Practical oxidative dearomatization of phenols with sodium hypochlorite pentahydrate

Article abstract of DOI:10.1246/cl.141130

A highly efficient and practical oxidative dearomatization of phenols using sodium hypochlorite pentahydrate as an inexpensive, strong oxidant is reported for the first time. The oxidation reactions proceeded very rapidly in the presence of water to give the desired products in excellent yields, and sodium chloride and water were the only by-products derived from the oxidant.

Full text of DOI:10.1246/cl.141130

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
Received: December 8, 2014 | Accepted: December 21, 2014 | Web Released: February 17, 2015
CL-141130
Practical Oxidative Dearomatization of Phenols with Sodium Hypochlorite Pentahydrate
Muhammet Uyanik,1 Niiha Sasakura,1 Mitsuyoshi Kuwahata,2 Yasukazu Ejima,2 and Kazuaki Ishihara*1,3
1Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603
2Kaneka Corporation, PVC & Chemical Division, 2-3-18 Nakanoshima, Kita-ku, Osaka 530-8288
3Japan Science and Technology Agency (JST), CREST, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi 464-8603
(E-mail: ishihara@cc.nagoya-u.ac.jp)
A highly efficient and practical oxidative dearomatization of
phenols using sodium hypochlorite pentahydrate as an inex-
pensive, strong oxidant is reported for the first time. The
oxidation reactions proceeded very rapidly in the presence of
water to give the desired products in excellent yields, and
sodium chloride and water were the only by-products derived
from the oxidant.
Mes
NH
Mes
O
a)
O
I
HN
O
O
OH
Br
O
Precatalyst (10 mol%)
m-CPBA (1.2 equiv)
O
O
CO2H
CH2Cl2, –20 °C, 23 h
Br
1a
2a: 95% yield, 98% ee
2a: 80% yield, 1% ee
The oxidative dearomatization of phenols and their ana-
logues has emerged as a promising tool for the synthesis of
various natural products or biologically active compounds.1 To
date, several protocols have been developed for these funda-
mental reactions.1 Here, we report a new practical protocol for
the oxidative dearomatization of phenols using sodium hypo-
chlorite pentahydrate as an oxidant.
Sodium hypochlorite pentahydrate (NaOCl¢5H2O) is a
strong but inexpensive oxidizing agent, and sodium chloride
and water are the only by-products derived from the oxidant.
This solid oxidant offers several advantages over conventional
aqueous sodium hypochlorite solution (ca. 10 wt %, pH ca. 13),
including higher chlorine content (ca. 42%), lower pH upon
dissolution (pH ca. 11), and high stability at lower temper-
atures.2 Recently, Kirihara, Kimura, and colleagues reported a
new variant of the 2,2,6,6-tetramethylpiperidinium oxy radical
(TEMPO)-catalyzed oxidation of alcohols to the corresponding
carbonyl compounds using NaOCl¢5H2O crystals, which did not
require pH adjustment.3a The same group has also used this solid
oxidant for the oxidation and chlorination of thiols or disulfides
to sulfonyl chloride in acetic acid.3b
We have developed the hypervalent organoiodine(III)-
catalyzed enantioselective oxidative dearomatizations of phenol
derivatives using meta-chloroperbenzoic acid (m-CPBA) as an
oxidant.4,5 However, m-CPBA is expensive and potentially
explosive, and is converted to meta-chlorobenzoic acid (m-
CBA) as an organic waste. Therefore, inspired by the afore-
mentioned works,3 we examined NaOCl¢5H2O as an alternative
oxidant for organoiodine(III)-catalysis instead of m-CPBA
(Scheme 1). The oxidative dearomatization of β-(2-hydroxy-
phenyl)carboxylic acid 1a using NaOCl¢5H2O, in the presence
of a chiral iodoarene catalyst, and n-tetrabutylammonium
hydrogen sulfate (n-Bu4NHSO4) as a phase-transfer catalyst
gave the desired spirolactone 2a in good yield, but as a racemate
(Scheme 1b). Interestingly, the oxidation of 1a in the absence
of organoiodine catalyst under identical conditions gave 2a in
similar yield (Scheme 1c). To the best of our knowledge, this is
the first example of the oxidative dearomatization of phenols
using sodium hypochlorite pentahydrate as an oxidant.6
b)
c)
Precat. (10 mol%)
NaOCl·5H2O (1.2 equiv)
1a
1a
n-Bu4NHSO4 (5 mol%)
CH2Cl2, 0 °C, 12 h
n-Bu4NHSO4 (5 mol%)
NaOCl·5H2O (1.2 equiv)
2a: 77% yield
CH2Cl2, 0 °C, 12 h
Scheme 1. Preliminary investigation of NaOCl¢5H2O as an oxidant
for the oxidative dearomatization of 1a.
boxylic acid 1b as a model substrate, using commercially
available NaOCl¢5H2O (Wako, pH ca. 11) (Table 1). First, we
confirmed that the use of a phase-transfer catalyst in a nonpolar
solvent, such as dichloromethane, at ¹20 °C gave 2b in higher
yield, as in the previous report (Entry 2 versus Entry 1).3a A brief
screening of the solvents revealed that polar solvents, such as
acetonitrile and ethyl acetate, were superior to other solvents
since NaOCl¢5H2O dissolved much more easily in these solvents
(Entries 3-6). Interestingly, the oxidation reaction proceeded
efficiently in ethyl acetate even in the absence of Bu4NHSO4,
and 2b was obtained quantitatively (Entry 7). The reaction with
NaOCl¢5H2O (Kaneka, pH ca. 10.5) proceeded about two-times
faster (Entry 8).7 Although the reason for the higher reactivity
of the Kaneka reagent is not yet clear, it dissolved much more
easily than the Wako reagent under the present conditions.8 Next,
NaOCl¢5H2O (Wako, pH ca. 11) and conventional aqueous
NaOCl solution (ca. 10 wt %, pH ca. 13) were compared under
identical conditions at 0 °C using a small amount of water
(EtOAc/H2O 79:1 v/v) (Entries 9 and 10).9 Interestingly, the
reaction was faster and went to completion within 2 h for both
oxidants in the presence of water as a cosolvent, which made the
oxidant dissolve completely. However, the chemical yield of the
desired spirolactone 2b was lower for conventional NaOCl due
to the formation of by-products. These results suggested that the
high chemoselectivity of NaOCl¢5H2O might be due to its lower
pH value. Finally, we found that the oxidation of 1b proceeded
more rapidly in a 20:1 v/v mixed solvent of EtOAc and H2O,
and 2b was obtained quantitatively within 5 min (Entry 11).
With these preliminary findings in hand, we next optimized
the reaction conditions using β-(1-hydroxynaphthalen-2-yl)car-
Chem. Lett. 2015, 44, 381–383 | doi:10.1246/cl.141130
© 2015 The Chemical Society of Japan | 381

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Table 1. NaOCl¢5H2O-mediated oxidative dearomatization of 1ba
OH
O
OH
O
NaOCl·5H2O (1.1 equiv)
NaOCl·5H2O (1 equiv)
O
n-Bu4NHSO4 (10 mol%)
EtOAc/H2O (30:1 v/v)
0 °C, 3 h
O
O
H
O
CO2H
Ph
3
Ph
Solvent, Conditions
4: 78% yield
Ph
Ph
1b
2b
OH
O
NaOCl·5H2O (2 equiv)
Entry
1c
2
3
4
5
6
7c
8c,d
9c
10c,f
11c,i
Solvent
Conditions
2b, Yield/%b
N
CH2Cl2
CH2Cl2
Toluene
t-BuOMe
CH3CN
EtOAc
EtOAc
EtOAc
EtOAc/H2Oe
EtOAc/H2Oe
EtOAc/H2Oj
¹20 °C, 9 h
¹20 °C, 9 h
¹20 °C, 9 h
¹20 °C, 9 h
¹20 °C, 8 h
¹20 °C, 7 h
¹20 °C, 9 h
¹20 °C, 4 h
17
71
58
73
97
99
98
99
92g
74g,h
96
Ms
EtOAc/H2O (70:1 v/v)
0 °C, 30 min
HN
Ph Ms
Ph
5
6: 80% yield
OH
O
NaOCl·5H2O (2 equiv)
EtOAc/H2O (6:1 v/v)
RT, 3 h
OH
0 °C, 2 h
0 °C, 2 h
0 °C, 5 min
7
8: 91% yield
OH
O
t-Bu
OH
t-Bu
O
NaOCl·5H2O (1.1 equiv)
aUnless otherwise noted, NaOCl¢5H2O (Wako) was used. bIsolated
yields of 2b are shown. cIn the absence of n-Bu4NHSO4. dNaOCl¢
5H2O (Kaneka) was used. eEtOAc/H2O (79:1 v/v). fConventional
aqueous NaOCl solution (ca. 10 wt %, pH 13) was used. gEvaluated
by NMR analysis. hHigh polarity side-products were generated.
iNaOCl¢5H2O (1.1 equiv) was used. jEtOAc/H2O (20:1 v/v). For
details, see the Supporting Information.
EtOAc/H2O (20:1 v/v)
0 °C, 40 min
t-Bu
t-Bu
10: 98% yield
9
OH
O
NaOCl·5H2O (1.1 equiv)
EtOAc/H2O (20:1 v/v)
0 °C, 20 min
Table 2. Substrate scopea
OH
11
O
12: 90% yield
OH
O
NaOCl·5H2O (1.1 equiv)
Scheme 2. NaOCl¢5H2O-mediated oxidation of various phenols.
O
R
R
O
CO2H
Method A: EtOAc, –20 °C
1
2
(EtOAc) with respect to reaction time and reproducibility.
However, Method A was found to be optimal for the oxidation
of phenols 1a and 1c and 4-halo-substituted 1-naphthols 1d and
1e to give the corresponding spirolactones 2 in high yields.
When these substrates were oxidized in the presence of water
(Method B), complex product mixtures were obtained and the
desired spirolactones 2 were obtained in only low yield.
Nevertheless, here again, the use of Kaneka’s oxidant for the
oxidation of 1c and 1d under Method A accelerated the desired
reaction. On the other hand, the oxidation of β-(1-hydroxynaph-
thalen-2-yl)carboxylic acids 1f-1k and β-(2-hydroxynaphthalen-
1-yl)carboxylic acid 1l in the presence of water as a cosolvent
(Method B) proceeded efficiently within 5 min to give the
desired spirolactones 2 quantitatively in most cases.
Method B: EtOAc/H2O (20:1 v/v), 0 °C
O
O
O
t-Bu
O
O
O
O
O
O
X
Br
t-Bu
2a
2c
2d (X = Cl)
A: 12 h, 78% yield
A: 3 h, 86% yield
A: 7 h, 99% yield
(1.5 h, 86% yield)b
(6 h, 99% yield)b
2e (X = Br)
A: 7 h, 91% yield
O
O
O
O
O
O
O
OBn
O
O
MeO
R
The present oxidative dearomatization using NaOCl¢5H2O
is not limited to only the spirolactonization of β-(2-hydroxy-
phenyl)carboxylic acids 1 (Scheme 2). The oxidation of 3-
(1-hydroxynaphthalen-2-yl)propanol 3 and amide 5 gave the
corresponding spiroether 4 and spiroamide 6 in high yields,
respectively. Moreover, the oxidation of 2,4,6-trimethylphenol
(7) gave the corresponding para-quinol 8 in excellent yield.
Furthermore, the clean oxidation of 1,2- and 1,4-hydroquinones,
9 and 11, gave the corresponding quinones 10 and 12 in
excellent yields, respectively.
In summary, we have serendipitously found a new oxidative
dearomatization protocol using NaOCl¢5H2O as an inexpensive
and atom-economical oxidant. This method is highly practical
since the oxidation reactions proceed very rapidly in the
presence of water to give the desired products in excellent
2j
2f (R = H)
2k
B: 5 min, 99% yield
B: 5 min, 78% yield
B: 5 min, 80% yield
2g (R = Me)
B: 5 min, 92% yield
O
O
2h [Ar = 3,5-(CF3)2C6H3]
B: 5 min, 99% yield
O
2l
B: 5 min, 99% yield
2i [Ar = 4-(MeO)C6H4]
B: 5 min, 96% yield
aUnless otherwise noted, NaOCl¢5H2O (Wako) was used. The Method,
reaction time, and isolated yield of 2 are shown. bNaOCl¢5H2O
(Kaneka) was used. For details, see the Supporting Information.
We examined various β-(2-hydroxyphenyl)carboxylic acids
1 under optimized conditions (Table 2).10 In most cases,
Method B (EtOAc/H2O 20:1 v/v) was superior to Method A
382 | Chem. Lett. 2015, 44, 381–383 | doi:10.1246/cl.141130
© 2015 The Chemical Society of Japan

Evaluation Only. Created with Aspose.PDF. Copyright 2002-2021 Aspose Pty Ltd.
yields. Furthermore, this protocol can be applied to the oxidation
of various phenols.
R. T. Morris, R. C. Ness, C. Richard, L. L. Scott, S. H.
Moore, A. P. Asuru, US0117278, 2014.
3
4
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Uyanik, K. Ishihara, J. Synth. Org. Chem., Jpn. 2012, 70,
1116.
For pioneering reports on the catalytic use of hypervalent
organoiodines(III) employing m-CPBA as an oxidant, see:
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Kita, Angew. Chem., Int. Ed. 2005, 44, 6193.
Conventional aqueous NaOCl or NaOCl on Celite have been
used as an oxidant for the oxidation of phenols. a) O. Tsuge,
H. Watanabe, S. Kanemasa, Chem. Lett. 1984, 1415. b) L.
Krumenacker, M. Costantini, F. Igersheim, FR2549044,
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Financial support for this project was partially provided by
JSPS. KAKENHI (Nos. 24245020 and 25105722) and Program
for Leading Graduate Schools “Integrative Graduate Education
and Research in Green Natural Sciences,” MEXT, Japan, and
JSPS Research Fellowships for Young Scientists (N.S.).
Supporting Information is available electronically on J-STAGE.
References and Notes
1
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7
8
NaOCl¢5H2O (Kaneka, pH ca. 10.5) is not commercially
available yet, but was provided by Kaneka Corporation.
Although the pH value of NaOCl¢5H2O (Kaneka, pH
ca. 10.5) upon dissolution is lower than that of NaOCl¢5H2O
(Wako, pH ca. 11), the influence of the pH on reactivity is not
yet clear.
The amount of water used in EtOAc/H2O (79:1 v/v) was
adjusted to the water contents of conventional aqueous
NaOCl solution (ca. 10 wt %).
9
10 For details, see the Supporting Information.
Chem. Lett. 2015, 44, 381–383 | doi:10.1246/cl.141130
© 2015 The Chemical Society of Japan | 383