Photoinduced electron transfer oxidation of α-methylstyrene with molecular oxygen sensitized by dimethoxybenzenes: A non-singlet-oxygen mechanism

Article abstract of DOI:10.1016/S0040-4039(01)00213-1

α-Methylstyrene (1) was photooxidized with oxygen in the presence of a series of alkylated dimethoxybenzenes as a sensitizer in acetonitrile, affording the cleaved ketone (2), epoxide (3) as well as a small amount of the ene product (4) in ca. 1:1:0.04 ratio. A non-singlet-oxygen mechanism is proposed, in which an excited sensitizer is quenched by oxygen to produce a sensitizer radical cation and a superoxide ion (O₂^·-), the former of which oxidizes 1, while O₂^·- reacts with the resulting 1^·+ to give the major oxidation products.

Full text of DOI:10.1016/S0040-4039(01)00213-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2505–2508
Photoinduced electron transfer oxidation of a-methylstyrene with
molecular oxygen sensitized by dimethoxybenzenes:
a non-singlet-oxygen mechanism
Tadashi Mori,a,* Makoto Takamoto,a Yoshimasa Tate,a Junya Shinkuma,a Takehiko Wadaa and
Yoshihisa Inouea,b,
*
aDepartment of Molecular Chemistry, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan
bInoue Photochirogenesis Project, ERATO, JST, 4-6-3 Kamishinden, Toyonaka 565-0085, Japan
Received 25 December 2000; revised 24 January 2001; accepted 2 February 2001
Abstract—a-Methylstyrene (1) was photooxidized with oxygen in the presence of a series of alkylated dimethoxybenzenes as a
sensitizer in acetonitrile, affording the cleaved ketone (2), epoxide (3) as well as a small amount of the ene product (4) in ca.
1:1:0.04 ratio. A non-singlet-oxygen mechanism is proposed, in which an excited sensitizer is quenched by oxygen to produce a
−
−
+
’
’
’
sensitizer radical cation and a superoxide ion (O2 ), the former of which oxidizes 1, while O2 reacts with the resulting 1 to
give the major oxidation products. © 2001 Elsevier Science Ltd. All rights reserved.
Photosensitized oxygenations of various olefins using
molecular oxygen have been extensively studied from
the environmental,1 synthetic and mechanistic points of
view.2 Photoactivation of molecular oxygen using Rose
Bengal (RB) and Methylene Blue (MB) has been much
investigated and shown to give a singlet oxygen (1O2) as
an essential intermediate. The photoinduced singlet-
oxygen formation is widely recognized in such dye-sen-
sitized oxygenations, although some other mechanisms
are known to operate in distinctive systems.3 For exam-
ple, singlet oxygen is almost inert to such olefins that
possess no (reactive) allylic proton: e.g. 1,1-
diphenylethylene, tetraarylethylene and adamantylide-
neadamanthane. However, electron-deficient sensitizers
such as dicyanoanthracene (DCA) are known to acti-
vate the photooxidation pathways. Electron transfer
from substrate to photoexcited DCA affords substrate
radical cation and DCA radical anion, the latter of
which oxidizes the ground state oxygen to give superox-
and photochemically generated) singlet oxygen, this
alkene is cleanly oxidized by molecular oxygen upon
irradiation with dimethoxybenzene added as a sensi-
tizer.5 However, in order to establish a practical
efficient photooxygenation system, photodegradation of
sensitizers is a serious problem that must be overcome.
It is well known that dye-sensitizers such as RB and
MB, or cyanosubstituted aromatic compounds, decom-
pose upon irradiation in the presence of oxygen.6 In
this study, we employed a variety of alkylated p-
dimethoxybenzenes as electron-donating sensitizers for
photooxidation of a-methylstyrene with molecular oxy-
gen, and investigated the effects of alkylation on the
chemical and quantum yields and the distribution of
oxidation products as well as the durability of the
sensitizer.
Irradiation of an oxygen-saturated acetonitrile solution
of a-methylstyrene (1, 2 mM) containing p-dimethoxy-
benzene (Sens=H, 1 mM) as a sensitizer at 0°C with a
high pressure mercury lamp (Pyrex filter, u>280 nm)
gave acetophenone (2) and 2-methyl-2-phenyloxirane
(3) in ca. 1:1 ratio, together with a small amount of the
ene product (4), as shown in Scheme 1. In the absence
of a sensitizer, the progress of the reaction was retarded
and the relative importance of the ene product 4 was
increased. Practically no reaction was observed under
an argon atmosphere. No ground-state interaction
between 1 and oxygen was observed, as the absorption
spectra in oxygen- and argon-saturated solutions of 1
were identical under the conditions for photooxidation.
−
−
’
’
ide ion (O2 ), while the former reacts with O2 to give
oxidation products.3
a-Methylstyrene is photooxidized in the presence of
MB, but the reaction details (such as yield and condi-
tions) are not clearly described in the literature.4
Although a-methylstyrene is almost inert to (chemically
Keywords: a-methylstyrene; dimethoxybenzenes; non-singlet-oxygen
mechanism; electron transfer oxidation; molecular oxygen.
* Corresponding authors. Fax: +81 6 6879 7923; e-mail: tmori@
ap.chem.eng.osaka-u.ac.jp; inoue@ap.chem.eng.osaka-u.ac.jp
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00213-1

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T. Mori et al. / Tetrahedron Letters 42 (2001) 2505–2508
Scheme 1.
Thus, the possible intervention of a charge–transfer
complex is ruled out in the present system. It is noted
that the progress of the reaction was extremely slow in
a non-polar solvent.
Me, 2,3-Me2, 2,5-Me2, 2,6-Me2, Me3, Me4, bis-C5, bis-
C6, MeVE) have low lying singlet excited state energies
which are accessible by Pyrex-filtered light.
Results of the photolyses are summarized in Table 1.
Although all of the sensitizers employed gave the same
oxidation products (2–4) in an almost similar ratio,7 the
relative reactivity varied dramatically. Thus, the quan-
tum yield of substrate consumption (bconv) critically
depends on the sensitizer employed, ranging from 0.04
to 0.22.8 This correlates well with the fluorescence
quantum yield (bfl) of each sensitizer in hexane, as
shown in Fig. 1. On the contrary, no direct correlation
was found between the oxidation potential (E0ox) of the
sensitizer and bconv, with serious deviations particularly
for sterically hindered sensitizers. These results are
obviously incompatible with the singlet oxygen mecha-
nism and clearly indicate that the reaction proceeds
through the singlet manifold and the steric bulk or
reduced oxidation potential of alkylated sensitizers are
not directly related to the product quantum yield,
Although a previous study5 claimed an exclusive forma-
tion of 2 and an 80% recovery of the sensitizer at 90%
conversion in the photosensitized oxidation of 1 with
p-dimethoxybenzene for 12 h, we could not reproduce
the same results. Instead we obtained 2 in less than 50%
yield with a poor recovery (10%) of the sensitizer and
an 80% consumption of 1 after 6 h irradiation. Not
only this particular photosensitizer but also others such
as RB and MB, are frequently photodecomposed upon
prolonged irradiations.6 For practical synthetic applica-
tions, it is desirable to develop efficient and durable
photosensitizers. In an attempt to obtain more durable
sensitizers against the photodegradation, we succes-
sively replaced the aromatic hydrogens of 1 by methyls
or more bulky bridged methylenes. All alkylated
methoxybenzenes employed in this study (Sens=H,
Table 1. Photoinduced electron transfer oxidation of a-methylstyrene (1) with oxygen in the presence of p-dimethoxybenzene
derivatives as a sensitizera
Sens
Irrad. time (h)
Conv. (%)
Yield (%)
bconv
2
3
4
Noneb
H
Me
2,3-Me2
2,5-Me2
2,6-Me2
Me3
12
12
6
6
6
12
6
12
12
12
12
48
\99
98
\99
99
\99
96
83
23
46
48
48
51
49
43
34
41
35
54
4
7
2
1
1
3
1
2
3
1
3
1
0.019
0.15
0.18
0.22
0.19
0.073
0.16
0.044
0.11
0.046
0.15
43
40
44
38
28
43
25
44
23
30
Me4
bis-C5
bis-C6
MeVE
\99
85
\99
a All irradiations were performed at 0°C in oxygen-saturated MeCN solutions containing sensitizer (1 mM) and 1 (2 mM) using a 300 W
high-pressure mercury lamp fitted with a Pyrex filter (u>280 nm), unless otherwise indicated.
b No sensitizer added.

T. Mori et al. / Tetrahedron Letters 42 (2001) 2505–2508
2507
Figure 1. Correlation between fluorescence quantum yield of sensitizers (bfl) and quantum yield of conversion (bconv).
which is rather accounted for in terms of the abundance
of the singlet species and the process derived therefrom.
Concerning the photodurability of sensitizers, we
obtained good to excellent sensitizer recoveries (>70%
after 80% conversion) particularly for tetrasubsituted
dimethoxybenzenes (Sens=Me4, bis-C5 and bis-C6),
while less hindered ones (Sens=Me3 or 2,6-Me2) gave
only <50% recoveries after 6 h irradiation.
substituted dimethoxybenzenes as a sensitizer. Mecha-
nistically, this photooxidation proceeds through the
initial quenching of an excited singlet sensitizer by
molecular oxygen producing a sensitizer radical cation
and a superoxide, followed by the electron transfer
from the substrate alkene to the sensitizer radical cation
and the subsequent recombination of the resulting sub-
strate radical cation with the superoxide, producing the
ketone and epoxide as the major oxidation products in
excellent combined yields. Photodurability of
dimethoxybenzene sensitizers is dramatically improved
by the tetraalkylation of dimethoxybenzene. It has been
demonstrated that the reactions of singlet oxygen with
trans-4-propenylanisole15 and with benzyl ethyl
sulfide16 can be completely changed by adding a cata-
lytic amount of acid. Similar switching of photoreactiv-
ity by acid has also been recognized by us17 and by
We propose an electron transfer oxidation mechanism
illustrated in Scheme 2 for the present system, since the
following observations clearly indicate the non-singlet-
oxygen mechanism: (a) strong solvent dependence,
which is not compatible with 1O2 reaction; (b) good
correlation between bfl and bconv, which is not expected
for the singlet-oxygen mechanism; (c) highly favorable
free energy change for electron transfer from excited
sensitizer to ground-state oxygen. DGET<−40 kcal/mol.9
As shown in Scheme 2, the singlet excited sensitizer
−
’
reduces molecular oxygen to generate superoxide (O2
)
(Eq. (1)), which in turn reacts with the substrate radical
+
’
cation (1 ) to form the perepoxide intermediate 5 (Eq.
+
’
(3)). 1 is presumably derived from the (fast) hole
transfer between the sensitizer radical cation and the
substrate (Eq. (2)). The perepoxide affords the corre-
sponding epoxide 3, either through the reaction with
singlet oxygen10 or through the recombination with
another molecule of 511 (Eqs. (4) or (5)). Dioxetane
intermediates are often isolated in the photooxygena-
tion of sterically hindered alkene substrates such as
adamanthylideneadamanthane.12 Hence, it is reason-
able to assume that this type of dioxetane (7) may be
formed but cannot survive under the reaction condi-
tions employed,13 affording the acetophenone (2) and
formaldehyde (8) (Eq. (6)). Barton-type oxidation,14 i.e.
the addition of triplet (ground state) oxygen to the
radical cation of the substrate, leading to the chain
oxidation process, may not be operative as a major
pathway because the quantum yields of the reaction are
much lower than unity.
In summary, an efficient photosensitized oxidation of
alkene with molecular oxygen was achieved using tetra-
Scheme 2.

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T. Mori et al. / Tetrahedron Letters 42 (2001) 2505–2508
others,18 recently. The effect of added acid, detailed
reaction mechanism and further synthetic applications
of this photosensitized oxidation are currently under
investigation.
5. Bhalerao, U. T.; Sridhar, M. Tetrahedron Lett. 1993, 34,
4341.
6. (a) Dougherty, T. J. Photochem. Photobiol. 1987, 45, 879;
(b) McCullough, J. J. Chem. Rev. 1987, 87, 811.
7. The relative product ratio was not significantly changed
during the photolysis. All of the products formed in the
present oxidation were almost stable and can be recov-
ered from the independent irradiations under the similar
photolysis conditions employed.
Acknowledgements
Financial support (to T.M.) of this work by a Grant-in-
Aid for Scientific Research from the Ministry of Educa-
tion, Science, Sports and Culture of Japan (No.
12740346) and from the Shorai Foundation for Science
and Technology are gratefully acknowledged.
8. Quantum efficiency of conversion (bconv) was determined
at low conversion stages (ꢀ10%) by using the photoreac-
tion of p-methylbenzonitrile in MeCN at 25°C under Ar
as a chemical actinometer: MacLeod, R. J.; Pincock, A.
L.; Pincock, J. A.; Thompson, K. A. J. Am. Chem. Soc.
1998, 120, 6443.
9. Rehm, D.; Weller, A. Isr. J. Chem. 1970, 8, 259.
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11. Bartlett, P. D.; Landis, M. E. J. Am. Chem. Soc. 1977,
99, 3033.
12. Schaap, A. P.; Faler, G. R. J. Am. Chem. Soc. 1973, 95,
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13. (a) Greer, A.; Vassilikogiannakis, G.; Lee, K.-C.; Koffas,
T. S.; Nahm, K.; Foote, C. S. J. Org. Chem. 2000, 65,
6876; (b) Richardson, W. H.; Montgomery, F. C.; Yelv-
ington, M. B.; O’Neal, H. E. J. Am. Chem. Soc. 1974, 96,
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