Efficient oxidation of 1,2-diols into a-hydroxyketones catalyzed by organotin compounds

Article abstract of DOI:10.1002/chem.200900159

Electrochemical oxidation of 1,2-diols with a catalytic amount of an organotin compound and a bromide ion as mediators has been developed. Various cyclic and acyclic 1,2-diols were oxidized into the corresponding α-hydroxyketones in good to excellent yields without C-C bond cleavage. Also, oxidation with the use of chemical oxidants was accomplished in the presence of a catalytic amount of an organotin compound. These reactions could discriminate 1,2-diols from isolated hydoxyl groups or 1,3-diols. In the case of a conformationally restricted cyclic 1,2-diol, the axial hydroxyl group was oxidized exclusively. Mono-, di-, and trialkylated tin compounds were examined as mediators and dialkylated tin compounds showed higher catalytic activity than mono- and trisubstituted ones. Me₂SnCl₂ was found to be the most suitable mediator for the selective oxidation..

Full text of DOI:10.1002/chem.200900159

DOI: 10.1002/chem.200900159
Efficient Oxidation of 1,2-Diols into ACTHUNRGTNEaNUG -Hydroxyketones Catalyzed by
Organotin Compounds
Toshihide Maki, Shinya Iikawa, Gen Mogami, Hitomi Harasawa,
Yoshihiro Matsumura, and Osamu Onomura*[a]
Abstract: Electrochemical oxidation of
presence of a catalytic amount of an
organotin compound. These reactions
could discriminate 1,2-diols from isolat-
ed hydoxyl groups or 1,3-diols. In the
case of a conformationally restricted
cyclic 1,2-diol, the axial hydroxyl group
1,2-diols with a catalytic amount of an
organotin compound and a bromide
ion as mediators has been developed.
Various cyclic and acyclic 1,2-diols
were oxidized into the corresponding
a-hydroxyketones in good to excellent
was oxidized exclusively. Mono-, di-,
and trialkylated tin compounds were
examined as mediators and dialkylated
tin compounds showed higher catalytic
activity than mono- and trisubstituted
ones. Me2SnCl2 was found to be the
most suitable mediator for the selective
oxidation.
Keywords: chemoselectivity · diols ·
À
yields without C C bond cleavage.
ketones
·
organotin catalysts
·
Also, oxidation with the use of chemi-
cal oxidants was accomplished in the
oxidation
Introduction
Scheme 1) in spite of their usefulness as intermediates for
organic synthesis.[6]
Oxidation of alcohols into their corresponding ketones is
one of the most basic organic reactions. However, most
Some of the methods involve the use of silver carbonate
on Celite (Fetizon reagent),[7] the Corey–Kim reagent,[8] per-
oxotungstophosphate with H2O2,[9] the Swern reagent,[10] N-
bromosuccinimide (NBS),[11] or nBu2Sn=O (I).[12] These re-
agents with the exception of I suffer from disadvantages,
such as relatively low yields, side reactions accompanying
common oxidizing reagents or methods, such as PbACTHNUTRGNEUNG
(OAc)4,[1]
À [2]
IO4 , CrIV,[3] CeIV[4] and electrochemical oxidation[5] cause
À
the oxidative C C bond cleavage of 1,2-diols (path b in
Scheme 1). Few methods are available for the selective oxi-
À
dation of 1,2-diols into a-hydroxyketones (path a in
C C bond cleavage especially for the oxidation of cyclic 1,2-
diols,[9] and over-oxidation to 1,2-diketones.[10]
On the other hand, the use of I has been recognized as a
highly selective method,[12] which proceeds in two stages:
formation of stannylene acetals by azeotropic condensation
of 1,2-diols with I followed by the oxidation of the stanny-
lene acetals with bromine (Scheme 2).
Since the method does not need any protection–deprotec-
tion procedures, it has been applied to the synthesis of (+)-
spectinomycin[13] and to the oxidation of a variety of sugars
into oxo-sugars.[12c] This method, however, requires more
than an equimolar amount of I to complete the oxidation. It
is troublesome and also unfavorable from an environmental
Scheme 1. Oxidation of 1,2-diols.
[a] Dr. T. Maki, S. Iikawa, G. Mogami, H. Harasawa,
Prof. Dr. Y. Matsumura, Prof. Dr. O. Onomura
Graduate School of Biomedical Sciences
Nagasaki University, 1–14 Bunkyo-machi
Nagasaki 852–8521 (Japan)
Fax : (+81)95-819-2429
E-mail: onomura@nagasaki-u.ac.jp
Scheme 2. Oxidation of 1,2-diols via a stannylene acetal.
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FULL PAPER
Table 1. Electrochemical oxidation of 1a and 1b by using organotin com-
pounds.
viewpoint. Previously, we reported an electrochemical
method for the effective oxidation of 1,2-diols in which both
I and a bromide ion worked as mediators to oxidize 1,2-
diols, and therefore only a catalytic amount (0.02 to
0.1 equiv) of I was enough to complete the oxidation.[14] In
our continuing study on this method, we examined a variety
of organotin compounds[15] and found a number of them
could work as more efficient mediators than I.[16] We report
herein the details of our results.
Entry
Organotin compound
(0.1 equiv)
Yield [%] of
a-hydroxyketone
2a[a] (2 FmolÀ1
)
2b[b] (3 FmolÀ1
)
1
nBu2Sn=O
nBu2Sn=O
nOct2Sn=O
nOct2Sn=O
nBu2SnCl2
nBu2SnBr2
Me2SnCl2
tBu2SnCl2
Ph2SnCl2
I
I
II
6
43
–
[d]
2[c]
3
96
40
95
79
71
70
89
63
59
77
57
10
4[c]
5
6
7
8
II
–
–
[d]
[d]
III
IV
V
VI
VII
VIII
IX
X
77
82
76
82
Results and Discussion
9
[d]
10
11
12
n-Bu3SnCl
G
–
66
11
Catalytic activity of various organotin mediators for the oxi-
dation of 1,2-diols: Electrochemical oxidation of cis-1,2-cy-
clohexanediol (1a) in methanol containing 0.1 equivalents
of I and Et4NBr at room temperature gave a-hydroxycyclo-
hexanone (2a) in 96% yield. This oxidation required pre-
heating of the solution prior to electrolysis to dissolve I.
Since it is well-known that heating of I in methanol contain-
ing 1a gives stannylene acetal (A1a) and as an electrochemi-
cal oxidation of 1a without I did not proceed, this means
that A1a would be oxidized by Br+, which was generated by
electrochemical oxidation of BrÀ (Scheme 3).
[a] Determined by GC analysis. [b] Isolated yield. [c] The reaction solu-
tion was heated at reflux for 1 h prior to the electrolysis. [d] Many un-
identified products formed with the product.
tion because of its applicability to both cyclic and acyclic
diols. Furthermore, V showed good solubility toward metha-
nol, and thus the procedure did not require heating at reflux
of the solution before the experiment, which was essential
in the case of II.[15] The procedure using V is therefore a
one-step procedure.
Electrochemical oxidation of various 1,2-diols by using V:
According to the procedure, a variety of 1,2-diols were oxi-
dized into a-hydroxyketones by the electrochemical method
by using V as a mediator [Eq. (1)]. The electrolysis was car-
ried out in the presence of 0.005 to 0.1 equivalents of V at
08C in methanol. During the electrolysis, a yellowish/green
solution was observed on the surface of the anode. The re-
sults are summarized in Table 2.
Scheme 3. Electrochemical oxidation of 1a by using I and BrÀ.
To explore the catalytic activity of organotin compounds,
we examined various organotin compounds I–X for the oxi-
dation of 1a and 1,2-dodecanediol (1b). Table 1 shows the
results.
For the oxidation of 1a, preheating was required to dis-
solve dialkyltin oxide I or II in methanol, whereas for the
oxidation of 1b by using I or II, preheating was an inhibitor
(Table 1, entries 1–4). Dialkylated and trialkylated tin com-
pounds III–VIII showed moderate to excellent catalytic ac-
tivity without preheating for the oxidation of cyclic diol 1a
(entries 5–10). On the other hand, oxidation of acyclic diol
1b to 2b was not satisfactorily achieved by nOct2Sn=O (II),
nBu2SnCl2 (III), or nBu3SnCl (VIII) (entries 4, 5, and 10),
whereas nBu2SnBr2 (IV), Me2SnCl2 (V), tBu2SnCl2 (VI), and
Ph2SnCl2 (VII) mediated the oxidation with moderate effi-
ciency (entries 6–9). Although (nBu3Sn)2O (IX) worked well
for the oxidation of both 1a and 1b (entry 11), nBuSnCl3
(X) was effective only for the oxidation of 1a (entry 12).
Thus, some organotin compounds showed catalytic activity
for the oxidation of 1,2-diols by an electrochemical method.
Among them, V looks promising as a catalyst for the oxida-
Cyclic cis-1,2-diols were selectively oxidized to a-hydroxyl
ketones 2 in good yields irrespective of their ring size and
À
without C C bond cleavage (Table 2, entries 1–4). The yield
of 2a from trans-1,2-cyclohexanediol (1 f) was relatively
lower than that from cis-isomer 1a, because oxidation of 1 f
proceeds more slowly than that of 1a as previously report-
ed[14] (entries 1 and 5). This relatively small reaction rate
may be due to the fact that both of the hydroxyl groups are
located in an equatorial position in 1 f and need to pass
through a high-energy transition state (see section on stereo-
selectivity). However, the yield of 2a from 1 f was improved
when the electrolysis was carried out at a lower current den-
sity in a mixed solvent system of dichloromethane and tri-
fluoroethanol in a ratio of 10:1, which are less oxidizable
solvents than methanol (entry 6). A larger amount of elec-
tricity was necessary to complete the oxidation of acyclic
diols than cyclic diols. The secondary hydroxyl group in acy-
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O. Onomura et al.
Table 2. Electrochemical oxidation of 1,2-diols mediated by V and BrÀ.
ary and primary hydroxyl
groups can act as an anchor for
the organotin catalyst to acti-
vate only their vicinal secon-
dary hydroxyl groups for the
selective oxidation. 1,3-Butane-
diol (4) was also inert under
the same conditions [Eq. 5)].
Thus, from these results we de-
duced that secondary alcohols
in 1,2-diols are selectively oxi-
dized by this reaction. This
tendency is contrastive with
the fact that organotin-cata-
lyzed monobenzoylation pre-
dominantly takes place at the
primary hydroxyl group of acy-
clic secondary/primary diols.[15]
Entry
1,2-Diol
V [equiv]
Electricity [FmolÀ1
]
Product
Yield [%][a]
1
2
3
4
a: n=2
c: n=1
d: n=3
e: n=4
0.1
0.1
0.1
0.1
3.0
3.0
3.0
3.0
89[b]
70[b]
84
87
5
0.1
0.1
3.0
2.0
41
74
6[c]
2a
7
8
0.1
0.005
3.0
4.6
76
72
9
0.1
3.0
56[d]
10
11
0.1
0.1
3.0
4.0
32[d]
76
[a] Isolated yield unless otherwise noted. [b] Determined by GC analysis. [c] Solvent: CH2Cl2/CF3CH2OH
10:1. [d] Isolated yield after benzoylation.
Stereoselectivity: The current
efficiency and chemical yield
clic 1,2-diols was selectively oxidized into a carbonyl group
in a moderate to good yield (entries 7–11). Although the
current efficiency was decreased, only 0.005 equivalents of
V was required for efficient reaction (entry 8).
Regioselectivity: Oxidation of a 1,2-diol, which is composed
of two secondary hydroxyl groups, such as 1j afforded a
mixture of two regioisomers of a-hydroxyketones 2j and
2j’. That is, when using nBu2SnCl2 (III) or Me2SnCl2 (V),
the more hindered hydroxyl group was oxidized predomi-
nantly in a ratio of 70 to 30, whereas the ratio decreased
from 55 to 45 when using tBu2SnCl2 (VI) as an organotin
catalyst [Eq. (2)].
of a-hydroxyketone
2 were
strongly affected by the struc-
ture of the 1,2-diols (Table 2,
entries 1 and 5). This result
prompted us to investigate the
stereoselectivity of this reac-
tion. Conformationally restrict-
ed cyclic 1,2-diols, such as 1m
Chemoselectivity: The reaction showed a high selectivity for
1,2-diols. For example, a mixture of an equimolar amount of
secondary/tertiary diol 1k and secondary alcohol 3 was sub-
jected to the electrolysis. After passing 5.5 FmolÀ1 of elec-
tricity, 2k was obtained quantitatively, whereas 3 remained
unchanged [Eq. (3)].
Primary/tertiary vicinal diols, such as 1l could not be oxi-
dized by this reaction [Eq. (4)]. These results indicate that
the oxidization of the primary hydroxyl group does not take
place in this reaction. Moreover, the result shows that terti-
and 1n, were prepared. After the electrochemical oxidation
of 1m and 1n in the presence of V and BrÀ, it was found
that their axial hydroxyl groups had been selectively oxi-
dized into carbonyl groups, such as 2m and 2n, respectively,
as a single isomer [Eqs. (6) and (7)].
This finding is in line with the result of the brominolysis
of stannylene acetals derived from sugars and I reported by
Tsuda et al.[12c] This could also account for the relatively
lower yield of 2a from 1 f than that from 1a (Table 2, en-
tries 1 and 5). In 1a, one of the hydroxyl groups occupies an
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Efficient Oxidation of 1,2-Diols
FULL PAPER
acetal or related complex A or A’ could be oxidized with a
combination of anodically generated oxidant (Br+) and
cathodically generated base (2MeOÀ) to afford a-hydroxy-
ketones 2 and to regenerate Me2SnACHTNUTRGNE(NUG OMe)2 (XI). In this
electrochemical method, it is important that both the oxi-
dant and the base are generated with an accurate molar
ratio so that the acidity of the whole system does not
change in the course of the reaction.
To further confirm the viability of this mechanism, XI,
prepared by the reported method,[17] smoothly supported
the electrochemical oxidation of 1a,b into 2a,b [Eq. (8)].
Thus, in place of the electrochemical method, chemical
methods including a combination of heterogeneous base and
oxidant were constructed for this catalytic system.
axial position that might be easily oxidized; this is not the
case in 1 f.
Oxidation potentials: Oxidation peak potentials of materials
used in these oxidations were measured by cyclic voltamme-
try. The results are shown in Table 3. The most oxidizable
Table 3. Oxidation peak potentials observed by cyclic voltammetry.
Entry
Substrates
Oxidation potential [V][a]
Chemical oxidation: Based on the speculated mechanism, a
similar chemical process has been examined. The oxidation
of cis-1,2-cyclooctanediol (1e) into 2-hydroxycyclooctanone
(2e) was carried out by using V (0.1 equiv) with a variety of
chemical oxidants and solvents at 08C [Eq. (9)]. The results
are summarized in Table 4.
1
2
3
4
5
6
Et4NBr
Me2SnCl2 (V)
diol 1e
mixture of 1e/V
a-hydroxyketone 2e
mixture of 2e/V
1.15
>3.0
2.13
2.04
2.59
2.59
[a] Cyclic voltammograms were recorded on each substrate solution
(10 mm) in MeCN containing Et4NBF4 (0.1m): Glassy carbon disk work-
ing electrode (1.6 mm); scan rate: 0.1 VsÀ1; Ag/AgNO3 as reference.
species was BrÀ, whereas Me2SnCl2 (V) was hardly oxidized
(entries 1 and 2). The intriguing point is that the oxidation
potential of 1,2-cis-cyclooctanediol (1e) shifted by À90 mV
in the presence of V (entries 3 and 4). On the other hand,
such a negative shift was not observed in the oxidation po-
tential of a-hydroxyketone 2e (entries 5 and 6).
Bromine (Br2) worked well as an oxidant for 1e in metha-
nol in the presence of K2CO3 as a heterogeneous base
(Table 4, entries 1 and 2), whereas iodine was not effective
Reaction mechanism for electrochemical oxidation: A plau-
sible reaction mechanism for the electrochemical oxidation
of 1,2-diols 1 is shown in Scheme 4. Dimethylstannylene
Table 4. Chemical oxidation of 1e by using a halogen cation species.
Entry
Oxidant
([equiv])
Solvent
Base
([equiv])
Reaction
Yield [%][a]
A
E
t
of 2e
1
2
3
4
5
6
7
8
Br2 (1.2)
Br2 (2.0)
Br2 (2.0)
I2 (1.2)
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
MeOH
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
AcOEt
AcOEt
MeCN
MeCN
K2CO3 (3.0)
K2CO3 (3.0)
–
K2CO3 (3.0)
–
–
–
K2CO3 (3.0)
–
–
-
30 min
30 min
30 min
3 h
3 h
3 h
3 h
30 min
3 h
3 h
3 h
3 h
3 h
30 min
3 h
30 min
3 h
71
79
24
4
NCS (1.2)
NBS (1.2)
NIS (1.2)
Br2 (1.2)
NBS (1.2)
NBS (2.0)
NIS (1.2)
NIS (2.0)
NIS (2.0)
Br2 (1.2)
NIS (2.0)
Br2 (1.2)
NIS (2.0)
trace
37
24
38
21
27
54
82
83
64
73
52
70
9
10
11
12
13
14
15
16
17
–
K2CO3 (3.0)
K2CO3 (3.0)
–
K2CO3 (3.0)
–
Scheme 4. Reaction mechanism for the electrochemical oxidation of 1,2-
diols.
[a] Isolated yield.
Chem. Eur. J. 2009, 15, 5364 – 5370
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O. Onomura et al.
(entry 4). The absence of K2CO3 led to a low yield (entry 3).
The use of dichloromethane, ethyl acetate, or acetonitrile as
the solvent in combination with Br2 as the oxidant afforded
a lower yield of 2e compared to when methanol was used
(entries 8, 14 and 16). NBS and N-iodosuccinimide (NIS)
oxidized 1e albeit in low yields in the absence of K2CO3 in
methanol (entries 6 and 7), whereas N-chlorosuccinimide
(NCS) hardly oxidized 1e (entry 5). In the case of NIS, the
yields of 2e improved when using other solvents, such as di-
chloromethane, ethyl acetate, or acetonitrile (entries 11, 15,
and 17). The use of 2.0 equivalents of NIS in dichlorome-
thane gave optimal reaction conditions. Addition of K2CO3
did not affect the yield of 2e (entries 12 and 13).
Although the yield of 2e was slightly lower than that ob-
tained when using the electrochemical method (87% yield,
Table 2, entry 4), this procedure was very convenient.
Next, the chemical oxidation of various 1,2-diols 1a–e by
using V was examined under the two optimized reaction
conditions: 1) method A: 2.0 equivalents of Br2, 0.1 equiva-
lents of V, and 3.0 equivalents of K2CO3 in methanol and
2) method B: 2.0 equivalents of NIS and 0.1 equivalenst of
V in dichloromethane [Eq. (10)]. The results are summar-
ized in Table 5.
conditions at 08C in methanol with interesting selectivity.
Also, the corresponding chemical oxidation with Br2 or NIS
was exploited for a convenient oxidation method. Since the
presented catalytic reaction proceeds by the selective activa-
tion of diols, the tolerance level of the oxidation technique
to coexisting functional groups could be controlled by the
proper choice of these chemical oxidants. The presented
procedure showed the following characteristics: 1) cyclic 1,2-
diols of various ring sizes could be oxidized into a-hydroxy-
ketones; 2) the reaction discriminated between 1,2-diols and
isolated hydroxyl groups or 1,3-diols; 3) The axial hydroxyl
group was oxidized exclusively if the ring conformation was
restricted (this information is useful for the prediction of re-
sults for the oxidation of cyclic diols); 4) dialkylated tin di-
halide compounds have good catalytic activity for the oxida-
tion and this made the procedure absolutely one step. Dime-
thyltin dichloride V was singled out as a suitable catalyst be-
cause of its solubility in organic solvents and good catalytic
activity for oxidation of both the cyclic- and acyclic 1,2-
diols. This result avails the possibility to design new catalysts
for other selective oxidations.
Experimental Section
General: Electrochemical reactions
were carried out by using
a DC
Power Supply (GP 050–2) from Taka-
sago Seisakusho, Inc. HPLC analyses
were achieved by using a LC-10AT
VP and a SPD-10A VP of Shimadzu
Seisakusho, Inc. 1H and 13CNMR
spectra were measured at 300 and
Table 5. Chemical oxidation of 1,2-diols mediated by V.
Entry
1,2-Diol
Product
Yield [%][a] of 2
Method A MethodB
75 MHz on a Varian Gemini 300 spectrometer or on a Varian UNITY-
plus 500 MHz NMR spectrometer with TMS as an the internal standard.
All melting points were measured on MICRO MELTING POINT AP-
PARATUS (Yanaco) and are uncorrected. IR spectra were obtained on a
Shimadzu FTIR-8100A. Mass spectra were obtained on a JEOL JMS-
DX 303 instrument.
1
2
3
4
1a
1b
1c
1d
1e
1e
1 f
1i
2a
2b
2c
2d
2e
2e
2a
2i
82[b,c]
86
84[c]
26
94[c]
74
54[c]
73
All reagents and solvents were used as supplied without further purifica-
tion. Organotin catalysts I–X, diols 1a–c, 1e–g, and 4, monol 3, and triols
1h,i were commercially available. Diols 1d,[18] 1j,[19] and 1k[20] were pre-
pared by osmium oxidation of cycloheptene, cis-2-decene, and ethylid-
5
79
82
6[d]
7
75
72
91[c]
62
81[c]
57
8
AHCTUNGTRENNUNG
enecyclohexane, respectively. Diol 1l[21] was synthesized by the reaction
[a] Isolated yield unless otherwise noted. [b] 1.2 equivalents of Br2 was
used. [c] Determined by GC analysis. [d] XI was used instead of V.
of 2b[22] with a large excess of methylmagnesium iodide. a-Hydroxyke-
tones 2a,[23] 2c,[23] 2d,[24] 2e,[24] 2g[24] (its O-benzoylated derivative[25]), 1,3-
dibenzoyloxyacetone[26] derived from 2h, 2i,[27] 2j,[28] 2j’,[29] and 2k[29] are
known compounds.
Method A was applicable to the oxidation of 1a–f,i to
afford 2a–e,i in good to high yields. On the other hand,
method B was applicable to the effective oxidation of 1a,c–
f,i, but it was not effective for the oxidation of 1,2-dodeca-
nediol 1b. Moreover, catalyst XI could also be used for the
oxidation (Table 5, entry 6).
Preparation of 1,2-diols
4-tert-Butyl-1,2-cyclohexanediol (1m,n): A solution of 4-tert-butylcyclo-
hexanol (15.6 g, 100 mmol) in dimethylsulfoxide (20 mL) in
a flask
equipped with a reflux condenser was heated up to 1808C in an oil bath.
After 24 h, distillation afforded crude 4-tert-butylcyclohexene (6.2 g) as
an oil. A solution of N-methylmorpholine-N-oxide (17.6 g, 150 mmol) in
acetonitrile (30 mL) containing water (5 mL) was carefully degassed by
nitrogen bubbling. The crude 4-tert-butylcyclohexene and aqueous OsO4
(3% w/v, 3 mL) were added to the degassed solution and stirred for 17 h
at ambient temperature. After the usual workup, diols 1m and 1n were
obtained as an 1:1 mixture (determined by the integral intensity of
1H NMR spectra); 33% from starting 4-tert-butylcyclohexanol. The mix-
ture of 1m and 1n was treated with benzoylchloride in the presence of 4-
dimethylaminopyridine in dichloromethane (50 mL) to give a mixture of
diastereomers 4m and 4n in 98% yield. The mixture was separable by
Conclusion
We have presented an organotin-catalyzed oxidation of 1,2-
diols into a-hydoxyketone by means of an electrochemical
procedure in which the oxidation proceeded under neutral
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Chem. Eur. J. 2009, 15, 5364 – 5370

Efficient Oxidation of 1,2-Diols
FULL PAPER
silica-gel column chromatography (n-hexane/AcOEt 20:1, polar isomer:
4m, less polar isomer: 4n). The stereochemistry of these isomers was
confirmed by observation of a NOE effect between 1H NMR spectro-
scopic signals of axial protons at C2, C4, and C6 in 4m, and at C1, C3,
and C5 in 4n (Figure 1).
Oxidation of 1b: Aqueous sat. NaCl (10 mL) was added to the resulting
reaction mixture. The organic portion was extracted with AcOEt (3ꢁ
40 mL). After the organic layer had been dried over MgSO4, the solvent
was removed in vacuo. The residue was subjected to silica-gel column
chromatography (n-hexane/AcOEt 10:1) to afford 2b.
Electrochemical oxidation of 1,2-diols by using I–XI: General procedure:
A solution of 1,2-diol 1a (1.0 mmol) and tin catalyst V (0.1 mmol) in
methanol (5 mL) was poured into a glass cell equipped with a platinum
anode and cathode (1 cmꢁ2 cm). Et4NBr (1.0 mmol) was added to the
solution as a supporting electrolyte and also mediator. Then the mixture
was subjected to constant current electrolysis (100 mA) at 08C until 1a
disappeared on TLC.
cis-3-tert-Butyl-2-hydroxycyclohexanone (2m): White solid; m.p. 64–
678C; H NMR (CDCl3): d=0.86–0.96 (m, 9H), 1.32 (q, J=12.5 Hz, 1H),
Figure 1. NOE experiment of 4m and 4n.
1
1.44 (dq, J=4.2, 12.9 Hz, 1H), 1.65 (tt, J=3.0, 12.7 Hz, 1H), 2.12 (m,
1H), 2.38 (m, 1H), 2.47 (m, 1H), 2.56 (m, 1H), 3.32 (m, 1H), 4.16 ppm
(m, 1H); 13C NMR (CDCl3): d=27.55, 28.4, 32.3, 35.8, 38.3, 45.1, 74.8,
211.6 ppm; IR: n˜ =3488, 2967, 2870, 1727, 1678, 1397, 1368, 1109, 1090,
872 cmÀ1; HR-EI: calcd for C10H18O2: 170.1307 [M]+; found: 170.1307.
1
1,2,4-cis-Dibenzoate (4m): White solid; m.p. 90–928C; H NMR (CDCl3):
d=0.96 (s, 9H), 2.34–2.49 (m, 2H), 2.64–2.73 (m, 2H), 2.81 (q, J=
10.1 Hz, 1H), 2.01–2.07 (m, 1H), 2.18–2.24 (m, 1H) 5.18 (ddd, J=2.7,
4.7, 11.8 Hz, 1H), 5.61 (brs, 1H), 7.29–7.34 (m, 2H), 7.44–7.50 (m, 3H),
7.56–7.60 (m, 1H), 7.89–7.93 (m, 2H), 8.03–8.12 ppm (m, 2H); 13C NMR
(CDCl3): d=20.5, 27.4, 27.6, 28.9, 32.4, 45.9, 69.7, 73.9, 128.1, 128.4,
129.4, 129.5, 130.2, 130.6, 132.7, 132.8, 165.55, 165.61 ppm; IR: n˜ =2961,
2870, 1721, 1451, 1316, 1175, 1098, 710 cmÀ1; HR-EI: m/z: calcd for
C24H28O4: 380.1988 [M]+; found: 380.1988.
1,2-cis-1,4-trans-Dibenzoate (4n): White solid; m.p. 95–988C; 1H NMR
(CDCl3): d=0.89 (s, 9H), 1.23–1.36 (m, 1H), 1.48–1.60 (m, 2H), 1.95–
2.08 (m, 3H), 2.17–2.21 (m, 1H), 5.09–5.12 (m, 1H), 5.71 (brs, 1H), 7.29–
7.31 (m, 2H), 7.43–7.52 (m, 3H), 7.58–7.61 (m, 1H), 7.89–7.93 (m, 2H),
8.07–8.15 ppm (m, 2H); 13C NMR (CDCl3): d=25.0, 26.6, 27.5, 30.6, 32.0,
41.0, 70.8, 73.5, 128.2, 128.4, 129.5, 129.6, 130.2, 130.7, 132.8, 132.9,
165.76, 165.82 ppm; IR: n˜ =2957, 2870, 1719, 1281, 1451, 1366, 1117,
1096, 712 cmÀ1; HR-EI: m/z: calcd for C24H28O4: 380.1988 [M]+; found:
380.1995.
trans-5-tert-Butyl-2-hydroxycyclohexanone (2n): White solid; m.p. 64–
678C; 1H NMR (CDCl3): d=0.86–0.94 (m, 9H), 1.40–1.53 (m, 2H), 1.72
(brs, 1H), 1.94 (dt, J=1.3, 10.0 Hz, 1H), 2.15 (t, J=13.0 Hz, 1H), 2.46
(dt, J=2, 4.6 Hz, 1H), 2.60 (dd, J=3.0, 13.0 Hz, 1H), 3.47 (s, 1H),
4.12 ppm (dd, J=7.0, 11.5 Hz, 1H); 13C NMR (CDCl3): d=24.4, 27.15,
32.7, 35.2, 40.95, 50.4, 75.0, 211.9 ppm; IR: n˜ =3490, 2971, 2872, 1728,
1678, 1480, 1451, 1429, 1331, 1161, 1119, 1059, 963, 858, 747 cmÀ1; HR-
EI: calcd for C10H18O2: 170.1307 [M]+; found: 170.1307.
Configuration of 2m and 2n were confirmed by observation of the NOE
between 1H NMR spectroscopic signals of axial protons at C2, C4, and
C6 in 2m, and at C2, C4, and C6 in 2n (Figure 2).
Alkaline hydrolysis of 4m and 4n afforded pure 1m and 1n, respectively,
as single isomers in quantitative yields.
1,2-cis-1,4-cis-isomer (1m): White solid; m.p. 104–1058C; 1H NMR
(CDCl3): d=0.88 (s, 9H), 0.99–1.06 (m, 1H), 1.12–1.49 (m, 4H), 1.72
(brd, 1H), 1.90–2.01 (m, 1H), 2.25 (brs, 1H), 3.55–3.65 (m, 1H),
3.94 ppm (brs, 1H); IR: n=3373, 2970, 2003, 1437, 1238, 1069,
Figure 2. NOE experiment of 2m and 2n.
1001 cmÀ1
172.1463.
;
HR-EI: m/z: calcd for C10H20O2: 172.1463 [M]+; found:
Oxidation of 1g: After the solvent had been removed in vacuo, dichloro-
methane (5 mL), 4-dimethylaminopyridine (1.7 mmol), and benzoylchlor-
ide (1.5 mmol) were added to the residue at 08C. After the mixture had
been stirred for 12 h, aqueous saturated Na2CO3 (10 mL) was added. The
organic portion was extracted with CH2Cl2 (3ꢁ20 mL). After the organic
layer had been dried over MgSO4, the solvent was removed in vacuo.
The residue was subjected to silica-gel column chromatography (n-
hexane/AcOEt 5:1) to afford 2g.
1,2-cis-1,4-trans-isomer (1n): White solid; m.p. 78–798C; 1H NMR
(CDCl3): d=0.84–0.88 (m, 9H), 0.92–1.82 (m, 6H), 1.90–2.05 (m, 1H),
2.50 (brs, 1H), 3.47–3.63 (m, 1H), 4.02 ppm (brd, 1H);IR: n˜ =3390,
2950, 2870, 1366, 1071, 988, 902, 828 cmÀ1
; HR-EI: m/z: calcd for
C10H20O2: 172.1463 [M]+; found: 172.1466.
Measurement of oxidation potentials: BAS CV-50W was used as a volta-
metric analyzer. A solution of substrate (0.1 mmol) in MeCN (10 mL)
containing 0.1m Et4NBF4 was measured. The reference electrode was Ag/
AgNO3 in saturated aqueous KCl, whereas glassy carbon was the work-
ing electrode, and platinum wire was the counter electrode. The scan rate
Oxidation of 1h: After the solvent had been removed in vacuo, dichloro-
methane (10 mL), 4-dimethylaminopyridine (3.4 mmol), and benzoyl-
chloride (3.0 mmol) were added to the residue at 08C. After the mixture
had been stirred for 12 h, aqueous sat. Na2CO3 (20 mL) was added. The
organic portion was extracted with CH2Cl2 (3ꢁ20 mL). After the organic
layer had been dried over MgSO4, the solvent was removed in vacuo.
The residue was subjected to silica-gel column chromatography (n-
hexane/AcOEt 5:1) to afford 2h.
was 100 mVsÀ1
.
Electrochemical oxidation of 1,2-diols 1a or 1b by using I or II under
preheating conditions: General procedure: A solution of 1,2-diol 1a or
1b (1.0 mmol) and tin oxide I (0.1 mmol) in methanol (5 mL) was heated
at reflux for 1 h before electrolysis. The resulting solution was transferred
into a glass cell equipped with a platinum anode and cathode (1ꢁ2 cm).
Et4NBr (1.0 mmol) was added to the solution as a supporting electrolyte
and also mediator. Then, the mixture was subjected to constant current
electrolysis (100 mA) at 08C until 1a or 1b disappeared, as determined
by TLC.
Chemical oxidation of 1,2-diols by using V and Br2: General procedure:
Bromine (1.0 mmol) was added dropwise at 08C under dark conditions
to a solution of 1,2-diol 1e (0.5 mmol), tin catalyst V (0.05 mmol), and
K2CO3 (1.5 mmol) in methanol (2 mL). After the reaction mixture had
been stirred for 30 min, aqueous sat. Na2S2O3 (10 mL) was added. The or-
ganic portion was extracted with AcOEt (3ꢁ40 mL). After the organic
layer had been dried over MgSO4, the solvent was removed in vacuo.
The residue was subjected to silica-gel column chromatography (n-
hexane/AcOEt 5:1) to afford 2e.
Oxidation of 1a: A solution of n-dodecane (1 mmol) in CH2Cl2 was
added to the resulting reaction mixture. The yield of 2a was determined
by GLC.
GLC conditions: DB-1 (J&W SCIENTIFIC) 30 mꢁ0.25 mmf; P:
100 kP; T: initial: 808C (5 min), then the temperature rose by 58CminÀ1
retention time: 5.9 (2a), 3.9 (2c), 13.5 min (n-dodecane).
,
Chemical oxidation of 1,2-diols by using V and NIS: General procedure:
NIS (1.0 mmol) was added at 08C under dark conditions to a solution of
Chem. Eur. J. 2009, 15, 5364 – 5370
ꢀ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
5369

O. Onomura et al.
1,2-diol 1e (0.5 mmol) and tin catalyst V (0.05 mmol) in dichloromethane
(2 mL). After the reaction mixture had been stirred for 3 h, aqueous sat.
Na2S2O3 (10 mL) was added. The organic portion was extracted with
chloroform (3ꢁ30 mL). After the organic layer had been dried over
MgSO4, the solvent was removed in vacuo. The residue was subjected on
silica-gel column chromatography (n-hexane/AcOEt 5:1) to afford 2e.
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Acknowledgements
This work was supported by the Naito Foundation.
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Received: January 20, 2009
Published online: April 6, 2009
5370
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