Chemiluminescent decomposition of a dioxetane bearing a 3-(1-cyanoethenyl)phenyl moiety induced by Michael addition of an anion of malonate

Article abstract of DOI:10.1016/j.tetlet.2004.03.086

A thermally stable dioxetane bearing a 3-(1-cyanoethenyl)phenyl group (1) was synthesized. Michael addition of an anion of malonate (3a,b) to a dioxetane (1) substituted with a 3-(1-cyanoethenyl)phenyl moiety took place to give an intermediary dioxetane b

Full text of DOI:10.1016/j.tetlet.2004.03.086

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 3779–3782
Chemiluminescent decomposition of a dioxetane bearing a
3-(1-cyanoethenyl)phenyl moiety induced by Michael addition
of an anion of malonate
Masakatsu Matsumoto,* Toshiyuki Mizuno and Nobuko Watanabe
Department of Materials Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan
Received 18 February 2004; revised 8 March 2004; accepted 12 March 2004
Abstract—A thermally stable dioxetane bearing a 3-(1-cyanoethenyl)phenyl group (1) was synthesized. Michael addition of an anion
of malonate (3a,b) to a dioxetane (1) substituted with a 3-(1-cyanoethenyl)phenyl moiety took place to give an intermediary
dioxetane bearing a benzylic anion, which decomposes rapidly with accompanying emission of crimson light. When an anion of
chloromalonate (3c) was used as a base, intramolecular cyclopropanation of 3c occurred concurrently with the Michael-addition-
induced chemiluminescent decomposition.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Dioxetanes substituted with an aromatic electron donor
such as an oxyanion of the hydroxyarene moiety
undergo intramolecular charge-transfer (CT)-induced
decomposition with accompanying luminescence.1–4 The
phenomenon has received much attention from the
viewpoint of mechanistic interest related to biolumi-
nescence and application to chemiluminescent bio-
assays.5 In addition to such oxyanion of hydroxyarene,
a benzylic carbanion has very recently been reported to
play a role of an electron donor as well for the CT-
induced chemiluminescent decomposition of a dioxe-
tane.6 This fact suggests that various reaction systems
producing an intermediary benzylic anion should
become an object to be investigated from a new viewpoint
of CT-induced chemiluminescence. Thus, we attempted
to design a dioxetane bearing a phenyl group substituted
with an electron-deficient olefinic function, to which the
addition of a nucleophile would lead to a benzylic anion
causing the CT-induced chemiluminescent decomposi-
tion of the dioxetane.
synthesis was effectively attained by means of singlet
oxygenation. When a solution of 4-tert-butyl-5-[3-(1-
cyanoethenyl)phenyl]-3,3-dimethyl-2,3-dihydrofuran (2)
(140 mg) was irradiated together with a catalytic amount
of tetraphenylporphin (TPP) in CH2Cl2 (10 mL)
under O2 atmosphere at ꢀ78 ꢁC for 1 h, the desired di-
oxetane (1) was produced as pale yellow granules (mp
123.3–124.0 ꢁC) in 73% yield after chromatographic
purification [SiO2/hexane–AcOEt (9:1)] followed by
recrystallization (hexane–CH2Cl2). The structure of
1
dioxetane (1) was determined by H NMR, 13C NMR,
IR, Mass (EI), and HR Mass (ESI) spectral analysis.7
Dioxetane (1) was quite stable enough to permit
handling at room temperature though it polymerizes
gradually by standing for a long period (Scheme 1).
First of all, dimethyl methylmalonate (3a) was chosen as
a source of stable carbanion that would attack the
1-cyanoethenyl moiety attached to a phenyl in dioxetane
(1).8 A solution of an anion of ester (3a) (1.0 ꢁ
10ꢀ1 mol dmꢀ3) was prepared by dissolving a malonate
(3a) together with an equimolar amount of 18-crown-6
and t-BuOK in benzene: an abbreviation [K ꢂ (18-
crown-6)]þ(3a)ꢀ is used here for this anionic system.
When a solution of a dioxetane (1) in benzene (1.0 ꢁ
10ꢀ3 mol dmꢀ3, 1 mL) was added to a solution of [K ꢂ
The dioxetane designed was 5-tert-butyl-4,4-dimethyl-
2,6,7-trioxabicyclo[3.2.0]heptane bearing a 3-(1-cyano-
ethenyl)phenyl group at the 1-position (1), of which the
18-crown-6)]þ(3a)ꢀ in benzene (1.0 · 10ꢀ1 mol dmꢀ3
,
Keywords: Dioxetane; Chemiluminescence; Michael addition; Cyclo-
propanation.
2 mL) at 25 ꢁC, the dioxetane (1) decomposed rapidly to
CL
max
emit flash crimson light (maximum wavelength k
¼
* Corresponding author. Fax: +81-463-58-9684; e-mail: matsumo@
chem.kanagawa-u.ac.jp
740 nm, UCL ¼ 5:6 ꢁ 10ꢀ6). This maximum wavelength
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.03.086

3780
M. Matsumoto et al. / Tetrahedron Letters 45 (2004) 3779–3782
O
O
t-Bu
t-Bu
3a: X = Me
3b: X = H
3c: X = Cl
X
H
COOMe
COOMe
CN
C
CN
O
O
2
1
O
O
O
O
t-Bu
t-Bu
[K ⊂ 18-crown-6] +(3)-
X =Me or H
O
X
1
O
X
COOMe
COOMe
COOMe
COOMe
NC
NC
5a: X = Me
5b: X = H
4a: X = Me
Light
4b: X = H
R
O
O
t-Bu
X = H, Proton-transfer
O
CN
O
O
t-Bu
H
6a: R = H
No CT-induced decay
O
6b: R = Me
COOMe
COOMe
NC
7
Scheme 1.
(kCmLax) was considerably longer than that for a dioxetane
light yield (UCL ¼ 1:5 ꢁ 10ꢀ6) was considerably low (UCL
for a reaction of 1 with 3a:UCL for a reaction of 1 with
3b ¼ 3.7:1), though both cases would lead to a very
similar intermediary benzylic anion of dioxetane (4a)
and (4b) as well as a very similar emitter (5a) and (5b),
respectively.
CL
max
bearing a 3-(cyanomethyl)phenyl moiety (6a) (k
¼
702 nm in TBAF/DMSO),6 while shorter than that for a
dioxetane bearing the 3-(1-cyanoethyl)phenyl moiety
CL
max
(6b) (k
¼ 788 nm), which was synthesized here. These
CL
max
differences in k
are presumably attributed to the
inductive effect of a substitutent attached at a benzylic
carbon of the (cyanomethyl)phenyl moiety.
The spent reaction mixture after the chemiluminescent
decomposition of 1 with [K ꢂ 18-crown-6]þ(3b)ꢀ gave
the expected product (neutral form of 5b) (28% yield)
derived from Michael-addition of an anion of 3b to 1
followed by CT-induced decay, along with a dioxetane
(neutral form of 4b) (39% yield), which was produced
only by the Michael addition of an anion of 3b to 1. The
formation of a dioxetane (neutral form of 4b) reveals
that a considerable quantity of an intermediary benzylic
anion (4b), produced initially by the Michael addition of
an anion of 3b to 1, would change into a more stable
anion (7) before causing the CT-induced decay to 5b.
This means surely that an exchange of the benzylic
anion into a malonate anion takes place as rapidly as the
CT-induced decay for a benzylic anion (4b). These facts
coincide with the decreased chemiluminescent efficiency
in the case of 1 with [K ꢂ 18-crown-6]þ(3b)ꢀ.
The spent reaction mixture of 1 with [K ꢂ 18-crown-
6]þ(3a)ꢀ after neutralization gave exclusively a ketoester
(neutral form of 5a); 5a was presumably produced by
the Michael addition of an anion of 3a to 1 giving an
anion (4a), which caused CT-induced chemiluminescent
decomposition of a dioxetane ring successively. Thus,
we prepared a dioxetane (neutral form of 4a) bearing a
phenyl substituted with a 1-cyano-3,3-bis(methoxycar-
bonyl)butyl group at the 3-position as a reference. On
treatment with a t-butoxide anion, [K ꢂ (18-crown-
6)]þt-BuOꢀ, in benzene (1.0 ꢁ 10ꢀ1 mol dmꢀ3, 2 mL) at
25 ꢁC,
a
dioxetane
(neutral
form
of
4a)
(1.0 ꢁ 10ꢀ3 mol dmꢀ3, 1 mL) underwent similarly the
CT-induced decay to emit light with chemiluminescent
properties: k
CL
¼ 740 nm, UCL ¼ 5:7 ꢁ 10ꢀ6, and the
max
rate constant of the CT-induced decay k ¼ 3:5 sꢀ1. The
spent reaction mixture of a dioxetane (neutral form of
4a) gave a ketoester (neutral form of 5a) exclusively after
neutralization. These results reveal that an emitter pro-
duced by the reaction of 1 with an anion of 3a is
undoubtedly a benzylic anion (5a). It should be noted
here that the t-butoxide anion, [K ꢂ (18-crown-6)]þ
The results described above suggested that the rate of
the reaction, which occurs concurrently to extinguish the
intermediary benzylic anion, can be estimated for the
system of the Michael addition-induced chemilumines-
cent decomposition of a dioxetane (1). Thus, we
attempted to examine such a reaction of benzylic anion
(4) that leads to the CT-induced decay and/or a con-
current reaction to extinguish it without decay of the
dioxetane ring.
t-BuOꢀ, induced also the chemiluminescent decompo-
CL
max
sition of 1, though the k
of emission (706 nm) was
shorter than that for the case of [K ꢂ 18-crown-
6]þ(3a)ꢀ.9
Dimethyl chloromalonate (3c) has been reported to
undergo base-induced reaction with an a,b-unsaturated
nitrile to give a cyclopropanedicarboxylate.10;11 The
reaction proceeds through addition of an anion of 3c to
acrylonitrile giving an intermediary carbanion (8), of
which the intramolecular nucleophilic attack to a carbon
Next, a reaction of 1 with a solution of an anion of
dimethyl malonate (3b), [K ꢂ 18-crown-6]þ(3b)ꢀ, in
place of [K ꢂ 18-crown-6]þ(3a)ꢀ, in benzene was carried
out. This case also gave crimson light (kmax ¼ 737 nm) as
in the case of [K ꢂ 18-crown-6]þ(3a)ꢀ. However, the

M. Matsumoto et al. / Tetrahedron Letters 45 (2004) 3779–3782
3781
O
O
O
O
t-Bu
t-Bu
[K ⊂ 18-crown-6] +(3c)-
O
Cl
COOMe
COOMe
1
O
Cl
COOMe
COOMe
NC
NC
5c
4c
Light
Cl
Cyclization
O
Cyclization
MeO2C
CN
MeO2C
8
O
O
O
t-Bu
t-Bu
COOMe
COOMe
COOMe
COOMe
X
O
O
NC
NC
9
10
Scheme 2.
bearing a chlorine furnishes a cyclopropanedicarboxyl-
ate. One mechanistically interesting point of this
cyclopropanation is that the intramolecular nucleophilic
attack of an anion of 3c should be more rapid than the
quenching of the anion by protonation, since the reac-
tion proceeds effectively even under weak basic condi-
tions where an anion (8) is hardly expected to form from
a conjugate acid of 8.
induced chemiluminescent decomposition of an inter-
mediary dioxetane, though it would be limited to a
reaction through a benzylic carbanion.
Acknowledgements
The authors gratefully acknowledge financial assistance
provided by a Grant-in-aid for Scientific Research by
the Ministry of Education, Science, Sports and Culture.
Thus, we carried out the reaction of a dioxetane (1) with
an anion of dimethyl chloromalonate (3c). Similarly to
the case of 4a, when a dioxetane (1) was treated with an
anion of dimethyl chloromalonate (3c), [K ꢂ 18-crown-
6]þ(3c)ꢀ, in benzene, crimson light (kmax ¼ 710 nm,
UCL ¼ 2:4 ꢁ 10ꢀ6, k ¼ 4:5 sꢀ1) was observed. After neu-
tralization, the spent reaction mixture afforded a keto-
ester (9) of a benzoic acid bearing a substituted
cyclopropyl at the 3-position in 71% yield together with
a cyclopropane derivative (10), in which the dioxetane
ring remained intact in 29% yield12 (Scheme 2).
References and notes
1. Schaap, A. P.; Chen, T.-S.; Handley, R. S.; DeSilva, R.;
Giri, B. P. Tetrahedron Lett. 1987, 28, 1155.
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3. McCapra, F. Mechanism in Chemiluminescence and
Bioluminescence-Unfinished Business. In Bioluminescence
and Chemiluminescence; Hastings, J. W., Kricka, L. J.,
Stanley, P. E., Eds.; Wiley: NY, 1996; pp 7–15.
4. Recent reports: Watanabe, N.; Nagashima, Y.; Yamazaki,
T.; Matsumoto, M. Tetrahedron 2003, 59, 4811–4819;
Matsumoto, M.; Sakuma, T.; Watanabe, N. Tetrahedron
Lett. 2002, 43, 8955–8958; Fujimori, K.; Wakasugi, K.;
Matsumoto, M. Chem. Lett. 2002, 762; Matsumoto, M.;
Ito, Y.; Murakami, M.; Watanabe, N. Luminescence 2002,
17, 305.
A dioxetane (10) was stable and decomposed little into a
ketoester (9) under the reaction conditions similar to the
case of 1 with [K ꢂ 18-crown-6]þ(3c)ꢀ. Therefore, a
reasonable explanation of the formation of 9 is that
an intermediary benzylic anion (4c), produced by the
Michael addition of an anion of 3c to 1, undergoes the
CT-induced decay into a benzylic anion (5c) with accom-
panying light, and, thereafter, the anion (5c) is trans-
formed into a cyclopropane (9) through intramolecular
cyclization. According to this explanation, the rate of
disappearance of 1 in the [K ꢂ 18-crown-6]þ(3c)ꢀ/benz-
ene system13 should be the sum of the rate for true CT-
induced decomposition of 4c and the rate for the reac-
tion of 4c leading to a dioxetane (10), since both paths
leading to 9 through 5c and to 10 through 4c would be
an intramolecular reaction. Therefore, referring to the
ratio 9 versus 10 ¼ 71:29, the rate constant of CT-
€
5. Reviews: Beck, S.; Koster, H. Anal. Chem. 1990, 62, 2258–
2270; Adam, W.; Reinhardt, D.; Saha-Moller, C. R.
€
Analyst 1996, 121, 1527–1531; Matsumoto, M. J. Synth.
Org. Chem. Jpn. 2003, 61, 595–604.
6. Matsumoto, M.; Mizuno, T.; Watanabe, N. J. Chem. Soc.,
Chem. Commun. 2003, 483–484.
1
7. Selected data for 1: H NMR (400 MHz, CDCl3) dH 0.98
(s, 9H), 1.17 (s, 3H), 1.39 (s, 3H), 3.85 (d, J ¼ 8:2 Hz, 1H),
4.60 (d, J ¼ 8:2 Hz, 1H), 6.16 (s, 1H), 6.38 (s, 1H), 7.48 (t,
J ¼ 7:8 Hz, 1H), 7.64 (d with fine coupling, J ¼ 7:8 Hz,
1H), 7.68 (d with fine coupling, J ¼ 7:8 Hz, 1H), 7.86 (s
with fine coupling, 1H); 13C NMR (125 MHz, CDCl3) dC
18.4 (CH3), 25.1 (CH3), 26.8 (CH3 ꢁ 3), 36.7 (C), 45.6 (C),
80.3 (CH2), 105.0 (C), 116.2 (C), 117.4 (C), 122.6 (C),
125.5 (CH), 127.0 (CH), 128.7 (CH), 128.8 (CH2), 129.8
(CH), 132.2 (C), 137.1 (C); IR (KBr) 2998, 2959, 2902,
2226 cmꢀ1; Mass (m=z, %) 281 (Mþ ꢀ 32, 8), 258 (22), 256
(33), 230 (40), 228 (26), 174 (41), 157 (13), 156 (100), 85
(40), 57 (75); HRMS (ESI) 336.1593, calcd for
C19H23NO3Na (M þ Naþ) 336.1576; Anal. Calcd for
C19H23NO3 Na: C, 72.82; H, 7.40; N, 4.47. Found: C,
72.52; H, 7.80; N, 4.17.
induced decomposition of 4c is estimated to be 3.2 sꢀ1
,
while the rate for the reaction leading to 10 is estimated
to be 1.3 sꢀ1
.
The results presented here show that the chemilumi-
nescent decomposition of a dioxetane induced by
Michael-type reaction with a nucleophile should provide
a new probe to know a feature of an intramolecular
reaction, which occurs concurrently with the CT-

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M. Matsumoto et al. / Tetrahedron Letters 45 (2004) 3779–3782
8. Bergmann, E. D.; Ginsburg, D.; Pappo, R. Org. React.
1959, 10, 179.
10. Joucla, M.; Le Brun, J. Tetrahedron Lett. 1985, 26, 3001–3004.
11. Le Menn, J.-C.; Tallec, A.; Sarrazan, J. Can. J. Chem.
1991, 69, 761–767.
12. Few products other than 9 and 10 were observed.
13. The formal rate of CT-induced decomposition of 1
was estimated by measuring the time-dependency of
the intensity of light emission. For the present system,
the rate followed pseudo-first-order kinetics independent
of the [K ꢂ 18-crown-6]þ(3)ꢀ under the conditions using
a large excess of the base as described here.
9. Neutralization of the spent reaction mixture of 1/[K ꢂ 18-
crown-6]þt-BuOꢀ system gave no expected ketoester,
namely, 2,2,4,4-tetramethyl-3-oxopentyl 3-(2-tert-butoxy-
1-cyanoethyl)benzoate, but 2,2,4,4-tetramethyl-3-oxopent-
yl 3-(1-cyanoethenyl)benzoate (14%) and a polymeric
ketoester. In this case, an initially produced adduct of a
t-butoxide to 1-cyanoethenyl moiety would remove easily
a t-butoxide to regenerate a cyanoethenyl moiety.