Facile and efficient synthesis of hydroxyalkyl esters from cyclic acetals through aerobic photo-oxidation using anthraquinone-2-carboxylic acid

Article abstract of DOI:10.1016/j.tetlet.2015.02.104

Abstract A convenient metal-free oxidation protocol of various cyclic acetals with molecular oxygen and anthraquinone-2-carboxylic acid under visible light irradiation by a fluorescent lamp afforded their corresponding hydroxyalkyl esters.

Full text of DOI:10.1016/j.tetlet.2015.02.104

Tetrahedron Letters 56 (2015) 1973–1975
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Tetrahedron Letters
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Facile and efficient synthesis of hydroxyalkyl esters from
cyclic acetals through aerobic photo-oxidation using
anthraquinone-2-carboxylic acid
Tomoaki Yamaguchi a, Yasuhisa Kudo a, Shin-ichi Hirashima b, Eiji Yamaguchi a, Norihiro Tada a,
Tsuyoshi Miura b, Akichika Itoh a,
⇑
a Gifu Pharmaceutical University, 1-25-4, Daigaku-nishi, Gifu 501-1196, Japan
b Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A convenient metal-free oxidation protocol of various cyclic acetals with molecular oxygen and
anthraquinone-2-carboxylic acid under visible light irradiation by a fluorescent lamp afforded their
corresponding hydroxyalkyl esters.
Received 16 January 2015
Revised 16 February 2015
Accepted 19 February 2015
Available online 2 March 2015
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Aerobic
Oxidation
Visible light
Anthraquinone
1,3-Dioxolanes are among the most widely used protective
groups for carbonyl compounds and vicinal diols.1 Oxidation of
2-aryl- and alkyl-1,3-dioxolanes derived from aldehydes provides
a useful route for the synthesis of hydroxyethyl esters, which have
been used in selective Diels–Alder reactions, because they can be
preferentially activated with Lewis acids by forming a chelated
structure in the presence of simple ester groups.2 Furthermore,
hydroxyethyl esters serve as cross-linking agents and fungicides.3
Metal reagents used for direct oxidative cleavage of 1,3-dioxolanes
include molecular oxygen–Co(II),4 potassium permanganate,5 and
tert-butylhydroperoxide in the presence of transition metals.6 In
addition, many methods that employ nonmetal reagents
such as ozone,7 hypochlorous acid,8 N-hydroxyphthalimide in
electrochemical oxidation,9 tert-butylhydroperoxide–iodine(III)
In contrast, molecular oxygen is thought to be the most desirable
oxidant with respect to environmental and economic consid-
erations. Although there have been transition metal-catalyzed
oxidative cleavage of cyclic acetals with molecular oxygen as a
terminal oxidant,4 to the best of our knowledge, no metal-free
catalytic reactions have been reported, probably because the
hydroxy group of hydroxyalkyl esters is easily oxidized in the usual
reaction conditions. To develop metal-free catalytic oxidative
cleavage of cyclic acetals with molecular oxygen as an oxygen
donor, a mild and selective reaction is required.
On the other hand, the effective use of visible light, plentiful in
our surroundings, is one of the most important research topics at
this time of the hoped-for development of new energy-conversion
and energy-using technologies. In our continuous interest in using
visible light in organic chemistry, we have been studying
photo-oxidative reactions with organo-photocatalysts such as
anthraquinones.18 These reactions proceed under mild reaction
conditions such as ambient temperature and pressure, thus it
occurred to us that the use of anthraquinones as catalysts makes
it possible to perform metal-free catalytic oxidative cleavage of
cyclic acetals with molecular oxygen as the terminal oxidant.
Herein, we report a facile and efficient oxidative cleavage of
cyclic acetals with molecular oxygen as the terminal oxidant under
visible light irradiation (Scheme 1).
compounds,10
IBX/Et4NBr,11
(diacetoxy)iodobenzene/LiBr,12
di-tert-butyl peroxide,13 electrophilic halogen,14 and m-chloroper-
benzoic acid in the presence of 2,20-bipyridinium chlorochromate
or boron trifluoride–diethyl ether,15 sodium perborate in acetic
anhydride,16 and oxone17 have been reported.
However, there are some problems related to these reactions,
such as low yield, hazardous reaction conditions, and the necessity
for stoichiometric amounts or environmental high impact catalysts.
Table 1 shows the results of the optimization of reaction
conditions for the transformation of 2-phenyl-1,3-dioxolane (1a),
⇑
Corresponding author. Tel./fax: +81 58 230 8108.
E-mail address: itoha@gifu-pu.ac.jp (A. Itoh).
http://dx.doi.org/10.1016/j.tetlet.2015.02.104
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.

1974
T. Yamaguchi et al. / Tetrahedron Letters 56 (2015) 1973–1975
Table 2
Oxidative cleavage of cyclic acetals
1) O2, hν (22 W fluorescent lamp)
AQN-2-CO2H (0.1 equiv)
EtOAc, 3 h
n
O
O
Scheme 1. Oxidative synthesis of hydroxyalkyl esters from cyclic acetals.
OH
O
R
R
O
n
2) aq. Na2S2O3
1
2
Entry
1
R
n
2
Yielda (%)
Table 1
Study of reaction conditions
1
2
3
4
5
6
7
8
1b
1c
1d
1a
1e
1f
1g
1h
1i
4-MeOC6H4
4-t-BuC6H4
4-MeC6H4
Ph
4-ClC6H4
4-CO2MeC6H4
4-NO2C6H4
2-NO2C6H4
4-BocNHC6H4
4-pyridinyl
2-thienyl
n-C5H11
n-C11H23
PhCH2
4-MeOC6H4
4-t-BuC6H4
4-MeC6H4
Ph
1
1
1
1
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2b
77
84
60
69
73
67
79b
66c
15d
7c
2c
2d
2a
2e
2f
2g
2h
2i
O
O
1) O2, hν (22 W fluorescent lamp)
catalyst, solvent, 3 h
OH
O
O
2) aq. Na2S2O3
1a
2a
Entry
Catalyst (equiv)
Solvent
Yielda (%)
9
1
2
3
4
5
6
7
8
Rose Bengal (0.1)
Methylene blue (0.1)
1,4-Benzoquinone (0.1)
2-Cl-AQN (0.1)
Anthraquinone (AQN) (0.1)
2-Me-AQN (0.1)
AQN-2-CO2H (0.1)
AQN-2-CO2H (0.1)
AQN-2-CO2H (0.1)
AQN-2-CO2H (0.1)
AQN-2-CO2H (0.1)
AQN-2-CO2H (0.1)
AQN-2-CO2H (0.1)
AQN-2-CO2H (0.05)
AQN-2-CO2H (0.2)
—
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
Acetone
MeCN
CH2Cl2
H2O
0
0
11
57
66
70
71 (69)
73 (64)
44
26
2
0
10
11
12
13
14
15
16
17
18
19
20
21
1j
1k
1l
2j
2k
2l
24c
69
64
45
61
75e
51
65b
49
20f
34
1m
1n
1o
1p
1q
1r
1s
1t
2m
2n
2o
2p
2q
2r
2s
2t
9
10
11
12
13
14
15
16
17
18
4-ClC6H4
4-NO2C6H4
n-C11H23
Benzene
i-PrOH
EtOAc
EtOAc
EtOAc
EtOAc
EtOAc
1u
2u
0
70 (64)
a
b
c
d
e
f
Isolated yields.
5 h.
9 h.
24 h.
With acetone as solvent.
With AQN-2-CO2H (0.2 equiv) for 9 h.
56
0
AQN-2-CO2H (0.1)
AQN-2-CO2H (0.1)
6b
8c
a
b
c
1H NMR yields. Numbers in parentheses are isolated yields.
Under Ar.
In the dark.
1,3-dioxanes were poor substrates (entry 21). Note that 2-
methyl-2-phenyl-1,3-dioxolane (1v), an -disubstituted substrate,
was intact under these conditions (Scheme 2). This result suggest-
ed that the cleavage of the C–H bond was the initial step of this
oxidation.
test substrate, to hydroxyethyl benzoate (2a) under a molecular
oxygen atmosphere (O2-balloon) and visible light irradiation at
room temperature. Rose Bengal and methylene blue were not
effective, in contrast to anthraquinone (AQN) derivatives, and
AQN-2-CO2H was especially suitable for this reaction (entries 1–
7). As the result of examination of solvents (entries 8–13), acetone
was also a good solvent to afford 2a in almost the same yield.
However, the isolated yield was superior when the reaction was
conducted with EtOAc, therefore we decided to use EtOAc as the
solvent (entry 7 vs 8). By checking the catalytic amount, 0.1 equiv
of AQN-2-CO2H was found to produce 2a in the highest yield
(entries 7, 14, and 15). Anthraquinone, molecular oxygen, and visi-
ble light irradiation are all necessary for this oxidative cleavage
because 2a cannot be satisfactorily obtained without them (entries
16–18).
With the optimum reaction conditions in hand, we next inves-
tigated the scope and limitations of the oxidative cleavage of 1,3-
dioxolanes and 1,3-dioxanes (Table 2).19 The corresponding
hydroxyethyl esters were obtained in good to high yields regard-
less of electron-donating or electron-withdrawing groups at the
para position on the aromatic nucleus (entries 1–7). Moreover,
1h, bearing a nitro group at the ortho position, was converted to
the desired product in good yields with prolonged reaction time
(entry 8). Substrate including NHBoc, pyridinyl, or thienyl was con-
verted to the corresponding hydroxyalkyl ester albeit in low yields
(entries 9–11). In addition, aliphatic 1,3-dioxolanes were also con-
verted to hydroxyethyl esters in moderate to good yields (entries
12–14). Although the corresponding hydroxypropyl esters were
obtained in good to moderate yields with an electron-donating
group at the para position on the aromatic nucleus (entries 15–
18), an electron-withdrawing group inhibited the reaction, and
resulted in low yields (entries 19 and 20). Furthermore, aliphatic
a
Scheme 3 shows a plausible path for this reaction, which is pos-
tulated by considering the need for irradiation, a catalytic amount
of anthraquinone-2-carboxylic acid, and molecular oxygen in this
reaction. 1,3-Dioxolane 1 initially reacts with photoexcited anthra-
quinone-2-carboxylic acid (AQN⁄) to generate radical species 5.18
Compound 5 traps molecular oxygen to afford peroxyradical 6,
which is subsequently transformed to hydroperoxide 7 by the
abstraction of a hydrogen atom from 1 or AQHÅ. Hydroxyalkyl ester
2 is formed from 7 with H2O or Na2S2O3 in the quench step.
In this reaction mechanism, there is a possibility of radical chain
process via C–H cleavage of 1 by reacting with radical species 6. To
demonstrate the hypothetical mechanism, we carried out the
experiment with intermittent exposure to visible light (Fig. 1). As
the result, we observed the conversion of substrate upon to irradiate
with fluorescent lamp. In contrast, no transformation was detected
in the dark period. This result indicated that the radical chain pro-
cess did not include and support our estimated mechanism. In addi-
tion, excitation of oxygen by photo-excited AQN is probably
occurred, but it does not affect this reaction; because both rose
Bengal and methylene blue which are known to produce the singlet
oxygen were not effective (Table 1, entries 1 and 2).
O2, hν (22 W fluorescent lamp)
AQN-2-CO2H (0.1 equiv)
O
O
1v was recovered
Me
EtOAc, 3 h
1v
Scheme 2. Oxidative cleavage of 2-methyl-2-phenyl-1,3-dioxolane.

T. Yamaguchi et al. / Tetrahedron Letters 56 (2015) 1973–1975
1975
References and notes
1. Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis; John Wiley
and Sons: New York, 1999.
2. Clapham, G.; Shipman, M. Tetrahedron Lett. 1999, 40, 5639–5642.
3. Babler, J. H.; Coghlan, M. J. Tetrahedron Lett. 1979, 20, 1971–1974.
4. (a) Ikeda, C. K.; Braun, R. A.; Sorenson, B. E. J. Org. Chem. 1964, 29, 286–290; (b)
Rieche, A.; Schmitz, E.; Beyer, E. Chem. Ber. 1958, 91, 1935–1941; (c) Karimi, B.;
Rajabi, J. Synthesis 2003, 2373–2377; (d) Karimi, B.; Rajabi, J. J. Mol. Catal. A:
Chem. 2005, 226, 165–169; (e) Chen, Y.; Wang, P. G. Tetrahedron Lett. 2001, 42,
4955–4958; (f) Li, P.; Alper, H. Can. J. Chem. 1993, 71, 84–89.
5. Nai-ju, H.; Liang-heng, X. Synth. Commun. 1990, 20, 1563–1567.
6. (a) Hosokawa, T.; Imada, Y.; Murahashi, S.-I. J. Chem. Soc., Chem. Commun. 1983,
1245–1246; (b) Murahashi, S.; Oda, Y.; Naota, T. Chem. Lett. 1992, 21, 2237–
2240; (c) Chidambaram, N.; Bhat, S.; Chandrasekaran, S. J. Org. Chem. 1992, 57,
5013–5015; (d) Choudary, B. M.; Reddy, P. N. Synlett 1995, 959–960.
7. Deslongchamps, P.; Atlani, P.; Fréhel, D.; Malaval, A.; Moreau, C. Can. J. Chem.
1974, 52, 3651–3664.
Scheme 3. Plausible reaction mechanism.
8. Sugai, S.; Kodama, T.; Akaboshi, S.; Ikegami, S. Chem. Pharm. Bull. 1984, 32, 99–
105.
9. Masui, M.; Kawaguchi, T.; Yoshida, S.; Ozaki, S. Chem. Pharm. Bull. 1986, 34,
1837–1839.
10. Sueda, T.; Fukuda, S.; Ochiai, M. Org. Lett. 2001, 3, 2387–2390.
11. Kuhakarn, C.; Panchan, W.; Chiampanichayakul, S.; Samakkanad, N.;
Pohmakotr, M.; Reutrakul, V.; Jaipetch, T. Synthesis 2009, 929–934.
12. Panchan, W.; Chiampanichayakul, S.; Snyder, D. L.; Yodbuntung, S.; Pohmakotr,
M.; Reutrakul, V.; Jaipetch, T.; Kuhakarn, C. Tetrahedron 2010, 66, 2732–2735.
13. Huyser, E. S.; Garcia, Z. J. Org. Chem. 1962, 27, 2716–2719.
14. (a) Wright, J. B. J. Am. Chem. Soc. 1955, 77, 4883–4884; (b) Cort, L. A.; Pearson, R.
G. J. Chem. Soc. 1960, 1682–1687; (c) Prugh, J. D.; McCarthy, W. C. Tetrahedron
Lett. 1966, 1351–1356; (d) Mingotaud, A.-F.; Florentin, D.; Marquet, A. Synth.
Commun. 1992, 22, 2401–2404.
15. (a) Luzzio, F. A.; Bobb, R. A. Tetrahedron Lett. 1997, 38, 1733–1737; (b) Kim, J. Y.;
Rhee, H.; Kim, M. J. Korean Chem. Soc. 2002, 46, 479–483.
16. Bhat, S.; Ramesha, A. R.; Chandrasekaran, S. Synlett 1995, 329–330.
17. Curini, M.; Epifano, F.; Marcotullio, M. C.; Rosati, O. Synlett 1999, 777–
779.
Figure 1. Plot of conversion (%) of 2-phenyl-1,3-dioxolane (1a) versus time (h).
Solid lines indicate periods of exposure to visible light. Dotted lines indicate periods
in the dark.
18. (a) Tada, N.; Hattori, K.; Nobuta, T.; Miura, T.; Itoh, A. Green Chem. 2011, 13,
1669–1671; (b) Cui, L.; Furuhashi, S.; Tachikawa, Y.; Tada, N.; Miura, T.; Itoh, A.
Tetrahedron Lett. 2013, 54, 162–165; (c) Matsusaki, Y.; Yamaguchi, T.; Tada, N.;
Miura, T.; Itoh, A. Synlett 2012, 2059–2062; (d) Tada, N.; Ikebata, Y.; Nobuta, T.;
Hirashima, S.; Miura, T.; Itoh, A. Photochem. Photobiol. Sci. 2012, 11, 616–619;
(e) Cui, L.; Tada, N.; Okubo, H.; Miura, T.; Itoh, A. Green Chem. 2011, 13, 2347–
2350; (f) Itoh, I.; Matsusaki, Y.; Fujiya, A.; Tada, N.; Miura, T.; Itoh, A.
Tetrahedron Lett. 2014, 55, 3160–3162; (g) Yamaguchi, T.; Nobuta, T.; Tada, N.;
Miura, T.; Nakayama, T.; Uno, B.; Itoh, A. Synlett 2014, 1453–1457; (h) Matsui,
K.; Ishigami, T.; Yamaguchi, T.; Yamaguchi, E.; Tada, N.; Miura, T.; Itoh, A.
Synlett 2014, 2613–2616; (i) Tachikawa, Y.; Cui, L.; Matsusaki, Y.; Tada, N.;
Miura, T.; Itoh, A. Tetrahedron Lett. 2013, 54, 6218–6221; (j) Shimada, Y.;
Hattori, K.; Tada, N.; Miura, T.; Itoh, A. Synthesis 2013, 45, 2684–2688.
19. A typical procedure (Table 2, entry 4): A dry EtOAc solution (3 mL) of the 2-
phenyl-1,3-dioxolane (1a, 0.3 mmol), AQN-2-CO2H (0.03 mmol) in a pyrex test
tube equipped with an O2 balloon, was irradiated for 3 h with four 22 W
fluorescent lamps, which were set up at a distance of 65 mm. aq Na2S2O3 was
added to reaction mixture and extracted with EtOAc, washed with sat. aq NaCl,
dried over MgSO4, and concentrated under reduced pressure. Pure product was
obtained by preparative TLC (n-hexane/EtOAc = 5:1) to give ethylene glycol
monobenzoate (2a) in 69% yield.
In conclusion, we have developed a convenient and environmen-
tally benign metal-free oxidative cleavage of various dioxolanes and
dioxanes in the presence of molecular oxygen under visible light
irradiation from a fluorescent lamp. This new oxidation reaction is
appealing to the notion of ‘Green Chemistry’ because of the nonuse
of heavy metals, waste reduction, the use of molecular oxygen, and
low cost of reagents. Further application of this oxidation to other
reactions is now in progress in our laboratory.
Acknowledgment
The authors would like to thank Enago (www.enago.jp) for the
English language review.