpy (0.1 mol%)
H2O (100 µL/mmol)
NO2
MeCN (0.1 M)
0 °C, 2 h
1e
O
O
O
NO2
+
2a
55%
7e
7.1%
We therefore achieved chemoselective sp3 C–H oxidation
of methyl ethers by using a reagent combination of a Mn/
t-Bu-terpy catalyst and MCPBA. The reactions are opera-
tionally simple and dialkyl ethers are oxidized chemose-
lectively under mild conditions without affecting
electron-deficient functionalities such as benzoyloxy, to-
syloxy, ester, or ketone groups. This method broadens the
synthetic utility of methyl ethers, not only as stable pro-
tective groups, but also as precursors to ketones.
Scheme 3 Oxidation of cyclododecyl 4-nitrobenzyl ether (1e) to cy-
clododecanone (2a) and cyclododecyl 4-nitrobenzoate (7e)
2 and 3). Oxidation using 1.0 mol% of Mn catalyst gave
4a in 40% isolated yield (entry 2), whereas a reduction in
the number of equivalents of MCPBA decreased the con-
version ratio (entry 3). The reaction conditions for benzyl-
ic oxidation were therefore fixed as shown in entry 2:
MnCl2·4H2O (1.0 mol%), t-Bu-terpy (1.0 mol%), water
(50 mL), and MCPBA (4 equiv; 70 wt%) in acetonitrile
(0.1 M).27
Direct Oxidation of Benzylic Compounds to Aryl Ke-
tones by Using the Manganese Catalyst/m-Chloro-
perbenzoic Acid System
Table 4 Optimization of Amounts of Manganese Catalyst and
MCPBA for Oxidation of Butylbenzene (3a)a
MCPBA (y equiv)
MnCl2⋅4H2O (x mol%)
t-Bu-terpy (x mol%)
H2O (100 µL/mmol)
The chemoselective oxidation of sp3 C–H bonds at ben-
zylic positions is an important transformation in organic
synthesis.23–26 Classically, stoichiometric quantities of an
oxidant such as potassium permanganate (KMnO4) or po-
tassium dichromate (K2Cr2O7) are used in these reactions.
The main disadvantages of the classical methods are the
tedious workup and the production of voluminous
amounts of environmentally hazardous metal-containing
residues that result from the use of a large excess of the re-
agent. Recent decades have seen the development of var-
ious oxidation catalysts that are designed to circumvent
these problems.
O
MeCN (0.1 M)
0 °C, 2 h
3a
4a
Entry
Catalyst (mol%)
MCPBA (equiv) Yield (%)b
1
2
3
0.1
1.0
1.0
4
4
3
15 (36)
40c (trace)
29 (21)
a Reaction conditions: BuPh (3a; 0.5 mmol), MCPBA (70 wt%),
MnCl2·4H2O, t-Bu-terpy, H2O (50 mL), MeCN (5 mL), 0 °C for 2 h.
b Yield calculated by 1H NMR analysis of the crude mixture unless
otherwise noted. The recovery of the starting material 3a is shown in
parentheses.
During our research on ether oxidation, we observed the
concomitant formation of benzoate 7e upon transforma-
tion of cyclododecyl 4-nitrobenzyl ether (1e) into cy-
clododecanone (2a) (Scheme 3). This showed that the
manganese catalyst/MCPBA reagent system can oxidize
an sp3 C–H bond at a benzylic position. We therefore set
about developing a new protocol for the oxidation of non-
ethereal benzylic C–H bonds by using the manganese cat-
alyst.
c Yield of isolated product.
The results for Mn-catalyzed benzylic C–H oxidation re-
actions are summarized in Table 5. The oxidation of bu-
tylbenzene derivatives 3a–c gave the corresponding aryl
ketones 4a–c in 21–44% yield (entries 1–3). The introduc-
tion of an electron-donating methoxy substituent at the
para-position of the aromatic ring (3b) increased the rate
of oxidation, and consequently the reaction was complet-
ed in a shorter time than the corresponding reaction of bu-
tylbenzene (3a; entry 2). On the other hand, the
introduction of an electron-withdrawing substituent (3c)
retarded the oxidation. Even after extra stirring at room
The reaction conditions were optimized for the oxidation
of the benzylic C–H bond of butylbenzene (3a; Table 4).
As anticipated, the Mn catalyst/MCPBA combination di-
rectly oxidized the benzylic position. The reaction of 3a
under the conditions used for the oxidation of ethers gen-
erated phenyl propyl ketone (4a) in 15% yield; the starting
material 3a was also recovered (entry 1). To improve the
yield, the amounts of the reagents were modified (entries
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Carbonyl Compounds Using a Manganese Catalyst
2481
Table 5 Manganese-Catalyzed Oxidation of Various Benzylic
temperature for two hours, only a low yield of 4c was ob-
tained, and a large amount of starting material was recov-
ered (entry 3). These results showed that the reactivity of
a benzylic C–H bond increases with increasing electron
density on the aromatic ring.
Compounda
Entry Substrate
Product
Yield (%)b
O
Next, we evaluated the tolerance of various functional
groups to the oxidation conditions to determine the appli-
cability of this method in syntheses of structurally com-
plex and functionalized organic molecules. Oxidation of
substrates having electron-withdrawing functionalities,
such as the ester group in 3d or the nitrile group in 3e and
3f, gave the corresponding ketones 4d–f in 30–45% yield
(entries 4–6). The reactions of acetate 3g and benzoate 3h
led to ketones 4g and 4h, respectively (entries 7 and 8),
showing that ester-protected hydroxy groups survive the
conditions. The oxidation of ibuprofen methyl ester (3i)
proceeded site-selectively to give the corresponding ke-
tone 4i (entry 9).14b Apparently, the electron-withdrawing
ester group in 3i suppresses the reactivity of the adjacent
benzylic C–H bond, and the oxidation takes place at the
more-electron-rich alkyl-substituted benzylic position.
The reaction of diphenylmethane (3j) was completed in
two hours at 0 °C to give benzophenone (4j; entry 10).
Triphenylmethane (3k) and cumene (3l), each of which
contains a tertiary C–H benzylic bond, gave the corre-
sponding tertiary benzyl alcohols 4k and 4l, respectively
(entries 11 and 12).
R
R
1c
2d
3
3a: R = H
3b: R = OMe
3c: R = Ac
4a
4b
4c
40
44
21 (25)
O
O
4
41 (14)
CO2Me
CO2Me
3d
4d
CN
CN
n
n
5
6
3e: n = 1
3f: n = 2
4e
4f
30 (31)
45 (18)
O
OR
OR
7
8
3g: R = Ac
3h: R = Bz
4g
4h
45 (11)
40 (30)
We have therefore shown that a reagent system consisting
of Mn/t-Bu-terpy catalyst and MCPBA can be used for the
direct oxidation of benzylic C–H bonds. The oxidation
takes place chemoselectively at the electron-rich benzylic
position at sub-ambient temperatures in an aerobic atmo-
sphere. This operationally simple method expands the
synthetic utility of benzylic compounds as protected aryl
ketones.
O
9
37 (20)
CO2Me
CO2Me
3i
4i
4j
O
Oxidation of Alcohols to Ketones and Carboxylic
Acids by Using the Manganese Catalyst/Potassium
Hydrogen Peroxysulfate System
10c
53
3j
The oxidation of an alcohol to the corresponding alde-
hyde, ketone, or carboxylic acid is a key transformation in
synthetic organic chemistry. A variety of methods have
been devised for this reaction, but there is still a need for
new and efficient catalytic oxidations that are compatible
with various functional groups.1 We therefore examined
the possibility of developing a new method by using the
Mn/t-Bu-terpy catalyst system.
11d
39
21
OH
OH
3k
3l
4k
4l
12c
The formation of octanoic acid (6a) during the manga-
nese-catalyzed direct oxidation of ether 1b to ketone 2a
(Scheme 4) suggested that the oxidation of a primary al-
cohol to a carboxylic acid occurs under these condi-
tions.28,29 However, it was not possible to isolate pure
octanoic acid by chromatography on silica gel because the
mixture was contaminated with m-chlorobenzoic acid
formed from MCPBA. Therefore, to develop a simple and
practical oxidation protocol, it appeared to be necessary to
a Reaction conditions: 3 (0.5 mmol), MCPBA (2 mmol, 70 wt%),
MnCl2·4H2O (5.0 mmol), t-Bu-terpy (5.0 mmol), H2O (50 mL), MeCN
(5 mL), 0 °C for 2 h then r.t. for 2 h.
b Yield of isolated product. The recovery of the starting material 3 is
shown in parentheses.
c The reaction was complete after 2 h at 0 °C.
d The reaction was complete after 20 min at 0 °C.
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

2482
S. Kamijo et al.
FEATURE ARTICLE
as alternatives to MCPBA that would simplify the purifi-
cation procedure. We focused on water-soluble inorganic
oxidants that would not contaminate the ketone or carbox-
ylic acid products. After several trials, we found that
MCPBA (5 equiv)
n-C7H15
O
MnCl2⋅4(H2O) (0.1 mol%)
t-Bu-terpy (0.1 mol%)
H2O (100 µL/mmol)
MeCN (0.1 M)
0 °C, 2 h then r.t., 2 h
30
KHSO5 worked as a primary oxidant in combination
with the Mn catalyst derived from MnCl2·4H2O and t-Bu-
terpy (19% yield; entry 2). The oxidative ability of the Mn
catalyst/KHSO5 system appeared to be lower than that of
its Mn catalyst/MCPBA counterpart. An increase in the
amount of Mn catalyst helped to improve the yield of ke-
tone 2a, although a significant quantity of the starting ma-
terial was recovered (entries 3 and 4).
O
1b
+
n-C7H15CO2H
2a
6a
59%
48% (NMR yield)
Because we believed that the slow reaction rate observed
in entries 2–4 originated from the low solubility of
KHSO5 in acetonitrile, we examined a range of solvents
(entries 5–9). The reaction was found to be retarded in a
less-polar solvent (CH2Cl2, entry 5), whereas a higher
conversion of alcohol 5a was observed in polar solvents
such as ethyl acetate or acetone (entries 6 and 7). The use
of a 1:1 mixture of acetone and water did not improve the
activity of the reagent (entry 8), although this result clear-
ly showed that the presence of excess water did not inter-
fere with oxidation of the alcohol. Furthermore, exclusion
of water during the preparation of the manganese catalyst
Scheme 4 Formation of octanoic acid (6a) during oxidation of cy-
clododecyl octyl ether (1b)
replace MCPBA with another primary oxidant that could
be easily separated from the reaction mixture.
To optimize the oxidation conditions, alcohol 5a was used
as a substrate (Table 6). Oxidation of 5a proceeded
smoothly under the standard conditions for direct ether
oxidation, resulting in the formation of ketone 2a in 76%
yield (entry 1). Having confirmed that the alcohol is suf-
ficiently reactive, we examined various primary oxidants
Table 6 Screening of Primary Oxidant and Reaction Conditions for Manganese-Catalyzed Oxidation of Alcohol 5a
oxidant (2 equiv)
MnCl2⋅4(H2O) (x mol%)
t-Bu-terpy (x mol%)
H2O (100 µL/mmol)
OH
O
solvent (0.1 M)
5a
2a
Entry
Oxidant
MCPBAc
KHSO5
KHSO5
KHSO5
KHSO5
KHSO5
KHSO5
KHSO5
KHSO5
KHSO5
Oxonef
Catalyst (mol%)
Conditionsa
Solvent
MeCN
Yield (%)b
76d (trace)
19 (81)
49 (45)
70 (23)
28 (72)
80
1
2
0.1
0.1
0.5
1.0
0.5
0.5
0.5
0.5
0.5
0.5
0.5
0 °C, 2 h; r.t., 2 h
0 °C, 2 h; r.t., 2 h
0 °C, 2 h; r.t., 2 h
0 °C, 2 h; r.t., 2 h
0 °C, 2 h; r.t., 2 h
0 °C, 2 h; r.t., 2 h
0 °C, 2 h; r.t., 2 h
0 °C, 2 h; r.t., 2 h
0 °C, 2 h; r.t., 2 h
r.t., 4 h
MeCN
3
MeCN
4
MeCN
5
CH2Cl2
6
EtOAc
7
acetone
acetone–H2O (1:1)
acetonee
t-BuOH
acetone
83 (17)
78 (19)
82d (16)
77
8
9
10
11
0 °C, 2 h; r.t., 2 h
61 (38)
a Reaction conditions: 5a (0.5 mmol), oxidant (1 mmol), MnCl2·4H2O, t-Bu-terpy, H2O (50 mL), solvent (5 mL).
b Yield calculated by 1H NMR analysis of the crude mixture unless otherwise noted. The recovery of the starting material 5a is shown in pa-
rentheses.
c MCPBA (70 wt%) was used.
d Yield of isolated product.
e The reaction was conducted without addition of H2O.
f 2KHSO5·KHSO4·K2SO4.
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Carbonyl Compounds Using a Manganese Catalyst
2483
Table 7 Manganese-Catalyzed Oxidation of Alcoholsa (continued)
had no effect on the yield or reproducibility (entry 9). Pro-
tic tert-butyl alcohol was found to be a good solvent for
this manganese-catalyzed oxidation (entry 10). Interest-
ingly, the use of Oxone (2KHSO5·KHSO4·K2SO4) as the
primary oxidant instead of KHSO5 reduced the oxidation
yield slightly (entry 11). On the basis of these results, the
conditions for alcohol oxidation were set as indicated in
entry 9: MnCl2·4H2O (0.5 mol%), t-Bu-terpy (0.5 mol%),
and KHSO5 (2 equiv) in acetone (0.1 M).31
Entry Substrate
Product
Yield
(%)b
OH
n-Pr
O
n-Pr
5
38 (36)
Ph
Ph
5e
2k
HO
HO
n-C9H19
n-C9H19
6
48
OH
O
Having identified the optimal conditions, we surveyed the
oxidation of various secondary alcohols (Table 7). As de-
scribed above, treatment of cyclododecanol (5a) with the
Mn catalyst/KHSO5 system gave ketone 2a in 82% yield,
along with 16% of the recovered starting material (entry
1). Oxidation of the substituted cyclohexanol diastereo-
mers 5b and 5c gave menthone (2i) in 59% and 39%
yield, respectively (entries 2 and 3). Changing the nitro-
gen ligand from t-Bu-terpy to the less-bulky 2,2¢:6¢,2¢¢-
terpyridine (terpy) slightly improved the yield of 2i from
5c, indicating that the steric bulk of the Mn/t-Bu-terpy cat-
alyst might have a negative influence on this particular
transformation (entry 3). The propargylic alcohol 5d and
the homopropargylic alcohol 5e were converted into the
corresponding alkynones 2j and 2k (entries 4 and 5). The
formation of the relatively unstable homopropargylic ke-
tone 2k highlighted the mildness of the Mn catalyst/
KHSO5 system. The absence of the formation of arylke-
tones in entries 4 and 5 showed that the hydroxy groups
are oxidized faster than benzylic C–H groups under the
present conditions. Diol 5f was oxidized chemoselective-
ly at the secondary hydroxy group to give the conjugated
alkynone 2l (entry 6).
5f
2l
n-C7H15
OH
n-C7H15CO2H
7
72
5g
6a
OH
58 (17)d
Ph
6b
O
CO2H
8
Ph
5h
OH
OH
O
9
59 (4.0)
Ph
Ph
5i
6c
CO2H
OH
R
R
10
11
12
5j: R = H
5k: R = t-Bu
5l: R = OBz
6d
6e
6f
87
89
83
OH
CO2H
13
41 (9)e
t-Bu
t-Bu
5m
6g
OH
Table 7 Manganese-Catalyzed Oxidation of Alcoholsa
14
68 (14)
OH
Ph
Ph CO2H
Entry Substrate
Product
Yield
(%)b
5n
6d
a Reaction conditions: 5 (0.5 mmol), KHSO5 (1 mmol), MnCl2·4H2O
(2.5 mmol), t-Bu-terpy (2.5 mmol), acetone (5 mL), 0 °C for 2 h then
r.t. for 2 h.
OH
O
b Yield of isolated product. The recovery of the starting material 5 is
shown in parentheses.
1
82 (16)
59 (29)
c 2,2¢:6¢,2¢¢-Terpyridine (terpy) was used instead of t-Bu-terpy.
d The oxo carboxylic acid 6b¢ was obtained in ~3.4% yield.
O
5a
2a
2i
OH
OH
O
O
6b′
Ph
CO2H
e Compound 6e was obtained in 13% yield.
2
5b
Next, we examined the oxidation of primary alcohols to
carboxylic acids (entries 7–14). Oxidation of octanol (5g)
gave octanoic acid (6a) in 72% yield (entry 7). In contrast
to the reaction in Scheme 4, pure 6a was isolated exclu-
sively by extraction and subsequent silica gel chromatog-
raphy, demonstrating that KHSO5 has practical
advantages over MCPBA. Oxidation of alcohol 5h, which
contains a phenyl group, produced the expected carboxy-
lic acid 6b along with a minute amount of the oxo carbox-
ylic acid 6b¢ (entry 8). The reaction of diol 5i afforded
39 (46)
53 (36)c
3
5c
2i
n-Pr
n-Pr
Ph
Ph
4
58 (22)
OH
O
5d
2j
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

2484
S. Kamijo et al.
FEATURE ARTICLE
lactone 6c as a single isolable product, presumably via the
six-membered hemiacetal (entry 9).
OMe
O
KHSO5 (4 equiv)
MnCl2⋅4(H2O) (0.5 mol%)
Treatment of the benzylic alcohols 5j–l with the Mn cata-
lyst/KHSO5 system gave the corresponding benzoic acids
6d–f in yields of over 83% (entries 10–12). Oxidation of
the one-carbon homologated phenethyl alcohol 5m gave
the phenylacetic acid derivative 6g as a major product, ac-
companied by a small amount of 4-tert-butylbenzoic acid
(6e; entry 13). Although over-oxidation to 6e was not
completely suppressed, it is noteworthy that the Mn-cata-
lyzed oxidation could be used in the preparation of the rel-
atively unstable phenylacetic acid 6g. Oxidative cleavage
of the glycol moiety took place in the case of 1,2-diol 5n,
and benzoic acid (6d) was the sole product (entry 14).
t-Bu-terpy (0.5 mol%)
acetone (0.1 M)
0 °C, 2 h then r.t., 2 h
35% NMR yield
1a
2a
(39% recovery)
KHSO5 (5 equiv)
MnCl2⋅4(H2O) (0.5 mol%)
t-Bu-terpy (0.5 mol%)
n-C7H15CO2H
n-C7H15
OMe
acetone (0.1 M)
0 °C, 2 h then r.t., 2 h
50%
1m
6a
KHSO5 (4 equiv)
MnCl2⋅4(H2O) (5 mol%)
t-Bu-terpy (5 mol%)
O
We have therefore developed a new reagent system con-
sisting of a Mn/t-Bu-terpy catalyst and KHSO5 for the ox-
idation of alcohols. Changing the primary oxidant to
KHSO5 from MCPBA simplifies the isolation of the prod-
uct, particularly in the case of carboxylic acids. Further-
more, this reagent system is effective for synthesizing
relatively unstable carbonyl compounds, such as propar-
gylic ketones and phenylacetic acid derivatives.
acetone (0.1 M)
0 °C, 2 h then r.t., 2 h
40% NMR yield
3a
4a
(9.6% recovery)
Scheme 5 Oxidation of methyl ethers and a benzylic compound
dized products. The Mn catalyst/KHSO5 system is
especially advantageous for one-step preparation of car-
boxylic acids from primary alcohols or ethers. All the ox-
idation reactions presented in this feature article are
operationally simple and predictable, and they proceed
under very mild reaction conditions at sub-ambient tem-
peratures in an aerobic atmosphere. In addition, carbon
center adjacent to alkoxy, hydroxy, or aryl groups are ox-
idized chemoselectively in the presence of electron-with-
drawing functionalities such as benzoate, tosylate, ketone,
ester, or nitrile groups. The present Mn-catalyzed oxida-
tion methods broaden the utility not only of alcohols, but
also of methyl ethers and benzylic compounds, as precur-
sors to carbonyl compounds.
Oxidation of Methyl Ethers and Benzylic Com-
pounds by Using the Manganese Catalyst/Potassium
Hydrogen Peroxysulfate System
Next, we examined the oxidation of methyl ethers and
benzylic compounds by using the Mn/t-Bu-terpy catalyst
in combination with KHSO5 as the reagent. Although in-
creased amounts Mn catalyst were required with KHSO5
to obtain yields that were comparable to those obtained by
using MCPBA, cyclododecyl methyl ether (1a), methyl
octyl ether (1m), and butylbenzene (3a) were transformed
into the oxidized products 2a, 6a, and 4a, respectively
(Scheme 5). [For comparison, see entry 3 (Table 1), entry
2 (Table 3), and entry 1 (Table 5).] Most importantly, this
alternative reagent system allowed chromatographic iso-
lation of octanoic acid (6a) produced by one-step oxida-
tion of the corresponding primary ether 1m. Overall, the
Mn catalyst/KHSO5 system proved to be effective for the
All the reactions were carried out under an aerobic atmosphere at
0 °C to r.t. MCPBA was used as supplied (~70 wt%) without further
purification, and purified KHSO5 was obtained by recrystallization
of Oxone according to the reported procedure.30 Analytical TLC
was performed on E. Merck silica gel 60 F254 pre-coated plates.
Flash column chromatography was performed by using 40–63 mm
oxidation, not only of alcohols, but also of ethers and ben- silica gel 60 (Merck). The 1H and 13C NMR spectra were recorded
zylic compounds.32
on JEOL JNM-ECX-500 (500 MHz), JNM-ECA-500 (500 MHz),
and JNM-ECS-400 (400 MHz) spectrometers. Chemical shifts are
reported in d (ppm) with reference to residual solvent signals [1H
NMR: CHCl3 (7.26); 13C NMR: CDCl3 (77.0)]. IR spectra were re-
Conclusion
corded on a JASCO FT/IR-4100 spectrometer. HRMS were record-
ed on a Bruker Daltonics BioTOF-Q spectrometer (ESI) or a JEOL
JMS-T100LP AccuTOF LC-plus spectrometer (DART). The yields
are reported in the corresponding tables.
We have developed a unified protocol for the oxidation of
ethers, benzylic compounds, and alcohols to carbonyl
compounds by using a catalytic amount of MnCl2·4H2O
and t-Bu-terpy. The reagent system, which consists of the
Mn catalyst and MCPBA, has a high reactivity in oxidiz-
ing the sp3 C–H bonds of methyl ethers and benzylic com-
pounds to form ketones. For the oxidation of alcohols, we
developed a Mn catalyst/KHSO5 reagent system, in which
the replacement of MCPBA by KHSO5 eliminates techni-
cal difficulties associated with the isolation of the oxi-
Direct Oxidation of Methyl Ethers by Using the Manganese
Catalyst/MCPBA System; Typical Procedure
A soln of MnCl2·4H2O (0.1 mg, 0.5 mmol), t-Bu-terpy (0.2 mg, 0.5
mmol), and distilled H2O (50 mL) in MeCN (5 mL) was stirred at r.t.
for 0.5 h. Ether 1a (99 mg, 0.5 mmol) was added to the soln at r.t.,
and the mixture was cooled to 0 °C. The soln was treated with
MCPBA (70 wt%, 500 mg, 2.0 mmol) and stirred for 2 h at 0 °C.
The mixture was then filtered through a short column of alumina
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Carbonyl Compounds Using a Manganese Catalyst
2485
[hexane–EtOAc (5:1)], and the filtrate was concentrated. The resi-
due was purified by flash column chromatography [silica gel, hex-
ane–Et2O (50:1 to 30:1)]; yield: 45.5 mg (50%).
1H NMR (400 MHz, CDCl3): d = 2.07 (quin, J = 7.0 Hz, 2 H), 2.45
(t, J = 7.0 Hz, 2 H), 3.06 (t, J = 7.0 Hz, 2 H), 3.68 (s, 3 H), 7.46 (dd,
J = 7.7, 7.0 Hz, 2 H), 7.56 (t, J = 7.0 Hz, 1 H), 7.96 (d, J = 7.7 Hz,
2 H).
Preparation of a Stock Solution of the Premixed Manganese
Complex for Oxidation of Ethers
13C NMR (100 MHz, CDCl3): d = 19.2, 33.1, 37.4, 51.6, 128.0,
128.6, 133.1, 136.7, 173.7, 199.4.
A stock soln of the premixed Mn complex was prepared by stirring
a mixture of MnCl2·4H2O (0.99 mg, 5.0 mmol), t-Bu-terpy (2.0 mg,
5.0 mmol), and H2O (0.5 mL) in MeCN (40 mL) for 30 min at r.t.
The resulting pale yellow soln was used for oxidation of ethers. In
the case of ether 1a, the stock soln (4 mL) and MeCN (1 mL) were
used to oxidize 1a (99 mg, 0.5 mmol).
1-Phenylhexane-1,5-dione (2g)
[CAS 6303-82-8]; colorless oil.
1H NMR (400 MHz, CDCl3): d = 1.99 (quin, J = 7.0 Hz, 2 H), 2.13
(s, 3 H), 2.55 (t, J = 7.0 Hz, 2 H), 2.99 (t, J = 7.0 Hz, 2 H), 7.43 (dd,
J = 8.0, 7.5 Hz, 2 H), 7.53 (t, J = 7.5 Hz, 1 H), 7.93 (d, J = 8.0 Hz,
2 H).
Cyclododecanone (2a)
[CAS 830-13-7]; colorless solid.
1H NMR (495 MHz, CDCl3): d = 1.24–1.31 (m, 14 H), 1.71 (quin,
J = 6.2 Hz, 4 H), 2.46 (t, J = 6.2 Hz, 4 H).
13C NMR (124 MHz, CDCl3): d = 22.2, 22.4, 24.1, 24.5, 24.6, 40.3,
212.8.
13C NMR (100 MHz, CDCl3): d = 18.0, 29.9, 37.3, 42.5, 127.9,
128.5, 133.0, 136.6, 199.6, 208.5.
Decane-2,6-dione (2h)
[CAS 103984-05-0]; colorless oil.
1H NMR (400 MHz, CDCl3): d = 0.89 (t, J = 7.2 Hz, 3 H), 1.28
(sext, J = 7.2 Hz, 2 H), 1.53 (tt, J = 7.5, 7.2 Hz, 2 H), 1.82 (quin,
J = 7.0 Hz, 2 H), 2.12 (s, 3 H), 2.37 (t, J = 7.5 Hz, 2 H), 2.43 (t,
J = 7.0 Hz, 2 H), 2.46 (t, J = 7.0 Hz, 2 H).
(5a)-Cholestan-3-one (2b)
[CAS 566-88-1]; colorless solid.
1H NMR (495 MHz, CDCl3): d = 0.64 (s, 3 H), 0.70 (m, 1 H), 0.83
(d, J = 7.0 Hz, 3 H), 0.84 (d, J = 7.0 Hz, 3 H), 0.88 (d, J = 6.5 Hz, 3
H), 0.98 (s, 3 H), 0.94–1.40 (m, 17 H), 1.46–1.58 (m, 5 H), 1.67 (dq,
J = 13.0, 3.0 Hz, 1 H), 1.80 (m, 1 H), 1.98 (m, 2 H), 2.06 (ddd,
J = 15.0, 3.5, 2.0 Hz, 1 H), 2.20–2.30 (m, 2 H), 2.36 (ddd, J = 15.0,
6.5, 6.5 Hz, 1 H).
13C NMR (100 MHz, CDCl3): d = 13.8, 17.6, 22.3, 25.9, 29.9, 41.4,
42.5, 42.5, 208.6, 210.9.
Cyclododecyl 4-Nitrobenzoate (7e)
[CAS 622836-12-8]; colorless solid.
1H NMR (495 MHz, CDCl3): d = 1.20–1.40 (m, 18 H), 1.69 (m, 2
H), 1.89 (m, 2 H), 5.33 (m, 1 H), 8.18 (br d, J = 8.5 Hz, 2 H), 8.32
(br d, J = 8.5 Hz, 2 H).
13C NMR (124 MHz, CDCl3): d = 20.8, 23.0, 23.2, 23.9, 24.1, 29.0,
74.3, 123.4, 130.5, 136.3, 150.3, 164.3.
13C NMR (124 MHz, CDCl3): d = 11.3, 11.9, 18.5, 21.3, 22.4, 22.7,
23.7, 24.1, 27.9, 28.1, 28.8, 31.6, 35.3, 35.5, 35.7, 36.0, 38.0, 38.4,
39.4, 39.8, 42.4, 44.6, 46.5, 53.7, 56.1, 211.8.
2-Oxocyclohexyl Benzoate (2c)
[CAS 7472-23-3]; colorless solid.
1H NMR (490 MHz, CDCl3): d = 1.66 (dtt, J = 12.5, 12.5, 3.5 Hz, 1
H), 1.82 (dtt, J = 12.5, 12.5, 3.5 Hz, 1 H), 1.92 (ddt, J = 12.5, 12.5,
3.5 Hz, 1 H), 2.02 (m, 1 H), 2.11 (m, 1 H), 2.38–2.48 (m, 2 H), 2.55
(m, 1 H), 5.39 (br dd, J = 12.5, 6.0 Hz, 1 H), 7.42 (br t, J = 7.3 Hz,
2 H), 7.55 (tt, J = 7.3, 1.5 Hz, 1 H), 8.07 (dd, J = 7.3, 1.5 Hz, 2 H).
13C NMR (123 MHz, CDCl3): d = 23.7, 27.1, 33.1, 40.7, 76.9,
128.3, 129.6, 129.8, 133.1, 165.5, 204.3.
Direct Oxidation of Benzylic Compounds by Using the Mn Cat-
alyst/MCPBA System; Typical Procedure
A soln of MnCl2·4H2O (1.0 mg, 5.0 mmol), t-Bu-terpy (2.0 mg, 5.0
mmol), and distilled H2O (50 mL) in MeCN (5 mL) was stirred at r.t.
for 0.5 h. BuPh (3a; 78 mL, 0.5 mmol) was added to the soln at r.t.,
and the mixture was cooled to 0 °C. The soln was treated with
MCPBA (70 wt%, 500 mg, 2.0 mmol) and stirred for 2 h at 0 °C.
The mixture was then filtered through a short column of alumina
[hexane–EtOAc (10:1)], and the filtrate was concentrated. The res-
idue was purified with flash column chromatography [silica gel,
hexane–EtOAc (80:1 to 60:1)]; yield: 29.7 mg (40%).
4-Oxocyclohexyl Benzoate (2d)
[CAS 23510-95-4]; colorless oil.
1H NMR (400 MHz, CDCl3): d = 2.13–2.31 (m, 4 H), 2.44 (ddd,
J = 16.0, 6.2, 6.2 Hz, 2 H), 2.66 (ddd, J = 16.0, 10.5, 6.2 Hz, 2 H),
5.44 (tt, J = 6.2, 3.1 Hz, 1 H), 7.46 (dd, J = 8.0, 8.0 Hz, 2 H), 7.59
(t, J = 8.0 Hz, 1 H), 8.06 (d, J = 8.0 Hz, 2 H).
1-Phenylbutan-1-one (4a)
[CAS 495-40-9]; colorless oil.
1H NMR (500 MHz, CDCl3): d = 1.01 (t, J = 7.2 Hz, 3 H), 1.78 (m,
2 H), 2.95 (t, J = 7.2 Hz, 2 H), 7.46 (t, J = 7.0 Hz, 2 H), 7.56 (dt,
J = 7.0, 1.0 Hz, 1 H), 7.96 (dd, J = 7.0. 1.0 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 30.5, 37.3, 69.0, 128.5, 129.5,
130.1, 133.2, 165.7, 209.9.
13C NMR (100 MHz, CDCl3): d = 13.9, 17.8, 40.5, 128.0, 128.5,
132.8, 137.1, 200.4.
4-Oxocyclohexyl Tosylate (2e)
[CAS 23511-04-8]; colorless oil.
1H NMR (400 MHz, CDCl3): d = 1.89–1.98 (m, 2 H), 2.10–2.18 (m,
2 H), 2.27 (ddd, J = 15.0, 5.0, 5.0 Hz, 2 H), 2.44 (s, 3 H), 2.55 (ddd,
J = 15.0, 11.0, 5.9 Hz, 2 H), 4.86 (tt, J = 5.2, 2.7 Hz, 1 H), 7.34 (d,
J = 8.3 Hz, 2 H), 7.80 (d, J = 8.3 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 21.6, 31.0, 36.4, 76.5, 127.5,
129.9, 133.8, 144.9, 208.6.
1-(4-Methoxyphenyl)butan-1-one (4b)
[CAS 4160-51-4]; colorless oil.
1H NMR (400 MHz, CDCl3): d = 0.99 (t, J = 6.2 Hz, 3 H), 1.75 (tt,
J = 6.5, 6.2 Hz, 2 H), 2.89 (t, J = 6.5 Hz, 2 H), 3.86 (s, 3 H), 6.92 (d,
J = 7.6 Hz, 2 H), 7.94 (d, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 13.9, 18.0, 40.2, 55.4, 113.6,
130.1, 130.3, 163.2, 199.1.
Methyl 5-Oxo-5-phenylpentanoate (2f)
[CAS 1501-04-8]; colorless oil.
1-(4-Acetylphenyl)butan-1-one (4c)
Colorless solid.
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S. Kamijo et al.
FEATURE ARTICLE
IR (neat): 1677, 1464, 830 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.48 (t, J = 6.1 Hz, 4 H), 7.59 (t,
J = 6.1 Hz, 2 H), 7.81 (d, J = 6.1 Hz, 4 H).
13C NMR (100 MHz, CDCl3): d = 128.2, 130.0, 132.3, 137.5, 196.7.
1H NMR (400 MHz, CDCl3): d = 0.99 (t, J = 7.1 Hz, 3 H), 1.75
(quin, J = 7.1 Hz, 2 H), 2.63 (s, 3 H), 2.96 (t, J = 7.1 Hz, 2 H), 7.97–
8.04 (m, 4 H).
Triphenylmethanol (4k)
[CAS 76-84-6]; colorless solid.
1H NMR (400 MHz, CDCl3): d = 2.84 (br s, 1 H), 7.27–7.36 (m, 15
H).
13C NMR (100 MHz, CDCl3): d = 13.8, 17.5, 26.9, 40.8, 128.1,
128.4, 139.9, 140.1, 197.5, 199.8.
HRMS (ESI): m/z [M + Na]+ calcd for C12H14NaO2: 213.0886;
found: 213.0887.
13C NMR (100 MHz, CDCl3): d = 82.0, 127.2, 127.8, 127.9, 146.8.
Methyl 4-Oxo-4-phenylbutanoate (4d)
[CAS 25333-24-8]; colorless oil.
2-Phenyl-2-propanol (4l)
[CAS 617-94-7]; colorless oil.
1H NMR (500 MHz, CDCl3): d = 1.59 (s, 6 H), 1.79 (br s, 1 H), 7.25
(t, J = 7.1 Hz, 1 H), 7.35 (t, J = 7.1 Hz, 2 H), 7.50 (d, J = 7.1 Hz, 2
1H NMR (400 MHz, CDCl3): d = 2.76 (t, J = 6.8 Hz, 2 H), 3.32 (t,
J = 6.8 Hz, 2 H), 3.71 (s, 3 H), 7.46 (dd, J = 7.8, 7.5 Hz, 2 H), 7.56
(t, J = 7.5 Hz, 1 H), 7.98 (d, J = 7.8 Hz, 2 H).
H).
13C NMR (100 MHz, CDCl3): d = 27.9, 33.3, 51.8, 128.0 128.6,
133.2, 136.4, 173.4, 198.0.
13C NMR (125 MHz, CDCl3): d = 31.7, 72.5, 124.3, 126.7, 128.2,
149.1.
4-Oxo-4-phenylbutanenitrile (4e)
[CAS 5343-98-6]; colorless solid.
1H NMR (400 MHz, CDCl3): d = 2.79 (t, J = 7.0 Hz, 2 H), 3.40 (t,
J = 7.0 Hz, 2 H), 7.50 (t, J = 7.1 Hz, 2 H), 7.62 (t, J = 7.1 Hz, 1 H),
7.96 (d, J = 7.1 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 11.8, 34.2, 119.2, 128.0, 128.8,
133.9, 135.6, 195.3.
Oxidation of Alcohols by Using the Manganese Catalyst/Potas-
sium Hydrogen Peroxysulfate System; Typical Procedure
A soln of MnCl2·4H2O (0.5 mg, 2.5 mmol) and t-Bu-terpy (1.0 mg,
2.5 mmol) in acetone (5 mL) was stirred at r.t. for 0.5 h. Cyclodo-
decanol (5a; 92 mg, 0.5 mmol) at r.t. was added to the soln, and the
mixture was cooled to 0 °C. The soln was treated with KHSO5 (152
mg, 1.0 mmol) and stirred for 2 h at 0 °C, then warmed to r.t. and
stirred for an additional 2 h. The mixture was then filtered through
a Celite pad [hexane–EtOAc (10:1)], and the filtrate was concen-
trated. The residue was purified by flash column chromatography
[silica gel, hexane–EtOAc (80:1 to 60:1)]; yield; 74.3 mg (82%).
5-Oxo-5-phenylpentanenitrile (4f)
[CAS 10413-00-0]; colorless solid.
1H NMR (400 MHz, CDCl3): d = 2.11 (quin, J = 7.0 Hz, 2 H), 2.52
(t, J = 7.0 Hz, 2 H), 3.17 (t, J = 7.0 Hz, 2 H), 7.47 (t, J = 7.6 Hz, 2
H), 7.58 (t, J = 7.6 Hz, 1 H), 7.95 (d, J = 7.6 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 16.6, 19.6, 36.2, 119.4, 127.9,
128.7, 133.4, 136.3, 198.1.
Menthone (2i)
[CAS 89-80-5]; colorless oil.
1H NMR (400 MHz, CDCl3): d = 0.84 (d, J = 6.0 Hz, 3 H), 0.90 (d,
J = 6.0 Hz, 3 H), 1.00 (d, J = 5.5 Hz, 3 H), 1.25–1.43 (m, 2 H),
1.80–2.17 (m, 6 H), 2.34 (m, 1 H).
13C NMR (100 MHz, CDCl3): d = 18.7, 21.2, 22.3, 25.9, 27.8, 33.9,
35.4, 50.9, 55.9, 212.4.
4-Oxo-4-phenylbutyl Acetate (4g)
[CAS 39755-06-1]; colorless solid.
1H NMR (400 MHz, CDCl3): d = 2.03 (s, 3 H), 2.09 (tt, J = 6.0, 5.5
Hz, 2 H), 3.06 (t, J = 6.0 Hz, 2 H), 4.16 (t, J = 5.5 Hz, 2 H), 7.45 (t,
J = 6.5 Hz, 2 H), 7.56 (t, J = 6.5 Hz, 1 H), 7.95 (d, J = 6.5 Hz, 2 H).
13C NMR (125 MHz, CDCl3): d = 20.9, 23.1, 34.8, 63.7, 127.9,
128.6, 133.1, 136.7, 171.0, 199.0.
1-Phenyloct-4-yn-3-one (2j)
[CAS 412022-19-6]; colorless oil.
1H NMR (400 MHz, CDCl3): d = 1.02 (t, J = 7.2 Hz, 3 H), 1.61
(sext, J = 7.2 Hz, 2 H), 2.34 (t, J = 7.2 Hz, 2 H), 2.87 (t, J = 7.2 Hz,
2 H), 2.99 (t, J = 7.2 Hz, 2 H), 7.17–7.22 (m, 3 H), 7.26–7.31 (m, 2
H).
4-Oxo-4-phenylbutyl Benzoate (4h)
[CAS 62973-33-5]; colorless oil.
13C NMR (100 MHz, CDCl3): d = 13.5, 20.9, 21.2, 30.0, 47.0, 80.9,
1H NMR (400 MHz, CDCl3): d = 2.26 (tt, J = 7.0, 6.5 Hz, 2 H), 3.17
(t, J = 7.0 Hz, 2 H), 4.44 (t, J = 6.5 Hz, 2 H), 7.41–7.56 (m, 6 H),
7.93–8.07 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 23.3, 34.9, 64.3, 128.0, 128.3,
128.6, 129.5, 130.2, 132.9, 133.2, 136.7, 166.5, 199.1.
94.7, 126.2, 128.3, 128.5, 140.4, 187.1.
1-Phenyloct-4-yn-2-one (2k)
Colorless oil.
IR (neat): 1726, 1455, 735, 699 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.99 (t, J = 7.1 Hz, 3 H), 1.54
(sext, J = 7.1 Hz, 2 H), 2.20 (tt, J = 7.2, 2.5 Hz, 2 H), 3.27 (t, J = 2.5
Hz, 2 H), 3.88 (s, 2 H), 7.21–7.35 (m, 5 H).
13C NMR (125 MHz, CDCl3): d = 13.5, 20.8, 22.1, 33.6, 48.1, 72.2,
85.3, 127.1, 128.7, 129.5, 133.8, 202.8.
HRMS (ESI): m/z [M + Na]+ calcd for C14H16NaO: 223.1093;
found: 223.1093.
Methyl 2-(4-Isobutyrylphenyl)propanoate (4i)
[CAS 1009647-55-5]; colorless oil.
1H NMR (400 MHz, CDCl3): d = 1.19 (d, J = 7.0 Hz, 6 H), 1.51 (d,
J = 7.0 Hz, 3 H), 3.52 (septet, J = 7.0 Hz, 1 H), 3.66 (s, 3 H), 3.78
(q, J = 7.0 Hz, 1 H), 7.38 (d, J = 8.2 Hz, 2 H), 7.91 (d, J = 8.2 Hz, 2
H).
13C NMR (100 MHz, CDCl3): d = 18.3, 19.1, 35.2, 45.3, 52.2,
127.7, 128.7, 135.0, 145.4, 174.3, 203.9.
1-Hydroxytridec-2-yn-4-one (2l)
Colorless oil.
IR (neat): 3397, 2217, 1677 cm–1.
Benzophenone (4j)
[CAS 119-61-9]; colorless solid.
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Carbonyl Compounds Using a Manganese Catalyst
2487
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 5.9 Hz, 3 H), 1.20–
1.35 (m, 12 H), 1.60–1.73 (m, 2 H), 1.75–1.85 (br s, 1 H), 2.56 (t,
J = 6.1 Hz, 2 H), 4.44 (s, 2 H).
13C NMR (100 MHz, CDCl3): d = 14.1, 22.7, 23.9, 28.9, 29.2, 29.3,
29.4, 31.8, 45.3, 50.9, 84.6, 89.1, 187.7.
4-Benzoylbenzoic Acid (6f)
[CAS 28547-23-1]; colorless solid.
1H NMR (400 MHz, DMSO-d6): d = 7.43 (d, J = 8.5 Hz, 2 H), 7.61
(t, J = 7.8 Hz, 2 H), 7.76 (t, J = 7.8 Hz, 1 H), 8.05 (d, J = 8.5 Hz, 2
H), 8.14 (d, J = 7.8 Hz, 2 H), 13.0 (br s, 1 H).
HRMS (DART): m/z [M + H]+ calcd for C13H23O2: 211.1693;
found: 211.1702.
13C NMR (100 MHz, DMSO-d6): d = 122.2, 128.6, 128.6, 129.0,
129.9, 131.0, 134.3, 154.1, 164.2, 166.7.
Octanoic Acid (6a)
[CAS 124-07-2]; colorless oil.
(4-tert-Butylphenyl)acetic Acid (6g)
[CAS 32857-63-9]; colorless solid.
1H NMR (400 MHz, CDCl3): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.25–
1.35 (m, 8 H), 1.63 (quin, J = 7.5 Hz, 2 H), 2.34 (t, J = 7.5 Hz, 2 H),
10.1 (br s, 1 H).
13C NMR (100 MHz, CDCl3): d = 14.0, 22.6, 24.7, 28.9, 29.0, 31.6,
34.0, 180.1.
1H NMR (400 MHz, CDCl3): d = 1.31 (s, 9 H), 3.62 (s, 2 H), 7.21
(d, J = 7.1 Hz, 2 H), 7.36 (d, J = 7.1 Hz, 2 H), 10.0 (br s, 1 H).
13C NMR (100 MHz, CDCl3): d = 31.3, 34.5, 40.4, 125.6, 129.0,
130.2, 150.2, 177.2.
Direct Oxidation of Methyl Octyl Ether to Octanoic Acid by Us-
ing the Manganese Catalyst/KHSO5 System
4-Phenylbutanoic Acid (6b)
[CAS 1821-12-1]; colorless solid.
1H NMR (400 MHz, CDCl3): d = 1.96 (quin, J = 7.9 Hz, 2 H), 2.37
(t, J = 7.9 Hz, 2 H), 2.67 (t, J = 7.9 Hz, 2 H), 7.16–7.30 (m, 5 H),
9.90 (br s, 1 H).
13C NMR (100 MHz, CDCl3): d = 26.2, 33.3, 35.0, 126.0, 128.4,
128.5, 141.2, 179.8.
A soln of MnCl2·4H2O (0.5 mg, 2.5 mmol) and t-Bu-terpy (1.0 mg,
2.5 mmol) in acetone (5 mL) was stirred at r.t. for 0.5 h. Methyl octyl
ether (1m; 72 mg, 0.5 mmol) was added to the soln at r.t., and the
mixture was cooled to 0 °C. The soln was treated with KHSO5 (380
mg, 2.5 mmol) and stirred for 2 h at 0 °C, then warmed to r.t. and
stirred for an additional 2 h. The mixture was then filtered through
a Celite pad [hexane–EtOAc (1:1)], and the filtrate was concentrat-
ed. The residue was purified by flash column chromatography [sil-
ica gel, hexane–EtOAc (10:1 to 3:1)]; yield: 36.1 mg (50%).
4-Oxo-4-phenylbutanoic Acid (6b¢)
[CAS 2051-95-8]; colorless solid.
1H NMR (400 MHz, CDCl3): d = 2.82 (t, J = 6.9 Hz, 2 H), 3.33 (t,
J = 6.9 Hz, 2 H), 7.47 (t, J = 7.2 Hz, 2 H), 7.58 (t, J = 7.2 Hz, 1 H),
7.99 (d, J = 7.2 Hz, 2 H).
Acknowledgments
This research was financially supported by Grant-in-Aids for
Young Scientists (S), the Uehara Memorial Foundation, TORAY
Science Foundation, and Sankyo Foundation of Life Science to
M.I., and Grant-in-Aids for Young Scientists (B) to S.K.
The signal of the carboxyl group is missing, probably because of the
presence of small amounts of inseparable impurities; the data listed
above are otherwise identical to those reported in the literature.33
6-Methyl-6-phenyltetrahydro-2H-pyran-2-one (6c)
Colorless oil.
References
IR (neat): 1731, 1257, 1066, 765, 702 cm–1.
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[CAS 98-73-7]; colorless solid.
1H NMR (400 MHz, CDCl3): d = 1.36 (s, 9 H), 7.50 (d, J = 8.7 Hz,
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Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

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(18) The addition of a small amount of water during preparation
of the Mn catalyst helped to give reproducible results. Water
dissolves the MnCl2 salt and promotes the formation of the
Mn catalyst.
(19) Over-oxidation took place to produce cyclodocecane-1,5-
dione as a byproduct (<5% yield).
(20) See the experimental section for details.
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Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York

FEATURE ARTICLE
Synthesis of Carbonyl Compounds Using a Manganese Catalyst
2489
Preparations, 2nd ed.; Wiley-VCH: New York, 1999, 1205–
1207.
(30) Travis, B. R.; Ciaramitaro, B. P.; Borhan, B. Eur. J. Org.
Chem. 2002, 3429.
(26) For pioneering works on benzylic C–H oxidation with a Mn/
terpy catalyst and tetrabutylammonium Oxone (TBA-
Oxone), see reference 14.
(27) A stock solution of the premixed manganese complex in
acetonitrile can be used.
(31) The reaction in the absence of the Mn catalyst gave no
oxidized product 2a, and quantitative recovery of alcohol 5a
was observed. This result eliminates the possibility that
dioxirane is formed from acetone under the reaction
conditions.
(28) For examples of Mn-catalyzed oxidation of alcohols, see:
(a) Berkessel, A.; Sklorz, C. A. Tetrahedron Lett. 1999, 40,
7965. (b) Brinksma, J.; Rispens, M. T.; Hage, R.; Feringa, B.
L. Inorg. Chim. Acta 2002, 337, 75. (c) Bagherzadeh, M.
Tetrahedron Lett. 2003, 44, 8943. (d) Bahramian, B.;
Mirkhani, V.; Moghadam, M.; Amin, A. H. Appl. Catal., A
2006, 315, 52. (e) Mardani, H. R.; Golchoubian, H.
Tetrahedron Lett. 2006, 47, 2349. (f) Rezaeifard, A.;
Jafarpour, M.; Moghaddam, G. K.; Amini, F. Bioorg. Med.
Chem. 2007, 15, 3097. (g) Romakh, V. B.; Therrien, B.;
Süss-Fink, G.; Shul’pin, G. B. Inorg. Chem. 2007, 46, 1315.
(29) For the oxidation of alcohols by stoichiometric amounts of
MnSO4 and Oxone, see: Sánchez, A. V.; Zárrage, J. G.
J. Mex. Chem. Soc. 2007, 51, 213.
(32) Treatment of an olefin with the Mn catalyst/KHSO5 system
resulted in clean formation of an epoxide (Scheme 6).
KHSO5 (2 equiv)
MnCl2⋅4(H2O) (0.5 mol%)
t-Bu-terpy (0.5 mol%)
O
OBz
acetone (0.1 M)
0 °C, 2 h then r.t., 2 h
64%
OBz
Scheme 6 Formation of an epoxide from an olefin
(33) Jõgi, A.; Paju, A.; Pehk, T.; Kailas, T.; Müürisepp, A.-M.;
Kanger, T.; Lopp, M. Synthesis 2006, 3031.
Synthesis 2010, No. 14, 2475–2489 © Thieme Stuttgart · New York