Base-induced chemiluminescent decomposition of stereoisomeric 5-tert-butyl-1-(3-tert-butyldimethylsiloxy)phenyl-4,4-dimethyl-3-phenyl- 2,6,7-trioxabicyclo[3.2.0]heptanes and their related dioxetanes

Article abstract of DOI:10.1016/S0040-4039(01)00171-X

Singlet oxygenation of 4-tert-butyl-5-(3-tert-butyldimethylsiloxy)phenyl-3,3-dimethyl-2-phenyl- 2,3-dihydrofuran (3a) in dichloromethane at 0°C gave a 95:5 mixture of stereoisomeric dioxetanes (anti-1a) and (syn-1a). The isomer (anti-1a) was more stable thermally than syn-1a. On treatment with tetrabutylammonium fluoride in DMSO or acetonitrile, both isomeric dioxetanes emitted intense blue light. Chemiluminescence efficiency (Φ_CL) of anti-1a was considerably higher than that of syn-1a; nevertheless, both of them gave the very same couple of two carbonyl fragments (2a). A methyl-analog (1b) was also synthesized and its chemiluminescent properties were examined.

Full text of DOI:10.1016/S0040-4039(01)00171-X

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 2349–2352
Base-induced chemiluminescent decomposition of stereoisomeric
5-tert-butyl-1-(3-tert-butyldimethylsiloxy)phenyl-4,4-dimethyl-
3-phenyl-2,6,7-trioxabicyclo[3.2.0]heptanes and their
related dioxetanes
Masakatsu Matsumoto,* Yoshihiro Ito, Jyunya Matsubara, Toshimitsu Sakuma, Yasuko Mizoguchi
and Nobuko Watanabe
Department of Materials Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1205, Japan
Received 25 December 2000; accepted 26 January 2001
Abstract—Singlet oxygenation of 4-tert-butyl-5-(3-tert-butyldimethylsiloxy)phenyl-3,3-dimethyl-2-phenyl-2,3-dihydrofuran (3a) in
dichloromethane at 0°C gave a 95:5 mixture of stereoisomeric dioxetanes (anti-1a) and (syn-1a). The isomer (anti-1a) was more
stable thermally than syn-1a. On treatment with tetrabutylammonium fluoride in DMSO or acetonitrile, both isomeric dioxetanes
emitted intense blue light. Chemiluminescence efficiency (FCL) of anti-1a was considerably higher than that of syn-1a;
nevertheless, both of them gave the very same couple of two carbonyl fragments (2a). A methyl-analog (1b) was also synthesized
and its chemiluminescent properties were examined. © 2001 Elsevier Science Ltd. All rights reserved.
Dioxetanes substituted with an aromatic electron donor
such as an aryl-O− moiety display chemically initiated
electron exchange luminescence (CIEEL).1,2 The phe-
nomenon has received a great deal of attention from
the viewpoint of mechanistic interests related to bio-
luminescence 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.3 How-
ever, a study of the structural relation of the CIEEL-
active dioxetanes to their chemiluminescence efficiency
(FCL) is still lacking, though there have been several
reports on the relationship between the aryl-O− moiety
on dioxetanes and their chemiluminescent properties.4–7
One difficulty hampering such a study is how to evalu-
ate the difference in the participation of another car-
bonyl fragment concomitantly formed with an emitter
between the CIEEL-active dioxetanes to be compared.
We attempted here to examine the CIEEL decay of a
pair of stereoisomeric dioxetanes affording the very
same couple of two carbonyl fragments as a rudimen-
tary study on the relationship between their structure
and chemiluminescence efficiency (FCL), while avoiding
the difficulty mentioned above.
Our choice of such stereoisomeric dioxetanes were the
anti-form of 5-tert-butyl-1-(3-tert-butyldimethylsiloxy)-
phenyl-4,4-dimethyl-3-phenyl-2,6,7-trioxabicyclo[3.2.0]-
heptane (anti-1a) and its syn-isomer (syn-1a), both of
which decompose by desilylation to afford the same
couple of an emitter and the remaining aliphatic car-
bonyl fragment which join together, i.e. a ketoester
(2a): the anti-1a possesses 3-phenyl lying anti to the
dioxetane ring, and syn-1a possesses the opposite stereo-
chemistry. When a dihydrofuran (3a) (300 mg) and a
catalytic amount of tetraphenylporphin (TPP) were
irradiated with a 940-W Na lamp in dichloromethane
(15 mL) under an oxygen atmosphere at 0°C for 1 h,
1,2-addition of singlet oxygen occurred to give a 95:5
mixture of anti-1a and syn-1a, which were separated by
O O
O O
O O
*
t-Bu
t-Bu
TBAF
t-Bu
TBAF
t-BuMe2SiO
t-BuMe2SiO
O
O
O
O
R
2
R
R
a: R = Ph
b: R = Me
syn-1
anti-1
Keywords: singlet oxygenation; 1,2-dioxetane; stereoisomer; CIEEL.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00171-X

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M. Matsumoto et al. / Tetrahedron Letters 42 (2001) 2349–2352
silica gel chromatography. Their structures were deter-
aprotic solvent such as DMSO and acetonitrile; their
desilylation with fluoride affords an unstable phenolate-
substituted dioxetane, which decomposes rapidly by the
CIEEL process. It has been reported very recently for
the fluoride-triggered CIEEL of 3-adamantylidene-4-(3-
tert-butyldimethylsiloxyphenyl)-4-methoxy-1,2-dioxe-
tane (6) that the CIEEL decay rate depends on both the
TBAF concentration and the substrate concentration,
though it follows pseudo-first-order kinetics indepen-
dent of the TBAF concentration when an excess of
fluoride concentration is used.11 To simplify the analy-
sis of fluoride-induced decomposition of the present
dioxetanes (1) we used also a large excess of TBAF.
When solutions of anti-1a and syn-1a in DMSO (1.0×
10−5 mol dm−3, 1 mL) were added to TBAF solutions in
DMSO (1.0×10−2 mol dm−3, 2 mL) at 25°C, the dioxe-
tanes (anti-1a) and (syn-1a) emitted intense blue light
with chemiluminescent properties, as shown in Table 2.
1H NMR analysis showed that both spent reaction
mixtures from anti-1a and syn-1a included exclusively a
1
1
mined by H NMR, 13C NMR, H–1H COSY, 13C–1H
COSY, NOE, IR, and mass spectral analysis.8 Similar
singlet oxygenation of a furan bearing a 2-methyl (3b)
also gave selectively the corresponding mixture of
stereoisomeric dioxetanes (anti-1b:syn-1b=65:35).9
Both of the stereoisomeric dioxetanes (anti-1) and (syn-
1) decomposed exclusively to the same ketoester (4) in
hot toluene. These decompositions followed first-order
kinetics and their rates were measured at 90–120°C in
toluene-d8 or p-xylene-d10 to estimate their activation
parameters. The results summarized in Table 1 show
that all dioxetanes (anti- and syn-1a, anti- and syn-1b)
are thermally persistent, and that the anti-isomers are
more stable than the parent dioxetane (5),10 while the
syn-isomers show reverse tendency.
The siloxyphenyl-substituted dioxetanes are triggered
with tetrabutylammonium fluoride (TBAF) in an
Table 1. Thermal decomposition of dioxetanes (1)a
1O2
∆
anti-1
O O
O O
t-Bu
t-Bu
t-Bu
TBAF
t-BuMe2SiO
O
O
O
t-BuMe2SiO
O
1O2
syn-1
∆
R
R
2
R
3
4
a: R = Ph
b: R = Me
O O
O O
t-Bu
t-BuMe2SiO
t-BuMe2SiO
MeO
O
6
5
Dioxetane
DH‡ (kcal mol−1
)
DS‡ (cal K−1 mol−1
)
DG‡ (kcal mol−1
)
t1/2 at 25°C (y)
Anti-1a
Syn-1a
Anti-1b
Syn-1b
5b
31.4
28.6
28.8
25.8
27.1
5.1
0.5
−1.5
−9.4
−6.8
29.9
28.5
29.2
28.6
29.1
87.6
8.5
25.2
8.6
22.1
a Thermal decomposition of 1 was carried out in toluene-d8 or xylene-d10 at 90–120°C, and ratios 1 versus 4 were measured by 1H NMR.
b Ref. 10.
Table 2. TBAF-induced chemiluminescent decomposition of (1a) and (1b) in DMSO and acetonitrilea,b,c
Dioxetane
DMSO
FS
Acetonitrile
FCL
umax (nm)
FCL
t1/2 (s)
umax (nm)
FS
t1/2 (s)
Anti-1a
Syn-1a
Anti-1b
Syn-1b
5
466
466
466
466
466
0.18
0.12
0.25
0.21
0.20
0.58
0.39
0.76
0.64
0.63d
4.0
1.8
9.8
16
471
471
470
470
469
0.075
0.052
0.077
0.077
0.075
0.29
0.20
0.43
0.43
0.31d
11
6.4
38
80
19
4.6
a Solutions of 1a and 1b in DMSO or acetonitrile (1.0×10−5 mol dm−3, 1 mL) were added to TBAF solutions in DMSO or acetonitrile (1.0×10−2
mol dm−3, 2 mL) at 25°C.
b Fluorescence quantum yields (FF) of 2 generated from 4 on treatment with TBAF in DMSO or acetonitrile at 25°C were as follows: 2a in
DMSO=0.31, 2a in acetonitrile=0.26, 2b in DMSO=0.33, 2b in acetonitrile=0.18. Yields (FS) of singlet-excited ester (2) were estimated in
accord with an equation FS=FCL/FF.
c Chemiluminescent yields (FCL) were based on the reported value for 6: FCL=0.29 in DMSO (Ref. 11).
d Yields (FS) of a singlet-excited ester produced from 5 were estimated by the use of reported values for FF of the ester: FF in DMSO=0.32,
FF in acetonitrile=0.24 (Ref. 14).

M. Matsumoto et al. / Tetrahedron Letters 42 (2001) 2349–2352
2351
O
O O
O O
O O
t-Bu
ET
t-Bu
t-Bu
O
O
R
O
O
O
O
O
O
O
R
9
R
R
direct
O
8
7
t-Bu
10
BET
O O
*
O
O
O
O
t-Bu
t-Bu
t-Bu
Ground state
R
H
O
O
O
O
hν
O
H
R
R
2
syn-9
anti-9
Scheme 1.
which the ketyl radical functionality is proximate to the
ester carbonyl, and its annihilation by a BET from the
ketyl radical part to the ester carbonyl results in a
singlet-excited ester (2). This chemiexcitation channel
has very recently been suggested by Adam15 to compete
with another channel giving the ground state product,
in which BET occurs from the ketyl radical to the
phenoxy group when these two groups approach each
other as 10 by conformational motion in 9. Thus, FS
reflects the efficiency of BET (giving an excited state),
which would change as the structure of a radical ion
pair changes. In the case of 1, since a steric repulsion
between the ketyl radical and a substituent R (=Ph or
Me) should be larger for a diradical (syn-9) from syn-1
than for anti-9 from anti-1, the ketyl radical of syn-9
should separate from the ester carbonyl more easily
than anti-9 so that syn-1 gives light less effectively than
anti-1.
free form of 4a as a decomposition product. The
fluoride-induced decomposition of 1b was also carried
out and the results are summarized in Table 2.
Both chemiluminescent spectra from anti-1a and syn-1a
were in good agreement not only with that of 6, whose
emitter has been established to be an oxy-anion of
methyl m-hydroxybenzoate,11 but also with the fluores-
cent spectrum of an oxy-anion of ketoester (2a) gener-
ated from
a
silyl-protected ketoester (4a) in
TBAF/DMSO or acetonitrile. Therefore, an oxy-anion
of the m-hydroxybenzoate moiety in 2a is unquestion-
ably the emitter for both the CIEEL decay of anti-1a
and syn-1a. Based on these results, yields of singlet
chemiexcitation (FS=FCL/FF) for anti-1a and syn-1a
were estimated from their FCL and fluorescence quan-
tum yield (FF) of 2a, which was measured at 0.31 in
TBAF/DMSO and 0.26 in TBAF/acetonitrile. The
results in Table 2 reveal that the chemiluminescent yield
(FCL) as well as the yield (FS) of singlet-excited 2a are
higher for anti-1a than for syn-1a both in DMSO and
in acetonitrile. A similar tendency in FS was also
observed for isomeric methyl-analogs (anti-1b) and
(syn-1b) in DMSO, as shown in Table 2.
The difference in FS between stereoisomers (anti-1) and
(syn-1) is most likely rationalized well by the ET–BET
chemiexcitation mechanism, as described above. How-
ever, the CT-induced direct chemiexcitation mechanism
cannot be ruled out because the stereochemistry of the
starting dioxetanes (1) is retained by means of a tetra-
hydrofuran ring in a transition state (8), which would
influence more or less the yield of singlet-excited state
when it decomposes directly to give 2.
The present results provide the first example that
stereoisomeric dioxetanes, giving the same decomposi-
tion product, emit light with the different efficiencies
for the CIEEL-decay. The phenomenon suggests that
the stereochemistry of a starting dioxetane is reflected
in the chemiexcitation process, though it cannot be
used at present to distinguish between two the main
mechanistic alternatives proposed for the CIEEL chemi-
excitation process, namely, a stepwise electron trans-
fer (ET)–electron back-transfer (BET) process1,11–15 and
charge transfer (CT)-induced concerted cleavage of
dioxetane leading to direct chemiexcitation.16,17
Acknowledgements
The authors gratefully acknowledge financial assistance
provided by a grant-in-aid for Science Research by the
Ministry of Education, Science, Sports, and Culture of
the Japanese Government.
As illustrated in Scheme 1, a pertinent feature of the
CIEEL process for a phenolate-substituted dioxetane,
such as 7 produced from 1, is that the intramolecular
ET from the phenolate moiety to the peroxide bond
causes OꢀO bond cleavage and the reaction proceeds
through a transition state as 8, irrespective of the
stepwise ET–BET or the concerted process. For the
ET–BET process, 8 leads to a radical ion pair (9), in
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