Intramolecular charge-transfer-induced chemiluminescent decomposition of 1,2-dioxetanes bearing a phenylmethanide anion

Article abstract of DOI:10.1016/j.tet.2005.07.081

Dioxetanes (1) bearing a phenyl moiety substituted with a methylène or methine having an electron-withdrawing group(s) (-CH₂-Ew or -CH(X)-Ew) and dioxetane (2) bearing a 3-(l-cyanoethenyl)phenyl group were synthesized. Treatment of dioxetanes (

Full text of DOI:10.1016/j.tet.2005.07.081

Tetrahedron 61 (2005) 9569–9585
Intramolecular charge-transfer-induced chemiluminescent
decomposition of 1,2-dioxetanes bearing a phenylmethanide anion
*
Nobuko Watanabe, Toshiyuki Mizuno and Masakatsu Matsumoto
Department of Materials Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan
Received 29 June 2005; accepted 23 July 2005
Available online 11 August 2005
Abstract—Dioxetanes (1) bearing a phenyl moiety substituted with a methylene or methine having an electron-withdrawing group(s)
(–CH2-Ew or –CH(X)-Ew) and dioxetane (2) bearing a 3-(1-cyanoethenyl)phenyl group were synthesized. Treatment of dioxetanes (1)
with tetrabutylammonium fluoride (TBAF) caused their decomposition with accompanying emission of light with maximum wavelength at
530–758 nm. The Michael addition of a bis(methoxycarbonyl)methanide anion to dioxetane (2) produced initially an unstable dioxetane
bearing a phenylmethanide anion, decomposition of which gave light with maximum wavelength at 710–740 nm. Intramolecular
cyclopropanation without decomposition of the dioxetane ring took place concurrently for the Michael reaction-induced decomposition of 2
with the bis(methoxycarbonyl)chloromethanide anion.
q 2005 Elsevier Ltd. All rights reserved.
1. Introduction
advantage of such type of chemiluminescent substrate
would be that a phenylmethanide anion can be generated not
only by proton-abstraction from a benzylic methylene or
methine but also by conjugate addition of an anion to an
ethenylphenyl moiety (Scheme 2).
Dioxetanes substituted with an aromatic electron donor such
as an arenoxide anion (aryl-OK) undergo intramolecular
charge-transfer (CT)-induced decomposition with accom-
panying luminescence (Scheme 1).1–4 The phenomenon has
received much attention from the viewpoints of mechanistic
interests related to bioluminescence and application to
chemiluminescent bioassays, and extensive research efforts
have been made to elucidate the chemiexcitation pathways
as well as to develop efficient chemiluminescent systems.5–7
However, there has been little known of dioxetanes bearing
a carbanion such as an arenemethanide anion (aryl-CK)
instead of the arenoxide anion (aryl-OK), though an
arenemethanide anion would play the role of electron
donor similarly to an arenoxide anion for the intramolecular
CT-induced chemiluminescent decomposition. One
This situation stimulated us to design a stable dioxetane,
which can be easily transformed into an unstable dioxetane
bearing a phenylmethanide anion. Thus-designed were
dioxetanes bearing a phenyl moiety substituted with a
methylene or methine having electron-withdrawing
group(s) (–CH2-Ew or –CH(X)-Ew) and their 3-(1-cyano-
ethenyl)phenyl-analog. We report here the synthesis of
these dioxetanes and their chemiluminescent decom-
position induced by various bases such tetrabutylammo-
nium fluoride (TBAF), and bis(methoxycarbonyl)methanide
anions.8,9
Scheme 1.
Keywords: Dioxetane; Chemiluminescence; Carbanion; Michael addition; Cyclopropanation.
*
Corresponding author. Tel.: C81 463 59 4111; fax: C81 463 58 9684; e-mail: matsumo@chem.kanagawa-u.ac.jp
0040–4020/$ - see front matter q 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2005.07.081

9570
N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
Scheme 2.
2. Results and discussion
to give a lithio derivative, to which N-methylformanilide
added to afford formylphenyl derivative (6b). Reduction of
(6b) with NaBH4, followed by halogenation with CBr4/
PPh3/THF, gave 3-(bromomethyl)phenyl-derivative (8b),
which was, in turn, converted to the desired dihydrofuran
bearing a 3-(cyanomethyl)phenyl moiety (3b) on treatment
with NaCN. Dihydrofurans (3a, 3c) were synthesized in a
similar manner to the case of 3b. The other dihydrofurans
were prepared from 3-(cyanomethyl)phenyl-derivative (3b)
as a key precursor. Methylation of the benzylic position in
3b with MeI/NaH gave 3-(1-cyanoethyl)phenyl-dihydro-
furan (3d). Hydrolysis of the nitrile group in 3b gave
3-(carboxymethyl)phenyl-dihydrofuran (9), which was
successively esterified into 3-(methoxycarboxylmethyl)-
phenyl-derivative (3e). Lithiation of 9 with butyllithium
followed by treatment with benzoyl chloride afforded
3-(benzoylmethyl)phenyl-dihydrofuran (3f). 3-[Cyano-
(methoxycarbonyl)methyl]phenyl-dihydrofuran (3g) was
synthesized by the Claisen condensation of 3b with dimethyl
2.1. Synthesis of 1,2-dioxetanes
Dioxetanes realized were 1-aryl-5-tert-butyl-4,4-dimethyl-
2,6,7-trioxabicyclo[3.2.0]heptanes (1),10,11 the aryl moiety
of which was substituted with a cyanomethyl group at the
ortho-(a), meta-(b), or para-position (c). Bicyclic dioxe-
tanes bearing a 3-(1-cyanoethyl)phenyl (1d), 3-(methoxy-
carbonylmethyl)phenyl (1e), 3-(benzoylmethyl)phenyl (1f),
3-[cyano(methoxycarbonyl)methyl]phenyl (1g) or 3-(1-
cyanoethenyl)phenyl (2) were also realized. Synthesis of
these dioxetanes was effectively attained by means of
singlet oxygenation of the corresponding dihydrofurans
(3a–g to 4). Dihydrofurans (3a–g to 4) were synthesized
from 5-bromophenyl-4-tert-butyl-3,3-dimethyl-2,3-di-
hydrofuran (5a–5c)12 in several steps, as shown in Scheme
3. For example, 3-bromophenyl in (5b) easily underwent
metal–halogen exchange reaction with butyllithium in THF
Scheme 3. Reagents: (i) BuLi/PhNMeCHO; (ii) NaBH4; (iii) TsCl/DMAP or CBr4/PPh3; (iv) NaCN/TBA-HS; (v) O2/TPP/hv; (vi) NaH/Mel; (vii) NaOH;
(viii) NaH/CO(OMe)2; (ix) NaHCO3/Mel; (x) BuLi/PhCOCl; (xi) K2CO3/(CHO)n/TBA-HS.

N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
9571
Scheme 4.
carbonate. Dihydrofuran bearing a 3-(1-cyanoethenyl)phenyl
(4) was synthesized by the base-catalyzed condensation of
3b with paraformaldehyde.
2.2. Base-induced chemiluminescent decomposition of
1,2-dioxetanes bearing a phenyl moiety substituted with
a methyl having an electron-withdrawing group
When a solution of dioxetane bearing a meta-(cyanomethyl)
phenyl group (1b) in DMSO (1!10K4 mol dmK3, 1 mL)
was added to a solution of tetrabutylammonium fluoride
(TBAF)13,14 in DMSO (0.1 mol dmK3, 2 mL) at 25 8C, 1b
Singlet oxygenation of dihydrofurans (3a–3g to 4) to the
corresponding dioxetanes (1a–1g to 2) was easily attained
by the irradiation of a solution of dihydrofuran (3a–3g to 4)
and a catalytic amount of tetraphenylporphin (TPP) in
CH2Cl2 with a 940 W Na lamp under O2 atmosphere at
K78w0 8C. All dioxetanes synthesized here except 2 were
fairly stable thermally at room temperature, though they
decomposed to give the corresponding ketoesters (10a–10g,
11) exclusively in refluxing p-xylene (Scheme 4). On the
other hand, dioxetane bearing a 3-(1-cyanoethenyl)phenyl
moiety (2) polymerized gradually on standing for a long
period at room temperature.
decomposed rapidly to emit flash crimson light (maximum
CL
wavelength: l Z702 nm, chemiluminescence efficiency:
max
CLZ3.3!10K5).15,16 The fresh spent reaction mixture
F
was confirmed to include keto ester (10b) exclusively.
Dioxetane bearing an ortho-(cyanomethyl)phenyl group
(1a) and its para-isomer (1c) decomposed also easily to give
the corresponding keto esters (10a) and (10c), though they
gave little light. Such phenomenon has been observed as
‘odd/even’ relationship for dioxetanes bearing a phenoxide
anion, among which the meta-oxidophenyl-isomer (odd-
pattern) gives light in far higher yield than the ortho-oxido-
phenyl- and para-oxidophenyl isomer (even-pattern).7,17–19
Similarly to the case of 1b, the other dioxetanes (1d–1g)
bearing a phenyl substituted with a 3-methyl bearing an
electron-withdrawing group(s) underwent the TBAF-
induced decomposition in DMSO to afford light as shown
CL
max
in Figure 1. The chemiluminescent properties, namely, l
,
t1/2 (half-life of chemiluminescent decomposition), kDICT
(rate constant of chemiluminescent decomposition: kDICTZ
loge 2/t1/2), FCL, are summarized together with those for 1b
in Table 1. It is noteworthy that, dioxetane bearing a 3-(1-
cyanoethyl)phenyl (1d) displayed light with l
CL
max
at 56 nm
longer region than that for 1b, while dioxetane bearing a
3-[cyano(methoxycarbonyl)methyl]phenyl (1g) exhibited
chemiluminescence with prominent efficiency FCL, though
with far slower decomposition rate (rate constant: kDICT
)
than those for the others (1b, 1d–1f). It
CL
and far shorter l
max
was confirmed that dioxetanes (1d–1g) were transformed
exclusively into the corresponding keto ester (10d–10g) for
TBAF-induced decomposition. However, fluorescence of
Figure 1. Chemiluminescene spectra for TBAF-induced decomposition of
dioxetanes (1b, 1d–1g) in DMSO.
Table 1. TBAF-induced chemiluminescent decomposition of dioxetanes (1b, 1d–1g) in DMSOa
kDICT/sK1
FCL b
pKa of CH2(X)Ewc
HOMO energyd/ev
CL
max
Dioxetane (1)
Ew
l
/nm
t1/2/s
X
1b
1d
1e
1f
–CN
–CN
–CO2Me
–COPh
–CN
H
Me
H
H
–CO2Me
702
758
666
622
530
!0.02
!0.05
0.42
0.43
2300
O35
O14
1.7
1.6
3.0!10K4
3.3!10K5
2.0!10K6
4.0!10K5
4.4!10K4
5.7!10K3
25
—
24.5
19
9
K2.58
K2.58
K2.88
K2.99
K3.61
1g
a A solution of a dioxetane (1) in DMSO (1!10K4 mol dmK3, 1 mL) was added to a solution of TBAF in DMSO (0.1 mol dmK3, 2 mL) at 25 8C.
b Chemiluminescent yields (FCL) were based on the reported value for TBAF-induced chemiluminescent decomposition of 3-(20-spiroadamantane)-4-
methoxy-4-(30-tert-butyldimethylsiloxy)phenyl-1,2-dioxetane in DMSO: FCLZ0.29 (Ref. 16).
c pKa of the corresponding parent carbon acid, CH2(X)Ew (Ref. 21).
d Based on an AM1 MO calculation for model phenymethanides, PhCK(X)Ew as a model of respective dioxetanes (12).

9572
N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
Scheme 5.
these spent reaction mixtures for dioxetane (1) was
unfortunately not observed except that for dioxetane 1g.
The authentic keto ester (10g), prepared by thermolysis of
order of 1gO1fO1eO1b (1d), so that stability of their
conjugate carbanions decreases in the same order as
illustrated in Figure 2. A similar tendency was observed
also in the relationship between loge kDICT and HOMO
energy estimated by an AM1 MO calculation for model
phenymethanides, PhCK(X)Ew (Fig. 2).
1g, showed fluorescence with maximum wavelength (lflmax),
CL
max
which coincided with l
of 1g in TBAF/DMSO, and its
efficiency (Ffl) was estimated to be 0.018.20 Furthermore,
when a solution of keto ester (10g) in TBAF/DMSO was
treated with methyl iodide, a methylation to an intermediary
benzylic anion (14g) took place to give product (15) in 77%
yield (Scheme 5). These facts reveal that the emitter
produced from 1g in TBAF/DMSO is undoubtedly a
carbanion of 10g, namely 13g. Hence, the singlet-
chemiexcitation efficiency (FSZFCL/Ffl) is estimated to
be 0.32 for the TBAF-induced decomposition of dioxetane
(1g) in DMSO. The emitters would be the corresponding
benzylic carbanions of keto esters (13b, 13d–13f) also for
the chemiluminescent decomposition of the other dioxe-
tanes (1b, 1d–1f), though little fluorescence was observed
even for the authentic keto esters (10b, 10d–10f) in TBAF/
DMSO.
Chemiluminescent decomposition did not occur for all
dioxetanes (1a–1g), when TBAF was absent in DMSO,
while it took place easily on treatment with tert-BuOK as
well as with TBAF. Considering this fact and that
phenylmethanide anion (13) would be an emitter, it is
reasonable to assume that proton-abstraction from 1 with
TBAF generates an unstable dioxetane 12 bearing a
phenymethanide anion, from which the intramolecular CT
occurs to induce decomposition of the dioxetane producing
excited carbanion 13 of keto ester by the mechanism similar
to the case of a dioxetane bearing an arenoxide anion.5–7 It is
worth to point out that the singlet-chemiexcitation efficiency
compares favorably with the value for dioxetanes bearing a
meta-phenoxide anion, as observed for dioxetane (1g).5–7
Figure 2. Relationship of loge kDICT for TBAF-induced decomposition of 1
with pKa of parent carbon acids, X-CH2-Ew and with HOMO energy of Ph-
CHK(X)-Ew.
2.3. Chemiluminescent decomposition of a dioxetane
bearing a 3-(1-cyanoethenyl)phenyl moiety induced by
the conjugate addition of a nucleophile
As described in the previous section, 3-(1-cyanoethyl)
phenyl-substituted dioxetane (1d) underwent chemilumi-
nescent decomposition through an intermediary dioxetane
bearing a phenylmethanide anion (12d). Such type of
phenylmethanide anion would be generated by the
conjugate addition of a nucleophile to a (1-cyanoethenyl)-
phenyl moiety. Thus, we attempted to react dioxetane (2)
bearing a 3-(1-cyanoethenyl)phenyl group with the tert-
BuOK anion as a preliminary experiment. When dioxetane
In analogy with the CT-induced decomposition of a
dioxetane bearing an arenoxide anion, it is inferring that
chemiluminescent decomposition of dioxetane (12) bearing
a phenylmethanide anion produced from 1 occurs the more
easily, as the phenylmethanide anion becomes the less
stable and the more easily oxidized. This idea is apparently
consistent with the fact that the rate of chemiluminescent
decomposition (kDICT) increases in the order of 1g!1f!
1e!1b (1d) (Table 1). Considering the order of acidity for
the parent carbon acids,21 namely CH2(CN)CO2Me[
CH3COPhOCH3CO2MeOCH3CN (Table 1), the acidity
of a benzylic position for 1 is presumed to decrease in the
(2) was treated with 18-crown-6 ether complex of tert-
CL
BuOK in benzene, emission of light (l Z706 nm) was
max
observed, though the spent reaction mixture was found to
include little product due to the conjugate addition of tert-
BuOK, but only 14% of keto ester (11) along with a
complex mixture (Scheme 6). These results suggest for tert-
BuOK-induced decomposition of 2 that dioxetane (16)
bearing a phenylmethanide anion produced initially might

N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
9573
Scheme 6.
decompose to an excited keto ester (17), from which the
tert-BuOK anion is eliminated to afford keto ester (11) after
the emission of light (Scheme 6), though the intermediacy of
neither 16 nor 17 was clear.
carbonyl)ethanide anion (18a), which would add irre-
versibly to an electron-deficient olefin. An anion of ester
(18a) (1.0!10K1 mol dmK3) was prepared by dissolving
malonate (18a) together with an equimolar amount of
18-crown-6 ether and tert-BuOK in benzene: the abbrevi-
ation [K3(18-crown-6)]C(18a)K is used here for this
anionic system. When a solution of a dioxetane (2) in
benzene (1.0!10K3 mol dmK3, 1 mL) was added to a
solution of [K3(18-crown-6)]C(18a)K in benzene (1.0!
The next examination was to react dioxetane (2) with an
anion of dimethyl methylmalonate, namely, 1,1-bis(methoxy-
10K1 mol dmK3, 2 mL) at 25 8C, dioxetane (2) decomposed
CL
rapidly to emit flash crimson light (l Z740 nm, FCLZ
max
5.6!10K6) as shown in Figure 3. The maximum
wavelength of chemiluminescence (l ) was between
that for dioxetane (1b) and that for dioxetane (1d) (Table1).
CL
max
The spent reaction mixture of 2 with [K318-crown-
6]C(18a)K after neutralization gave exclusively keto ester
(19). The result suggested that the emitter was carbanion
(20), which was produced from an unstable Michael adduct,
namely, dioxetane bearing a phenylmethanide anion (21).
Thus, we synthesized authentic dioxetane (22), which was a
neutral form of 21, as a reference: the singlet oxygenation of
dihydrofuran (23), which was prepared from dihydrofuran
(4) and an anion of 18a, gave 22 in high yield. On treatment
with [K3(18-crown-6)]Ct-BuOK in benzene (1.0!10K1
mol dmK3, 2 mL) at 25 8C, dioxetane (22) (1.0!10K3
mol dmK3, 1 mL) decomposed rapidly to emit light with
Figure 3. Chemiluminescene spectra for base-induced decomposition of
dioxetane (2) and (22) in benzene.
Scheme 7.

9574
N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
chemiluminescent properties: l Z740 nm, FCLZ5.7!
CL
undergo base-induced reaction with an a,b-unsaturated
nitrile to give a cyclopropanedicarboxylate.23,24 The
reaction proceeds through the Michael addition of (18c)K
to acrylonitrile giving an intermediary carbanion (28),
whose intramolecular nucleophilic attack to an adjacent
carbon bearing a chlorine furnishes a cyclopropanedicar-
boxylate (29). One mechanistically interesting point of this
cyclopropanation is that the intramolecular nucleophilic
attack of (18c)K should be more rapid than the quenching of
the anion by protonation, since the reaction proceeds
effectively even under weak basic conditions where anion
(28) is hardly expected to form from a conjugate acid of 28.
max
10K6, and the rate constant kDICTZ8.1 sK1 22
Keto ester
.
(19) was also obtained from the neutralized spent reaction
mixture exclusively. These results are in good agreement
with those for the decomposition of 2 with [K318-crown-
6]C(18a)K. Therefore, anionic dioxetane (21) is undoubt-
edly produced as an intermediate for the chemiluminescent
decomposition of 2 induced by [K318-crown-6]C(18a)K
(Scheme 7).
When dioxetane (2) was treated with a solution of
bis(methoxycarbonyl)methanide complex (18b), [K318-
crown-6]C(18b)K, in benzene, 2 decomposed also to
display crimson light (lmaxZ737 nm, FCLZ1.5!10K6
)
Thus, we carried out the reaction of dioxetane (2) with an
anion of dimethyl chloromalonate, namely, bis(methoxy-
carbonyl)chloromethanide anion (18c). When 2 was treated
with an anion of dimethyl chloromalonate (18c), [K318-
crown-6]C(18c)K, in benzene, emission of crimson light
(lmaxZ710 nm, FCLZ2.4!10K6) was observed. After
neutralization, the spent reaction mixture afforded ester
(30) of a benzoic acid bearing a cyclopropyl group at the
3-position (71% yield) together with a cyclopropane
derivative (31), in which the dioxetane ring remained intact
(29% yield) (Scheme 9).
as in the case of anion (18a)K (Scheme 8). The spent
reaction mixture gave the expected product 24 (39% yield),
derived from the Michael addition of anion (18b)K to 2
followed by the CT-induced decomposition, and dioxetane
(25) (28% yield), produced only by the Michael addition of
(18b)K to 2. The formation of dioxetane (25) reveals that a
considerable quantity of initially-produced phenylmetha-
nide anion (26) would change into a more stable anion (27)
without causing the CT-induced decomposition to 24. This
means surely that the change of the phenylmethanide anion
(26) into a bis(methoxycarbonyl)methanide anion (27) takes
place as rapidly as the CT-induced decomposition of 26, and
should explain the fact that the chemiluminescent efficiency
was considerably lower for the triggering with the (18b)K
anion than for that with the (18a)K anion.
Dioxetane (31) was stable and hardly decomposed into
ketoester (30) under the conditions similar to the case of 2
with [K318-crown-6]C(18c)K. Therefore, a reasonable
explanation of the formation of 30 is that an intermediary
phenylmethanide anion 32, produced by the Michael
addition of an anion of 18c to 2, undergoes the CT-induced
decomposition into phenylmethanide anion (33) with
accompanying light, and, thereafter, 33 is transformed into
a cyclopropane 30 through intramolecular cyclization.
According to this explanation, the ratio of (rate for CT-
induced decomposition of 32) versus (rate for the reaction of
32 leading to a dioxetane 31) equals the product ratio of 30
to 31. Thus, the rate for intramolecular cyclopropanation of
32 is estimated roughly to be kZ3.3 sK1, since the rate for
CT-induced decomposition of 32 is presumably not so much
different from the rate for the case of 22 with [K318-
crown-6]Ct-BuOK.
The results described above suggest a possibility that, when
an intermediary phenylmethanide anion such as 26 under-
goes another reaction competing with the intramolecular
CT-induced chemiluminescent decomposition, its rate can
be estimated by examining the chemiluminescent decompo-
sition rate for the system of dioxetane (2), if the
stoichiometry of products is clear and accurate. Thus, we
attempted further to examine a reaction of dioxetane (2) that
leads both to the CT-induced decomposition and a
competitive reaction to extinguish it without causing the
decay of the dioxetane ring.
Dimethyl chloromalonate (18c) has been reported to
Scheme 8.

N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
9575
Scheme 9.
2.4. 1,3-Dipolar cycloaddition of diazomethanes to the
(1-cyanoethenyl)phenyl moiety attached to a dioxetane
ring
reaction of 2 with 34b proceeded similarly to give
dihydropyrazole (35b). These results are consistent with
an idea that the reaction of 2 with 34 proceeds presumably
by the concerted mechanism. On the other hand, Diels–
Alder reaction of dioxetane (2) with a diene such as
Danishefsky’s diene (37a) and 2,3-dimethoxy-1,3-buta-
diene (37b) took place sluggishly at room temperature,
though these dienes are well known to be very reactive to
various dienophiles (Scheme 10).
The results described earlier show a possibility that the
chemiluminescent decomposition of dioxetane (2) induced
by the conjugate addition of an anion provides a new probe
to know a feature of an intramolecular reaction competing
with the CT-induced chemiluminescent decomposition of
an intermediary dioxetane. Thus, we dared finally to apply
dioxetane (2) to a pericyclic reaction such as 1,3-dipolar
cycloaddition and Diels–Alder reaction, which proceeds
generally by a concerted mechanism and not by a stepwise
ionic mechanism. 1,3-Dipoles chosen here were diphenyl-
diazomethane (34a) and trimethylsilyldiazometane (34b).
When dioxetane (2) was treated with diazomethane (34a) in
CH3CN at room temperature, 1,3-dipolar addition pro-
ceeded smoothly and completed within 120 min to afford
dihydropyrazole (35a) without accompanying decompo-
sition of the dioxetane ring. Adduct (35a) was synthesized
also by the singlet oxygenation of dihydrofuran (36), which
was prepared by the 1,3-dipolar addition of 34a to 4. The
3. Conclusion
Dioxetanes (1) bearing a phenyl moiety substituted with a
methyl having an electron-withdrawing group(s) (–CH2-Ew
or –CH(X)-Ew) were effectively triggered with a base such
as fluoride to decompose rapidly with accompanying
emission of light ranging in color from yellow to crimson.
The base-induced reaction of dioxetane (1) was clarified to
proceed through dioxetanes bearing a phenymethanide
anion, from which the intramolecular CT causes chemi-
luminescent decomposition of the dioxetane. The rate of
Scheme 10.

9576
N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
CT-induced decomposition for dioxetanes (1) in TBAF/
DMSO was found to relate with the acidity of the parent
carbon acids (CH2(X)-Ew). This relationship provides a
possibility to estimate the acidity of carbon acids by the use
of chemiluminescent decomposition of dioxetanes.
Similarly to the case of 6b, 4-tert-butyl-5-(2-formylphenyl)-
3,3-dimethyl-2,3-dihydrofuran (6a) was synthesized from
2-bromphenyl isomer (5a) as a yellow oil in 90.1% yield. 1H
NMR (400 MHz, CDCl3): dH 1.01 (s, 9H), 1.38 (s, 6H), 3.94
(s, 2H), 7.38 (d with fine coupling, JZ7.6 Hz, 1H), 7.48 (t,
JZ7.6 Hz, 1H), 7.58 (td, JZ7.6, 1.3 Hz, 1H), 7.95 (dd, JZ
7.6, 1.3 Hz, 1H), 10.2 (s, 1H) ppm. 13C NMR (125 MHz,
CDCl3): dC 27.2, 32.3, 32.5, 47.5, 83.4, 126.7, 128.9, 129.5,
131.5, 133.4, 134.4, 139.4, 145.0, 192.0 ppm. IR (liquid
film): 2959, 2868, 2745, 1699 cmK1. Mass (m/z, %): 258
(MC, 17), 243 (38), 202 (18), 201 (100), 187 (45), 171 (25),
159 (28), 149 (40), 133 (45), 105 (30), 85 (27), 77 (26), 57
(44). HRMS (ESI): 281.1525, calcd for C17H22O2Na (MC
NaC) 281.1518.
Dioxetane (2) bearing a 3-(1-cyanoethenyl)phenyl group
underwent the Michael addition of a bis(methoxycarbo-
nyl)methanide anion to generate unstable dioxetane bearing
a phenylmethanide anion, which decomposed with accom-
panying emission of light. When bis(methoxycarbonyl)-
methanide anion or bis(methoxycarbonyl) chloro-
methanide anion was used, the CT-induced decomposition
of an intermediary dioxetane competed with the intra-
molecular proton transfer or cyclopropanation. These
findings suggest that the chemiluminescent properties,
especially the rate, for the Michael addition-induced
decomposition of 2 should become a probe to know the
features of the intramolecular reactions, which occur
concurrently.
Similarly to the case of 6b, 4-tert-butyl-5-(4-formylphenyl)-
3,3-dimethyl-2,3-dihydrofuran (6c) was synthesized from
4-bromphenyl isomer (5c) as a colorless columns, melted at
41.6–42.2 8C (from hexane) in 78.4% yield. 1H NMR
(400 MHz, CDCl3): dH 1.05 (s, 9H), 1.35 (s, 6H), 3.90 (s,
2H), 7.48 (d, JZ8.2 Hz, 2H), 7.86 (d, JZ8.2 Hz, 2H), 10.0
(s, 1H) ppm. 13C NMR (125 MHz, CDCl3): dC 27.2, 32.4,
32.5, 47.4, 83.3, 127.1, 129.2, 130.6, 135.8, 142.6, 148.5,
191.9 ppm. IR (KBr): 2962, 2865, 1696 cmK1. Mass (m/z,
%): 258 (MC, 18), 244 (18), 243 (100), 187 (33), 133 (40),
105 (12), 57 (16).
4. Experimental
4.1. General
Melting points were measured with a Yanako MP-S3
melting point apparatus and are uncorrected. IR spectra
were taken on a JASCO FT/IR-300 infrared spectrometer.
1H and 13C NMR spectra were recorded on JEOL EX-400
and JEOL EPC-500 spectrometer. Mass spectra were
obtained by using JEOL JMS-AX-505H, JEOL JMS-T-
100LC mass spectrometers. Reagents were purchased from
Aldrich, Tokyo Chemical Industries, Wako Pure Chemical
Industries, and/or Kanto Chemical Industries. Column
chromatography was carried out with silica gel, unless
otherwise stated.
4.1.2. 4-tert-Butyl-5-[3-(hydroxymethyl)phenyl]-3,3-
dimethyl-2,3-dihydrofuran (7b): typical procedure.
NaBH4 (870 mg, 23.0 mmol) was added to a solution of
4-tert-butyl-5-(3-formylphenyl)-3,3-dimethyl-2,3-dihydro-
furan (6b) (11.8 g, 45.6 mmol) in CH2Cl2 (100 mL) at 0 8C
under nitrogen atmosphere. To the solution MeOH (10 mL)
was added and stirred for 30 min. The reaction mixture was
poured into satd aq NH4Cl and extracted with AcOEt. The
organic layer was washed with satd aq NaCl, dried over
anhydrous MgSO4, and concentrated in vacuo. The residue
was chromatographed on silica gel with AcOEt–hexane
(1/4) to give 11.4 g of 7b as a colorless oil in 96.0% yield.
1H NMR (400 MHz, CDCl3): dH 1.05 (s, 9H), 1.34 (s, 6H),
3.87 (s, 2H), 4.69 (s, 2H), 7.21–7.25 (m, 1H), 7.29–7.34 (m,
3H) ppm. 13C NMR (100 MHz, CDCl3): dC 27.4, 32.4, 32.6,
47.1, 64.8, 83.0, 125.7, 126.4, 127.9, 128.1, 128.9, 136.1,
140.5, 149.6 ppm. IR (liquid film): 3415, 2957, 2869,
1653 cmK1. Mass (m/z, %): 260 (MC, 20), 246 (17), 245
(100), 243 (23), 171 (19), 135 (45). HRMS (ESI): 283.1662,
calcd for C17H24O2Na (MCNaC) 283.1674.
4.1.1. 4-tert-Butyl-5-(3-formylphenyl)-3,3-dimethyl-2,3-
dihydrofuran (6b): typical procedure. BuLi (1.61 M in
hexane, 30.1 mL, 48.5 mmol) was added to a solution of
5-(3-bromophenyl)-4-tert-butyl-3,3-dimethyl-2,3-dihydro-
furan (5b)12 (14.3 g, 46.2 mmol) in THF (100 mL) at
K78 8C under nitrogen atmosphere and was stirred for
30 min. To the solution, N-methylformanilide (6.27 mL,
50.8 mmol) was added and was stirred for 30 min. The
reaction mixture was poured into 1 N HCl and then
extracted with ethyl acetate (AcOEt). The organic layer
was washed with satd aq NaCl, dried over anhydrous
MgSO4, and concentrated in vacuo. The residue was
chromatographed on silica gel with AcOEt–hexane (1/4)
to give 11.5 g of 6b as a pale yellow oil in 96.3% isolated
yield. 1H NMR (400 MHz, CDCl3): dH 1.04 (s, 9H), 1.35 (s,
6H), 3.90 (s, 2H), 7.51 (t, JZ7.6 Hz, 1H), 7.57 (d with fine
coupling, JZ7.6 Hz, 1H), 7.82 (s with fine coupling, 1H),
7.84 (d with fine coupling, JZ7.6 Hz, 1H), 10.0 (s,
1H) ppm. 13C NMR (125 MHz, CDCl3): dC 27.3, 32.5,
32.6, 47.3, 83.2, 127.0, 128.6, 129.2, 131.3, 135.9, 136.1,
137.3, 148.4, 192.0 ppm. IR (liquid film): 2959, 2868, 2723,
1702 cmK1. Mass (m/z, %): 259 (MCC1, 14), 258 (MC,
69), 244 (81), 243 (100), 187 (78), 159 (38), 133 (95).
HRMS (ESI): 281.1538, calcd for C17H22O2Na (MCNaC)
281.1518.
Similarly to the case of 7b, 4-tert-butyl-5-[2-(hydroxy-
methyl)phenyl]-3,3-dimethyl-2,3-dihydrofuran (7a) was
synthesized from 2-formylphenyl isomer (6a) as a colorless
granules, melted at 59.3–60.0 8C (from hexane–CH2Cl2) in
97.1% yield. 1H NMR (400 MHz, CDCl3): dH 1.03 (s, 9H),
1.37 (s, 6H), 2.65 (t, JZ6.5 Hz, 1H), 3.89 (s, 2H), 4.60
(broad s, 2H), 7.27–7.38 (m, 3H), 7.42 (d, JZ7.6 Hz,
1H) ppm. 13C NMR (125 MHz, CDCl3): dC 27.1, 32.1, 32.5,
47.1, 64.2, 82.8, 127.3, 127.3, 128.7, 129.0, 131.0, 134.7,
139.9, 147.7 ppm. IR (KBr): 3475, 2957, 2872, 1647 cmK1
.
Mass (m/z, %): 261 (MCC1, 11), 260 (MC, 56), 246 (20),
245 (100), 227 (26), 173 (46), 171 (72), 135 (66), 133 (27),
57 (20). HRMS (ESI): 283.1665, calcd for C17H24O2Na
(MCNaC) 283.1674.

N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
9577
Similarly to the case of 7b, 4-tert-butyl-5-[4-(hydroxy-
methyl)phenyl]-3,3-dimethyl-2,3-dihydrofuran (7c) was
synthesized from 4-formylphenyl isomer (6c) as a colorless
columns melted at 56.1–57.0 8C (from hexane) in 96.6%
methyl)phenyl]-3,3-dimethyl-2,3-dihydrofuran (8c) was
synthesized from 4-(hydroxymethyl)phenyl isomer (7c) as
pale yellow oil and crude product was used to the next
1
reaction without further purification. H NMR (400 MHz,
1
yield. H NMR (400 MHz, CDCl3): dH 1.04 (s, 9H), 1.33
CDCl3): dH 1.04 (s, 9H), 1.33 (s, 6H), 3.87 (s, 2H), 4.49 (s,
2H), 7.27 (d, JZ8.1 Hz, 2H), 7.35 (d, JZ8.1 Hz, 2H) ppm.
13C NMR (125 MHz, CDCl3): dC 27.4, 32.4, 32.6, 33.2,
47.2, 83.1, 126.2, 128.6, 130.3, 136.4, 137.5, 149.3 ppm. IR
(liquid film): 2957, 2868, 1651 cmK1. Mass (m/z, %): 324
(MC, 20), 322 (MC, 21), 310 (17), 309 (99), 308 (19), 307
(100), 263 (26), 243 (32), 228 (20), 199 (25), 197 (24), 171
(43), 118 (27), 90 (29), 57 (72).
(s, 6H), 1.66 (t, JZ6.0 Hz, 1H), 3.87 (s, 2H), 4.70 (d, JZ
6.0 Hz, 2H), 7.29 (d, JZ8.1 Hz, 2H), 7.33 (d, JZ8.1 Hz,
2H) ppm. 13C NMR (125 MHz, CDCl3): dC 27.4, 32.4, 32.6,
47.2, 65.1, 83.1, 125.9, 126.4, 130.1, 135.6, 140.6,
149.8 ppm. IR (KBr): 3272, 2957, 2867, 1648 cmK1
.
Mass (m/z, %): 260 (MC, 20), 246 (18), 245 (100), 243
(18), 171 (25), 135 (30), 77 (11), 57 (17). HRMS (ESI):
283.1671, calcd for C17H24O2Na (MCNaC) 283.1674.
4.1.5.
4-tert-Butyl-5-[3-(cyanomethyl)phenyl]-3,3-
4.1.3.
4-tert-Butyl-5-[2-(chloromethyl)phenyl]-3,3-
dimethyl-2,3-dihydrofuran (3a); typical procedure.
A solution of 5-[3-(bromomethyl)phenyl]-4-tert-butyl-3,3-
dimethyl-2,3-dihydrofuran (8b) (3.81 g, 11.8 mmol), NaCN
(804 mg, 16.4 mmol) and tetra-n-butylammonium hydrogen
sulfate (804 mg, 2.37 mmol) in THF–H2O (5/1) (36 mL)
was stirred under nitrogen atmosphere at refluxing
temperature for 28 h. The reaction mixture was poured
into satd aq NaCl and extracted with AcOEt. The organic
layer was washed with satd aq NaCl, dried over MgSO4, and
concentrated in vacuo. The residue was chromatographed
on silica gel and eluted with AcOEt–hexane (1/9) to give
dimethyl-2,3-dihydrofuran (8a). 4-(N,N-Dimethylamino)-
pyridine (DMAP) (382 mg, 3.13 mmol) and p-toluenesulfo-
nyl chloride (TsCl) (658 mg, 3.45 mmol) were added to a
solution of 4-tert-butyl-5-[2-(hydroxymethyl)phenyl]-3,3-
dimethyl-2,3-dihydrofuran (7a) (739 mg, 2.84 mmol) in
THF (5 mL) at room temperature under nitrogen atmos-
phere and refluxed for 6 h. The reaction mixture was poured
into satd aq NH4Cl and then extracted with AcOEt. The
organic layer was washed with satd aq NaCl, dried over
anhydrous MgSO4, and concentrated in vacuo. The residue
was chromatographed on silica gel with AcOEt–hexane
(9/1) to give 411 mg of 8a as a pale yellow oil in 51.8%
1
2.43 g of 3a as a colorless oil in 76.4% yield. H NMR
(400 MHz, CDCl3): dH 1.04 (s, 9H), 1.34 (s, 6H), 3.76 (s,
2H), 3.88 (s, 2H), 7.26–7.31 (m, 3H), 7.35 (t, JZ7.8 Hz,
1H) ppm. 13C NMR (100 MHz, CDCl3): dC 23.5, 27.4, 32.5,
32.6, 47.3, 83.2, 117.6, 126.3, 127.4, 128.6, 129.2, 129.4,
129.6, 137.2, 148.8 ppm. IR (liquid film): 2957, 2869,
2251 cmK1. Mass (m/z, %): 269 (MC, 11), 255 (16), 254
(100), 144 (42), 116 (16), 57 (14). HRMS (ESI): 292.1663,
calcd for C18H23NONa (MCNaC) 292.1677.
1
yield. H NMR (400 MHz, CDCl3): dH 1.04 (s, 9H), 1.36
(s, 6H), 3.88 (s, 2H), 4.65 (broad s, 2H), 7.23–7.30 (m, 2H),
7.36 (ddd, JZ7.6, 7.1, 2.0 Hz, 1H), 7.50 (d, JZ7.6 Hz,
1H) ppm. 13C NMR (125 MHz, CDCl3): dC 27.2, 32.1, 32.6,
43.6, 47.2, 83.0, 127.6, 127.7, 129.0, 129.5, 130.8, 135.1,
136.3, 147.0 ppm. IR (liquid film): 2957, 2867, 1648 cmK1
.
Mass (20 eV, m/z, %): 280 (MC, 9), 278 (MC, 32), 265 (33),
264 (13), 263 (100), 171 (29), 57 (13). HRMS (ESI):
303.1316, calcd for C17H23ClONa (MCNaC) 303.1306 and
301.1341, calcd for C17H23ClONa (MCNaC) 301.1335.
Similarly to the case of 3b, 4-tert-butyl-5-[2-(cyano-
methyl)phenyl]-3,3-dimethyl-2,3-dihydrofuran (3a) was
synthesized from 2-(chloromethyl)phenyl isomer (8a) as a
1
colorless oil in 78.9% yield. H NMR (400 MHz, CDCl3):
4.1.4. 5-[3-(Bromomethyl)phenyl]-4-tert-butyl-3,3-
dimethyl-2,3-dihydrofuran (8b); typical procedure.
CBr4 (3.94 g, 11.8 mmol) was added to a solution of PPh3
(3.65 g, 13.9 mmol) and 4-tert-butyl-5-[3(-hydroxymethyl)-
phenyl]-3,3-dimethyl-2,3-dihydrofuran (7b) (3.03 g,
11.6 mmol) in THF (30 mL) at room temperature under
nitrogen atmosphere and stirred for 50 min. The reaction
mixture was poured into satd aq NaCl and then extracted
with AcOEt. The organic layer was washed with satd aq
NaCl, dried over anhydrous MgSO4, and concentrated in
vacuo. The residue was chromatographed on silica gel with
AcOEt–hexane (1/9) to give 3.55 g of 8b as a pale yellow oil
dH 1.03 (s, 9H), 1.36 (s, 6H), 3.78 (s, 2H), 3.88 (s, 2H), 7.28–
7.41 (m, 3H), 7.50 (d, JZ7.6 Hz, 1H) ppm. 13C NMR
(100 MHz, CDCl3): dC 21.2, 27.3, 32.1, 32.6, 47.3, 83.1,
117.8, 127.5, 127.9, 128.0, 129.2, 129.2, 131.1, 135.0,
146.8 ppm. IR (liquid film): 2958, 2869, 2250 cmK1. Mass
(m/z, %): 269 (MC, 19), 255 (17), 254 (100), 198 (40), 171
(19), 144 (30), 130 (60), 91 (66), 57 (30). HRMS (ESI):
292.1675, calcd for C18H23NONa (MCNaC) 292.1677.
Similarly to the case of 3b, 4-tert-butyl-5-[4-(cyano-
methyl)phenyl]-3,3-dimethyl-2,3-dihydrofuran (3c) was
synthesized from 4-(bromomethyl)phenyl isomer (8c) as
pale yellow plates, melted at 68.7–69.1 8C (from hexane–
1
in 94.3% yield. H NMR (400 MHz, CDCl3): dH 1.04 (s,
9H), 1.34 (s, 6H), 3.87 (s, 2H), 4.48 (s, 2H), 7.23 (d with fine
coupling, JZ7.2 Hz, 1H), 7.28–7.36 (m, 3H) ppm. 13C
NMR (100 MHz, CDCl3): dC 27.4, 32.4, 32.6, 33.2, 47.2,
83.1, 126.1, 128.2, 128.5, 129.8, 130.5, 136.6, 137.2,
1
CH2Cl2) in 62.0% yield. H NMR (400 MHz, CDCl3): dH
1.04 (s, 9H), 1.33 (s, 6H), 3.76 (s, 2H), 3.87 (s, 2H), 7.28–
7.34 (m, 4H) ppm. 13C NMR (125 MHz, CDCl3): dC 23.4,
27.3, 32.4, 32.6, 47.2, 83.1, 117.7, 126.3, 127.4, 129.6,
130.7, 136.2, 149.0 ppm. IR (KBr): 2959, 2924, 2869,
2250 cmK1. Mass (m/z, %): 269 (MC, 18), 255 (20), 254
(100), 171 (11), 144 (41), 116 (13), 57 (22). HRMS (ESI):
292.1662, calcd for C18H23NONa (MCNaC) 292.1677.
149.1 ppm. IR (liquid film): 2958, 2867, 1653, 1597 cmK1
.
Mass (m/z, %): 324 (MC, 17), 322 (MC, 17), 310 (18), 309
(100), 308 (17), 307 (97), 243 (25), 228 (38), 199 (44), 197
(44), 172 (16), 171 (23), 90 (22), 57 (50). HRMS (ESI):
345.0841, calcd for C17H23BrONa (MCNaC) 345.0830 and
347.0819, calcd for C17H23BrONa (MCNaC) 347.0810.
4.1.6.
dimethyl-2,3-dihydrofuran (3d).
4-tert-Butyl-5-[3-(1-cyanoethyl)phenyl]-3,3-
solution of
Similarly to the case of 8b, 4-tert-butyl-5-[4-(bromo-
A

9578
N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
4-tert-butyl-5-[3-(cyanomethyl)phenyl]-3,3-dimethyl-2,3-
dihydrofuran (3b) (497 mg, 1.84 mmol) in dry THF
(2.5 mL) was added to a suspension of NaH (60% in oil,
74.9 mg, 1.87 mmol) in dry THF (2.5 mL) under nitrogen
atmosphere at 0 8C. To the solution MeI (0.13 mL,
2.09 mmol) was added and stirred at room temperature for
2 h. The reaction mixture was poured into saturated aq
NH4Cl and extracted with AcOEt. The organic layer was
washed with saturated aq NaCl, dried over MgSO4 and
concentrated in vacuo. The residue was chromatographed
on silica gel with hexane–AcOEt (9/1) to give 337 mg of 3d
(20), 287 (100), 177 (46), 171 (29), 57 (25). HRMS (ESI):
325.1787, calcd for C19H26O3Na (MCNaC) 325.1780.
4.1.9. 4-tert-Butyl-5-[3-(benzoylmethyl)phenyl]-3,3-
dimethyl-2,3-dihydrofuran (3f). A solution of 4-tert-
butyl-5-[3-(carboxymethyl)phenyl]-3,3-dimethyl-2,3-di-
hydrofuran (9) (304 mg, 1.05 mmol) in dry THF (2 mL) was
added dropwise over 10 min to a solution of butyllithium
(1.62 M in hexane, 1.35 mL, 2.19 mmol) in dry THF
(1.5 mL) at K78 8C under nitrogen atmosphere and was
stirred for 30 min. Benzoyl chloride (0.13 mL, 1.12 mmol)
was added to the solution and stirred for 1 h. The reaction
mixture was poured into 1 N HCl and then extracted with
AcOEt. The organic layer was washed with satd aq NaCl,
dried over MgSO4, and concentrated in vacuo. The residue
was chromatographed on silica gel and eluted with AcOEt–
hexane (1/9) to give 96 mg of 3f as a yellow oil in 26.2%
yield. 1H NMR (500 MHz, CDCl3): dH 0.99 (s, 9H), 1.32 (s,
6H), 3.86 (s, 2H), 4.27 (s, 2H), 7.17 (d, JZ7.6 Hz, 1H), 7.21
(s, 1H), 7.21 (d, JZ7.6 Hz, 1H), 7.28 (t, JZ7.6 Hz, 1H),
7.43 (t, JZ7.4 Hz, 2H), 7.53 (t with fine coupling, JZ
7.4 Hz, 1H), 7.98 (d, JZ7.4 Hz, 2H) ppm. 13C NMR
(125 MHz, CDCl3): dC 27.4, 32.3, 32.5, 45.5, 47.1, 83.1,
125.8, 128.2, 128.3, 128.6, 128.6, 129.0, 131.0, 133.0,
134.1, 136.5, 136.5, 149.7, 197.4 ppm. IR (liquid film):
2957, 2869, 1720, 1683 cmK1. Mass (m/z, %): 348 (MC,
22), 334 (27), 333 (100), 277 (17), 223 (38), 105 (67), 91
(13), 77 (27), 57 (29). HRMS (ESI): 371.1987, calcd for
C24H28O2Na (MCNaC) 371.1987.
1
as a pale yellow oil in 64.5% yield. H NMR (400 MHz,
CDCl3): dH 1.04 (s, 9H), 1.34 (s, 6H), 1.64 (d, JZ7.3 Hz,
3H), 3.88 (s, 2H), 3.90 (q, JZ7.3 Hz, 1H), 7.25–7.38 (m,
4H) ppm. 13C NMR (125 MHz, CDCl3): dC 21.5, 27.3, 31.1,
32.4, 32.5, 47.2, 83.2, 121.4, 126.3, 126.4, 128.2, 128.7,
129.6, 136.6, 137.2, 149.1 ppm. IR (liquid film): 2957,
2870, 2243 cmK1. Mass (m/z, %): 283 (MC, 11), 268 (63),
243 (26), 228 (26), 159 (15), 158 (100), 57 (55). HRMS
(ESI): 306.1804, calcd for C19H25NONa (MCNaC)
306.1834.
4.1.7. 4-tert-Butyl-5-[3-(carboxymethyl)phenyl]-3,3-
dimethyl-2,3-dihydrofuran (9). 4-tert-butyl-5-[3-(cyano-
methyl)phenyl]-3,3-dimethyl-2,3-dihydrofuran
(3b)
(8.52 g, 31.6 mmol) was added to a solution of NaOH
(6.31 g, 158 mmol) in EtOH (80 mL) and H2O (8 mL) and
refluxed for 2 h. The reaction mixture was poured into 1 N
HCl and extracted with AcOEt. The organic layer was
washed with satd aq NaCl, dried over anhydrous MgSO4,
and concentrated in vacuo. The residue was chromato-
graphed on silica gel with AcOEt–hexane (1/1) to give
8.44 g of 9 as a colorless leaflets melted at 95.5–96.1 8C
(from hexane–CH2Cl2) in 97.4% yield. 1H NMR (500 MHz,
CDCl3): dH 1.03 (s 9H), 1.33 (s, 6H), 3.64 (s, 2H), 3.87 (s,
2H), 7.20–7.25 (m, 3H), 7.29 (t, JZ7.3 Hz, 1H ppm). 13C
NMR (125 MHz, CDCl3): dC 27.4, 32.4, 32.5, 40.9, 47.2,
83.1, 126.0, 128.1, 128.8, 129.0, 130.9, 132.8, 136.5, 149.6.
4.1.10.
4-tert-Butyl-5-{3-[cyano(methoxycarbonyl)
methyl]phenyl}-3,3-dimethyl-2,3-dihydrofuran (3g).
A solution of 4-tert-butyl-5-[3-(cyanomethy)lphenyl]-3,3-
dimethyl-2,3-dihydrofuran (3b) (511 mg, 1.90 mmol) and
dimethyl carbonate (0.24 mL, 2.85 mmol) in toluene (4 mL)
was added dropwise over 5 min to a suspension of NaH
(60% in oil, 161 mg, 4.03 mmol) in toluene (4 mL) under
nitrogen atmosphere and stirred for 1 h. The reaction
mixture was poured into 1 N HCl and then extracted with
AcOEt. The organic layer was washed with satd aq NaCl,
dried over MgSO4, and concentrated in vacuo. The residue
was chromatographed on silica gel and eluted with AcOEt–
hexane (1/9) to give 582 mg of 3g as a pale orange oil in
93.7% yield. 1H NMR (400 MHz, CDCl3): dH 1.03 (s, 9H),
1.34 (s, 6H), 3.79 (s, 3H), 3.88 (s, 2H), 4.73 (s, 1H), 7.34 (d
with fine coupling, JZ7.1 Hz, 1H), 7.37–7.45 (m, 3H) ppm.
13C NMR (100 MHz, CDCl3): dC 27.4, 32.5, 32.6, 43.4,
47.3, 53.9, 83.2, 115.3, 126.7, 127.4, 128.8, 129.2, 129.5,
130.7, 137.3, 148.6, 165.1 ppm. IR (liquid film): 2957,
2869, 2252, 1753 cmK1. Mass (m/z, %): 327 (MC, 13), 313
(21), 312 (100), 202 (42), 115 (10), 57 (56), 55 (11). HRMS
(ESI): 350.1725, calcd for C20H25NO3Na (MCNaC)
350.1732.
177.3 ppm. IR (KBr): 2983, 2955, 2916, 2869, 1711 cmK1
.
Mass (m/z, %): 288 (MC, 18), 274 (19), 273 (100), 171 (14),
163 (35), 57 (16). HRMS (ESI, negative): 287.1629, calcd
for C18H23O3 287.1647.
4.1.8.
4-tert-Butyl-5-[3-(methoxycarbonylmethyl)-
phenyl]-3,3-dimethyl-2,3-dihydrofuan (3e). NaHCO3
(512 mg, 6.09 mmol) was added to a solution of 4-tert-
butyl-5-[3-(carboxymethyl)phenyl]-3,3-dimethyl-2,3-di-
hydrofuran (9) (1.17 g, 4.06 mmol) in dry DMF (10 mL) at
room temperature under nitrogen atmosphere and stirred
for 20 min. To the solution methyl iodide (0.51 mL,
8.19 mmol) was added and stirred overnight. The reaction
mixture was poured into satd aq NH4Cl and then extracted
with AcOEt. The organic layer was washed with satd aq
NaCl, dried over MgSO4, and concentrated in vacuo. The
residue was chromatographed on silica gel and eluted with
AcOEt–hexane (1/4) to give 1.10 g of 3e as a colorless oil in
4.1.11. 4-tert-Butyl-5-[3-(1-cyanoethenyl)phenyl]-3,3-
dimethyl-2,3-dihydrofuran (4). A solution of 4-tert-
butyl-5-[3-(cyanomethyl)phenyl]-3,3-dimethyl-2,3-di-
hydrofuran (3b) (521 mg, 1.93 mmol), paraformaldehyde
(87.8 mg, 2.92 mmol), K2CO3 (429 mg, 3.10 mmol) and
Bu4NI (14.7 mg, 0.0398 mmol) in toluene (10 mL) was
stirred under nitrogen atmosphere at 80 8C for 15 min. The
reaction mixture was poured into satd aq NaCl and then
extracted with AcOEt. The organic layer was washed with
1
89.7% yield. H NMR (400 MHz, CDCl3): dH 1.04 (s 9H),
1.33 (s, 6H), 3.62 (s, 2H), 3.67 (s, 3H), 3.87 (s, 2H), 7.18–
7.30 (m, 4H) ppm. 13C NMR (100 MHz, CDCl3): dC 27.4,
32.4, 32.6, 41.1, 47.2, 51.9, 83.1, 125.8, 128.0, 128.5, 128.8,
130.7, 133.4, 136.3, 149.7, 171.6 ppm. IR (liquid film):
2955, 2870, 1742 cmK1. Mass (m/z, %): 302 (MC, 18), 288

N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
9579
satd aq NaCl, dried over anhydrous MgSO4 and concen-
trated in vacuo. The residue was chromatographed on silica
gel with hexane–AcOEt (9/1) to give 441 mg of (4) as a
yellow oil in 81.3% yield. 1H NMR (400 MHz, CDCl3): dH
1.05 (s, 9H), 1.35 (s, 6H), 3.89 (s, 2H), 6.12 (s, 1H), 6.35 (s,
1H), 7.35 (d with fine coupling, JZ7.6 Hz, 1H), 7.40 (t, JZ
7.6 Hz, 1H), 7.52 (s with fine coupling, 1H), 7.56 (d with
fine coupling, JZ7.6 Hz, 1H) ppm. 13C NMR (125 MHz,
CDCl3): dC 27.4, 32.5, 32.6, 47.3, 83.2, 117.6, 122.7, 125.4,
126.7, 127.1, 128.3, 128.6, 131.5, 132.0, 137.2, 148.8 ppm.
IR (liquid film): 2957, 2868, 2228 cmK1. Mass (m/z, %):
281 (MC, 20), 267 (22), 266 (100), 210 (19), 156 (69), 128
(22), 101 (12), 57 (64). HRMS (ESI): 304.1654, calcd for
C19H23NONa (MCNaC) 304.1677.
47.0, 47.1, 83.1, 121.3, 126.1, 127.2, 127.5, 127.8, 127.8,
128.3, 128.8, 129.1, 129.2, 129.3, 129.7, 132.4, 136.6,
138.0, 141.1, 149.1 ppm. IR (liquid film): 2957, 2868, 2233,
1652 cmK1. Mass (m/z, %): 475 (MC, trace), 447 (22), 433
(37), 432 (100), 376 (16), 322 (20). HRMS (ESI): 470.2455,
calcd for C32H33NONa (MKN2CNaC) 470.2460.
4.2. Synthesis of bicyclic dioxetanes (1): general
procedure
A solution of 5-aryl-4-tert-butyl-3,3-dimethyl-2,3-dihydro-
furan (3) (100–300 mg) and tetraphenylporphin (TPP)
(ca.1 mg) in CH2Cl2 (10 mL) was irradiated externally
with 940 W Na lamp under oxygen atmosphere at 0 8C for
1–2 h, except the case of dihydrofuran (4), singlet
oxygenation of which was carried out at K78 8C. The
photolysate was concentrated in vacuo. The residue was
chromatographed on silica gel to give the corresponding
5-tert-butyl-1-aryl-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]-
heptane (1).
4.1.12. 4-tert-Butyl-5-{3-[1-cyano-3,3-bis(methoxycarbo-
nyl)butyl]pheny}-3,3-dimethyl-2,3-dihydrofuran (23).
Dimethyl methylmalonate (18a) (203 mg, 1.39 mmol) was
added to 18-crown-6 (331 mg, 1.25 mmol) and tert-BuOK
(1.0 M in THF, 1.2 mL, 1.20 mmol) in dry toluene (15 mL)
at room temperature under nitrogen atmosphere. To the
solution 4-tert-butyl-5-[3-(1-cyanoethenyl)phenyl]-3,3-
dimethyl-2,3-dihydrofuran (4) (339 mg, 1.20 mmol) in dry
toluene (5 mL) was added at room temperature under
nitrogen atmosphere and stirred for 8 min. The reaction
mixture was poured into satd aq NH4Cl and extracted with
AcOEt. The organic layer was washed with satd aq NaCl,
dried over anhydrous MgSO4 and concentrated in vacuo.
The residue was chromatographed on silica gel with
hexane–ethyl ether (3/1) to give 272 mg of 23 as a colorless
viscous oil in 52.8% yield. 1H NMR (400 MHz, CDCl3): dH
1.04 (s, 9H), 1.34 (s, 6H), 1.57 (s, 3H), 2.35 (dd, JZ14.6,
3.7 Hz, 1H), 2.50 (dd, JZ14.6, 10.3 Hz, 1H), 3.77 (s, 6H),
3.88 (s, 2H), 4.04 (dd, JZ10.3, 3.7 Hz, 1H), 7.25–7.38 (m,
4H) ppm. 13C NMR (125 MHz, CDCl3): dC 20.9, 27.4, 27.4,
32.4, 32.6, 33.2, 42.1, 47.3, 52.8, 52.9, 52.9, 83.2, 120.4,
126.5, 127.0, 128.7, 128.8, 129.9, 136.0, 137.3, 149.0,
171.3, 171.6 ppm. IR (liquid film): 2956, 2870, 2243,
1734 cmK1. Mass (m/z, %): 427 (MC, 17), 413 (31), 412
(100), 410 (10), 302 (11), 266 (13), 236 (12), 57 (12).
HRMS (ESI): 450.2257, calcd for C25H33NO5Na (MC
NaC) 450.2256.
4.2.1.
5-tert-Butyl-1-[3-(cyanomethyl)phenyl]-4,4-
dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (1b). Pale
yellow granules melted at 99.8–100.6 8C (from hexane–
CH2Cl2), 88.9% yield. 1H NMR (400 MHz, CDCl3): dH 0.98
(s, 9H), 1.16 (s, 3H), 1.39 (s, 3H), 3.79 (s, 2H), 3.83 (d, JZ
8.2 Hz, 1H), 4.59 (broad d, JZ8.2 Hz, 1H), 7.39 (d, JZ
7.6 Hz, 1H), 7.44 (t, JZ7.6 Hz, 1H), 7.59 (broad s, 1H),
7.62 (d, JZ7.6 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3):
dC 18.5, 23.7, 25.2, 26.8, 36.7, 45.7, 80.3, 104.9, 116.2,
117.4, 127.8, 128.1, 128.7, 128.9, 129.7, 137.1 ppm. IR
(KBr): 3000, 2966, 2902, 2251 cmK1. Mass (20 eV, m/z,
%): 302 (MCC1, 2), 269 (7), 246 (15), 244 (40), 218 (52),
216 (23), 162 (48), 144 (89), 125 (11), 111 (14), 97 (12), 85
(66), 57 (100), 56 (39). HRMS (ESI): 324.1587, calcd for
C18H23NO3Na (MCNaC) 324.1576. Anal. Calcd for
C18H23NO3: C, 71.73; H, 7.69; N, 4.65. Found: C, 71.86;
H, 8.08; N, 4.73.
4.2.2.
5-tert-Butyl-1-[2-(cyanomethyl)phenyl]-4,4-
dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (1a). Pale
yellow columns melted at 98.3–99.0 8C (from hexane–
CH2Cl2), 94.8% yield. 1H NMR (400 MHz, CDCl3): dH 0.98
(s, 9H), 1.22 (s, 3H), 1.44 (s, 3H), 3.89 (d, JZ8.3 Hz, 1H),
3.98 (d, JZ18.8 z, 1H), 4.29 (d, JZ18.8 Hz, 1H), 4.57 (d,
JZ8.3 Hz, 1H), 7.38–7.48 (m, 2H), 7.58 (d, JZ7.3 Hz, 1H),
7.86 (d, JZ7.2 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3):
dC 19.3, 23.1, 25.8, 26.4, 36.7, 45.5, 80.2, 106.0, 117.3,
118.1, 127.7, 129.2, 130.3, 130.5, 131.3, 133.4 ppm. IR
(KBr): 2978, 2905, 2251 cmK1. Mass (20 eV, m/z, %): 301
(MC, 1), 269 (7), 254 (11), 246 (36), 244 (50), 218 (34), 216
(27), 163 (11), 162 (100), 145 (13), 144 (86), 134 (14), 85
(32), 57 (69), 56 (17). HRMS (ESI): 324.1583, calcd for
C18H23NO3Na (MCNaC) 324.1576.
4.1.13. 4-tert-Butyl-5-[3-(3-cyano-4,5-dihydro-5,5-di-
phenyl-3H-pyrazole-3-yl)phenyl]-3,3-dimethyl-2,3-dihy-
drofuran (36a). A solution of (diphenyl)diazomethane
(1.0 mmol: prepared from benzophenone hydrazone and
mercury oxide in hexane and ethanol in the presence of
catalytic amount of EtONa and used crude product) in
acetonitrile (1.0 mL) was added to a solution of 4-tert-butyl-
5-[3-(1-cyanoethenyl)phenyl]-3,3-dimethyl-2,3-dihydro-
furan (4) (184 mg, 0.65 mmol) and 2,6-di-tert-butyl-4-
methylphenol (2.5 mg) in acetonitlile (2 mL) at room
temperature under nitrogen atmosphere and stirred for
3.5 h. The reaction mixture was concentrated in vacuo and
chromatographed on silica gel with hexane–AcOEt (10/1–5/
1) to give 298 mg of 36a as colorless viscous oil in 96.0%
yield. 1H NMR (500 MHz, CDCl3): dH 0.90 (s, 9H), 1.31 (s,
3H), 1.31 (s, 3H), 2.45 (d, JZ6.2 Hz, 1H), 2.62 (d, JZ
6.2 Hz, 1H), 3.84 (s 2H), 6.97–7.16 (m, 8H), 7.18 (s with
fine coupling, 1H), 7.28 (d with fine coupling, JZ7.3 Hz,
1H), 7.35–7.40 (m, 2H), 7.58–7.62 (m, 2H) ppm. 13C NMR
(125 MHz, CDCl3): dC 24.6, 27.3, 27.3, 27.4, 32.3, 32.6,
4.2.3.
5-tert-Butyl-1-(4-cyanomethyl)phenyl-4,4-
dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (1c). Pale
yellow granules melted at 69.3–70.2 8C (from hexane–
CH2Cl2), 80.3% yield. 1H NMR (400 MHz, CDCl3): dH 0.97
(s, 9H), 1.16 (s, 3H), 1.38 (s, 3H), 3.79 (s, 2H), 3.83 (d, JZ
8.1 Hz, 1H), 4.58 (d, JZ8.1 Hz, 1H), 7.37 (d, JZ8.5 Hz,
2H), 7.65 (d, JZ8.5 Hz, 2H) ppm. 13C NMR (100 MHz,
CDCl3): dC 18.4, 23.4, 25.0, 26.7, 36.6, 45.6, 80.2, 104.9,

9580
N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
116.3, 117.5, 127.5, 129.1, 131.3, 136.0 ppm. IR (KBr):
2969, 2897, 2251 cmK1. Mass (20 eV, m/z, %): 302 (MCC
1, 1), 269 (2), 246 (13), 244 (56), 216 (19), 177 (21), 162
(24), 145 (11), 144 (100), 85 (79), 57 (73), 56 (24). HRMS
(ESI): 324.1584, calcd for C18H23NO3Na (MCNaC)
324.1576.
128.2, 128.2, 128.9, 128.9, 129.0, 129.0, 129.3, 129.3,
129.6, 137.4, 137.4, 165.1, 165.1 ppm. IR (liquid film):
2962, 2898, 2254, 1753 cmK1. Mass (20 eV, m/z, %): 360
(MCC1, 1), 327 (4), 304 (12), 302 (26), 287 (29), 276 (63),
274 (23), 220 (63), 203 (11), 202 (100), 85 (43), 57 (69), 56
(23). HRMS (ESI): 382.1626, calcd for C20H25NO5Na
(MCNaC) 382.1630.
4.2.4.
5-tert-Butyl-1-[3-(1-cyanoethyl)phenyl]-4,4-
dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (1d). Pale
yellow plates melted at 134.7–135.5 8C (from hexane–
CH2Cl2), 78.6% yield. 1H NMR (400 MHz, CDCl3): dH 0.97
(s, 9H), 1.16 (s, 3H), 1.39 (s, 3H), 1.64 (d, JZ7.3 Hz, 3H),
3.84 (d, JZ8.1 Hz, 1H), 3.95 (q, JZ7.3 Hz, 1H), 4.59 (d,
JZ8.1 Hz, 1H), 7.40–7.46 (m, 2H), 7.59–7.62 (m, 2H) ppm.
13C NMR (125 MHz, CDCl3): dC 18.4, 21.3, 21.5, 25.1,
26.7, 31.2, 31.3, 36.7, 45.6, 80.2, 80.3, 104.9, 116.3, 121.2,
126.8, 126.9, 127.7, 127.8, 128.1, 128.2, 128.8, 136.8,
4.2.8. 5-tert-Butyl-1-[3-(1-cyanoethenyl)phenyl]-4,4-
dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (2). Pale
yellow granules melted at 123.3–124.0 8C (from hexane–
CH2Cl2), 89.7% yield. 1H NMR (400 MHz, CDCl3): dH 0.98
(s, 9H), 1.17 (s, 3H), 1.39 (s, 3H), 3.85 (d, JZ8.2 Hz, 1H),
4.60 (d, JZ8.2 Hz, 1H), 6.16 (s, 1H), 6.38 (s, 1H), 7.48 (t,
JZ7.8 Hz, 1H), 7.64 (d with fine coupling, JZ7.8 Hz, 1H),
7.68 (d with fine coupling, JZ7.8 Hz, 1H), 7.86 (s with fine
coupling, 1H) ppm. 13C NMR (125 MHz, CDCl3): dC 18.4,
25.1, 26.8, 36.7, 45.6, 80.3, 105.0, 116.2, 117.4, 122.6,
125.5, 127.0, 128.7, 128.8, 129.8, 132.2, 137.1 ppm. IR
(KBr): 2998, 2959, 2902, 2226 cmK1. Mass (20 eV, m/z,
%): 281 (MCK32, 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 (MCNaC)
336.1576. Anal. Calcd for C19H23NO3: C, 72.82; H, 7.40;
N, 4.47. Found: C, 72.52; H, 7.80; N, 4.17.
136.9, 137.1 ppm. IR (KBr): 2992, 2966, 2890, 2242 cmK1
.
Mass (20 eV, m/z, %): 283 (MCK32, 4), 260 (15), 258 (33),
232 (57), 230 (26), 177 (12), 176 (63), 159 (11), 158 (100),
85 (38), 57 (72). HRMS (ESI): 338.1752, calcd for
C19H25NO3Na (MCNaC) 338.1732.
4.2.5. 5-tert-Butyl-1-[3-(methoxycarbonylmethyl)-
phenyl]-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane
1
(1e). Pale yellow oil, 85.6% yield. H NMR (400 MHz,
CDCl3): dH 0.97 (s 9H), 1.16 (s, 3H), 1.38 (s, 3H), 3.66 (s,
2H), 3.67 (s, 3H), 3.82 (d, JZ8.1 Hz, 1H), 4.59 (broad d,
JZ8.1 Hz, 1H), 7.30 (d with fine coupling, JZ7.6 Hz, 1H),
7.35 (dd, JZ7.8, 7.6 Hz, 1H), 7.52–7.56 (m, 2H) ppm. 13C
NMR (125 MHz, CDCl3): dC 18.5, 25.1, 26.7, 36.7, 41.1,
45.6, 52.0, 80.2, 104.8, 116.5, 127.1, 128.1, 129.3, 130.3,
133.7, 136.2, 171.6 ppm. IR (liquid film): 2962, 2896,
1740 cmK1. Mass (20 eV, m/z, %): 334 (MC, trace), 302
(trace), 277 (18), 195 (13), 178 (10), 177 (100), 57 (12).
HRMS (ESR): 357.1686, calcd for C19H26O5Na (MCNaC)
357.1678.
4.2.9. 5-tert-Butyl-1-{3-[1-cyano-3,3-bis(methoxycarbo-
nyl)butyl]phenyl}-4,4-dimethyl-2,6,7-trioxabicyclo-
[3.2.0]heptane (22). Pale yellow oil, 82.8% yield (1:1
mixture of diastereoisomers). 1H NMR (400 MHz, CDCl3):
dH 0.97 (s, 4.5H), 0.97 (s, 4.5H), 1.16 (s, 3H), 1.39 (s, 1.5H),
1.40 (s, 1.5H), 1.57 (s, 1.5H), 1.57 (s, 1.5H), 2.32 (dd, JZ
14.5, 3.5 Hz, 0.5H), 2.35 (dd, JZ14.5, 3.5 Hz, 0.5H), 2.49
(dd, JZ14.5, 7.6 Hz, 0.5H), 2.52 (dd, JZ14.5, 7.6 Hz,
0.5H), 3.77 (broad s, 6H), 3.84 (d, JZ8.1 Hz, 0.5H), 3.84 (d,
JZ8.1 Hz, 0.5H), 4.04–4.12 (m, 1H), 4.59 (d, JZ8.1 Hz,
1H), 7.42–7.46 (m, 2H), 7.57–7.68 (m, 2H) ppm. 13C NMR
(125 MHz, CDCl3): dC 18.4, 18.4, 20.8, 20.9, 25.1, 26.7,
33.2, 33.3, 36.7, 41.9, 42.1, 45.6, 52.8, 52.8, 52.9, 52.9,
80.2, 80.3, 105.0, 116.2, 120.2, 120.2, 127.3, 127.3, 128.3,
128.3, 128.4, 128.4, 128.8, 128.9, 136.1, 136.2, 137.2,
171.2, 171.2, 171.5, 171.5 ppm. IR (liquid film): 2958,
2898, 2243, 1731 cmK1. Mass (20 eV, m/z, %): 427 (MCK
32, 6), 320 (24), 303 (18), 302 (100), 57 (10). HRMS (ESI):
482.2143, calcd for C25H33NO7Na (MCNaC) 482.2155.
4.2.6. 5-tert-Butyl-1-[3-(benzoylmethyl)phenyl]-4,4-
dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (1f). Pale
yellow granules, melted at 110.0–110.9 8C (from hexane–
CH2Cl2), 90.2% yield. 1H NMR (500 MHz, CDCl3): dH 0.92
(s, 9H), 1.14 (s, 3H), 1.35 (s, 3H), 3.81 (d, JZ8.2 Hz, 1H),
4.32 (s, 2H), 4.57 (d, JZ8.2 Hz, 1H), 7.30 (d, JZ7.6 Hz,
1H), 7.36 (dd, JZ8.2, 7.6 Hz, 1H), 7.44 (dd, JZ8.3, 7.3 Hz,
2H), 7.51–7.57 (m, 3H), 7.99 (d with fine coupling, JZ
8.3 Hz, 2H) ppm. 13C NMR (125 MHz, CDCl3): dC 18.5,
25.1, 26.7, 36.6, 45.5, 45.6, 80.2, 104.9, 116.6, 126.9, 128.2,
128.6, 128.6, 129.5, 130.5, 133.2, 134.3, 136.3, 136.5,
197.2 ppm. IR (KBr): 2971, 2906, 1688 cmK1. Mass
(20 eV, m/z, %): 348 (MCK32, 1), 323 (20), 241 (21),
224 (17), 223 (100), 105 (24). HRMS (ESI): 403.1894, calcd
for C24H28O4Na (MCNaC) 403.1885.
4.2.10. 5-tert-Butyl-1-[3-(3-cyano-4,5-dihydro-5,5-di-
phenyl-3H-pyrazol-3-yl)phenyl]-4,4-dimethyl-2,6,7-
trioxabicyclo[3.2.0]heptane (35a). Pale yellow granules
melted at 151.0–153.0 8C (from MeOH–CH2Cl2), 99.3%
yield (45:55 mixture of diastereoisomers). 1H NMR
(500 MHz, CDCl3): dH 0.81 (s, 4.95H), 0.87 (s. 4.05H),
1.13 (s, 1.65H), 1.13 (s, 1.35H), 1.32 (s, 1.35H), 1.33 (s,
1.65H), 2.48 (d, JZ6.2 Hz, 0.55H), 2.49 (d, JZ6.2 Hz,
0.45H), 2.62 (d, JZ6.2 Hz, 0.45H), 2.65 (d, JZ6.2 Hz,
0.55H), 3.78 (d, JZ8.2 Hz, 0.55H), 3.82 (d, JZ8.2 Hz,
0.45H), 4.54 (d, JZ8.2 Hz, 0.55H), 4.56 (d, JZ8.2 Hz,
0.45H), 6.98–7.11 (m, 5H), 7.18–7.41 (m, 5.55H), 7.48 (d,
JZ7.8 Hz, 0.45H), 7.53–7.62 (m, 3H) ppm. 13C NMR
(125 MHz, CDCl3): dC 18.4 (CH3), 24.7, 24.9, 25.0, 25.0,
26.7, 26.8, 27.4, 36.5, 36.5, 45.5, 46.9, 47.2, 80.1, 80.2,
104.9, 104.9, 116.2, 116.3, 121.1, 121.1, 126.5, 127.2,
127.2, 127.7, 127.8, 127.8, 128.0, 128.4, 128.4, 128.4,
4.2.7. 5-tert-Butyl-1-[3-cyano(methoxycarbonyl)methyl-
phenyl]-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane
(1g). Pale yellow oil in 88.9% yield (1:1 mixture of
1
diastereoisomers). H NMR (400 MHz, CDCl3): dH 0.96
(s, 9H), 1.17 (s, 3H), 1.38 (s, 1.5H), 1.39 (s, 1.5H), 3.78 (s,
1.5H), 3.79 (s, 1.5H), 3.85 (d, JZ8.2 Hz, 1H), 4.59 (d, JZ
8.2 Hz, 1H), 4.78 (s, 1H), 7.45–7.55 (m, 2H), 7.65–7.76 (m,
2H) ppm. 13C NMR (125 MHz, CDCl3): dC 18.4, 25.1, 26.7,
36.7, 43.4, 45.6, 54.0, 80.3, 80.3, 105.0, 115.2, 115.2, 116.0,

N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
9581
128.8, 128.9, 129.0, 129.1, 129.5, 129.6, 129.6, 132.7,
136.4, 136.5, 137.9, 138.0, 141.0 ppm. IR (KBr): 2968,
2894, 2234 cmK1. Mass (m/z, %): 479 (MCKN2, 3), 452
(8), 339 (16), 338 (15), 323 (26), 322 (100), 321 (21), 312
(14), 295 (16), 294 (22), 293 (68), 217 (11), 216 (14), 165
(22), 141 (51), 57 (42). HRMS (ESI): 502.2352, calcd for
C32H33NO3Na (MKN2CNaC) 502.2358.
JZ7.3 Hz, 3H), 3.95 (q, JZ7.3 Hz, 1H), 4.42 (s, 2H), 7.47
(t, JZ7.8 Hz, 1H), 7.58 (d with fine coupling, JZ7.8 Hz,
1H), 7.93 (d with fine coupling, JZ7.8 Hz, 1H), 7.96 (s with
fine coupling, 1H) ppm. 13C NMR (125 MHz, CDCl3): dC
21.3, 23.6, 23.7, 28.1, 31.1, 45.9, 49.1, 72.4, 121.0, 127.8,
129.2, 129.4, 131.0, 131.2, 137.5, 165.5, 215.9 ppm. IR
(liquid film): 2980, 2875, 2243, 1722, 1686 cmK1. Mass
(20 eV, m/z, %): 316 (MCC1, 2), 260 (12), 258 (26), 232
(36), 230 (20), 177 (12), 176 (48), 159 (11), 158 (100), 85
(25), 57 (59). HRMS (ESI): 338.1737, calcd for
C19H25NO3Na (MCNaC) 338.1732.
4.3. Thermolysis of bicyclic dioxetanes (1a–1g); general
procedure
A solution of 5-tert-butyl-4,4-dimethyl-2,6,7-trioxabi-
cyclo[3.2.0]heptane bearing a substituted phenyl (1)
(30 mg) in p-xylene (5 mL) was stirred under nitrogen
atmosphere for 2 h at 140 8. After cooling, the reaction
mixture was concentrated in vacuo. 1H NMR Spectral
analysis showed that the residue included the desired ester
(10) exclusively. Chromatographic purification [silica gel/
AcOEt–hexane (1/4)] of the residue gave the corresponding
2,2,4,4-tetramethyl-3-oxopentyl benzoate (10).
4.3.5. 3-(Methoxycarbonylmethyl)benzoic acid 2,2,4,4-
tetramethyl-3-oxopentyl ester (10e). Colorless oil. 1H
NMR (400 MHz, CDCl3): dH 1.28 (s, 9H), 1.38 (s, 6H), 3.66
(s, 2H), 3.70 (s, 3H), 4.41 (s, 2H), 7.39 (t, JZ7.8 Hz, 1H),
7.48 (d, JZ7.8 Hz, 1H), 7.86–7.90 (m, 2H) ppm. 13C NMR
(100 MHz, CDCl3): dC 23.8, 28.2, 40.9, 45.9, 49.2, 52.2,
72.1, 128.2, 128.6, 130.3, 130.3, 133.8, 134.3, 165.9, 171.3,
215.7 ppm. IR (liquid film): 2958, 2874, 1741, 1722,
1686 cmK1. Mass (20 eV, m/z, %): 334 (MC, trace), 277
(18), 195 (16), 178 (11), 177 (100), 57 (11). HRMS
(ESI): 357.1673, calcd for C19H26O5Na (MCNaC)
357.1678.
4.3.1. 2-(Cyanomethyl)benzoic acid 2,2,4,4-tetramethyl-
3-oxopentyl ester (10a). Colorless oil. 1H NMR (400 MHz,
CDCl3): dH 1.28 (s, 9H), 1.40 (s, 6H), 4.23 (s, 2H), 4.39 (s,
2H), 7.41 (td, JZ7.3, 2.0 Hz, 1H), 7.54–7.62 (m, 2H), 7.95
(d with fine coupling, JZ7.3 Hz, 1H) ppm. 13C NMR
(125 MHz, CDCl3): dC 23.0, 23.5, 28.1, 45.8, 49.0, 72.3,
117.8, 128.1, 128.3, 130.1, 131.1, 132.2, 133.1, 165.9,
4.3.6. 3-(Benzoylmethyl)benzoic acid 2,2,4,4-tetra-
methyl-3-oxopentyl ester (10f). Colorless oil. H NMR
1
(400 MHz, CDCl3): dH 1.27 (s, 9H), 1.37 (s, 6H), 4.33 (s,
2H), 4.40 (s, 2H), 7.39 (t, JZ7.6 Hz, 1H), 7.44–7.50 (m,
3H), 7.58 (t with fine coupling, JZ7.4 Hz, 1H), 7.85–7.90
(m, 2H), 7.98–8.03 (m, 2H) ppm. 13C NMR (100 MHz,
CDCl3): dC 23.8, 28.2, 45.1, 45.9, 49.2, 72.1, 128.0, 128.4,
128.6, 128.7, 130.3, 130.6, 133.3, 134.2, 134.8, 136.3,
165.9, 196.7, 215.8 ppm. IR (liquid film): 2973, 2873, 1721,
1684 cmK1. Mass (20 eV, m/z, %): 381 (MCC1, trace), 323
(17), 241 (22), 224 (17), 223 (100), 105 (35), 57 (10).
HRMS (ESI): 403.1873, calcd for C24H28O4Na (MCNaC)
403.1885.
215.8 ppm. IR (liquid film): 2979, 2246, 1714, 1681 cmK1
.
Mass (20 eV, m/z, %): 301 (MC, 1), 246 (35), 244 (45), 218
(31), 216 (28), 163 (11), 162 (100), 145 (14), 144 (94), 85
(18), 57 (56), 56 (13). HRMS (ESI): 324.1533, calcd for
C18H23NO3Na (MCNaC) 324.1576.
4.3.2. 3-(Cyanomethyl)benzoic acid 2,2,4,4-tetramethyl-
3-oxopentyl ester (10b). Colorless oil. 1H NMR (400 MHz,
CDCl3): dH 1.29 (s, 9H), 1.39 (s, 6H), 3.79 (s, 2H), 4.41 (s,
2H), 7.46 (t, JZ7.8 Hz, 1H), 7.55 (d with fine coupling, JZ
7.8 Hz, 1H), 7.92–7.95 (m, 2H) ppm. 13C NMR (100 MHz,
CDCl3): dC 23.5, 23.7, 28.2, 45.9, 49.2, 72.4, 117.1, 128.9,
129.1, 129.3, 130.3, 131.0, 132.2, 165.3, 215.7 ppm. IR
(liquid film): 2972, 2874, 2250, 1721, 1685 cmK1. Mass
(20 eV, m/z, %): 302 (MCC1, trace), 246 (13), 244 (35),
218 (43), 216 (31), 162 (48), 145 (11), 144 (100) 85 (46), 57
(85), 56 (32). HRMS (ESI): 324.1581, calcd for
C18H23NO3Na (MCNaC) 324.1576.
4.3.7. 3-[Cyano(methoxycarbonyl)methyl]benzoic acid 2,
2,4,4-tetramethyl-3-oxopentyl ester (10g). Colorless oil.
1H NMR (400 MHz, CDCl3): dH 1.29 (s, 9H), 1.40 (s, 3H),
1.40 (s, 3H), 3.82 (s, 3H), 4.41 (s, 2H), 4.79 (s, 1H), 7.51 (t,
JZ7.8 Hz, 1H), 7.68 (d with fine coupling, JZ7.8 Hz, 1H),
8.01 (d with fine coupling, JZ7.8 Hz, 1H), 8.06 (s with fine
coupling, 1H) ppm. 13C NMR (125 MHz, CDCl3): dC 23.7,
23.7, 28.2, 43.3, 45.9, 49.2, 54.1, 72.5, 114.9, 129.0, 129.5,
130.3, 130.3, 131.3, 132.2, 164.8, 165.0, 215.7 ppm. IR
(liquid film): 2960, 2252, 1754, 1723, 1685 cmK1. Mass
(20 eV, m/z, %): 360 (MCC1, trace), 304 (11), 302 (28),
277 (12), 276 (66), 274 (20), 220 (74), 203 (12), 202 (100),
85 (38), 57 (71), 56 (25). HRMS (ESI): 382.1609, calcd for
C20H25NO5Na (MCNaC) 382.1630.
4.3.3. 4-(Cyanomethyl)benzoic acid 2,2,4,4-tetramethyl-
3-oxopentyl ester (10c). Colorless needles, melted at
66.1–66.5 8C (from hexane–ether). 1H NMR (400 MHz,
CDCl3): dH 1.28 (s, 9H), 1.39 (s, 6H), 3.81 (s, 2H), 4.41 (s,
2H), 7.41 (d, JZ8.4 Hz, 2H), 7.99 (d, JZ8.4 Hz, 2H) ppm.
13C NMR (100 MHz, CDCl3): dC 23.7, 23.7, 28.2, 45.9,
49.2, 72.2, 117.0, 127.9, 129.9, 130.2, 134.8, 165.4,
215.7 ppm. IR (KBr): 2978, 2929, 2873, 2246, 1719,
1683 cmK1. Mass (20 eV, m/z, %): 246 (MCK55, 14),
244 (MC, 46), 216 (13), 162 (24), 145 (11), 144 (100), 85
(46), 57 (59), 56 (23). HRMS (ESI): 324.1530, calcd for
C18H23NO3Na (MCNaC) 324.1576.
4.3.8. 3-(1-Cyanoethenyl)benzoic acid 2,2,4,4-tetra-
methyl-3-oxopentyl ester (11). A solution of 5-tert-butyl-
1-[3-(1-cyanoethenyl)phenyl]-4,4-dimethyl-2,6,7-trioxa-
bicyclo[3.2.0]heptane (2) (17.5 mg, 0.056 mmol) and 2,6-
di-tert-butyl-4-methylphenol (3 mg) in p-xylene (1.5 mL)
was stirred under nitrogen atmosphere for 8 h at 120 8C.
After cooling, the reaction mixture was concentrated in
vacuo and chromatographed on silica gel with hexane–
AcOEt (5/1) to give 10.5 mg of 11 as colorless oil in 60.0%
4.3.4. 3-(1-Cyanoethyl)benzoic acid 2,2,4,4-tetramethyl-
3-oxopentyl ester (10d). Colorless oil. 1H NMR (400 MHz,
CDCl3): dH 1.29 (s, 9H), 1.39 (s, 3H), 1.40 (s, 3H), 1.66 (d,

9582
N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
yield. 1H NMR (400 MHz, CDCl3): dH 1.29 (s, 9H), 1.40 (s,
6H), 4.42 (s, 2H), 6.18 (s, 1H), 6.40 (s, 1H), 7.51 (t, JZ
7.8 Hz, 1H), 7.79 (d with fine coupling, JZ7.8 Hz, 1H),
8.00 (d with fine coupling, JZ7.8 Hz, 1H), 8.21 (s with fine
coupling, 1H) ppm. 13C NMR (125 MHz, CDCl3): dC 23.7,
28.2, 45.9, 49.2, 72.5, 117.2, 122.2, 126.5, 129.1, 129.2,
130.2, 130.6, 131.0, 132.7, 165.2, 215.6 ppm. IR (liquid
film): 2972, 2875, 2229, 1724, 1685 cmK1. Mass (20 eV,
m/z, %): 256 (MCK57, 14), 230 (15), 228 (16), 174 (28),
157 (14), 156 (100), 128 (17), 101 (11), 85 (21), 57 (69).
HRMS (ESI): 336.1578, calcd for C19H23NO3Na (MC
NaC) 336.1576.
in THF, 0.55 mL, 0.55 mmol) in benzene (4.4 mL) and
stirred at room temperature under nitrogen atmosphere for
10 min.
4.5. Isolation of ketoesters (10) from the spent reaction
mixture after chemiluminescent decomposition of
dioxetanes (1): typical procedure
A solution of TBAF (1 M in THF, 0.1 mL) in DMSO
(0.9 mL) was added to a solution of the dioxetane (1g)
(20 mg) in DMSO (3 mL) at room temperature under
nitrogen atmosphere. After stirring for 1 h, H2O (1 mL) was
added to the solution, and then, the reaction mixture was
poured into satd aq NH4Cl and extracted with AcOEt. The
organic layer was washed with satd aq NaCl, dried over
MgSO4, and concentrated in vacuo. 1H NMR spectral
analysis showed that the residue was comprised of ketoester
(10g) without detectable amount of other products. The
residue was purified by column chromatograpy on silica gel
with AcOEt–hexane (1/4) to give the corresponding
ketoester (10g) as a colorless oil in 78.6% yield.
4.4. Chemiluminescence measurement: general
procedure
Chemiluminescence were measured using a Hitachi FP-750
spectrometer and/or Hamamatsu Photonics PMA-11 multi-
channel detector.
Freshly prepared solution (2 mL) of TBAF (1.0!10K1 mol/
L) in DMSO was transferred to a quartz cell (10!10!
50 mm) and the latter placed into the spectrometer, which
was thermostated with stirring at 25 8C. After 3–5 min, a
solution of the dioxetane in DMSO (1.0!10K3 mol/L or
1.0!10K4 mol/L 1 mL) was added by means of a syringe
with immediate starting of measurement. The intensity of
the light emission time-course was recorded and processed
according to first-order kinetics. The total light emission
was estimated by comparing it with that of an adamantyl-
idene dioxetane, whose chemiluminescent efficiency FCL
has been reported to be 0.29 and was used here as
standard16.
4.5.1. 3-[1-Cyano-1-(methoxycarbonyl)ethyl]benzoic
acid 2,2,4,4-tetramethyl-3-oxopentyl ester (15). TBAF
(1 M in THF, 0.5 mL) was added to a solution of
3-[cyano(methoxycarbonyl)methyl]benzoic acid 2,2,4,4-
tetramethyl-3-oxopentyl ester (10g) (82.9 mg, 0.231 mmol)
in DMSO (2 mL) at room temperature under nitrogen
atmosphere. After 5 min, MeI (0.05 mL, 0.80 mmol) was
added to the solution. After stirring for 5 min, the reaction
mixture was poured into satd aq NH4Cl and extracted with
AcOEt. The organic layer was washed with satd aq NaCl,
dried over MgSO4, and concentrated in vacuo. The residue
was chromatographed on silica gel and eluted with AcOEt–
hexane (1/4) to give 15 as a colorless oil in 76.6% yield. 1H
NMR (400 MHz, CDCl3): dH 1.29 (s, 9H), 1.40 (s, 3H), 1.40
(s, 3H), 1.98 (s, 3H), 3.80 (s, 3H), 4.41 (s, 2H), 7.50 (t, JZ
7.8 Hz, 1H), 7.75 (ddd, JZ7.8, 2.1, 1.2 Hz, 1H), 7.99 (d
with fine coupling, JZ7.8 Hz, 1H), 8.13 (s with fine
coupling, 1H) ppm. 13C NMR (125 MHz, CDCl3): dC 23.6,
23.7, 24.8, 28.1, 45.9, 47.9, 49.1, 54.1, 72.6, 118.9, 126.8,
129.4, 130.0, 130.4, 131.2, 136.1, 165.2, 168.0, 215.8 ppm.
Chemiluminescence measurement using a 18-crown-6 ether
complex of tert-BuOK or potassium bis(methoxycarbonyl)
methanide as a base was carried out in benzene similarly to
the case of TBAF/DMSO. Complex of 18-crown-6 ether
with a base was prepared in benzene as follows.
[K3(18-crown-6)]Ct-BuOK: tert-BuOK (1 M in THF,
1.10 mL, 1.10 mmol) was added to a solution of 18-
crown-6 ether (294 mg, 1.11 mmol) in benzene (30 mL) at
room temperature under nitrogen atmosphere, and stirred
for 10 min.
IR (liquid film): 2962, 2875, 2246, 1751, 1724, 1686, cmK1
.
Mass (20 eV, m/z, %): 374 (MCC1, trace), 316 (25), 318
(10), 290 (56), 288 (15), 234 (71), 217 (14), 216 (100), 85
(23), 57 (42). HRMS (ESI): 396.1798, calcd for
C21H27NO5Na (MCNaC) 396.1787.
[K3(18-crown-6)]C(18a)K: tert-BuOK (1 M in THF,
1.10 mL, 1.10 mmol) was added to a solution of 18-
crown-6 ether (291 mg, 1.10 mmol) and dimethyl methyl-
malonate, CH3CH(CO2CH3)2 (18a) (0.16 mL, 1.2 mmol) in
benzene (30 mL) and stirred at room temperature under
nitrogen atmosphere for 10 min.
4.5.2. Chemiluminescent decomposition of a dioxetane
(2) with [K3(18-crown-6)]Ct-BuOK: isolation of 3-(1-
cyanoethenyl)benzoic acid 2,2,4,4-tetramethyl-3-oxo-
pentyl ester (11). To a solution of 5-tert-butyl-1-[3-(1-
cyanoethenyl)phenyl]-4,4-dimethyl-2,6,7-trioxabicyclo-
[3.2.0]heptane (2) (31.4 mg, 0.10 mmol) in benzene
(1 mL), a solution of [K3(18-crown-6)]Ct-BuOK (3 mL,
0.1 mmol) in benzene was added with a syringe at 25 8C
under nitrogen atmosphere for 1 min, during which
emission of orange light was observed. The reaction mixture
was poured into satd aq NH4Cl and then extracted with
AcOEt. The organic layer was washed with satd aq NaCl,
dried over anhydrous MgSO4, and concentrated in vacuo.
Chromatographic purification (silica gel) of the residue with
hexane–AcOEt (4/1–1/1) gave 11 in 14% yield.
[K3(18-crown-6)]C(18b)K: tert-BuOK (1 M in THF,
1.10 mL, 1.10 mmol) was added to a solution of 18-
crown-6 ether (291 mg, 1.10 mmol), and dimethyl malo-
nate, CH2(CO2CH3)2 (18b), (0.12 mL, 1.2 mmol) in
benzene (30 mL) and stirred at room temperature under
nitrogen atmosphere for 10 min.
[K3(18-crown-6)]C(18c)K: dimethyl chloromalonate,
ClCH(CO2CH3)2 (18c), (0.077 mL) was added to a solution
of 18-crown-6 (148 mg, 0.56 mmol), and tert-BuOK (1 M

N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
9583
4.5.3. Chemiluminescent decomposition of a dioxetane
(2) with [K318-crown-6]C(18a)K: isolation of 3-[1-
cyano-3,3-bis(methoxycarbonyl)butyl]benzoic acid
2,2,4,4-tetramethyl-3-oxopentyl ester (19). To a solution
of 5-tert-butyl-1-[3-(1-cyanoethenyl)phenyl]-4,4-dimethyl-
2,6,7-trioxabicyclo[3.2.0]heptane (2) (31.4 mg, 0.10 mmol)
in benzene (1 mL), a solution of [K3(18-crown-
6)]C(18a)K (3 mL, 0.10 mmol) in benzene was added
with a syringe at 25 8C under nitrogen atmosphere for 1 min,
during which emission of crimson light was observed. The
reaction mixture was poured into satd aq NH4Cl and then
extracted with AcOEt. The organic layer was washed with
satd aq NaCl, dried over anhydrous MgSO4, and concen-
13C NMR (125 MHz, CDCl3): dC 23.6, 23.7, 28.1, 34.4,
34.9, 45.9, 48.9, 49.1, 53.0, 53.0, 72.5, 119.2, 128.5, 129.6,
129.7, 131.3, 131.8, 135.1, 165.3, 168.3, 168.4, 215.9 ppm.
IR (liquid film): 2958, 2875, 2243, 1734, 1685 cmK1. Mass
(20 eV, m/z, %): 414 (MCK31, 1), 388 (7), 306 (23), 289
(33), 288 (100), 256 (17), 165 (21), 133 (35), 113 (68), 85
(27), 57 (64). HRMS (ESI): 468.2002, calcd for
C24H31NO7Na (MCNaC) 468.1998.
1
Compound 25 (1:1 mixture of diastereisomers). H NMR
(500 MHz, CDCl3): dH 0.97 (s, 4.5H), 0.97 (s, 4.5H), 1.16
(s, 3H), 1.38 (s, 1.5H), 1.39 (s, 1.5H), 2.43–2.50 (m, 2H),
3.50–3.57 (m, 1H), 3.75 (s, 1.5H), 3.75 (s, 1.5H), 3.78 (s,
1.5H), 3.79 (s, 1.5H), 3.84 (d, JZ8.3 Hz, 0.5H), 3.84 (d, JZ
8.3 Hz, 0.5H), 4.00–4.05 (m, 1H), 4.59 (d, JZ8.3 Hz, 1H),
7.40–7.48 (m, 2H), 7.58–7.66 (m, 2H) ppm. 13C NMR
(125 MHz, CDCl3): dC 18.4, 25.1, 26.7, 34.3, 34.4, 35.1,
35.1, 36.7, 45.6, 48.9, 53.0, 53.0, 80.3, 80.3, 105.0, 116.2,
119.4, 119.4, 127.4, 128.5, 128.5, 128.7, 128.7, 129.0,
134.3, 134.4, 137.4, 137.4, 168.4, 168.4, 168.5, 168.5 ppm.
IR (liquid film): 2960, 2892, 2243, 1736 cmK1. Mass
(20 eV, m/z, %): 445 (MC, trace), 413 (3), 373 (21), 306
(11), 289 (19), 288 (100), 143 (12), 113 (21), 85 (11), 57
(45). HRMS (ESI): 468.1983, calcd for C24H31NO7Na
(MCNaC) 468.1998.
1
trated in vacuo. H NMR spectrum of the residue showed
that 3-[1-cyano-3,3-bis(methoxycarbonyl)butyl]benzoic
acid 2,2,4,4-tetramethyl-3-oxo-pentyl ester (19) was pro-
duced exclusively. Chromatographic purification of the
residue on silica gel with CH2Cl2:hexane–AcOEt (4/5/1)
1
gave 19 as a pale yellow oil in 39.1% yield. H NMR
(500 MHz, CDCl3): dH 1.29 (s, 9H), 1.40 (s, 3H), 1.40 (s,
3H), 1.56 (s, 3H), 2.36 (dd, JZ14.7, 3.7 Hz, 1H), 2.50 (dd,
JZ14.7, 10.1 Hz, 1H), 3.76 (s, 3H), 3.77 (s, 3H), 4.12 (dd,
JZ10.1, 3.7 Hz, 1H), 4.41 (s, 2H), 7.47 (t, JZ7.8 Hz, 1H),
7.61 (broad d, JZ7.8 Hz, 1H), 7.94 (broad d, JZ7.8 Hz,
1H), 8.01 (broad s, 1H) ppm. 13C NMR (125 MHz, CDCl3):
dC 20.9, 23.6, 23.7, 28.1, 33.1, 42.0, 45.9, 49.1, 52.7, 52.9,
52.9, 72.4, 120.0, 128.4, 129.4, 129.4, 131.1, 131.8, 136.8,
165.4, 171.2, 171.4, 215.9 ppm. IR (liquid film): 2956,
2875, 2242, 1730, 1686 cmK1. Mass (20 eV, m/z, %): 402
(MCK57, 11), 376 (12), 320 (27), 303 (19), 302 (100), 270
(9), 57 (17). HRMS (ESI): 482.2143, calcd for
C25H33NO7Na (MCNaC) 482.2155.
4.5.5. Chemiluminescent decomposition of a dioxetane
(2) with [K318-crown-6]C(18c)K: isolation of 3-[1-
cyano-2,2-bis(methoxycarbonyl)cyclopropyl]benzoic
acid 2,2,4,4-tetramethyl-3-oxopentyl ester (30) and 1-{3-
[1-cyano-2,2-bis(methoxycarbonyl)cyclopropyl]phenyl}-
5-tert-butyl-4,4-dimethyl-2,6,7-trioxabicyclo-[3.2.0]hep-
tane (31). To a solution of 5-tert-butyl-1-[3-(1-cyanoethe-
nyl)phenyl]-4,4-dimethyl-2,6,7-trioxabicyclo-[3.2.0]hep-
tane (2) (31.4 mg, 0.10 mmol) in benzene (1 mL), a solution
of [K3(18-crown-6)]C(18c)K (3 mL, 0.1 mmol) in ben-
zene was added by means of a syringe at 25 8C under
nitrogen atmosphere for 1 min, during which emission of
red light was observed. The reaction mixture was poured
into satd aq NH4Cl and then extracted with AcOEt. The
organic layer was washed with satd aq NaCl, dried over
4.5.4. Chemiluminescent decomposition of a dioxetane
(2) with [K318-crown-6]C(18b)K: isolation of 3-[1-
cyano-3,3-bis(methoxycarbonyl)propyl]benzoic acid
2,2,4,4-tetramethyl-3-oxopentyl ester (24) and 5-tert-
butyl-1-{3-[1-cyano-3,3-bis(methoxycarbonyl)propyl]-
phenyl}-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane
(25). To a solution of 5-tert-butyl-1-[3-(1-cyanoethenyl)-
phenyl]-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (2)
(31.4 mg, 0.10 mmol) in benzene (1 mL), a solution of
[K3(18-crown-6)]C(18b)K (3 mL, 0.1 mmol) in benzene
was added with a syringe at 25 8C under nitrogen
atmosphere for 1 min, during which emission of red light
was observed. The reaction mixture was poured into satd aq
NH4Cl and then extracted with AcOEt. The organic layer
was washed with satd aq NaCl, dried over anhydrous
1
anhydrous MgSO4, and concentrated in vacuo. H NMR
spectrum of the residue showed that 3-[1-cyano-2,2-
bis(methoxycarbonyl)cyclopropyl]benzoic acid 2,2,4,4-tet-
ramethyl-3-oxopentyl ester (30) (71%) and was produced
along with 1-{3-[1-cyano-2,2-bis(methoxycarbonyl)pro-
pyl]phenyl}-5-tert-butyl-4,4-dimethyl-2,6,7-trioxabicyclo-
[3.2.0]heptane (31) (29%). Chromatographic purification of
the residue on silica gel with hexane–AcOEt (4/1–1/1) gave
30 as a colorless viscous oil in 52% yield and 31 as a
colorless oil in 23% yield.
1
MgSO4, and concentrated in vacuo. H NMR spectrum of
the residue showed that 3-[1-cyano-3,3-bis(methoxycarbo-
nyl)propyl]benzoic acid 2,2,4,4-tetramethyl-3-oxopentyl
ester (24) (39%) was produced along with 5-tert-butyl-1-
{3-[1-cyano-3,3-bis(methoxycarbonyl) propyl]phenyl}-4,4-
dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (25) (28%).
Chromatographic purification of the residue with hexane–
AcOEt (4/1–1/1) gave 24 as a colorless viscous oil in 26.9%
yield and 25 as a colorless oil in 16.2% yield.
1
Compound 30. H NMR (400 MHz, CDCl3): dH 1.30 (s,
9H), 1.39 (s, 3H), 1.40 (s, 3H), 2.41 (t, JZ6.2 Hz, 1H), 2.58
(d, JZ6.2 Hz, 1H), 3.39 (s, 3H), 3.92 (s, 3H), 4.40 (s, 2H),
7.45 (t, JZ7.8 Hz, 1H), 7.63 (d with fine coupling, JZ
7.8 Hz, 1H), 7.94–7.98 (m, 2H) ppm. 13C NMR (125 MHz,
CDCl3): dC 22.8, 23.6, 23.7, 27.5, 28.1, 41.9, 45.9, 49.1,
53.1, 53.7, 72.5, 117.7, 129.1, 129.7, 130.4, 130.8, 131.2,
133.5, 164.1, 165.1, 165.7, 215.8 ppm. IR (liquid film):
2958, 2875, 2240, 1746, 1731, 1685 cmK1. Mass (20 eV,
m/z, %): 386 (MCK57, 17), 360 (23), 305 (14), 304 (74),
1
Compound 24. H NMR (500 MHz, CDCl3): dH 1.29 (s,
9H), 1.40 (s, 3H), 1.40 (s, 3H), 2.48 (t, JZ7.8 Hz, 2H), 3.57
(t, JZ7.8 Hz, 1H), 3.75 (s, 3H), 3.79 (s, 3H), 4.04 (t, JZ
7.8 Hz, 1H), 4.41 (s, 2H), 7.48 (t, JZ7.8 Hz, 1H), 7.57 (d
with fine coupling, JZ7.8 Hz, 1H), 7.93–7.98 (m, 2H) ppm.

9584
N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
287 (16), 286 (100), 272 (12), 57 (14). HRMS (ESI):
466.1828, calcd for C24H31NO7Na (MCNaC) 466.1842.
(32), 242 (100), 169 (30), 73 (38), 57 (46). HRMS (ESI):
422.2116, calcd for C23H33NO3SiNa (MKN2CNaC)
422.2127.
1
Compound 31 (1:1 mixture of diastereoisomers). H NMR
(500 MHz, CDCl3): dH 0.96 (s, 9H), 1.16 (s, 3H), 1.37 (s,
1.5H), 1.39 (s, 1.5H), 2.38 (d, JZ6.1 Hz, 0.5H), 2.39 (d, JZ
6.1 Hz, 0.5H), 2.58 (d, JZ6.1 Hz, 0.5H), 2.59 (d, JZ
6.1 Hz, 0.5H), 3.36 (s, 3H), 3.83 (d, JZ8.2 Hz, 1H), 3.91 (s,
1.5H), 3.91 (s, 1.5H), 4.58 (d, JZ8.2 Hz, 1H), 7.38–7.46
(m, 2H), 7.60–7.72 (m, 2H) ppm. 13C NMR (125 MHz,
CDCl3): dC 18.4, 18.4, 22.8, 22.9, 25.0, 25.1, 26.7, 26.7,
27.7, 27.8, 36.6, 41.9, 41.9, 45.6, 53.0, 53.1, 53.7, 80.2,
80.3, 105.0, 116.0, 116.0, 117.8, 117.9, 128.4, 128.5, 128.9,
129.4, 129.5, 129.8, 130.1, 130.5, 130.5, 137.0, 137.1,
164.1, 164.1, 165.9 ppm. IR (liquid film): 2961, 2241,
1743 cmK1. Mass (20 eV, m/z, %): 411 (MCK32, 2), 386
(14), 360 (23), 327 (11), 305 (13), 304 (70), 287 (19), 286
(100), 272 (12), 57 (17). HRMS (ESI): 466.1828, calcd for
C24H29NO7Na (MCNaC) 466.1842.
Acknowledgements
The authors gratefully acknowledge financial assistance
provided by a Grant-in Aid (No. 14540506 and No.
15550043) for Scientific Research by the Ministry of
Education, Culture, Sports, Science, and Technology,
Japan.
References and notes
1. Schaap, A. P.; Chen, T.-S.; Handley, R. S.; DeSilva, R.; Giri,
B. P. Tetrahedron Lett. 1987, 28, 1155–1158.
4.5.6. 5-tert-Butyl-1-[3-(3-cyano-4,5-dihydro-5,5-diphe-
nyl-3H-pyrazole-3-yl)phenyl]-4,4-dimethyl-2,6,7-tri-
2. McCapra, F. J. Photochem. Photobiol. A: Chem. 1990, 15,
21–28.
oxabicyclo[3.2.0]heptane (35a).
A
solution of
3. McCapra, F. In Mechanism in Chemiluminescence and
Bioluminescence-Unfinished Business, in Bioluminescence
and Chemiluminescence; Hastings, J. W., Kricka, L. J.,
Stanley, P. E., Eds.; Wiley: New York, 1996; pp 7–15.
4. Recent reports: (a) Matsumoto, M.; Hamaoka, K.; Takashima,
Y.; Yokokawa, M.; Yamada, K.; Watanabe, N.; Ijuin, H. K.
Chem. Commun. 2005, 808–810. (b) Watanabe, N.;
Nagamatsu, K.; Mizuno, T.; Matsumoto, M. Luminescence
2005, 20, 63–72. (c) Watanabe, N.; Ichikawa, M.; Ono, A.;
Murakami, H.; Matsumoto, M. Chem. Lett. 2005, 34, 718–719.
(diphenyl)diazomethane (0.50 mmol: prepared from benzo-
phenone hydrazone and HgO in hexane–ethanol in the
presence of catalytic amount of EtONa and used crude
product) in acetonitrile (0.5 mL) was added to a solution of
5-tert-butyl-1-[3-(1-cyanoethenyl)phenyl]-4,4-dimethyl-
2,6,7-trioxabicyclo[3.2.0]heptane (2) (92 mg, 0.29 mmol)
and 2,6-di-tert-butyl-4-methylphenol (2 mg) in acetonitlile
(3 mL) at room temperature under nitrogen atmosphere and
stirred for 2 h. The reaction mixture was concentrated in
vacuo and chromatographed on silica gel with hexane–
AcOEt (10/1–5/1) to give 142 mg of 35a as pale
yellow granules in 95.2% yield (45:55 mixture of
diastereoisomers).
¨
5. Beck, S.; Koster, H. Anal. Chem. 1990, 62, 2258–2270.
¨
6. Adam, W.; Reinhardt, D.; Saha-Moller, C. R. Analyst 1996,
121, 1527–1531.
7. Matsumoto, M. J. Photochem. Photobiol. C: Photochem. Rev.
2004, 5, 27–53.
4.5.7. 5-tert-Butyl-1-[3-(3-cyano-4,5-dihydro-5-tri-
methylsilyl-3H-pyrazole-3-yl)phenyl]-4,4-dimethyl-2,6,
7-trioxabicyclo[3.2.0]heptane (35b). A solution of (tri-
methylsilyl)diazomethane (2.0 M in hexane, 1 mL, 2 mmol)
was added to a solution of 5-tert-butyl-1-[3-(1-cyano-
ethenyl)phenyl]-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]-
heptane (2) (52.4 mg, 0.17 mmol) and 2,6-di-tert-butyl-4-
methylphenol (2 mg) in acetonitlile (2 mL) at room
temperature under nitrogen atmosphere and stirred for
1.5 h. The reaction mixture was concentrated in vacuo and
chromatographed on silica gel with hexane–AcOEt (10/1–5/
1) to give 41.4 mg of 35b as colorless viscous oil in 58.0%
yield (1:1 mixture of diastereoisomers). 1H NMR
(500 MHz, CDCl3): dH 0.22 (s, 4.5H), 0.23 (s. 4.5H), 0.57
(dd, JZ10.7, 5.8 Hz, 0.5H), 0.59 (dd, JZ10.7, 5.8 Hz,
0.5H), 0.96 (s, 9H), 1.16 (s, 3H), 1.39 (s, 3H), 1.59 (dd, JZ
5.8, 4.6 Hz, 0.5H), 1.60 (dd, JZ5.8, 4.6 Hz, 0.5H), 1.66 (dd,
JZ10.7, 4.6 Hz, 0.5H), 1.69 (dd, JZ10.7, 4.6 Hz, 0.5H),
3.83 (d, JZ8.1 Hz, 1H), 4.58 (d, JZ8.1 Hz, 1H), 7.35–7.43
(m, 2H), 7.49–7.55 (m, 2H) ppm. 13C NMR (125 MHz,
CDCl3): dC K2.08, 17.5, 18.4, 19.9, 20.2, 21.4, 21.5, 25.0,
25.1, 26.7, 36.7, 45.6, 80.2, 80.2, 104.9, 104.9, 116.3, 116.3,
121.7, 121.8, 125.1, 125.4, 127.1, 127.2, 127.4, 127.4,
128.4, 136.7, 137.6, 137.7 ppm. IR (liquid film): 2961,
2897, 2232 cmK1. Mass (m/z, %): 399 (MCKN2, 3), 343
(20), 342 (15), 314 (10), 260 (21), 259 (19), 244 (13), 243
8. A part of this work has been reported as preliminary
communications.9
9. (a) Matsumoto, M.; Mizuno, T.; Watanabe, N. Chem.
Commun. 2003, 483–484. (b) Matsumoto, M.; Mizuno, T.;
Watanabe, N. Tetrahedron Lett. 2004, 45, 3779–3782.
10. 1-Aryl-5-tert-butyl-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]-
heptane has been reported to provide a dioxetane skeleton with
high thermal stability.11
11. Matsumoto, M.; Murakami, H.; Watanabe, N. Chem.
Commun. 1998, 2319–2320.
12. Dihydrofurans (5) were synthesized easily from the corre-
sponding 7-bromophenyl-2,2,4,4-tetramethyl-6-oxaheptan-3-
one according to a procedure reported for related dihydro-
furans [4b].
13. TBAF has been widely used as a strong base for carbanion-
participated reactions in an aprotic solvent.14
14. Clark, J. H. Chem. Rev. 1980, 80, 429–452. Paquette, L. A.,
Ed.; Encyclopedia of Reagents for Organic Synthesis; Wiley:
New York, 1995; Vol. 7, pp 4728–4732.
15. Chemiluminescence efficiency (FCL) was estimated by the use
of a reported value for 3-(20-spiroadamantane)-4-methoxy-4-
(30-tert-butyldimethylsiloxy)phenyl-1,2-dioxetane
standard.16
as
a
16. Trofimov, A. V.; Mielke, K.; Vasil’ev, R. F.; Adam, W.
Photochem. Photobiol. 1996, 63, 463–467.
17. McCapra, F. Tetrahedron Lett. 1993, 34, 6941–6944.

N. Watanabe et al. / Tetrahedron 61 (2005) 9569–9585
18. Matsumoto, M.; Suganuma, H.; Azami, M.; Aoshima, N.; 22. Rate constant reported in Ref. 9b is revised.
9585
Mutoh, H. Heterocycles 1995, 41, 2419–2422.
19. Adam, W.; Trofimov, A. V. J. Org. Chem. 2000, 65,
6474–6978.
23. Joucla, M.; Le Brun, J. Tetrahedron Lett. 1985, 26,
3001–3004.
24. Le Menn, J.-C.; Tallec, A.; Sarrazan, J. Can. J. Chem. 1991,
69, 761–767.
20. Quinine bisulfate was used as the fluorescence standard.
21. Isaacs, N. S. Physical Organic Chemistry; Longman Scientific
Technical: UK, 1987; pp 220–254.