Synthesis of 1-(3-tert-butyldimethylsiloxy)phenyl-5,5-dimethyl-2,7,8-trioxabicyclo[4.2.0] octanes: New dioxetanes giving high chemiexcitation yields in thermolysis and in fluoride-induced CIEEL-decay

Article abstract of DOI:10.1016/S0040-4039(02)00052-7

Dioxetanes with annelated six-membered ring, 1-(3-tert-butyldimethylsiloxy)phenyl-5,5-dimethyl-2,7,8-trioxabicyclo[4.2.0] octanes (2a-2c) were synthesized by singlet oxygenation of the corresponding aryl-substituted dihydropyrans (3). Thermolysis of 2a-2c gave the corresponding ketoesters (5a-5c) as a normal decomposition product together with a considerable amount (23-26%) of ester (6) derived from Norrish type I reaction of the triplet-excited ester (5). On the other hand, treatment with tetrabutylammonium fluoride (TBAF) in DMSO induced rapid decomposition of 2 to emit blue light in high chemiexcitation yield (72-75%) of the oxyanion of a ketoester (10). These results show that the chemiexcitation efficiency of dioxetanes (2) was higher than that of their five-membered ring analog (1) not only for thermolysis and but also for the base-induced CIEEL.

Full text of DOI:10.1016/S0040-4039(02)00052-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 1523–1527
Synthesis of 1-(3-tert-butyldimethylsiloxy)phenyl-
5,5-dimethyl-2,7,8-trioxabicyclo[4.2.0]octanes: new dioxetanes
giving high chemiexcitation yields in thermolysis and in
fluoride-induced CIEEL-decay
Masakatsu Matsumoto,* Junko Murayama, Masao Nishiyama, Yasuko Mizoguchi,
Toshimitsu Sakuma and Nobuko Watanabe
Department of Materials Science, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1205, Japan
Received 5 December 2001; accepted 28 December 2001
Abstract—Dioxetanes with annelated six-membered ring, 1-(3-tert-butyldimethylsiloxy)phenyl-5,5-dimethyl-2,7,8-trioxabicy-
clo[4.2.0]octanes (2a–2c) were synthesized by singlet oxygenation of the corresponding aryl-substituted dihydropyrans (3).
Thermolysis of 2a–2c gave the corresponding ketoesters (5a–5c) as a normal decomposition product together with a considerable
amount (23–26%) of ester (6) derived from Norrish type I reaction of the triplet-excited ester (5). On the other hand, treatment
with tetrabutylammonium fluoride (TBAF) in DMSO induced rapid decomposition of 2 to emit blue light in high chemiexcitation
yield (72–75%) of the oxyanion of a ketoester (10). These results show that the chemiexcitation efficiency of dioxetanes (2) was
higher than that of their five-membered ring analog (1) not only for thermolysis and but also for the base-induced CIEEL. © 2002
Elsevier Science Ltd. All rights reserved.
Rather simple dioxetanes with annelated six-membered
rings have been known to be far less stable thermally
than their analogs with annelated five- or seven-mem-
bered rings.1–6 On the other hand, it has very recently
been reported for a dioxetane with annelated five-mem-
bered ring (1) and related dioxetanes that the steric
interaction of a bulky tert-butyl group at the 5-position
with two methyls at the 4-position should improve
markedly the thermal persistency of the peroxide
ring.7,8 We report here that (a) this substitution pattern
is also very effective to design a thermally stable dioxe-
tane with an annelated six-membered ring, and (b) the
thus-realized dioxetanes9–12 namely, 6-tert-butyl-1-(3-
tert-butyldimethylsiloxy)phenyl-5,5-dimethyl-2,7,8-tri-
oxabicyclo[4.2.0]octane (2a) and its 6-isopropyl- and
6-(1,1-dimethyl-2-phenylethyl)- derivatives (2b, 2c)
exhibit chemiexcitation more effectively than their five-
membered ring analog (1) not only for thermolysis but
also for base-induced intramolecular CIEEL (chemi-
cally initiated electron exchange luminescence).13,14
R
R
O O
O O
a: R = Me
b: R = H
c: R = -CH2Ph
t-BuMe2SiO
t-BuMe2SiO
t-BuMe2SiO
O
O
2
O
1
3
O
R
O
O
O O
H(D)
t-BuMe2SiO
t-BuMe2SiO
t-BuMe2SiO
O
O
O
4
5
6
Keywords: singlet oxygenation; 1,2-dioxetane; Norrish type I decomposition; CIEEL.
* Corresponding author. E-mail: matsumo@chem.kanagawa-u.ac.jp
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00052-7

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M. Matsumoto et al. / Tetrahedron Letters 43 (2002) 1523–1527
A dihydropyran (3a) (100 mg) and a catalytic amount
of tetraphenylporphin (TPP) were irradiated with a 940
W Na lamp in CH2Cl2 (5 mL) under an O2 atmosphere
at 0°C for 9 h. It should be noted that the singlet
oxygenation of 3a proceeded far more slowly than in
the case to produce 1 from the corresponding dihydro-
furan, and a substantial reaction did not take place at
−78°C. After the irradiation, the photolysate was chro-
matographed on silica gel and eluted with hexane–ether
(30:1) to give a dioxetane (2a) as an oil in 74% yield.
moiety in ketoesters (5) should occur to produce ester
(6) together with radical fragments leading to 7–9, as
illustrated in Scheme 1, where a plausible decomposi-
tion pathway of 2c is shown as a representative. In
analogy with di-tert-butyl ketone, which undergoes
Norrish type I photodecomposition very effectively
(F=0.71),18 the type I decomposition of a branched-
alkyl ketone moiety of 5 at an excited state(s) would
proceed very effectively. Thus, thermolysis of 2a–2c in
toluene can be reasonably assumed to produce an
excited carbonyl (5a–5c) with an efficiency of 31–37%,
based on the yields of 6. Considering that (a) thermoly-
sis of a dioxetane produces in general a triplet-excited
carbonyl fragment predominantly, and (b) the type I
process of di-tert-butyl ketone has been reported to
occur much more rapidly from the triplet state than the
singlet excited state,18 the type I reaction producing 6 is
thought to be attributed predominantly to the triplet
excited state of 5. On the other hand, a keto-ester (4)
was a sole product formed from a five-membered ring
analog (1) on thermolysis in hot toluene as reported,7
though 4 possesses a di-tert-alkyl ketone moiety simi-
larly to 5a. This fact suggests that a five-membered ring
analog (1) produces an excited ketoester (4) far less
effectively on thermolysis than a six-membered analog
(2). It is noteworthy that the thermal decomposition of
2a in toluene was accompanied with light emission
(umax=408 nm, F=1.4×10−4), which is presumably
derived from the singlet-excited ketone moiety of 5a,19–21
while a similar thermolysis of 1 gave little light. Conclu-
sively, the present results reveal that dioxetane with
fused six-membered ring (2) decomposes thermally to
produce an excited ketoester (5), which undergoes type
I decomposition, far more effectively than the five-
membered ring analog (1).
1
The structure of dioxetane (2a) was determined by H,
13C NMR, IR, and HRMass spectral analysis.15 Isopro-
pyl- (2b) and 1,1-dimethyl-2-phenylethyl-analog (2c)
were similarly synthesized from the corresponding dihy-
dropyrans (3b) and (3c) in 85 and 58% yield,
respectively.
A dioxetane (2a) was as stable thermally as the fused
five-membered ring dioxetane (1): DG‡=29.3 kcal
mol−1, t1/2 at 25°C=28.9 y for 2a, while DG‡=29.1 kcal
mol−1, t1/2 at 25°C=22.1 y for 1.7 However, features of
the thermolysis for 2 were markedly different from
those for 1, which affords ketoester (4) exclusively as
the normal decomposition product.7 When the thermol-
ysis of dioxetane (2a) was carried out in hot toluene,
the expected normal product (5a) was produced in 74%
yield along with a considerable amount (26%) of the
3-methylbutyl ester of m-siloxybenzoic acid (6). The
other dioxetanes (2b, 2c) also decomposed thermally to
give the corresponding ketoesters (5b, 5c) together with
6 (5b:6=77:23, and 5c:6=78:22). All reaction mixtures
after the thermolysis of dioxetanes (2a–2c) included
1,2-diphenylethane (7), which should be a coupling
product of benzyl radicals. In addition to these prod-
ucts, thermolysis of 2c gave 2-methylpropylbenzene (8)
and 2,2-dimethyl-1,3-diphenylpropane (9). Both prod-
ucts (8 and 9) should be derived from a 1,1-dimethyl-2-
phenylethyl fragment produced concomitantly with 6,
though the corresponding products derived from a tert-
butyl fragment for 2a or isopropyl fragment for 2b were
scarcely detected. It should be noted here that (a)
thermolysis of 2a–2c in toluene-d8 gave a 3-deuterio-3-
methylbutyl ester (deuterio-6) in place of 6, and (b)
esters (5a–5c) were stable and did not undergo any
decomposition in hot toluene.
A siloxyphenyl-substituted dioxetane is triggered with
tetrabutylammonium fluoride (TBAF) in aprotic sol-
vent such as DMSO and acetonitrile; its 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 process of a siloxyphenyl-sub-
stituted dioxetane that the CIEEL-decay rate of dioxe-
tane follows pseudo-first-order kinetics independent of
the TBAF concentration when an excess of fluoride
concentration is used.22 To simplify the analysis of
fluoride-induced decomposition of the present dioxe-
The results described above suggest strongly that Nor-
rish type I reaction16,17 of a branched-alkyl ketone
CH2Ph
Ph-CH3
8
CO
CH2Ph
*
Ph
Ph
CH2Ph
O
O
∆
Type I
9
YO
2c
O
PhCH2
Ph
Ph
O
7
5c
6
YO
O
Ph-CH3
Y = t-BuMe2Si-
Scheme 1.

M. Matsumoto et al. / Tetrahedron Letters 43 (2002) 1523–1527
1525
tanes (2), we also used a large excess of TBAF. When
solutions of 2a–2c in DMSO (1.0×10−6 mol dm−3, 1
mL) were added to TBAF solutions in DMSO (1.0×
10−3 mol dm−3, 2 mL) at 25°C, the dioxetanes (2a–2c)
emitted intense blue light. The results summarized in
Table 1 show that the present dioxetanes (2a–2c) afford
light more effectively than their five-membered ring
analog (1) in DMSO. The chemiluminescence spectra
for 2a–2c coincided with fluorescence spectra for the
oxyanions (10) formed from 5 on treatment with TBAF
in DMSO. Fluorescence efficiency (Ffl) of the authentic
emitters (10a–10c) was observed to differ little from
that of the authentic emitter for 1 (Scheme 2).23 These
results show that the singlet-chemiexcitation yield (Fs=
F
CIEEL/Ffl) from dioxetanes with an annelated six-mem-
bered ring (2a–2c) is higher than that of their
five-membered ring analog (1) for fluoride-induced
CIEEL-decay in DMSO (Table 1).
The present results show that dioxetanes with an
annelated six-membered ring (2) cause chemiexcitation
more effectively than the analog (1) with an annelated
five-membered ring, not only for thermolysis but also
for TBAF-induced CIEEL-decay in DMSO. This trend
of chemiexcitation efficiency poses a question, which
has been little discussed so far, whether the chemiexci-
tation process for thermolysis of dioxetane relates or
does not relate to that for intramolecular CIEEL. The
thermolysis of dioxetane has been believed to involve a
two-step mechanism, in which OꢀO bond homolysis
occurs first, leading to a diradical intermediate, fol-
lowed by fast CꢀC bond cleavage (11“4 or 5 in
Scheme 3). A very recent theoretical study by Tanaka
and Tanaka has elucidated that (a) the energy curve of
a dioxetane at the ground state (S0) intersects the
energy curve of the excited state (T1) after the OꢀO
bond cleavage, so that an excited carbonyl fragment
is produced, (b) the magnitude of activation energy
(EaC–C) requisite for the CꢀC bond cleavage (the second
step) affects chemiexcitation efficiency significantly, and
(c) the chemiexcitation occurs effectively for tetra-
methyldioxetane possessing a considerably puckered
four-membered ring, which requires far smaller EaC–C
than unsubstituted dioxetane giving very low chemiex-
citation yield.24 According to this elucidation, the
marked difference in the thermal chemiexcitation
Table 1. Fluoride-induced chemiluminescent decomposi-
tion of dioxetanes (2) in TBAF/DMSOa
Dioxetane
umax (nm)
k (s−1
)
t1/2 (s)
FCIEELb Fsc,d
2a
2b
2c
1
469
469
469
466
0.063
0.16
0.042
0.15
11
4.3
16
0.23
0.23
0.24
0.20
0.72
0.72
0.75
0.63
4.6
a Solutions of 2a–2c in DMSO (1.0×10−6 mol dm−3, 1 mL) were
added to TBAF solutions in DMSO (1.0×10−3 mol dm−3, 2 mL) at
25°C.
b Chemiluminescence yields (FCIEEL) were based on the reported
value for 3-(2%-spiroadamantane)-4-methoxy-4-(3¦-tert-butyldimeth-
ylsiloxy)phenyl-1,2-dioxetane: FCIEEL=0.29.22
c Singlet-chemiexcitation yields (Fs) were estimated in accord with an
equation Fs=FCIEEL/Ffl.
d Fluorescence yield (Ffl) of the authentic emitters: Ffl=0.34 for
2a–2c based on Ffl=0.32 for 1.23
*
R
O
O
TBAF
2
O
Light
DMSO
O
a: R = Me
b: R = H
10
c: R = -CH2Ph
Scheme 2.
Scheme 3.

1526
M. Matsumoto et al. / Tetrahedron Letters 43 (2002) 1523–1527
efficiency between 1 and 2 might be attributed to the
5. Kopecky, K. R.; Lockwood, P. A.; Gomez, R. R.; Ding,
J.-Y. Can. J. Chem. 1981, 59, 851–858.
difference in stereochemistry of the dioxetane ring.25
6. Adam, W.; Peters, E.-M.; Peters, K.; Platsch, H.;
Schmidt, E.; Von Schnering, H. G.; Takayama, K. J.
Org. Chem. 1984, 49, 3920–3928.
7. Matsumoto, M.; Watanabe, N.; Kasuga, N. C.;
Hamada, F.; Tadokoro, K. Tetrahedron Lett. 1997, 38,
2863–2866.
8. Matsumoto, M.; Ishihara, T.; Watanabe, N.; Hiroshima,
T. Tetrahedron Lett. 1999, 40, 4571–4574.
9. There have been several reports on bicyclic dioxetanes,
2,7,8-trioxabicyclo[4.2.0]octanes, though all of them are
rather unstable thermally.10–12
10. Jefford, C. W.; Wang, Y.; Bernardinelli, G. Helv. Chim.
Acta 1988, 71, 2042–2052.
11. Chan, Y.-Y.; Li, X.; Zhu, C.; Li, X.; Zhang, Y.; Leung,
H.-K. J. Org. Chem. 1990, 55, 5497–5504.
12. Gollnick, K.; Knutzen-Mies, K. J. Org. Chem. 1991, 56,
4017–4027.
Two mechanisms have been proposed for the
intramolecular CIEEL. The first mechanism (ET-BET
mechanism) comprises an initial electron transfer caus-
ing decomposition of dioxetane to form a radical ion
pair of two carbonyl fragments as the first elementary
step and successive annihilation of the radical ion pair
by electron back transfer (BET) to give an excited
carbonyl as the secondary step (12“13“BET“10 or
15 in Scheme 3).22,23,26–28 According to the ET-BET
mechanism, the radical ion pair produced from 2
should possess a structure(s) to cause BET more effec-
tively than that from 1, since the BET step should affect
decisively the yield of a carbonyl at the singlet-excited
state as suggested by Adam.28 The second is a mecha-
nism in which an intermediate produced by charge-
transfer-induced OꢀO bond cleavage gives an excited
carbonyl directly and not through the distinct forma-
tion of a radical ion pair (14“direct“10 or 15 in
Scheme 3).29,30 The second mechanism for the
intramolecular CIEEL resembles the thermal chemiex-
citation mechanism especially in the CꢀC bond cleavage
at the second step, and appears to be in agreement with
ab initio molecular orbital studies.31 Although the
present results do not give definitive information either
to rationalize the mechanism of charge-transfer induced
chemiluminescent decomposition of dioxetane or to
answer the above question, they clarify that the struc-
ture of dioxetane not participating formally in chemiex-
citation affects the yield of excited carbonyls, and
provides a clue to study the relation between thermal
chemiexcitation and CIEEL.
13. The CIEEL has been originally proposed by Schuster
for intermolecular system including initial electron-trans-
fer from an electron donor to a peroxide, giving a radi-
cal ion pair, annihilation of which by electron back
transfer affords a singlet excited species.14
14. Schuster, G. B. Acc. Chem. Res. 1979, 12, 366–373.
15. Selected spectral data for 2a: 1H NMR (400 MHz,
CDCl3) lH 0.18 (s, 6H), 0.98 (s, 9H), 0.99 (s, 9H), 1.16
(s, 3H), 1.40 (ddd, J=13.2, 9.3 and 2.4 Hz, 1H), 1.58 (s,
3H), 3.00 (dt, J=13.2 and 9.3 Hz, 1H), 4.11 (dt, J=10.7
and 9.3 Hz, 1H), 4.42 (ddd, J=10.7, 9.3, and 2.4 Hz,
1H), 6.80 (d with fine coupling, J=8.3 Hz, 1H), 6.88–
7.20 (broad m, 2H), 7.21 (t, J=8.3 Hz, 1H). 13C NMR
(100 MHz, CDCl3) lC −4.3, 18.2, 25.6, 25.7, 28.6, 29.4,
37.1, 38.4, 39.4, 59.7, 100.6, 109.9, 118.4, 119.4, 120.0,
128.8, 142.1, 155.3. Mass (m/z, %) 406 (M+, trace), 349
(12), 321 (4), 305 (4), 279 (5), 253 (15), 235 (100).
HRMS 406.2552, calcd for C23H38O4Si 406.2539.
16. Thermal decomposition of 3,3-dibenzyl-1,2-dioxetane
has been reported to give Norrish type I product, 1,2-
diphenylethane, in 2.2% yield.17
Acknowledgements
The authors express their appreciation to Professors J.
Tanaka and M. Ohashi, and Dr. C. Tanaka of Kana-
gawa University for many helpful discussions. The
authors gratefully acknowledge financial assistance pro-
vided by a grant-in-aid for Scientific Research by the
Ministry of Education, Science, Sports and Culture.
17. Richardson, W. H.; Montgomery, F. C.; Yelvington, M.
B. J. Am. Chem. Soc. 1972, 94, 9277–9278.
18. Yang, N. C.; Feit, E. D.; Hui, M. H.; Turro, N. J.;
Dalton, J. C. J. Am. Chem. Soc. 1970, 92, 6974–6976.
19. Alkyl esters of 3-(tert-butyldimethylsiloxy)benzoic acid
emitted fluorescence at umax=328–330 nm (in
acetonitrile).
References
20. Enhanced luminescence with 9,10-diphenylanthracene
was observed for thermolysis of 2a and singlet-chemiex-
citation yield was estimated to be F=0.011. On the
other hand, an attempt to estimate the chemienergized
triplet state(s) by the use of 9,10-dibromoanthracene
(DBA: rate constant for triplet-singlet energy transfer=
1. Lechtken, P.; Reissenweber, G.; Grubmuller, P. Tetra-
hedron Lett. 1977, 2881–2884.
2. Baumstark, A. L.; Wilson, C. E. Tetrahedron Lett. 1979,
2569–2570.
3. Baumstark, A. L.; Wilson, C. E. Tetrahedron Lett. 1981,
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4. Such stability trends have been rationalized in terms of
the degree of puckering of the dioxetane ring, caused by
conformational effects of the annelated rings. It was
argued that six-membered ring annelation compels the
most puckered dioxetane ring and hence lowest stability,
while five- and/or seven-membered ring annelation
1×109 M−1 s−1 21
was unsuccessful. This result may be
)
consistent since the type I reaction of the triplet-excited
highly-branched-alkyl ketone moiety of 5 occurs pre-
sumably as rapidly as that of di-tert-butyl ketone (k=7–
9×109 sec−1).18
21. Turro, N. J.; Lechtken, P.; Schuster, G.; Orell, J.; Stein-
metzer, H.-C.; Adam, W. J. Am. Chem. Soc. 1974, 96,
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obliges
a planar dioxetane ring and hence highest
stability.5,6

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1527
22. Trofimov, A. V.; Mielke, K.; Vasil’ev, R. F.; Adam, W.
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of an oxy-anion of 3-(m-hydroxyphenyl)-1,2-dioxetane
suggest that the CIEEL should proceed through (a) elec-
tron-transfer from a phenoxide to OꢀO, (b) OꢀO bond
cleavage giving a pair of radical and anion, such as 14
rather than 12, in which the negative charge is localized
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dihedral angle (q) of OꢀCꢀCꢀO of the dioxetane ring is
13° for 2a, while q=4° for 1 (q=8° by X-ray analysis).7
26. Adam, W.; Bronstein, I.; Trofimov, A. V.; Vasil’ev, R. F.
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