Sodium Hypochlorite Pentahydrate as a Reagent for the Cleavage of trans-Cyclic Glycols

Article abstract of DOI:10.1021/acs.joc.9b01132

Sodium hypochlorite pentahydrate (NaOCl·5H₂O) can be used toward the efficient glycol cleavage of trans-cyclic glycols, which are generally resistant to this transformation. Interestingly, the reaction of cis-cyclic glycols with NaOCl·5H₂O is slower than that observed for the corresponding trans-isomer. This trans selectivity is in sharp contrast to traditional oxidants used for glycol cleavage. Acyclic glycols can also react efficiently with NaOCl·5H₂O to form their corresponding carbonyl compounds in high yield.

Full text of DOI:10.1021/acs.joc.9b01132

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Note
Sodium Hypochlorite Pentahydrate as a Reagent
for the Cleavage of trans-Cyclic Glycols
Masayuki Kirihara, Rie Osugi, Katsuya Saito, Kouta Adachi,
Kento Yamazaki, Ryoji Matsushima, and Yoshikazu Kimura
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01132 • Publication Date (Web): 22 May 2019
Downloaded from http://pubs.acs.org on June 4, 2019
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Sodium Hypochlorite Pentahydrate as a Reagent for the Cleavage of trans-Cyclic Glycolsꢀ
a*
a
a
a
a
a
Masayuki Kirihara, Rie Osugi, Katsuya Saito, Kouta Adachi, Kento Yamazaki, Ryoji Matsushima, and
Yoshikazu Kimura b
aDepartment of Materials and Life Science, Shizuoka Institute of Science and Technology, 2200-2 Toyosawa,
Fukuroi, Shizuoka 437-8555, Japan
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bResearch and Development Department, Iharanikkei Chemical Industry Co. Ltd., Kambara, Shimizu-ku,
Shizuoka 421-3203, Japan
R1
O
NaOCl·5H O (3 eq.)
2
R1
OH
OH
R2
Bu NHSO (10 mol%)
4
4
O
CH Cl , H O
2
2
2
R2
trans
cis
very fast
R1
The same condition
OH
OH
slow
Opposit reactivity to the conventional
reagents [Pb(OAc) , NaIO , Ph(IOAc) ]
2
R
4
4
2
ABSTRACT: Sodium hypochlorite pentahydrate (NaOCl·5H O) can be used toward the efficient glycol cleavage
2
of trans-cyclic glycols, which are generally resistant to this transformation. Interestingly, the reaction of cis-cyclic
glycols with NaOCl·5H O is slower than that observed for the corresponding trans-isomer. This trans selectivity
2
is in sharp contrast to traditional oxidants used for glycol cleavage. Acyclic glycols can also react efficiently with
NaOCl·5H O to form their corresponding carbonyl compounds in high yield.
2
The cleavage of bicyclic bis-tertiary glycols such as octahydronaphthalene- 4a,8a-diol (1a) is an attractive
procedure for the synthesis of macrocyclic compounds.1-3 For example, Paquette and co-workers have reported
that 1a can be prepared as a 3:1 diastereomeric mixture upon reaction of cyclohexane-1,2-dione with allyl indium
followed by metathesis using 1st generation Grubbs catalyst and hydrogenation (Scheme 1). They then performed
the glycol cleavage reaction of 1a using lead tetraacetate [Pb(OAc) ] to produce the desired ten-membered ring
4
diketone (2a).2a,b
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Scheme 1. Synthesis of 2a achieved by Paquette et al.
Br
1
2
) In,
OH
O
O
O
) Grubbs 1st
Pb(OAc)4
CH Cl
3
) H , Pd/C
2
2
2
OH
O
2a (79%)
1
a (88% in 3 steps)
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In general, the cleavage of sterically-hindered cyclic glycols, especially trans-glycols, is not easy using reagents
4
other than Pb(OAc) . However, there are serious drawbacks when using Pb(OAc) . It is highly toxic, and no less
4
4
than a stoichiometric amount of reagent is required for the reaction, which produces a large amount of toxic lead
diacetate over the course of the reaction. Recently, less toxic hypervalent iodine reagents, such as phenyliodine
5
diacetate [PhI(OAc) ], have been used as an alternative to Pb(OAc) by Krische and co-workers. The method,
2
4
however, are required stoichiometric amount (1.2 equiv) of the relatively expensive PhI(OAc) reagent.
2
To avoid the use of large amounts of toxic [Pb(OAc) ] or expensive [PhI(OAc) ] reagents, we have explored
4
2
6
the use of several alternative oxidants, and discovered that sodium hypochlorite pentahydrate crystals
NaOCl·5H O) is an extraordinary reagent for glycol cleavage. (Table 1, run 6) The reagent reacts easily with
(
2
hindered trans-glycols (such as trans-1a), which are not particularly reactive using classical oxidants, to form the
corresponding dicarbonyl compounds.
We initially focused on aqueous sodium hypochlorite (aq. NaOCl) is an inexpensive and environmentally-
7
benign oxidant which has been previously reported to carry out glycol cleavage. However, aq NaOCl was useless
for the oxidative cleavage of cis- and trans-1a. (Table 1, runs 1-4) The reaction of these compounds with
NaOCl·5H O was next approached, because we recently have reported that NaOCl·5H O is a superior reagent to
2
2
8
conventional aq. NaOCl in the oxidation of organic compounds. For comparison, we also examined the reaction
9
10
with conventional reagents including sodium periodate (NaIO ), Pb(OAc) and PhI(OAc) . Our results are
4
4
2
summarized in Table 1.
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Table 1. Glycol cleavage of cis-1a and trans-1a using several oxidants
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9
1
1
1
1
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1
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5
5
5
6
OH
OH
O
oxidant
or
solvent
r.t.
OH
cis-1a
OH
trans-1a
O
2a
Run
Reaction Condition
Substrate Time (h) Yield of
2
a (%)
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3
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a
1
2
aq. 13% NaOCl (3 eq.) cis-1a
5
5
N.R.
N.R.
CH CN
3
trans-1a
a
aq. 13% NaOCl (3 eq.)
Bu NHSO (10 mol%)
2b
6b
3
4
cis-1a
4
4
4
trans-1a
1
CH Cl2
2
NaOCl· 5H O (3 eq.)
Bu NHSO4 (10 mol%)
5
6
2
cis-1a
2
76
93
4
trans-1a
0.2
CH Cl / H O
2
2
2
7
8
cis-1a
50
70
74
NaIO (6 eq.)
THF / H O
4
2
trans-1a
N.R.
9
Pb(OAc) (2.2 eq.)
cis-1a
0.3
79
33
4
1
0
2
CH Cl2
trans-1a
117
1
1
1
2
PhI(OAc) (6 eq.)
cis-1a
2.6
52
89
64
2
2
CH Cl2
trans-1a
aCommercial aqueous solution (Nikkei ZiasoTM) was used.
bMost of 1a was recovered.
As shown in Table 1, NaOCl·5H O exhibited excellent results (runs 5 and 6) more than another reagent
2
1
1
systems. Surprisingly, NaOCl·5H O reacted with trans-1a much faster than cis-1a to produce 2a in high yield.
2
This result was in sharp contrast to that observed using conventional reagents [NaIO , Pb(OAc) and PhI(OAc) ],
4
4
2
which prefer cis-1a as the substrate in the glycol cleavage reaction. Conventional reagents cause glycol cleavage
12
via a cyclic intermediate. Therefore, glycols that retard the formation of this cyclic intermediate, (such as trans-
1
a) are not good substrates for the reaction. The unique reactivity of NaOCl·5H O means that the mechanism of
2
glycol cleavage using NaOCl·5H O is completely different from that of conventional glycol cleavage reagents.
2
(
vide infra)
We envisage that NaOCl·5H O will be a superior reagent for the glycol cleavage reaction of sterically hindered
2
trans-cyclic glycols which are difficult to react with conventional reagents. The reactions of several trans-cyclic
glycols (trans-1a d) with NaOCl·5H O were examined, and the results are shown in Table 2.
2
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The reactions using conventional reagents [NaIO , Pb(OAc) ] were also examined for comparison. For
4
4
NaOCl·5H O, each trans-cyclic glycol reacted rapidly to form the corresponding carbonyl compound in high
2
yield. Conversely, NaIO did not show any reactivity with the trans-cyclic glycols studied. Although Pb(OAc)
4
4
reacted with trans-cyclic glycols to produce the desired products, the reactions proceeded slowly and provided
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the product in lower yield.
Table 2. Glycol cleavage of sterically hindered trans-cyclic glycols
O
R1
oxidanta
R1
R2
OH
OH
R2
O
solvent, rt
NaOCl·5H O (3 eq.)
Bu NHSO (10 mol%)
Pb(OAc)4
2.2 eq.)
CH Cl
2
(
4
4
Glycol (1)
Products
CH Cl / H O
2
2
2
2
2
OH
O
33% (117 h)b
9
3% (0.2 h)
trans-1a
OH
O
2a
HO OH
Ph Ph
Ph
Ph
O
O
quant (0.2 h)
92% (3 h)
2
b
trans-1b
O
HO
OH
H
27% (25 h)b
90% (0.2 h)
O
(2c:70%)
(2c: trace)
(3c: 27%)
(
3c: 20%)
R
trans-1c
2c (R=H)
c (R=OH)
3
C H
8
17
30% (25 h)c
H
89% (0.6 h)
2d: 69%)
(3d: 20%)
H
(
(2d only)
H
H
H
O
AcO
O
HO
AcO
OH
trans-1d
R
2
3
d (R=H)
d (R=OH)
a
NaIO (6 eq.) did not react with any grycols on this table in THF-H O for 25 h or more.
4
2
b
While the starting material (trans-1c) disappeared, several unidentified by-products were
produced.
c
Much of the starting material (trans-1d) remained unreacted.
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Subsequently, we examined the glycol cleavage of cis-1d (Scheme 2). cis-1d immediately reacted with
Pb(OAc) to produce the desired products in quantitative yield. Interestingly, NaOCl·5H O hardly reacted with
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9
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1
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1
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1
1
2
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3
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6
4
2
cis-1d and produced only a trace amount (< 1%) of the desired glycol cleavage compound (2d). After 20.8 h, a
significant amount of unreacted cis-1d remained in the reaction mixture, and the corresponding hydroxyl ketone
0
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(
4d) was obtained as the major product (36% yield) together with several unidentified by-products.
Scheme 2. Reaction of cis-1d with Pb(OAc) or NaOCl·5H O
4
2
C8H17
C8H17
Pb(OAc)4
(2.2 eq.)
H
H
H
O
H
H
H
H
CH2Cl2
15 min
O
AcO
AcO
HO
OH
cis-1d
Glycol cleavage
2
d (quant.)
C8H17
NaOCl·5H2O
(3 eq.)
Bu4NHSO4
(10 mol%)
H
unreacted
cis-1d (18%)
H
O
H
+
AcO
CH2Cl2 / H2O
+
HO
2d (trace)
2
0.8 h
Glycol cleavage
4d (36%)
hydroxyketone
with several
unidentified by-products
When an equimolar mixture of cis-1e and trans-1e was treated with NaOCl·5H O under the same reaction
2
conditions, the selective reaction of trans-1e was observed with cis-1e recovered in almost quantitative yield
(
Scheme 3). The control experiment clearly exhibits that the cleavage of trans-glycol is much faster than that of
cis-glycol.
Scheme 3. Glycol cleavage of an equimolar mixture of cis- and trans-1d using NaOCl·5H O
2
C8H17
C8H17
H
H
H
H
H
H
AcO
NaOCl·5H O
(0.25 mmol)
2
AcO
HO
HO
OH
OH
cis-1d (0.25 mmol)
Bu4NHSO4
cis-1d (unreacted)
(95%)
(
0.025 mmol)
+
+
H
H
CH2Cl2 / H2O
30 min
H
H
H
H
O
AcO
O
AcO
HO
AcO
HO
OH
OH
H
trans-1d (0.25 mmol)
2d (70%)
trans-1d (unreacted)
30%)
(
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Next, the reactions of several acyclic glycols (1e-j) using NaOCl·5H O were then investigated (Table 3).
2
Glycol cleavage was observed in all cases and the corresponding aldehydes, carboxylic acids, and ketones were
obtained in high yield. The glycol substrate containing a cyclopropyl moiety (1j) provided the corresponding
cyclopropyl phenyl ketone (2j) as the sole product. Allyl phenyl ketone (2j’) was not observed (Table 3, run 6).
This result meant that radical intermediates were not produced during the glycol cleavage reaction.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
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Table 3. Glycol cleavage of acyclic-glycols
NaOCl·5H2O (3 eq.)
O
O
HO OH
R1
Bu4NHSO4 (10 mol%)
CH Cl2 / H O, r.t.
+
2
R1
R3
R2
R4
R
R3
R
4
2
2
Run
Glycol
OH
Time (h)
Products
5%a
7
O
1
Ph
a
0.3
2e(40% R=H)
Ph
a
Ph
R
3e (35% R=OH)
OH
OH
1
e
75%b
2f (68% R=H)
O
R
2
(p-OMe)Ph
.3
b
(
p-OMe)Ph
0
(p-OMe)Ph
R
b
3f (7% R=OH)
OH
1
f
OH
78%a
g (2%a R=H)
O
3
4
Ph
2
Ph
6
Ph
a
3
g (76% R=OH)
OH
1g
Bu OH
Ph
O
93%a
a
Ph
0.3
2e (92% R=H)
Ph
Ph
R
a
3e(1% R=OH)
OH
1
hc
O
2h (quanta)
Bu
HO OH
Ph Ph
O
5
6
2i (82%d)
0.5
1
Ph Ph
Ph
Ph
1
i
O
O
OH
Ph
Ph
Ph
Ph
2j'
HO
j (89%d)
not detected
1
j
2
a
b
c
d
GC-yield using 1-chloronaphthalene as an internal standard.
GC-yield using decalin as an internal standard.
2.0 eq. NaOCl・5H2O was used.
Isolated yield.
A plausible reaction mechanism for the glycol cleavage of trans- and cis-1a using NaOCl·5H O is shown in
2
1
3
8b
Scheme 4. Hypochloric acid (HOCl) derived from NaOCl·5H O and Bu NHSO may be the active species,
2
4
4
which reacts with one of the hydroxyl groups in the glycol substrate to form hypochlorite intermediate (A). In the
case of the trans-isomer, the resulting hypochlorite substituent and the unreacted hydroxyl group of trans-A are
fixed in an anti-periplanar configuration, and therefore, a Grob-type fragmentation occurs immediately to produce
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the desired product (2a). On the other hand, cis-A must be syn-periplanar for the glycol cleavage reaction to occur,
but this conformation is not thermodynamically favorable for cis-A. Therefore, cis-1a reacts much slower than
trans-1a. In the case of cis-1d, since the syn-periplanar conformation of either mono-chlorinated intermediate (B,
B’) are unfavored, the glycol cleavage reaction is very difficult. The secondary alcohol in cis-1d was oxidized to
the corresponding carbonyl group via intermediate B to form 4d.
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
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3
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3
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4
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4
4
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5
5
5
5
5
5
5
5
6
0
1
2
3
4
5
6
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8
9
0
1
2
3
4
5
6
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8
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0
1
2
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0
1
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3
4
5
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0
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8
9
0
Scheme 4. A plausible reaction mechanism for glycol cleavage reaction.
Cl
OH
OH
O
HOCl
fast
OH
O
OH
H
trans-A
O
trans-1a
anti-periplaner
Cl
O
OH
OH
OH
O
HO
HOCl
O
2a
slow
H
cis-A
cis-1a
syn-periplaner
(
unfavorable
conformation)
H3C
H3C
H3C
H
AcO
AcO
AcO
HOCl
O
OH
O
HO
HO
4d
HO
Cl
B
cis-1d
HOCl
H3C
AcO
OH
O
Cl
B'
In order to prove hypochloric acid (HOCl) is an active species, the reaction of trans-1a in dichloromethane
with aqueous HOCl prepared from NaOCl·5H O being adjusted to pH 5- 6 upon adding conc. HCl was examined.
2
In this biphasic mixture trans-1a in the organic phase was slowly converted to 2a (Scheme 5). This result indicates
that HOCl in the aqueous phase was gradually transferred into the organic phase and reacted with trans-1a to
cause glycol the cleavage reaction. This result strongly suggests that HOCl is the active species.
Scheme 5. The reaction of trans-1a with aq. HOCl.
NaOCl·5H2O (1.5 mmol)
H2O (1.5 mL)
aq. NaOCl
aq. HCl
OH
O
aq. HOCl (pH 5.9)
r.t., 1.5 h
CH2Cl2
0.5 mL)
OH
trans-1a
0.5 mmol)
O
(
2a (62%)
(
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Although conventional aq. NaOCl has been used as an oxidant for glycol cleavage, it is not effective in
cleaving highly hindered bicyclic glycol 1a, as shown in Table 1 (runs 1- 4). This is because aq. NaOCl is not
effective to have high pH value (>13) compared to be low pH (10 11) of NaOCl·5H O crystals in several
2
8
oxidation reactions. Therefore, the effect of pH on the glycol cleavage reaction was examined using 1e as a
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substrate (Table 4). Although the reaction rate of the glycol cleavage of 1e using conventional aq. 13% NaOCl
was slow to be recovered a half of 1e (run 2), the reaction of 1e using aq. 13% NaOCl prepared from NaOCl·5H O
2
and water exhibited faster (run 1). Furthermore, conventional aq. NaOCl adjusted using hydrochloric acid to
lower the pH (run 3) gave results similar to those of aq. NaOCl prepared from NaOCl·5H O, but they were not
2
identical.
Table 4. Effect of pH on glycol cleavage
aq. NaOCl (3 eq.)
Bu NHSO (10 mol%)
OH
O
O
4
4
Ph
+
Ph
Ph
H
Ph
OH
CH Cl / H O
2
2
2
OH
r.t. 0.5 h
2e
3e
1
e
pH of
Yield (GC%)
Run
aq. NaOCl
aq. NaOCl
2e
3e
35.4
1.3
Total
1
3% aq NaOCl prepared from
1
2
10.4
40.2
50.7
75.6
52.0
NaOCl·5H O and water
2
Conventional 13% NaOCl aq.
Conventional 13% NaOCl aq.
13.3
3
10.4
47.0
30.2
77.2
+
aq.HCl
Hence, we have carefully examined the reaction of trans-1a with aq. NaOCl (pH = 10) prepared from
conventional 13% aq NaOCl and hydrochloric acid (Scheme 6). Although the reaction went to completion
immediately, recyclized compound 4a, (produced via an intramolecular aldol reaction of 2a) was formed. When
several experiments were carried out under the same reaction conditions, the ratio of 2a to 4a varied widely. This
phenomenon was a difference in the reaction of trans-1a with NaOCl·5H O which consistently produced 2a as
2
the major product. Conventional aq. NaOCl is not as pure as NaOCl·5H O and contains some impurities (NaCl,
2
NaOCl etc.) which may affect the product ratio.
3
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Scheme 6. The reaction of trans-1a with aq. NaOCl (pH = 10.1) prepared from conventional 13% aq NaOCl
and aq. HCl
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4
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7
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9
1
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6
O
O
1
3% aq. NaOCl (3 eq.)
+ aq. HCl (pH = 10)
OH
+
O
2a
4aOH
OH
Bu4NHSO4 (10 mol%)
CH Cl , rt, 15 min
yields of 2a + 4a = 83~76%
ratio of 2a:4a = >99:trace ~
2
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trans-1a
29:71
In conclusion, the glycol cleavage of trans-cyclic glycols using NaOCl·5H O proceeded much faster than their
2
corresponding cis-cyclic glycols. This reactivity was in sharp contrast with that observed using the conventional
glycol cleavage oxidants for which cis-glycols react much faster. NaOCl·5H O was a superior reagent for glycol
2
cleavage of sterically hindered trans-glycols. Hypochloric acid (HOCl) derived from NaOCl·5H O was likely to
2
be the active species.
Experimental Section
General Information: All reagents were purchased from Nacalai Tesque, Wako Pure Chemicals Industries,
Kanto Kagaku, Kishida Reagents Chemical Co., Tokyo Chemical Industry or Aldrich, and used without any
further purification. Melting points were measured on a Yanaco micro melting point apparatus (MP-J3) and are
uncorrected. NMR spectra were recorded on a JEOL (JNM-EX400) spectrometer as solutions in CDCl using
3
TMS or the residual solvent peak as an internal standard. GC analyses were run on a Shimadzu GC-2014
instrument with flame-ionization detectors, equipped with an NB-1 (0.25 mm×60 m, df¼0.4 mm) GC column
using helium as the carrier gas. GC yields were determined using 1-chloronaphtalene (for the reaction of 1e, 1g
and 1h) or decalin (for the reaction of1f) as an internal standard.
Preparation of the starting materials (glycols): All of the starting materials (glycols) are known compounds.
14
14
15
16
17
Several of them were prepared according to the literature (cis-1a, trans-1a, 1b, 1c and 1d ), and one was
1
8
2a
19
20
21
purchased as a commercial reagent [benzopinacol (1j)]. Glycols 1e, 1f, 1g, 1h and 1j were prepared via
the following procedures. Most of the glycols (1e, 1f, 1g, 1h and 1j) were prepared as a mixture of diastereomers.
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,2-Diphenylethane-1,2-diol (1e). Sodium borohydride (1.14 g, 30.1 mmol) was added to a stirred solution of
benzoin (4.25 g, 20.0 mmol) in methanol (100 mL) at 0 °C and the reaction mixture was stirred at room
temperature for 80 min. Water was added and the mixture was concentrated in vacuo. The residue was partitioned
with dichloromethane and water. The organic layer was separated and dried using anhydrous sodium sulfate. The
dried extract was filtered and concentrated in vacuo to give the crude product as a white solid. Recrystallization
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from toluene methanol gave pure 1e (3.66 g, 85%) as colorless crystals.
2
a
1,2-Di-p-anisilethane-1,2-diol (1f). Sodium borohydride (0.568 g, 15.0 mmol) was added to a stirred solution
of 1,2-di-p-anisil-2-hydroxyethan-1-one (2.72 g, 10.0 mmol) in methanol (100 mL) at 0 °C and the resulting
reaction mixture was stirred at room temperature for 50 min. Water was added and the mixture was concentrated
in vacuo. The residue was partitioned with ethyl acetate and water. The organic layer was separated and dried
using anhydrous sodium sulfate. The dried extract was filtered and concentrated in vacuo to provide the crude
product as a white solid. The crude product was purified by silica gel column chromatography using hexane ethyl
2
a
acetate = 2:1 (v/v) as the eluent to give 1f (1.52 g, 50%) as pale yellow crystals.
1
,6-Diphenylhexane-3,4-diol (1g). 19 Sodium borohydride (284 mg, 7.51 mmol) was added to a stirred solution
of 1,6-diphenyl-4-hydroxyhexan-4-one(1.34 g, 5.00 mmol) in methanol (10 mL) at 0 °C and the reaction mixture
was stirred at room temperature for 40 min. Water was added and the mixture was concentrated in vacuo. The
residue was partitioned with dichloromethane and water. The organic layer was separated and dried using
anhydrous magnesium sulfate. The dried extract was filtered and concentrated in vacuo to provide the crude
product as a white solid. The crude product was purified by silica gel column chromatography using hexane
1
9
ethyl acetate = 5:1 (v/v) as the eluent to give 1g (798 mg, 63%) as colorless crystals.
1
,2-Diphenylhexane-1,2-diol (1h). 20 A hexane solution of butyllithium (1.59 M, 13.0 mL, 20.7 mmol) was
added to a stirred solution of benzoin (1.00 g, 4.71 mmol) in tetrahydrofuran (10 mL) at 78 °C under a nitrogen
atmosphere. The reaction mixture was stirred for 1 h under the same conditions. Saturated aqueous ammonium
chloride (3 mL) was added to the reaction mixture, which was then warmed to room temperature. Water (5 mL)
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was added and the resulting mixture was extracted with dichloromethane (20 mL × 3). The combined organic
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layers were dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo. The residue was purified
2
0
by silica gel column chromatography using hexane ethyl acetate = 5:1 (v/v) as the eluent to give 1h (798 mg,
6
3%) as colorless crystals.
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,2-Dicyclopropyl-1,2-diphenylethane-1,2-diol (1j). 21 A tetrahydrofuran solution of cyclopropylmagnesium
bromide (0.5 M, 22 mL, 11 mmol) was slowly added to a stirred solution of benzyl (1.05 g, 5.0 mmol) in
tetrahydrofuran (60 mL) at 0°C under a nitrogen atmosphere. The reaction mixture was stirred for 4 h 10 min at
room temperature. Saturated aqueous ammonium chloride (3 mL) was added to the reaction mixture, which was
then extracted with ethyl acetate (20 mL×3). The combined organic layers were washed with brine, dried over
anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column
chromatography using hexane ethyl acetate = 10:1 (v/v) as the eluent to give 1j 21 (416 mg, 28%) as colorless
crystals.
Standard experimental procedure for the glycol cleavage reaction using NaOCl·5H O: Sodium hypochlorite
2
pentahydrate (606 mg, 3.68 mmol) was added to a stirred solution of trans-1a (210 mg, 1.23 mmol) and
tetrabutylammonium hydrogen sulfate (42.2 mg 0.12 mmol) in dichloromethane (10 mL) and water (3 mL) at
0
°C, and the resulting mixture was stirred for 0.2 h under the same conditions. Water (3 mL) was added, and the
reaction mixture was extracted with dichloromethane (40 mL×2). The combined organic layers were dried over
anhydrous sodium sulfate, filtered and then concentrated in vacuo. The residue was purified by silica gel column
chromatography using hexane ethyl acetate = 10:1 (v/v) as the eluent to give 1,6-cyclodecanedione 2a (183 mg,
9
3%) as colorless crystals.
,6-Cyclodecanedione (2a). m.p.: 99 °C (lit. : 99 100 °C). H-NMR (CDCl ): δ (ppm) 1.84 1.86 (m, 8H),
1
a
1a
1
1
3
1
3
1
2
.35 2.36 (m, 8H). C{ H }-NMR (CDCl ): δ (ppm) 23.4, 42.2, 214.1.
3
2
2
[
1,1'-Biphenyl]-2,2'-diylbis(phenylmethanone) (2b). Following the standard procedure, 1b (182 mg, 0.50
mmol) was reacted with sodium hypochlorite pentahydrate (247 mg, 1.5 mmol) and tetrabutylammonium
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hydrogen sulfate (17.0 mg 0.05 mmol) for 0.2 h to produce 2b (182 mg, quant.) as colorless crystals. This product
2
2
1
was sufficiently pure and required no further purification. m.p.: 174 175 °C (lit. : 172 173 °C). H-NMR
1
3
1
(
CDCl ): δ (ppm) 7.15 7.35 (m, 14H), 7.61 7.64 (m, 4H). C{ H }-NMR (CDCl ): δ (ppm) 126.7, 127.9, 129.3,
3
3
1
30.0, 130.3, 131.4, 132.7, 137.3, 138.2, 140.2, 197.5.
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(
1S,3S)-3-Acetyl-2,2-dimethylcyclobutaneacetaldehyde
(2c)23
and
(1S,3S)-3-acetyl-2,2-
2
4
dimethylcyclobutaneacetic acid (3c). Following the standard procedure, 1c (85.7 mg, 0.50 mmol) was reacted
with sodium hypochlorite pentahydrate (495 mg, 3.0 mmol) and tetrabutylammonium hydrogen sulfate (17.0 mg
0
.05 mmol) for 0.2 h to produce a mixture of 2c and 3c. The crude mixture was dissolved in ethyl acetate (30 mL)
and extracted with saturated sodium bicarbonate (10 mL). The remaining ethyl acetate solution was washed with
brine (5 mL × 2), dried over anhydrous sodium sulfate and concentrated in vacuo to give crude product 2c. Crude
2
2
c was purified by silica gel column chromatography using hexane ethyl acetate = 1:1 (v/v) as the eluent to give
c (84.1 mg, 70% yield) as a pale yellow oil. The combined saturated sodium bicarbonate layers were acidified
using concentrated hydrochloric acid and extracted with ethyl acetate (30 mL × 2). The combined organic layers
were washed with brine (5 mL × 2), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to
give 3c (21.5 mg, 23%) as colorless crystals. This product was sufficiently pure and required no further
purification.
1
2
c: Pale yellow oil. H-NMR (CDCl ): δ (ppm) 0.83 (s, 3H), 1.32 (s, 3H), 1.90-1.99 (m, 2H), 2.03 (s, 3H), 2.38-
3
1
3
1
2.48 (m, 3H), 2.90 (m, 1H), 9.72 (m, 1H). C{ H }-NMR (CDCl ): δ (ppm) 17.6, 22.8, 30.1, 30.3, 35.7, 43.3,
3
5
4.1, 54.3, 201.4, 207.4 .
c: Colorless crystals. m.p.: 64 65 °C (lit. : 68 °C). H-NMR (CDCl ): δ (ppm) 0.86 (s, 3H), 1.31 (s, 3H), 1.87
24
1
3
1
3
3
1
3
1
.99 (m, 2H), 2.03 (s, 3H), 2.24 2.40 (m, 3H), 2.86 (m, 1H). C{ H }-NMR(CDCl ): δ (ppm) 17.3, 23.0, 30.2,
3
0.2, 34.8, 37.7, 43.3, 54.2, 178.0, 207.7.
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Reaction of trans-1d with NaOCl·5H O: 3β-Acetoxy-5-oxo-5,6-secocholestan-6-al (2d) and 3β-acetoxy-5-
2
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6
2
6
oxo-5,6- secocholestan-6-oic acid (3d). Following the standard procedure, trans-1d (232 mg, 0.50 mmol) was
reacted with sodium hypochlorite pentahydrate (250 mg, 1.5 mmol) and tetrabutylammonium hydrogen sulfate
(
17.0 mg 0.05 mmol) for 0.6 h to give a mixture of 2d and 3d. Purification by silica-gel column chromatography
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2
3
4
5
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using hexane ethyl acetate = 5:1 → 2:1 (v/v) as the eluent gave 2d (159 mg, 69%) and 3d (49 mg, 20%).
1
2
d: Colorless oil. H-NMR (CDCl ): δ (ppm) 0.68 (s, 3H), 0.85 2.46 (m, 42H), 3.06 (dd, J = 14.0, 4.8 Hz, 1H),
3
1
3
1
5.37 (brs, 1H), 9.61 (brs, 1H). C{ H }-NMR (CDCl ): δ (ppm) 11.5, 17.6, 18.5, 21.2, 22.5, 22.8, 23.1, 23.7,
3
2
2
5.1, 25.3, 27.8, 28.0, 34.3, 34.8, 35.7, 36.0, 39.4, 39.8, 42.1, 42.5, 43.2, 44.0, 52.3, 54.1, 56.1, 73.4, 170.2, 202.6,
16.1.
1
3
d: Colorless oil. H-NMR (CDCl ): δ (ppm) 0.69 (s, 3H), 0.85 2.46 (m, 43H), 3.19 (dd, J = 14.4, 4.4Hz, 1H),
3
1
3
1
5.39 (br s, 1H). C{ H }-NMR (CDCl ): δ (ppm) 11.7, 17.7, 18.6, 21.2, 22.5, 22.8, 23.0, 23.8, 24.4, 25.2, 27.9,
3
2
8.0, 34.0, 34.4, 35.6, 35.7, 36.0, 39.4, 39.7, 41.5, 42.6, 43.1, 52.3, 54.4, 55.9, 73.5, 170.3, 178.5, 216.3.
Reaction of cis-1d with NaOCl·5H O: 3-Acetocy-5-hydroxy-10,13-dimethyl-17-octyl-6-
2
2
5
oxohexadecahydrocyclopenta[a]phenanthrene (4d). Following the standard procedure, cis-1d (232 mg, 0.50
mmol) was treated with sodium hypochlorite pentahydrate (250 mg, 1.5 mmol) and tetrabutylammonium
hydrogen sulfate (17.0 mg 0.05 mmol) for 20 h 50 min to give a mixture of cis-1d and 4d and several other
1
compounds. The yields of cis-1d (18%) and 4d (36%) were determined by H-NMR spectroscopy using 1-chloro-
4
-(trifluoromethyl)benzene as an internal standard.
2
7
28
Benzaldehyde (2e) and benzoic acid (3e). Following the standard procedure, 1e (214 mg, 1.00 mmol) was
reacted with sodium hypochlorite pentahydrate (500 mg, 3.0 mmol) and tetrabutylammonium hydrogen sulfate
(
35.1 mg 0.10 mmol) to produce the crude product as a mixture of 2e and 3e. The yields of 2e (40%) and 3e (35%)
were determined by GC.
2
9
30
p-Methoxybenzaldehyde (2f) and p-methoxybenzoic acid (3f). Following the standard procedure, 1f (274
mg, 1.00 mmol) was reacted with sodium hypochlorite pentahydrate (500 mg, 3.0 mmol) and
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6
tetrabutylammonium hydrogen sulfate (35.1 mg 0.10 mmol) to produce the crude product as a mixture of 2f and
3
f. The yields of 2f (68%) and 3f (7%) were determined by GC.
3
1
32
3
-Phenylpropanal (2g) and 3-phenylpropanoic acid (3g). Following the standard procedure, 1g (270 mg,
0
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2
3
4
5
6
7
8
9
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2
3
4
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7
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4
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1
.00 mmol) was reacted with sodium hypochlorite pentahydrate (500 mg, 3.0 mmol) and tetrabutylammonium
hydrogen sulfate (35.1 mg 0.10 mmol) for 6 h to produce the crude product as a mixture of 2g and 3g. The yields
of 2g (2%) and 3g (76%) were determined by GC.
3
3
Benzaldehyde (2e), benzoic acid (3e) and 1-phenylpentan-1-one (2h). Following the standard procedure, 1h
(270 mg, 1.00 mmol) was reacted with sodium hypochlorite pentahydrate (500 mg, 3.0 mmol) and
tetrabutylammonium hydrogen sulfate (35.1 mg 0.10 mmol) to produce the crude product as a mixture of 2e, 3e
and 2g. The yields of 2e (40%), 3e (35%) and 2g (quant.) were determined by GC.
3
4
Benzophenone (2i). Following the standard procedure, 1i (367.5 mg, 1.00 mmol) was reacted with sodium
hypochlorite pentahydrate (500 mg, 3.0 mmol) and tetrabutylammonium hydrogen sulfate (35.1 mg 0.10 mmol)
to produce crude product 2i. Purification by silica gel column chromatography using hexane ethyl acetate = 10:1
3
4
1
(
v/v) as the eluent gave pure 2i (297.1 mg, 82%) as colorless crystals. m.p.: 48 °C (lit. : 47.8 49.4 °C). H-NMR
1
3
1
(
CDCl ): δ (ppm) 7.47 7.50 (m, 4H), 7.57 7.61 (m, 2H), 7.80 7.82 (m, 4H). C{ H }-NMR (CDCl ): δ (ppm)
3
3
128.2, 130.0, 132.4, 137.6, 196.7.
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5
Cyclopropylphenylmethanone. (2j) Following the standard procedure, 1j (147.5 mg, 0.50 mmol) was reacted
with sodium hypochlorite pentahydrate (250 mg, 1.5 mmol) and tetrabutylammonium hydrogen sulfate (17.0 mg
0
.05 mmol) to produce crude product 2j. Purification by silica gel column chromatography using hexane ethyl
1
acetate = 15:1 (v/v) as the eluent gave pure 2j(130.1 mg, 89%) as a colorless oil. H-NMR (CDCl ): δ (ppm) 1.02
3
13
1
1
.07 (m, 2H), 1.23 1.27 (m, 2H), 2.68 (septet, J=4.1 Hz, 1H), 7.48 (m, 2H), 7.56 (m, 1H), 8.02 (m, 2H). C{ H
}
-NMR (CDCl ): δ (ppm) 11.6, 17.1, 128.0, 128.5, 132.7, 138.0, 200.6.
3
Standard experimental procedure for glycol cleavage using Pb(OAc) : Lead tetraacetate (975 mg, 2.2 mmol)
4
was added to a stirred solution of glycol 1a (170.1 mg, 1.00 mmol) in dichloromethane (10 mL) at room
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temperature, and stirred for 117 h under the same conditions. Water (3 mL) was added, and the reaction mixture
was extracted with dichloromethane (40 mL×2). The combined organic layers were dried over anhydrous sodium
sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography using
hexane ethyl acetate = 10:1 v/v as the eluent to give 1,6-cyclodecanedione 2a (56.5 mg, 33%) as colorless crystals.
This product was identical to 2a prepared using sodium hypochlorite pentahydrate.
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[1,1'-Biphenyl]-2,2'-diylbis(phenylmethanone) (2b). According to the standard procedure, 1b (199 mg, 0.55
mmol) was reacted with lead tetraacetate (536 mg, 1.20 mmol) for 3 h to produce 2b (181 mg, 92%) as colorless
crystals. This product was identical to 2b prepared using sodium hypochlorite pentahydrate.
(1S,3S)-3-Acetyl-2,2-dimethylcyclobutaneacetaldehyde
(2c)
and
(1S,3S)-3-acetyl-
2,2-
dimethylcyclobutaneacetic acid (3c). Following the standard procedure, 1c (85.0 mg, 0.50 mmol) was reacted
with lead tetraacetate (488 mg, 1.1 mmol) for 25 h to produce 3c, accompanied by a trace amount of 2c and
several byproducts. The crude mixture was dissolved in ethyl acetate (30 mL) and extracted with saturated sodium
bicarbonate (10 mL). The combined saturated sodium bicarbonate layers were acidified using concentrated
hydrochloric acid and extracted with ethyl acetate (30 mL × 2). The combined organic layers were washed with
brine (5 mL × 2), dried over anhydrous sodium sulfate, filtered and evaporated to provide 3c (26.6 mg, 27%) as
colorless crystals. This product was identical to the 3c prepared using sodium hypochlorite pentahydrate. Since
the amount of 2c produced was very small and accompanied by many other by-products, it was impossible to
obtain 2c in its pure form from the residual ethyl acetate solution.
Reaction with trans-1d: 3β-Acetoxy-5-oxo-5,6-secocholestan-6-al (2d). Following the standard procedure,
trans-1d (231 mg, 0.50 mmol) was reacted with lead tetraacetate (488 mg, 1.1 mmol) for 25 h to produce the
crude product. Purification by silica gel column chromatography using hexane ethyl acetate = 5:1 → 2:1 (v/v)
as the eluent gave 2d (69.4 mg, 30%) as a colorless oil. This product was identical to 2d prepared using sodium
hypochlorite pentahydrate.
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Reaction of cis-1d: 3β-Acetoxy-5-oxo-5,6-secocholestan-6-al (2d). Following the standard procedure, cis-1d
232 mg, 0.50 mmol) was reacted with lead tetraacetate (508 mg, 1.1 mmol) in dichloromethane (5 mL) for 15
min to produce 2d. Purification by silica-gel column chromatography using hexane ethyl acetate = 5:1 → 2:1
v/v) as the eluent gave 2d (230 mg, quant.) as a colorless oil. This product was identical to 2d prepared using
sodium hypochlorite pentahydrate.
(
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Glycol cleavage of an equimolar mixture of cis-1d and trans-1dwith NaOCl·5H O: Sodium hypochlorite
2
pentahydrate (45.7 mg, 0.25 mmol) was added to a stirred solution of cis-1d (115.8 mg, 0.25 mmol), trans-1d
(
116.0 mg, 0.25 mmol) and tetrabutylammonium hydrogen sulfate (17.3 mg 0.25 mmol) in dichloromethane (10
mL) and water (3 mL) at 0 °C, and the resulting mixture was stirred for 40 min at room temperature. Water (3
mL) was added, and the react ion mixture was extracted with dichloromethane (40 mL × 2). The combined organic
layers were dried over anhydrous sodium sulfate, filtered and concentrated in vacuo to produce the crude product
as a mixture of cis-1d, trans-1d and 2d. The yields of cis-1d (95%), trans-1d (30%) and 2d (70%) were
1
determined by H-NMR spectroscopy using 1-chloro-4-(trifluoromethyl)benzene as an internal standard.
Glycol cleavage of trans-1a using aq. HOCl prepared from NaOCl·5H O, water and hydrochloric acid: The
2
pH was adjusted to 5.9 by adding conc. hydrochloric acid to aq. NaOCl prepared upon dissolving NaOCl·5H O
2
(248 mg, 1.5 mmol) in water (1.5 mL). The resulting aq. HOCl was added to a stirred solution of trans-1a (85
mg, 0.5 mmol) in dichloromethane (5 mL) at room temperature. The resulting suspension was stirred for 1.5 h
under the same conditions. The reaction mixture was cooled to 0 °C, diluted with water (10 mL) and extracted
with dichloromethane (20 mL × 2). The combined organic layers were dried over anhydrous sodium sulfate,
filtered and concentrated in vacuo to provide the crude product as a colorless solid. Analysis of the crude product
1
by H-NMR spectroscopy using 1-chloro-4-(trifluoromethyl)benzene as an internal standard indicated that the
yield of 2a was 62%.
ASSOCIATED CONTENT
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Supporting Information
The Supporting Information is available free of charge on the ACS Publications website.
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H-NMR and C{ H}-NMR spectra of the obtained products. (PDF)
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GC trace for reactions of 1e, 1f, 1g and1h. (Table 3, runs 1 4), (PDF)
AUTHOR INFORMATION
Corresponding Author
*E-mail: kirihara.masayuki@sist.ac.jp.
ACKNOWLEDGMENT
This work was financially supported by JSPS KAKENHI Grant Number JP23590024.
REFERENCES
(
1) (a) Balskus, E. P.; Méndez-Andino, J.; Arbit R. M.; Paquette, L A. Intercalation of Multiple Carbon Atoms
between the Carbonyls of -Diketones. J. Org. Chem. 2001, 66, 6695 6704. (b) Méndez, J.; Paquette, L. A.
Tandem Deployment of Indium-, Ruthenium-, and Lead-Promoted Reactions. Four-Carbon Intercalation
between the Carbonyl Groups of Open-Chain and Cyclic α-Diketones. Org. Lett., 2000, 2, 1263 1265. (c)
Inoue, M.; Sato T.; Hirama M. Total Synthesis of Merrilactone A. J. Am. Chem. Soc., 2003, 125, 10772
10773. (d) Inoue, M.; Lee, N.; Kasuya, S.; Sato, T.; Hirama, M.; Moriyama, M.; Fukuyama, Y. Total Synthesis
and Bioactivity of an Unnatural Enantiomer of Merrilactone A: Development of an Enantioselective
Desymmetrization Strategy. J. Org. Chem., 2007, 72, 3065 3075.
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(
2) Recently published papers on glycol-cleavage: (a) Zhou, Z.; Liu, M.; Lv, L.; Li, C. Silver(I)-Catalyzed Widely
Applicable Aerobic 1,2-Diol Oxidative Cleavage. Angew. Chem. Int. Ed. 2018, 57, 2616 2620. (b) Miyamoto,
K.; Yamashita, J.; Narita, S.; Sakai, Y.; Hirano, K;. Saito, T.; Wang, C.; Ochiai M;. Uchiyama, M. Iodoarene-
catalyzed oxidative transformations using molecular oxygen. Chem. Commun. 2017, 53, 9781̶ 9784. (c)
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Escande, V.; Lam, C. H.; Coish, P.; Anastas, P. T. Heterogeneous Sodium-Manganese Oxide Catalyzed
Aerobic Oxidative Cleavage of 1,2-Diols. Angew. Chem. Int. Ed. 2017, 56, 9561 9565. (d) Obara, N.;
Hirasawa, S.; Tamura, M.; Nakagawa, Y.; Tomishige, K. Oxidative Cleavage of Vicinal Diols with the
Combination of Platinum and Vanadium Catalysts and Molecular Oxygen. Chem. Cat. Chem. 2016, 8, 1732
1738. (e) García, N.; Rubio-Presa, R.; García-García, P.; Fernández-Rodríguez, M. A.; Pedrosa, M. R.;
Arnáiza, F. J.; Sanz, R. A Selective, Efficient and Environmentally Friendly Method for the Oxidative
Cleavage of Glycols. Green Chem. 2016, 18, 2335-2339. (f) Shibuya, M.; Shibuta, T.; Fukuda, H.; Iwabuchi,
Y. Nitroxyl Radical/PhI(OAc) : One-Pot Oxidative Cleavage of Vicinal Diols to (Di)Carboxylic Acids. Org.
2
Lett. 2012, 14, 5010 5013.
(
3) Reviews of glycol-cleavage: (a) Schmidt, A. C.; Stark, C. B. W. The Glycol Cleavage in Natural Product
Synthesis: Reagent Classics and Recent Advances. Synthesis 2014, 46, 3283 3308. (b) T. K. M. Shing, in
Comprehensive Organic Synthesis; Vol. 7, ed. B. M. Trost and I. Fleming, Pergamon Press, Oxford, 1991, p.
7
03.
4) (a) R.Criegee, in Oxidation in Organic Chemistry; ed. K. Wiberg, Academic Press: New York, 1965, Part A.
b) G. M. Rubottom, in Oxidation in Organic Chemistry, Vol. 5, ed. W. S. Trahanovsky, Academic Press,
(
(
New York, 1982, Part D, p. 1.
(
5) (a) Nicolaou, K. C.; Adsool V. A.; Hale, C. R. H. An Expedient Procedure for the Oxidative Cleavage of
Olefinic Bonds with PhI(OAc) , NMO, and Catalytic OsO . Org. Lett. 2010, 12, 1552 1555. (b) Kasun, Z.
2
4
A.; Geary, L. M.; Krische, M. J. Ring expansion of cyclic 1,2-diols to form medium sized rings via ruthenium
catalyzed transfer hydrogenative [4+2] cycloaddition. Chem. Commun. 2014, 50, 7545 7547.
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(
6) We developed the aerobic oxidative cleavage of bis-tertiary glycols catalyzed by oxytrichlorovanadium
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(
VOCl ) as an environmentally benign reaction (Kirihara, M.; Yoshida, K.; Noguchi, T.; Naito, S.;
3
Matsumoto, N.; Ema, Y.; Torii, M.; Ishizuka, Y.; Souta, I. Effective cleavage of ditertiary glycols via
vanadium(V)-catalyzed aerobic oxidation. Tetrahedron Lett. 2010, 51, 3619 3622). Therefore, a VOCl3-
catalyzed aerobic oxidative cleavage of 1a was examined. Contrary to our expectation, 1a proved to be
unreactive under catalytic VOCl -O conditions. The reaction of 1a with an excess of VOCl was similarly
0
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unsuccessful. Thus, we believe that highly hindered bicyclic glycols such as 1a do not react with vanadium
compounds.
(
7) Khurana, J. M.; Sharma, P.; Gogia, A.; Kandapal, B. M. OXIDATIVE CLEAVAGE OF 1,2-DIOLS, -
KETOLS AND 1,2-DIKETONES WITH AQUEOUS SODIUM HYPOCHLORITE. Org. Prep. Proceed. Int.
2007, 39, 185 189.
(
8) (a) Kirihara, M.; Okada, T.; Sugiyama, Y.; Akiyoshi, M.; Matsunaga, T.; Kimura, Y. Sodium Hypochlorite
Pentahydrate Crystals (NaOCl·5H O): A Convenient and Environmentally Benign Oxidant for Organic
2
Synthesis. Org. Process Res. Dev. 2017, 21, 1925 1937. (b) Okada, T.; Asawa, T.; Sugiyama, Y.; Iwai, T.;
Kirihara, M.; Kimura, Y. Sodium hypochlorite pentahydrate (NaOCl·5H O) crystals; An effective re-oxidant
2
for TEMPO oxidation. Tetrahedron 2016, 72, 2818. (c) Okada, T.; Asawa, T.; Sugiyama, Y.; Kirihara, M.;
Iwai T.; Kimura, Y. Sodium Hypochlorite Pentahydrate (NaOCl·5H O) Crystals as an Extraordinary Oxidant
2
for Primary and Secondary Alcohols. Synlett 2014, 25, 596 598. (d) Okada, T.; Matsumuro, H.; Kitagawa,
S.; Iwai, T.; Yamazaki, K.; Kinoshita, Y.; Kimura, Y.; Kirihara, M. Selective Synthesis of Sulfoxides through
Oxidation of Sulfides with Sodium Hypochlorite Pentahydrate Crystals. Synlett 2015, 26, 2547 2552. (e)
Okada, T.; Matsumuro, H.; Iwai, T.; Kitagawa, S.; Yamazaki, K.; Akiyama, T.; Asawa, T.; Sugiyama, Y.;
Kimura, Y.; Kirihara, M. An Efficient Method for the Preparation of Sulfonyl Chlorides: Reaction of
Disulfides or Thiols with Sodium Hypochlorite Pentahydrate (NaOCl·5H O) Crystals. Chem. Lett. 2015, 44,
2
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85 187. (f) Kitagawa, S.; Mori, H.; Odagiri, T.; Suzuki, K.; Kikkawa, Y.; Osugi, R.; Takizawa, S.; Kimura
Y.; Kirihara, M. A Concise, Catalyst-Free Synthesis of Davis' Oxaziridines using Sodium Hypochlorite.
SynOpen 2019, 3, 21 25.
(
9) (a) Sudalai, A.; Khenkinb A.; Neumann, R. Sodium periodate mediated oxidative transformations in organic
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synthesis. Org. Biomol. Chem. 2015, 13, 4374 4394. (b) Rezaeivalla, M. Sodium Periodate (NaIO )–A
4
Versatile Reagent in Organic Synthesis. Synlett 2006, 3550 3551. (c) Wolfrom, M. L.; Yosizawa, Z. Synthesis
of 2-Amino-2-deoxy-L-Arabinose (L-Arabinosamine). J. Am. Chem. Soc. 1959, 81, 3477 3478.
(
10) Glycol cleavage of cis- and trans-1a using Pb(OAc) in acetic acid has been examined by Griegee et al.
4
They reported that cis-1a reacted 100 times faster than trans-isomer; Criegee, R.; Büchner, E.; Walther, W.
Die Geschwindigkeit der Glykolspaltung mit BleiIV-acetat in Abhängigkeit von der Konstitution des Glykols.
Chem. Ber. 1940, 73, 571-575.
(
11) The reaction was not complete when less than 3 equivalents of NaOCl·5H O was used. Since HOCl is not
2
a stable compound, some of HOCl is decomposed before it participates in the glycol cleavage reaction.
(
12) (a) Buist, G. J.; Bunton, C. A.; Miles, J. H. The Mechanism of Oxidation of -Glycols by Periodic Acid.
Part II. Propane-l:2-, 2-Methylpopune-l:2-, Butune-2:3- and 2-Methylbutane-2:3-diol. J. Chem. Soc. 1957,
4
567 4574. (b) Buist, G. J.; Bunton, C. A.; Miles, J. H. The Mechanism of Oxidation of -Glycols by Periodic
Acid. Part III. Spectroscopic Evidence for the Formation of an Intermediate. J. Chem. Soc. 1957, 4575 4579.
(c) Buist, G. J.; Bunton, C. A. The Mechanism of Oxidation of -Glycols by Periodic Acid. Part IV. The
Oxidation of 2-Methylbutane-2:3-diol at pH 4.5. J. Chem. Soc. 1957, 4580 4584. (d) Speer, R. J.; Mahler, H.
R. Phenoxyacetaldehyde. J. Am. Chem. Soc. 1949, 71, 1133. (e) Pausacker, K. H. The oxidation of glycols by
aryl iodosoacetates. A kinetic study. J. Chem. Soc. 1953, 107 109.
(
13) Khurana et al proposed a similar mechanism for glycol cleavage using conventional aq. NaOCl.7
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(
14) Criegee, R.; Höger, E.; Huber, G.; Kruck, P.; Marktscheffel, F.; Schellenberger, H. Die Geschwindigkeit
der Glykolspaltung mit Bleitetraacetat in Abhängigkeit von Konstitution und Konfiguration des Glykols. (III.
Mitteilung). Liebigs Ann. Chem. 1956, 599, 81 124.
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15) Varea, T.; Medio, M.; Ballesteros, R.; Oniga, O.; Asensio, G. C-C Bond Cleavage in O-Centered Mono-
and Dianions Derived from α-Dicarbonyl Compounds. Tetrahedron 1995, 36, 10093 10100.
16) Hobuß, D.; Hasenjäger, J.; Driessen-Hölscher, B.; Baro, A.; Axenov, K. V.; Laschat, S.; Frey, W. Novel
α-pinene-derived mono- and bisphosphinite ligands: Synthesis and application in catalytic hydrogenation.
Inorg. Chim. Acta. 2011, 374, 94 103.
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17) Carvalho, J. F. S.; Silva, M. M. C.; SáeMelo, M. L. Efficient trans-diaxial hydroxylation of Δ -steroids.
Tetrahedron 2010, 66, 2455 2462.
18) Xu, X.; Hirao, T. Vanadium-Catalyzed Pinacol Coupling Reaction in Water. J. Org. Chem. 2005, 70, 8594
8596.
19) Muramatsu, Y.; Kanehira, S.; Tanigawa, M.; Miyawaki, Y.; Harada, T. Catalytic Enantioselective
Alkylation and Arylation of Aldehydes by Using Grignard Reagents. Bull. Chem. Soc. Jpn. 2010, 83, 19 32.
(20) Tanaka, N.; Kasai, T. Reactions of 5,6-Dilithioacenaphthene-N-N,N’,N’-Tetramethyl-1,2-ethanediamine
Complex with α-Diketones. II. Competitive Oxophilic and Carbophilic Additions and Redox Reactions. Bull.
Chem. Soc. Jpn. 1981, 54, 3026 3032.
(21) Mandell, L.; Johnston, J. C.; Day, Jr., R.A. Controlled-potential reduction of cyclopropyl ketones. J. Org.
Chem. 1978, 43, 1616 1618.
(
22) Zhang, C.; Rao, Y. Weak Coordination Promoted Regioselective Oxidative Coupling Reaction for 2,2’-
Difunctional Biaryl Synthesis in Hexafluoro-2-propanol. Org. Lett. 2015, 17, 4456 4459.
(23) Barton, D. H. R.; Fontana, G. Radical Chemistry Based on (+)-cis-Pinononic and (+)-cis-Pinonic Acids.
Synth. Commun. 1996, 26, 1953 1968.
(
24) Fernández, F.; López, C.; Hergueta, A. R. Synthesis of a precursor of cyclobutane carbocyclic nucleosides
from α-pinene. Tetrahedron 1995, 51, 10317 10322.
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2
3
3
3
3
3
3
3
3
3
3
4
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4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(
25)
Yates, P.; Stiver, S. Photochemistry of cyclic α-hydroxy ketones. III. The nature of the photoproducts
from 5-hydroxy-5β-cholest-3-en-6-one and the relationship of these to the photoproducts from analogous
saturated 5-hydroxycholestan-6-ones. Can. J. Chem. 1988, 66, 1209 1218
(
26) Dauben, W. G.; Fonken, G. J. Reactions of B-Norcholesterol. J. Am. Chem. Soc. 1956, 78, 4736 4743.
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
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6
7
8
9
0
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2
3
4
5
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7
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9
0
1
3
1
(
27) H. W. Whitlock, in The Aldrich Library of C and H FT NMR Spectra Edition 1, C. J. Pouchert and J.
Behnke eds., Aldrich Chemical Company, Inc., USA, 1993, vol. 2, p. 932B.
1
3
1
(
(
(
(
28) H. W. Whitlock, in The Aldrich Library of C and H FT NMR Spectra Edition 1, C. J. Pouchert and J.
Behnke eds., Aldrich Chemical Company, Inc., USA, 1993, vol. 2, p. 1063B.
1
3
1
29) H. W. Whitlock, in The Aldrich Library of C and H FT NMR Spectra Edition 1, C. J. Pouchert and J.
Behnke eds., Aldrich Chemical Company, Inc., USA, 1993, vol. 2, p. 941A.
13
1
30) H. W. Whitlock, in The Aldrich Library of C and H FT NMR Spectra Edition 1, C. J. Pouchert and J.
Behnke eds., Aldrich Chemical Company, Inc., USA, 1993, vol. 2, p. 1079B.
1
3
1
31) H. W. Whitlock, in The Aldrich Library of C and H FT NMR Spectra Edition 1, C. J. Pouchert and J.
Behnke eds., Aldrich Chemical Company, Inc., USA, 1993, vol. 2, p. 925B.
1
3
1
(32) H. W. Whitlock, in The Aldrich Library of C and H FT NMR Spectra Edition 1, C. J. Pouchert and J.
Behnke eds., Aldrich Chemical Company, Inc., USA, 1993, vol. 2, p. 985A.
1
3
1
(
33) H. W. Whitlock, in The Aldrich Library of C and H FT NMR Spectra Edition 1, C. J. Pouchert and J.
Behnke eds., Aldrich Chemical Company, Inc., USA, 1993, vol. 2, p. 803B.
(
34) Jin, C.; Zhang, L.; Su, W. Direct Benzylic Oxidation with Sodium Hypochlorite Using a New Efficient
Catalytic System: TEMPO/Co(OAc) . Synlett 2011, 1435 1438.
2
(
35) House, H. O.; Prabhu, A. V.; Wilkins, J. M.; Lee, L. F. Reactions involving electron transfer. 9. Reaction
of lithium dimethylcuprate with alkyl aryl ketones. J. Org. Chem. 1976, 41, 3067 3076.
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