Metal-free epoxidation of alkenes with molecular oxygen and benzaldehyde under visible light irradiation

Article abstract of DOI:10.1055/s-0029-1218271

A new convenient metal-free oxidation protocol of a wide variety of alkenes with molecular oxygen and benzaldehyde under visible light irradiation of fluorescent lamp afforded their corresponding epoxides in 49-99% yields. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-0029-1218271

3024
LETTER
Metal-Free Epoxidation of Alkenes with Molecular Oxygen and Benzaldehyde
under Visible Light Irradiation
M
etal-Free Epoxid
o
ation of
A
lk
r
e
nes ihiro Tada, Hiroaki Okubo, Tsuyoshi Miura, Akichika Itoh*
Gifu Pharmaceutical University, Mitahora-higashi, Gifu 502-8585, Japan
Fax +81(58)2378573; E-mail: itoha@gifu-pu.ac.jp
Received 8 July 2009
served in the reaction with 2 equivalents of benzaldehyde
and initial exposure for 3 hours to afford stereospecifical-
ly trans-stilbene oxide (2) in 93% yield without the for-
mation of the cis-isomer (entries 7–11). It is worth noting
that the epoxidation proceeds in good yield under air at-
mosphere instead of O2 balloon (entry 12). Both molecu-
lar oxygen and visible light irradiation are necessary for
this epoxidation since 2 cannot be satisfactorily obtained
without them (entries 13 and 14).
Abstract: A new convenient metal-free oxidation protocol of a
wide variety of alkenes with molecular oxygen and benzaldehyde
under visible light irradiation of fluorescent lamp afforded their cor-
responding epoxides in 49–99% yields
Key words: aerobic, epoxidation, visible light, benzaldehyde
Since epoxides are versatile intermediates for a variety of
chemicals, epoxidation of alkenes is a most important
functional-group transformation in organic synthesis.1
Generally epoxidations of alkenes have been carried out
with peracids; however, caution is necessary due to their
explosivility. As such development of new safe and effec-
tive oxidants for epoxidation has been studied. Molecular
oxygen is thought to be the most desirable oxidant with re-
spect to environmental and economic consideration, and
much effort has been made to develop direct epoxidation
of alkenes with molecular oxygen as an oxygen donor. Al-
though there have been many reports on the metal-cata-
lyzed epoxidation of alkenes with molecular oxygen as a
terminal oxidant,2 only a limited number of metal-free
methods have been reported.3 Among them, epoxidation
of alkenes using peracids, prepared by oxidation of alde-
hyde with molecular oxygen in situ, under photoirradia-
tion conditions is an important and a promising method;4
however, the previous methods were carried out under
UV irradiation or applicable to the limited alkenes.3a,d An
effective use of visible light appears optimal development
of novel energy conversion and energy-using technology.
Towards this goal, we have previously reported photo-
oxidation using visible light from a general purpose fluo-
rescent lamp;5 in this letter, we report a general and
convenient synthetic method for metal-free epoxidation
of alkenes using molecular oxygen and benzaldehyde un-
der visible light irradiation.
Table 1 Study of Reaction Conditions
1) hν (fluorescent lamp), O2
benzaldehyde (equiv)
solvent, r.t., time
O
2) 1, r.t., 10 h, N2
1 (0.3 mmol)
2
Entry
Solvent
Benzaldehyde Time
Yield
(%)a
(equiv)
2.0
2.0
2.0
2.0
2.0
2.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
2.0
(h)
5
5
5
5
5
5
5
3
3
3
1
3
5
5
1
2
CH2Cl2
THF
0
0
3
EtOAc
acetone
MeOH
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
MeCN
73
67
0
4
5
6
92
69
93
82
0
7
8
9b
10c
11
12d
13e
14f
65
83
24
0
Table 1 shows the results of study of reaction conditions
for the epoxidation. The conditions were examined with
benzaldehyde under the molecular oxygen atmosphere
(O2 balloon) and visible light irradiation at room temper-
ature, followed by the reaction with trans-stilbene (1) un-
der nitrogen atmosphere at room temperature, and
acetonitrile was found to be most suitable solvent among
our examination (entries 1–6).6 A better result was ob-
a The yields were determined by integration of 1H NMR with internal
standard.
b 4-Methoxybenzaldehyde was used instead of benzaldehyde.
c 4-Nitrobenzaldehyde was used instead of benzaldehyde.
d The reaction was carried out under air.
e The reaction was carried out in the dark.
f The reaction was carried out under N2.
SYNLETT 2009, No. 18, pp 3024–3026
x
x
.x
x
.2
0
0
9
Advanced online publication: 08.10.2009
DOI: 10.1055/s-0029-1218271; Art ID: U06709ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Metal-Free Epoxidation of Alkenes
3025
Table 2 shows scope and limitation of this epoxidation namyl alcohol, and 1,2-dihydronaphthalene, afforded ste-
with various alkenes such as aromatic alkenes, aliphatic reospecifically the corresponding epoxides in good to
alkenes, and allylic alcohols under the optimized reaction excellent yield without formation of the geometrical iso-
conditions.7 Disubstituted aromatic alkenes, such as mers (entries 1–5). Monosubstituted styrenes with tert-
trans-stilbene, cis-stilbene, trans-b-methylstyrene, cin- butyl and chloro groups at para position afforded the cor-
Table 2 Epoxidation of Aromatic and Aliphatic Alkenes
1) hν (fluorescent lamp), O2
benzaldehyde (2 equiv)
MeCN, r.t., 3 h
substrate
product
(0.3 mmol)
2) substrate, r.t., time (h), N2
Entry
1
Substrate
Product
Time (h)
10
Yield (%)a
89c
O
O
2
10
80c
O
3
4
5
5
5
5
85
82
66
O
O
OH
OH
O
6
5
76c
O
7
8
10
10
73c
49c
Cl
Cl
O
O
O2N
O2N
O
9
24
10
81
10
70c
O
11
12
10
5
99
78
O
OH
OH
13
5
27 (89)b
O
a Isolated yields. Numbers in parentheses are 1H NMR yields.
b cis-Cyclooctene oxide is unstable under preparative TLC.
c The substrate recovery was 10%, 13%, 5%, 6%, 50%, and 8% for entries 1, 2, 6–8, and 10.
Synlett 2009, No. 18, 3024–3026 © Thieme Stuttgart · New York

3026
N. Tada et al.
LETTER
Chem. Soc. 1985, 107, 5790. (c) Takai, T.; Yamada, T.;
responding epoxides in good yields; however, electron-
withdrawing nitro group retarded this reaction (entries 6–
8). Furthermore, both mono- and disubstituted aliphatic
alkenes gave the corresponding epoxides in good to excel-
lent yields (entries 9–13).
Mukaiyama, T. Chem. Lett. 1990, 1657. (d) Mukaiyama,
T.; Takai, T.; Yamada, T.; Rhode, O. Chem. Lett. 1990,
1661. (e) Yamada, T.; Takai, T.; Rhode, O.; Mukaiyama, T.
Chem. Lett. 1991, 1. (f) Takai, T.; Hata, E.; Yamada, T.;
Mukaiyama, T. Bull. Chem. Soc. Jpn. 1991, 64, 2513.
(g) Yamada, T.; Takai, T.; Rhode, O.; Mukaiyama, T. Bull.
Chem. Soc. Jpn. 1991, 64, 2109. (h) Yamada, T.; Imagawa,
K.; Mukaiyama, T. Chem. Lett. 1992, 2109. (i) Murahashi,
S.-I.; Oda, Y.; Naota, T.; Komiya, N. J. Chem. Soc., Chem.
Commun. 1993, 139. (j) Punniyamurthy, T.; Bhatia, B.;
Iqbal, J. Tetrahedron Lett. 1993, 34, 4657. (k) Hamamoto,
M.; Nakayama, K.; Nishiyama, Y.; Ishii, Y. J. Org. Chem.
1993, 58, 6421. (l) Yorozu, K.; Takai, T.; Yamada, T.;
Mukaiyama, T. Bull. Chem. Soc. Jpn. 1994, 67, 2195.
(m) Mukaiyama, T.; Yamada, T. Bull. Chem. Soc. Jpn. 1995,
68, 17. (n) Iwahama, T.; Sakaguchi, S.; Ishii, Y. Chem.
Commun. 1999, 727. (o) Iwahama, T.; Hatta, G.; Sakaguchi,
S.; Ishii, Y. Chem. Commun. 2000, 163.
A plausible reaction path is shown in Scheme 1. Perben-
zoic acid, usual epoxidation reactant, is assumed to be
formed in situ, since we could detect perbenzoic acid in
50% yield when benzaldehyde was irradiated with visible
light under molecular oxygen atmosphere at room temper-
ature for 3 hours.8 This result agrees with the requirement
of two equivalents of benzaldehyde to complete this ep-
oxidation. Furthermore, perbenzoic acid was obtained
only in 15% yield when the reaction was carried out in the
dark, visible light was found to accelerate the generation
of perbenzoic acid.
(3) (a) Raymond, E. J. Chim. Phys. 1931, 28, 480. (b) Swern,
D.; Findley, T. W.; Scanlan, J. T. J. Am. Chem. Soc. 1944,
66, 1925. (c) Swernindley, D. J. Am. Chem. Soc. 1950, 72,
4315. (d) Kaneda, K.; Haruna, S.; Imanaka, T.; Hamamoto,
M.; Nishiyama, Y.; Ishii, Y. Tetrahedron Lett. 1992, 33,
6827. (e) Iwahama, T.; Sakaguchi, S.; Ishii, Y. Chem.
Commun. 1999, 727.
O
O
O
hν (vis)
O2
H
OOH
OH
O
(4) (a) When the aldehyde is exposed to oxygen or air, aldehyde
is slowly oxidized to the corresponding peracid, and the rate
of oxidation is increased by light and certain catalysts, See:
McNesby, J. R.; Heller, C. A. Jr. Chem. Rev. 1954, 54, 325.
(b) Niclause, M. Selecta Chim. 1956, 15, 57. (c) Niclause,
M.; Lemaire, J. Adv. Photochem. 1966, 4, 25.
(5) (a) Hirashima, S.; Itoh, A. J. Synth. Org. Chem. Jpn. 2008,
66, 748. (b) Sugai, T.; Itoh, A. Tetrahedron Lett. 2007, 48,
9096. (c) Hirashima, S.; Itoh, A. Photochem. Photobiol. Sci.
2007, 6, 521. (d) Hirashima, S.; Itoh, A. Green Chem. 2007,
9, 318. (e) Nakayama, H.; Itoh, A. Tetrahedron Lett. 2007,
48, 1131. (f) Nakayama, H.; Itoh, A. Chem. Pharm. Bull.
2006, 54, 1620.
Scheme 1 Plausible path
In conclusion, we have developed the convenient and en-
vironmentally benign metal-free epoxidation of various
alkenes in the presence of molecular oxygen and benzal-
dehyde under visible light irradiation of fluorescent lamp.
This method is of great value from the view point of using
visible light and applicable to a wide variety of alkenes.
Further application of this oxidation to other reactions is
now in progress in our laboratory.
(6) Exposure of benzaldehyde to the molecular oxygen under
visible light irradiation in the presence of trans-stilbene (1)
result in the no reaction, probably because trans-stilbene (1)
inhibits photooxidation of benzaldehyde. On the other hand,
11% of trans-5-decene oxide was produced when using
trans-5-decene instead of 1.
Acknowledgment
This work was supported in part by Grants-in-Aid for Scientific Re-
search (C) (No19590007) from the Japan Society for the Promotion
of Science.
(7) Typical Procedure of the Epoxidation
A dry MeCN solution (1 mL) of the benzaldehyde (63.7 mg,
0.6 mmol) in a 30 mL round-bottom flask equipped with
an O2 balloon was stirred and irradiated with four 22 W
fluorescent lamps, which were set up at a distance of 65 mm,
for 3 h. The temperature of the final stage of this reaction
was about 50 °C. Then, trans-stilbene (1, 54.1 mg, 0.3
mmol) was added to the reaction mixture and stirred without
irradiation for 10 h at r.t. The reaction mixture was
concentrated under reduced pressure. The residue was
purified by preparative TLC to afford the pure product 2
(52.4 mg, 89%).
References and Notes
(1) (a) van Leeuwen, P. W. N. M. Homogeneous Catalysis;
KluwerAcademic Publishers: Dordrecht, 2004.
(b) Encyclopedia of Catalysis, Vol. 3; Horvath, I. T., Ed.;
John Wiley and Sons: Hoboken, 2002. (c) Oxidation in
Organic Chemistry; Hudlucky, M., Ed.; ACS: Washington/
DC, 1990. (d) Metal-Catalyzed Oxidations of Organic
Compounds; Sheldon, R. A.; Kochi, J. K., Eds.; Academic
Press: New York, 1981.
(8) Yield of perbenzoic acid was determined by integration of
(2) (a) Kaneda, K.; Jitsukawa, K.; Itoh, T.; Teranishi, S. J. Org.
1H NMR with internal standard (1,1,2,2,-tetrachloroethane).
Chem. 1980, 45, 3004. (b) Groves, J. T.; Quinn, R. J. Am.
Synlett 2009, No. 18, 3024–3026 © Thieme Stuttgart · New York

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