Singlet oxygenation of 4-(4-tert-butyl-3,3-dimethyl-2,3-dihydrofuran-5- yl)-2-pyridone: Non-stereospecific 1,4-addition of singlet oxygen to a 1,3- diene system and thermal rearrangement of the resulting 1,4-endoperoxides to stable 1,2-dioxetanes

Article abstract of DOI:10.1039/b002161j

Singlet oxygen adds easily to a 1,3-diene 1, whose E-Z double bond isomerization can not take place, to give a mixture of stereoisomeric 1,4- endoperoxides 2 which rearranges into a thermally stable 1,2-dioxetane 5 selectively on heating in benzene.

Full text of DOI:10.1039/b002161j

Singlet oxygenation of 4-(4-tert-butyl-3,3-dimethyl-2,3-dihydrofuran-5-yl)-
2-pyridone: non-stereospecific 1,4-addition of singlet oxygen to a 1,3-diene
system and thermal rearrangement of the resulting 1,4-endoperoxides to stable
1,2-dioxetanes
Masakatsu Matsumoto,* Shigeru Nasu, Manabu Takeda, Hiroyuki Murakami and Nobuko Watanabe
Department of Materials Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1205, Japan.
E-mail: matsumo@info.kanagawa-u.ac.jp
Received (in Cambridge, UK) 3rd February 2000, Accepted 30th March 2000
Published on the Web 20th April 2000
Singlet oxygen adds easily to a 1,3-diene 1, whose E–Z
double bond isomerization can not take place, to give a
mixture of stereoisomeric 1,4-endoperoxides 2 which rear-
ranges into a thermally stable 1,2-dioxetane 5 selectively on
heating in benzene.
gives a mixture of stereoisomeric 1,4-endoperoxides though
neither of the carbon–carbon double bonds of the diene system
can undergo E–Z isomerization.
The rather simple 1,3-diene, (E,E)-hexa-2,4-diene (E,E-3)
undergoes stereospecific 1,4-addition of singlet oxygen to give
a cis-endoperoxide (cis-4), whereas singlet oxygenation of
(E,Z)-hexa-2,4-diene (E,Z-3) affords a mixture of cis-4 (main
product) and its trans-isomer (trans-4).1,2 Gollnick has sug-
gested that the (E,Z)-diene isomerizes to the (E,E)-isomer prior
to the concerted 1,4-addition of singlet oxygen as shown in
Scheme 2,1 and his suggestion has very recently been supported
by Motoyoshiya et al. who have observed a similar phenome-
non for the sensitized photooxygenation of 1-arylpenta-
1,3-dienes.3 On the other hand, O’Shea and Foote have
suggested that the non-stereospecific endoperoxide formation
from E,Z-3 is most likely rationalized by the formation of a
zwitterion which causes the isomerization leading to the cis-
endoperoxide (cis-4) as shown in Scheme 3.2 However, neither
mechanism would apply to the present oxygenation of 1 giving
2 without any revision, since no E-Z double bond isomerization
and only s-cis–s-trans isomerization can occur for the fur-
anylpyridones 1.
Diels–Alder addition of singlet oxygen to certain 1,3-dienes has
been reported to give 1,4-endoperoxides with lack of ster-
eospecificity, for which two mechanisms have been proposed.
The first is a mechanism where E–Z double bond isomerization
of 1,3-diene proceeds under the reaction conditions and is
followed by a concerted Diels–Alder addition of singlet
oxygen.1 The second is a stepwise addition of singlet oxygen,
including participation of zwitterions, which causes isomeriza-
tion of the initial 1,3-diene unit prior to the intramolecular
cyclization.2 Although these two are crucially different from
each other (concerted or stepwise process), both mechanisms
include, in common, isomerization of the initial double bond in
the substrate followed by cyclization giving the endoperoxide.
However, there formally remain other pathway(s) for Diels–
Alder addition of singlet oxygen leading to a mixture of
stereoisomeric endoperoxides without any isomerization of the
initial double bond in a substrate; especially for the stepwise
mechanism, if the intramolecular attack of a peroxidic inter-
mediate such as peroxirane and zwitterion occurs onto both p-
faces of the remaining double bond, the Diels–Alder addition
would give a mixture of stereoisomeric endoperoxides (the third
mechanism). We report here an example of non-stereospecific
1,4-addition of singlet oxygen for which the third mechanism
would be the most advantageous. In addition, we report a unique
rearrangement of the resulting 1,4-endoperoxides which occurs
simply on heating without any catalyst to yield thermally stable
1,2-dioxetanes exclusively.
The concerted Diels–Alder reaction of singlet oxygen with 1
would give only cis-2 so that this mechanism should be ruled
out for the reaction giving trans-2, though trans-2 could be
formally produced by an antarafacial attack of singlet oxygen.
Thus, a stepwise mechanism should be considered to rationalize
In the course of our investigation on the design of highly
efficient chemiluminescent substrates, we attempted to examine
the singlet oxygenation of N-benzyl-4-(4-tert-butyl-3,3-dime-
thyl-2,3-dihydrofuran-5-yl)-2-pyridone 1a. When a pyridone 1a
(100 mg) was irradiated together with a catalytic amount of
tetraphenylporphin (TPP) in dichloromethane (5 mL) with a 940
W Na-lamp at 278 °C, singlet oxygenation proceeded smoothly
(1 h) to give a 65+35 mixture of stereoisomeric 1,4-endoper-
oxides 2a exclusively (Scheme 1).† The mixture was separated
into cis-2a (major isomer, colorless granules, mp
127.0–128.0 °C) and trans-2a (minor isomer, colorless oil) by
silica gel chromatography. These two endoperoxides were
characterized by 1H and 13C NMR, 1H–1H COSY, 13C–1H
COSY, NOE, IR and mass spectral analysis.‡ It should be noted
that little isomerization between cis- and trans-2a was observed
under the reaction conditions and even at higher temperature.
The parent pyridone 1b and N-methyl analog 1c were similarly
oxygenated to give the corresponding mixture of isomeric
endoperoxides 2b and 2c, respectively, though these mixtures
could not be separated into pure isomers. These results provide
the first example wherein singlet oxygenation of a 1,3-diene
Scheme 1
Scheme 2
DOI: 10.1039/b002161j
Chem. Commun., 2000, 821–822
This journal is © The Royal Society of Chemistry 2000
821

Table 1 Thermal rearrangement of 1,4-endoperoxides 2a to 1,2-dioxetanes
5a and thermal decomposition of 5a to ketoesters 6aab
DH‡/kcal
DS‡/cal K21 DG‡/kcal
Peroxide
mol21
mol21
mol21
t1/2 (25 °C)/yr
cis-2a
trans-2a
5a
29.8
29.1
26.2
13.9
11.9
29.5
25.7
25.5
29.1
0.07
0.05
19.6
Scheme 3
a Rearrangement of 2a to 5a was carried out in toluene-d8 at 40–60 °C,
whereas decomposition of 5a to 6a was performed in toluene-d8 at
90–110 °C. b For all the Arrhenius plots, r > 0.999.
parameters were estimated from Arrhenius plots as summarized
in Table 1, which shows that dioxetanes 5a are far more stable
than endoperoxides 2a. The other endoperoxides 2b and 2c
rearranged thermally also into the corresponding dioxetanes 5b
and 5c, whose thermolysis gave ketoesters 6b and 6c,
respectively. Free energies of activation (DG‡/kcal mol21) for
these peroxides were also estimated as follows; 2b: 24.3–24.4,
2c: 24.4–24.7, 5b: 27.1 and 5c: 28.4.
Various 1,4-endoperoxides have been known to undergo
acid-catalyzed decomposition to carbonyl fragments, pre-
sumably through 1,2-dioxetanes, whose spectroscopic identi-
fication and/or isolation has not been achieved in most cases.
Schaap et al. have reported a successful spectroscopic identi-
fication of a dioxetane formed by the rearrangement of
endoperoxide, and suggested that the relatively unstable
dioxetane as a chemiluminescent substrate can be ‘stored’ as a
precursor endoperoxide and generated when needed.6 In
contrast, the present dioxetanes 5 are far more stable than
endoperoxides 2 so that they can be stored as such rather than be
regarded as precursors.
Scheme 4
the present non-stereospecific 1,4-addition of singlet oxygen.
Since no E–Z isomerization of the double bond in pyridone and
dihydrofuran rings can occur for 1, the isomerization of an
intermediary zwitterion as in Scheme 3 can not proceed. The
most likely explanation is that the initially formed peroxirane or
zwitterion attacks the remaining double bond of the starting
1,3-diene from both p-faces. This process should be operable
when two ethylene units of the 1,3-diene lie far from apart in the
same plane as illustrated in Scheme 4 in which a peroxirane
intermediate is adopted for convenience. Such structure of a
1,3-diene system is most likely feasible for 1 because of steric
repulsion between the pyridone ring and a tert-butyl group in
the dihydrofuran ring.§ Although singlet oxygen attacks
possibly in the first step to a double bond of the pyridone and/or
the double bond of dihydrofuran for 1, the initial addition of
singlet oxygen to the former may be more likely since the
addition to the latter may lead more or less to a dioxetane as in
the case of 4-tert-butyl-3,3-dimethyl-2,3-dihydrofurans bearing
an aryl4 or a styryl group5 at the 5-position.
Although endoperoxides cis and trans-2a were not iso-
merized to each other, both endoperoxides changed gradually
into a dioxetane 5a even at room temperature. On heating in hot
benzene, 2a was transformed selectively into 5a (colorless
needles, mp 114.0–115.0 °C)¶ which was stable enough for
handling at room temperature though it decomposed into a
ketoester 6a in hot toluene (Scheme 5). It should be noted that
the thermolysis of 5a (90 °C, toluene) gave light (lmax = 411
nm) whose spectrum was in good agreement with the fluores-
cence spectrum of 6a. Both reaction rates for isomerization of
endoperoxide 2a to 1,2-dioxetane 5a and for decomposition of
dioxetane 5a to ketoester 6a followed first-order kinetics. Thus,
these reaction rates were measured in toluene-d8 at various
Notes and references
† Similar singlet oxygenation of 1a at 0 °C gave a 57+43 mixture of cis and
trans isomers of 2a.
‡ Selected data: for cis-2a: dH(500 MHz, CDCl3) 1.11 (s, 3H), 1.15 (s, 9H),
1.25 (s, 3H), 3.81 (d, J 8.2 Hz, 1H), 4.41 (d, J 15.1 Hz, 1H), 4.45 (d, J 8.2
Hz, 1H), 4.82 (d, J 15.1 Hz, 1H), 5.13 (d, J 2.3 Hz, 1H), 5.59 (d, J 5.7 Hz,
1H), 6.95 (dd, J 5.7 and 2.3 Hz, 1H), 7.16–7.20 (m, 2H), 7.28–7.38 (m, 3H);
dC(125 Hz, CDCl3) 18.1, 24.9, 26.4, 36.5, 45.3, 47.0, 78.1, 80.6, 82.6,
106.0, 113.1, 128.1, 128.2, 129.0, 134.9, 135.1, 138.3, 167.4; MS (m/z, %)
369 (M+, 46), 325 (4), 313 (9), 285 (12), 284 (16), 230 (33), 212 (60), 91
(100).
For trans-2a: dH(500 MHz, CDCl3) 1.11 (s, 3H), 1.12 (s, 9H), 1.28 (s,
3H), 3.79 (d, J 8.2 Hz, 1H), 4.31 (d, J 15.4 Hz, 1H), 4.49 (d, J 8.2 Hz, 1H),
5.06 (d, J 15.4 Hz, 1H), 5.23 (d, J 2.3 Hz, 1H), 5.61 (d, J 5.5 Hz, 1H), 6.93
(dd, J 5.5, 2.3 Hz, 1H), 7.19–7.23 (m, 2H), 7.30–7.39 (m, 3H); dC(125 Hz,
CDCl3) 18.0, 24.8, 26.7, 36.3, 45.3, 46.9, 78.8, 80.7, 83.2, 105.7, 113.4,
128.0, 128.3, 129.1, 134.5, 135.2, 138.2, 167.0; MS (m/z, %) 369 (M+, 47),
313 (10), 285 (13), 284 (17), 230 (35), 212 (63), 91 (100).
§ An MM2 calculation suggested that the torsion angle between the
pyridone ring and the dihydrofuran ring in 1a was 73.4° at the most stable
conformation.
1
temperatures by H NMR spectroscopy, and their activation
¶ Selected data for 5a: dH(500 MHz, CDCl3) 1.08 (s, 9H), 1.13 and 1.31 (2
s, 6H), 3.80 (d, J 8.3 Hz, 1H), 4.54 (d, J 8.3 Hz, 1H), 5.09 (d, J 14.4 Hz, 1H),
5.20 (d, J 14.4 Hz, 1H), 6.32 (dd, J 7.4, 1.8 Hz, 1H), 6.94 (d, J 1.8 Hz, 1H),
7.23–7.38 (m, 6H); dC(125 Hz, CDCl3) 18.2, 24.9, 27.0, 36.7, 45.5, 51.8,
80.7, 105.3, 105.7, 114.7, 121.4, 128.1, 128.1, 129.0, 135.9, 136.7, 147.8,
161.9; MS (m/z, %) 369 (M+, 51), 337 (M+ 2 O2, 2), 313 (11), 230 (39), 212
(71), 185 (15), 91 (100).
1 K. Gollnick and A. Griesbeck, Tetrahedron Lett., 1983, 24, 3303.
2 K. E. O’Shea and C. S. Foote, J. Am. Chem. Soc., 1988, 110, 7167.
3 J. Motoyoshiya, Y. Okuda, I. Matsuoka, S. Hayashi, Y. Takaguchi and H.
Aoyama, J. Org. Chem., 1999, 64, 493.
4 M. Matsumoto, H. Murakami and N. Watanabe, Chem. Commun., 1998,
2319.
5 M. Matsumoto, T. Ishihara, N. Watanabe and T. Hiroshima, Tetrahedron
Lett., 1999, 40, 4571.
6 A. P. Schaap, P. A. Burns and K. A. Zaklika, J. Am. Chem. Soc., 1977, 99,
1270.
Scheme 5
822
Chem. Commun., 2000, 821–822