Synthesis of thermally stable acylamino-substituted bicyclic dioxetanes and their base-induced chemiluminescent decomposition

Article abstract of DOI:10.1021/jo101114b

Hydroxyaryl-substituted dioxetanes 2-4 fused with a pyrrolidine ring were selectively synthesized by singlet oxygenation of the corresponding dihydropyrroles 5-7. These N-acylamino-substituted bicyclic dioxetanes were quite stable thermally, and 2a and 2b

Full text of DOI:10.1021/jo101114b

pubs.acs.org/joc
Synthesis of Thermally Stable Acylamino-Substituted Bicyclic
Dioxetanes and Their Base-Induced Chemiluminescent Decomposition
Nobuko Watanabe, Yusuke Sano, Haruna Suzuki, Masatoshi Tanimura, Hisako K. Ijuin,
and Masakatsu Matsumoto*
Department of Chemistry, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293 Japan
matsumo-chem@kanagawa-u.ac.jp
Received June 20, 2010
Hydroxyaryl-substituted dioxetanes 2-4 fused with a pyrrolidine ring were selectively synthesized by
singlet oxygenation of the corresponding dihydropyrroles 5-7. These N-acylamino-substituted bicyclic
dioxetanes were quite stable thermally, and 2a and 2b were estimated to possess half-lives of 32 and 34 y at
25 °C. When treated with TBAF (tetrabutylammonium fluoride) in DMSO, these dioxetanes underwent
charge-transfer-induced decomposition (CTID) to emit yellow-orange light. The chemiluminescence
efficiencies ΦCL for dioxetanes 2 ranged from 10-6 to 10-2. On the other hand, dioxetane 4 bearing
a 4-(benzothiazol-2-yl)-3-hydroxyphenyl moiety showed chemiluminescent decomposition with high
efficiency (ΦCL = 0.15) comparable to its oxy-analogue 26. Prominent characteristics for CTID of the
present dioxetanes were that the N-acylamino-group influenced the color of chemiluminescence as well
as the rate of decomposition kCTID, and furthermore an N-acyl substituent could decisively affect the
singlet-chemiexcitation efficiency, as observed for the case of 2b.
Introduction
has been established as a reliable method for preparing a
dioxetane with sufficient thermal stability.1-6 Another advan-
tage is that such a dioxetane undergoes base-induced decom-
position to give an excited aromatic ester, which is expected to
emit light more effectively than a related aromatic ketone.7,8
An amino-substituted dioxetane should also be a promising
entry to novel chemiluminescence compounds to give an
An oxy-substituted dioxetane bearing a hydroxyaryl group
provides one of the most versatile skeletons for the design and
synthesis of high-performance chemiluminescence com-
pounds, since the singlet oxygenation of a precursor enol ether
(1) For reviews of singlet oxygen, See: (a) Denny, R. W.; Nickon, A.
Sensitized Photooxygnenation of Olefins; In Organic Reactions; Wiley: New
York, 1973; Vol. 20, pp 133-336. (b) Schaap, A. P.; Zaklica, K. A. In Singlet
Oxygen; Wasserman, H. H., Murray, R. W., Eds.; Academic Press: New
York, 1979; pp 173-242. (c) Baumstark, A. L. In Singlet O2; Frimer, A. A.,
Ed.; CRC Press: Boca Raton, FL, 1985; Vol. 2, pp 1-35.
(2) For reviews of 1,2-dioxetane, see: (a) Bartlett, P. D.; Landis, M. E. In
Singlet Oxygen; Wasserman, H. H., Murray, R. W., Eds.; Academic Press: New
York, 1979; pp 243-286. (b) Adam, W. In The Chemistry of Peroxide; Patai, S.,
Ed.; Wiley: New York, 1983; pp 829-920. (c) Adam, W. In Small Ring
Heterocycles; Hassner, A., Ed.; Wiley: New York, 1986; pp 351-429. (d) Adam,
W.; Heil, M.; Mosandl, T.; Saha-Moller, C. R. In Organic Peroxides; Ando, W.,
Ed.; Wiley: New York, 1992; pp 221-254. (e) Saha-Moller, C. R.; Adam, W. In
Comprehensive Heterocyclic Chemistry II. Review of the Literature
1982-1995; Padwa, A., Ed.; Pergamon: New York, 1996; pp 1041-1082. (f)
Adam, W.; Trofimov, A. V. In The Chemistry of Peroxides; Rappoport, Z., Ed.;
Wiley: New York, 2006; Vol. 2, pp 1171-1209. (g) Baader, W. J.; Stevani, C. V.;
Bastos, E. L. In The Chemistry of Peroxides; Rappoport, Z., Ed.; Wiley: New
York, 2006; Vol. 2, pp 1211-1278.
(3) (a) Schaap, A. P.; Gagnon, S. D. J. Am. Chem. Soc. 1982, 104, 3504–
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B. P. Tetrahedron Lett. 1987, 28, 1155–1158.
(4) For reviews of dioxetane-based chemiluminescence, see: (a) Beck, S.;
€
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and Chemiluminescence, Fundamentals and Applied Aspects; Campbell, A. K.,
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1989, 4, 99–111. (b) Edwards, B.; Sparks, A.; Voyta, J. C.; Bronstein, I. J.
Biolumin. Chemilumin. 1990, 5, 1–4. (c) Trofimov, A. V.; Vasil’ev, R. F.; Mielke,
K.; Adam, W. Photochem. Photobiol. 1995, 62, 35–43. (d) Adam, W.; Bronstein,
I.; Edwards, B.; Engel, T.; Reinhardt, D.; Schneider, F. W.; Trofimov, A. V.;
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(7) An aromatic ketone generally causes a low-lying n-π* state, which
results in a substantial decrease in fluorescence efficiency.8
(8) (a) Turro, N. J. Modern Molecular Photochemistry of Organic Molecules;
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Published on Web 08/04/2010
DOI: 10.1021/jo101114b
r
2010 American Chemical Society

Watanabe et al.
JOCArticle
CHART 1. Acylamino-Substituted Dioxetanes 2, 3, and 4 and
SCHEME 1. Oxy-Substituted Dioxetane and Amino-Substi-
tuted Dioxetane
Their Precursors 5-10
amide or imide as an emitter (Scheme 1). However, little is
known about amino-substituted dioxetanes that show suffi-
cient thermal stability to permit handling at room tempera-
ture, though the 1,2-addition of singlet oxygen to enamine
precursors, such as enecarbamates, readily takes place.1,2,9
In the course of our investigation of high-performance
chemiluminescence compounds, we attempted to realize ther-
mally stable amino-substituted dioxetanes by modifying the
skeleton of oxy-substituted bicyclic dioxetane 1, which shows
marked thermal stability.10 The thus-realized dioxetanes were
2-acyl-1-aryl-5-tert-butyl-4,4-dimethyl-2-aza-6,7-dioxabicyclo-
[3.2.0]heptanes 2a-d, 3, and 4.11,12 In addition to the synthesis
of these dioxetanes, we report here that the base-induced
decomposition of these N-acylamino-substituted dioxetanes
showed unique chemiluminescence, the properties of which
changed with an N-acyl substituent as well as with an aromatic
moiety (Chart 1).
N-(Boc)benzylamines have been known to produce a ben-
zylic anion by the action of a base such as LDA.13 Thus, we
conducted the LDA-mediated intramolecular cyclization of
13 at 45 °C to give a stereoisomeric mixture of hydroxypyr-
rolidine 14a (14a-trans:14a-cis = 2:3) in 94% yield. These
stereoisomers could be isolated in pure form by column
chromatography on SiO2. The stereochemistry of 14a-trans
was determined by X-ray single crystallographic analysis: the
ORTEP view of 14a-trans is shown in the Supporting
Information [Figure S1(a)].
Results and Discussion
The dehydration of alcohol 14a-trans was achieved by the use
of SOCl2/pyridine in ether to give dihydropyrrole 8a in quanti-
tative yield, while 14a-cis underwent dehydration sluggishly
under similar conditions to give 8a in only 30% yield. However,
14a-cis could be effectively reused, since its retrocyclization took
place to give 13 upon treatment with t-BuOK in N-methylpyr-
rolidone (NMP). Therefore, we decided to use a deprotected
form of 14a-trans, e.g., N-free pyrrolidine 15, as a key inter-
mediate to synthesize 8b-d. Deprotection of N-Boc in 14a-trans
was carried out by catalysis with trifluoroacetic acid to give
exclusively 15. N-Acylation of 15 with benzoyl chloride, acetic
anhydride, or piperidinocarbonyl chloride gave the correspond-
ing N-acylpyrrolidines, 14b-d-trans, in 75-90% yields. These
hydroxypyrrolidines were smoothly dehydrated to the corre-
sponding dihydropyrroles 8b-d in 83-97% yields. Demethyla-
tion of a methoxyphenyl group in 8a-d proceeded with sodium
methylthioate in hot DMF to give the corresponding hydroxy-
phenyl-substituted dihydropyrroles 5a-d in 73-99% yields.
Dihydropyrrole derivative 6 bearing a 4-hydroxyphenyl
group was synthesized through 17, 18, and 9 according to the
synthetic sequences from 12 to 5a by the use of 4-methoxy-
benzyl chloride (16) instead of 12. Synthesis of dihydropyrrole 7
bearing a 4-(benzothiazol-2-yl)-3-hydroxyphenyl moiety started
from the N-substitution of 11 with benzothiazolyl-substituted
benzyl chloride 19 to give aminoketone 20. As in the case of 13,
aminoketone 20 was subjected to base-mediated cyclization to
give 21, which was followed by dehydration to 10 and subse-
quent demethylation to give 7.
1. Synthesis of Acylamino-Substituted Bicyclic Dioxetanes.
Acylamino-substituted bicyclic dioxetanes 2a-d, 3, and 4 were
prepared by singlet oxygenation of the corresponding N-acyl-5-
aryl-4-tert-butyl-3,3-dimethyl-2,3-dihydropyrroles 5a-d, 6, and
7. These precursors were synthesized through several steps start-
ing from 1-(N-Boc)amino-2,2,4,4-tetramethylpentan-3-one 11
as illustrated in Scheme 2. (N-Boc)aminoketone 11 was obtained
by oxidation of 1-(N-Boc)amino-2,2,4,4-tetramethylpentan-3-
ol, which was synthesized from commercially available pivaloyl-
acetonitrile by the introduction of two methyls followed by
reduction with LiAlH4. The first step in the synthetic sequences
leading to 5a-d was the N-substitution of 11 with 3-methoxy-
benzyl chloride 12 to give N-benzyl-N-(Boc)aminoketone 13.
(9) (a) Adam, W.; Bosio, S. G.; Turro, N. J. J. Am. Chem. Soc. 2002, 124,
8814–8815. (b) Adam, W.; Bosio, S. G.; Turro, N. J. J. Am. Chem. Soc. 2002,
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Lett. 2001, 42, 8869–8872. (d) Matsumoto, M.; Akimoto, T.; Matsumoto, Y.;
Watanabe, N. Tetrahedron Lett. 2005, 46, 6075–6078.
(11) A part of this work has been reported as
a preliminary
communication.12
(12) Matsumoto, M.; Sano, Y.; Watanabe, N.; Ijuin, H. K. Chem. Lett.
2006, 35, 882–883.
(13) (a) Park, Y. S.; Boys, M. L.; Beak, P. J. Am. Chem. Soc. 1996, 118,
3757–3758. (b) Faibish, N. C.; Park, Y. S.; Lee, S.; Beak, P. J. Am. Chem. Soc.
1997, 119, 11561–11570. (c) Kim, B. J.; Park, Y. S.; Beak, P. J. Org. Chem.
1999, 64, 1705–1708.
When N-(Boc)dihydropyrrole 5a was irradiated together
with a catalytic amount of tetraphenylporphin (TPP) in
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SCHEME 2. Synthetic Pathway of N-Substituted Dioxetanes 2, 3, and 4
CHART 2. Keto Imides 22, 23, and 24 As a Product of Thermal
Decomposition of N-Acylamino-Substituted Dioxetanes 2, 3,
and 4
that the thermolysis of these dioxetanes proceeded according to
first-order kinetics. Thus, the following thermodynamic para-
meters were estimated from Eyring plots: ΔHq/kJ mol-1, ΔSq/J
K-1 mol-1, and ΔGq/kJ mol-1 were 124, -4.7, and 125 for 2a,
and 125, -0.5, and 125 for 2b, respectively (Supporting Infor-
mation, Figures S2 and S3). From these values, the half-lives
(t1/2) were estimated to be 32 y for 2a and 34 y for 2b at 25 °C.
These results showed that the acylamino-substituted dioxetanes
synthesized here belonged to a class of dioxetanes with high
thermal stability.2 The marked thermal stability of 2 is most
likely attributed to the synergetic effect of a fused five-membered
ring and a bulky tert-butyl group as a prop or wall14 to prevent
twisting of the dioxetane ring: stretching of the O-O bond has
been believed to cause decomposition of the dioxetane ring.2,15
The effect of an electron-withdrawing group on a nitrogen may
also contribute to the stabilization of dioxetanes 2.
CH2Cl2 with a Na-lamp under an O2 atmosphere at 0 °C,
singlet oxygenation of 5a proceeded smoothly to give dioxetane
2a exclusively. Chromatographic purification of the photolysate
gave pure 2a in 97% yield. Dihydropyrrole analogues 5b-d, 6,
and 7 were similarly dioxygenated with singlet oxygen to afford
the corresponding bicyclic dioxetanes 2b-d, 3, and 4 in isolated
yields of 85-100%. The structure of these dioxetanes was
determined by 1H NMR, 13C NMR, IR, mass, HRMass spec-
tral data, and elemental analyses. Among these dioxetanes,
X-ray single crystallographic analysis was only attained for 4,
the ORTEP view of which is shown in the Supporting Informa-
tion [Figure S1(b)].
All of these N-acyldioxetanes 2a-d, 3, and 4 were thermally
stable enough to permit handling at room temperature, though
they decomposed quantitatively into the corresponding keto
imides 22a-d, 23, and 24 when heated in p-xylene (Chart 2). To
determine the thermodynamic profiles for the thermolysis
of these dioxetanes, we selected 2a and 2b as representative
compounds and heated them individually at 90-110 °C in
p-xylene-d10. The time-courses monitored by 1H NMR showed
Notably, dioxetanes 2a-d and 4 displayed two groups of
peaks due to conformational isomerism in 13C NMR and 1H
NMR spectra: isomeric ratios were 55:45 for 2a, 50:50 for 2b
and 2c, 76:24 for 2d, and 52:48 for 4 in CDCl3 at 25 °C. For
these dioxetanes, two types of conformational isomerism can
formally exist, as shown in Scheme 3, in which 2a is shown as
a representative compound. Type A isomerism occurs
around the axis that joins Boc carbonyl to nitrogen to give
rotamers 2a-antiacyl and 2a-syn-acyl, whereas the other type
(type B) occurs around the axis that joins 3-methoxyphenyl
(14) (a) Watanabe, N.; Kikuchi, M.; Maniwa, Y.; Ijuin, H. K.; Matsumoto,
M. J. Org. Chem. 2010, 75, 879–884. (b) Tanimura, M.; Watanabe, N.; Ijuin,
H. K.; Matsumoto, M. J. Org. Chem. 2010, 75, 3678–3684.
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7589. (b) Turro, N. J.; Lechtken, P.; Shore, N. E.; Schuster, G.; Steinmetzer,
H.-C.; Yekta, A. Acc. Chem. Res. 1974, 7, 97–105. (c) Adam, W.; Baader,
W. J. J. Am. Chem. Soc. 1985, 107, 410–416. (d) Reguero, M.; Bernardi, F.;
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TABLE 1. TBAF-Induced Chemiluminescence of Acylamino-Substituted Bicyclic Dioxetanes 2a-d, 3, and 4a
dioxetane
λmax/nm
ΦCL b
Φfl
ΦS
kCTIDfast/s-1
kCTIDslow/s-1
2a
2b
2c
2d
3
571
600
588
564
471
542
467
492
8.5 ꢀ 10-3
3.4 ꢀ 10-6
4.4 ꢀ 10-3
1.8 ꢀ 10-2
1.1 ꢀ 10-7
0.15
3.9 ꢀ 10-2
2.0 ꢀ 10-3
2.1 ꢀ 10-2
8.4 ꢀ 10-2
0.22
0.70
1.2
4.0 ꢀ 10-2
1.4 ꢀ 10-1
7.5 ꢀ 10-2
0.0017
0.21
0.21
2.3
2.7 ꢀ 10-3
0.14
4
0.64
0.24d
0.24
0.46
0.42
1.2 ꢀ 10-4
2.8 ꢀ 10-2
4.5 ꢀ 10-4
1c
0.11
0.28
26e
0.66 f
aUnlessotherwise stated, reactions were carriedout in DMSO at 25 °C. bΦCL values were estimatedbased on the value reported for 3-adamantylidene-
4-methoxy-4-(3-siloxyphenyl)-1,2-dioxetane.19,20 cReference 10c. Chemiluminescent decomposition was carried out in a TBAF/acetonitrile system.
dReference 10b. eReference 14b. Chemiluminescent decomposition was carried out in a TBAF/acetonitrile system at 45 °C. fReference 10d.
SCHEME 3. Rotational Isomerism of N-Acylamino-Substi-
tuted Bicyclic Dioxetane 2a
to a dioxetane carbon to afford rotamers 2a-antiaryl and
2a-syn-aryl. The fact that neither the 13C NMR nor 1H NMR
spectrum of 4-hydroxyphenyl-analogue 3 showed any evi-
FIGURE 1. Chemiluminescence spectra of dioxetanes 2a-d and 3.
dence of syn-anti isomerism strongly suggests that the iso-
respectively. When a solution of 2a in DMSO was added to a
merism observed for 2a-d and 4 was due to type B rotational
large excess of tetrabutylammonium fluoride (TBAF) in
DMSO, 2a decomposed to give yellow light with maximum
wavelength (λmaxCL) = 571 nm and chemiluminescence effi-
ciency (ΦCL) = 8.5 ꢀ 10-3 (Figure 1, Table 1).19,20 TBAF simi-
larly induced the decomposition of 2b-d to give green to yellow
light, the spectra of which are shown in Figure 1. The chemi-
luminescence properties for 2a-d are summarized together
with those for 3 and 4, and oxy-analogues 1 and 26 (vide infra).
The results in Table 1 show that an N-acyl group considerably
isomerism. Such rotational isomerism appeared to readily
occur at room temperature. Crystalline 4 used for X-ray
single crystallographic analysis showed a 1H NMR spectrum
of a mixture of rotamers (52:48) when dissolved in CDCl3 at
room temperature.
2. Base-Induced Chemiluminescent Decomposition of Acyl-
amino-Substituted Bicyclic Dioxetanes. A dioxetane bearing
an oxidophenyl anion produced from a phenolic dioxetane
such as 1 decomposes rapidly to give an aromatic ester accom-
panied by the emission of light by an intramolecular charge-
transfer-induced decomposition (CTID) mechanism.4,16-18
Dioxetanes 2a-d were also expected to undergo CTID to
give a new type of emitter bearing an imide moiety 22a-d,
CL
affected ΦCL as well as λmax of 2: while ΦCL increased in
the order 2b , 2c < 2a < 2d, λmaxCL decreased in the order
2b > 2c > 2a > 2d.
All of the freshly spent reaction mixtures of 2a-d gave the
corresponding imides 22a-d in high yields after careful
neutralization. Oxidophenyl anions 25a-d generated from
authentic 22a-d in TBAF/DMSO showed fluorescence, the
spectra of which coincided with those of the corresponding
chemiluminescences from 2a-d. Therefore, 25a-d were
undoubtedly the emitters produced from 2a-d, respectively
(Scheme 4). On the basis of their fluorescence efficiencies
(Φfl), chemiexcitation efficiencies (ΦS = ΦCL/Φfl) were esti-
mated. As summarized in Table 1, ΦS values were 0.21-0.22
for 2a, 2c, and 2d, but only 0.0017 for 2b. For 2b, not only ΦS
but also Φfl of the emitter were far smaller than those for 2a,
2c, and 2d. The results show that an N-acyl substituent of 2
could significantly affect ΦS as well as λmaxCL and Φfl. The π-
electron system of an aromatic carbonyl spread over the
imide moiety would change with the character of the N-acyl
(16) The chemiluminescent (CL) decomposition of hydroxyphenyl-
substituted dioxetanes has been proposed to proceed by
a
CIEEL9
(chemically initiated electron exchange luminescence) mechanism, where
an initially formed radical ion pair annihilates by back electron transfer
(BET) to afford an excited aromatic carbonyl compound. However, it is
unclear whether such a CL reaction includes BET as a fundamental process.
Therefore, we have recently been using the term CTID, which includes
CIEEL and other CT-induced mechanisms.
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K.; Saito, I. Bull. Chem. Soc. Jpn. 1999, 72, 213–225. (b) Tanaka, J.; Tanaka,
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CL
group for emitter 25. Thus, we can imagine that both λmax
and Φfl would change with the structure of the emitter imide.
(19) ΦCL was estimated based on the value 0.29 for the chemiluminescent
decomposition of 3-adamantylidene-4-methoxy-4-(3-oxidophenyl)-1,2-di-
oxetane in an TBAF/DMSO system.20
(20) Trofimov, A. V.; Mielke, K.; Vasil’ev, R. F.; Adam, W. Photochem.
Photobiol. 1996, 63, 463–467.
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Watanabe et al.
JOCArticle
parent 1, 2.83 eV for oxido anion of 27, while ΔE was 2.87 eV
for 25a and 2.81 eV for oxido anion of 24.21
The time-course of CTID showed that 2a underwent dual-
phase decomposition, consisting of fast and slow reactions
(Supporting Information, Figure S5). A kinetic analysis re-
vealed that both reactions proceeded according to pseudo-first-
order kinetics, and their rate constants kCTIDfast and kCTID
slow
were estimated to be 0.70 and 0.040 s-1, respectively. Dioxe-
tanes 2b and 2c similarly underwent dual-phase CTID.22 On
the other hand, 4-hydroxyphenyl-analogue 3 decomposed
simply according to pseudo-first-order kinetics to give blue
light (kCTID =0.14 s-1, λmaxCL =471 nm, ΦCL =1.1ꢀ10-7
)
FIGURE 2. Comparison in chemiluminescence spectra between
oxy-substituted dioxetanes 1 and 26 and N-(Boc)amino-substituted
dioxetanes 2a and 4.
(Table 1, Figure 1).23,24 Such a simple single-phase decomposi-
tion has been recognized as a rather normal feature for most
known CTID of dioxetanes such as furan-analogue 1, forwhich
rotational isomerism has hardly been observed.2
SCHEME 4. Base-Induced Chemiluminescence of N-Acylamino-
Substituted Dioxetanes
These facts suggested a formal feature that one rotamer
(syn or anti) decomposed rapidly while the other decom-
posed slowly for the CTID of 2a. However, it was not clear
whether the rotamer with kCTIDslow decomposed directly or
first isomerized to another rotamer with kCTIDfast and then
decomposed: these two processes might occur concurrently.
Thus, we carried out a preliminary control experiment as
follows. The TBAF-induced decomposition of 2a was
quenched with trifluoroacetic acid after CTID with kCTID
fast
was almost completed. When TBAF was again added to this
solution after an appropriate period, chemiluminescence due
to the fast CTID was observed again (Supporting Informa-
tion, Figure S6). This result showed that isomerization of the
rotamer with kCTIDslow into another with kCTIDfast occurred
during the TBAF-induced decomposition of 2a, though
direct decomposition of the former could not be denied.
CHART 3. Oxy-Substituted Dioxetane 26 Bearing a Benzo-
thiazolyl Group and Its Decomposition Product 27
Conclusion
The acylamino-substituted bicyclic dioxetanes 2, 3, and 4
designed and synthesized here were quite stable thermally
and, in fact, showed higher thermal stability than most
known dioxetanes. These dioxetanes were found to undergo
base-induced chemiluminescent decomposition to give light
with moderate to high efficiencies. In particular, dioxetane 4
underwent CTID with highly efficient chemiluminescence
comparable to its oxy-analogue 26. A notable characteristic
of CTID for the present acylamino-substituted dioxetanes
was that an N-acylamino-group influenced the color of the
However, it is unclear why even ΦS was significantly affected
by an N-acyl group as observed for 2b.
We finally examined the CTID of dioxetane 4 and com-
pared its chemiluminescence properties with those for its
oxy-analogue 26 as well as with those for 2a-d: 26 has very
recently been reported as an excellent chemiluminescence
compound with high ΦCL (Chart 3).14b Upon treatment with
a large excess of TBAF in DMSO at 25 °C, 4 decomposed to
effectively emit yellow light (Figure 2) with properties sum-
marized in Table 1, which also gives the chemiluminescence
properties for 26. We can see from Table 1 that ΦCL of 4 was
far higher than those of 2a-d and was comparable to that of
26. The high ΦCL of 4 was due to high Φfl as in the case of 26:
the Φfl of the oxidoanion of 24 was measured to be 0.64, so
that the chemiexcitation efficiency ΦS of 4 was estimated to
be 0.24 (Table 1). Another characteristic was that λmaxCL for
4 was considerably shorter than that of parent 2a, in contrast
chemiluminescence and the rate of the decomposition kCTID
,
(21) An MO calculation suggested that LUMO for an anion of 24 spred
over imino moiety as well as an aromatic ring differently from that for an
anion of 27, which was localized on an aromatic ester (see the Supporting
Information, Figure S4).
(22) Dioxetane 2d underwent practically single-phase decomposition,
though it also showed rotational isomerism as described previously. The
rate of CTID was most likely far slower than syn-anti isomerization for 2d
(Table 1), so that the reaction was practically observed to proceed in a single
phase. This was also the case for the CTID of 4.
(23) The phenomenon in which CTID of a p-oxidophenyldioxetane gives
light with shorter λmaxC Land far lower ΦCL than its meta-isomer for oxy-
substituted dioxetanes such as 1 has been referred to as an “odd/even”
relationship.6b,24
(24) (a) McCapra, F. Tetrahedron Lett. 1993, 34, 6941–6944. (b) Ed-
wards, B.; Sparks, A.; Voyta, J. C.; Bronstein, I. J. Org. Chem. 1990, 55,
6225–6229. (c) Matsumoto, M.; Hiroshima, T.; Chiba, S.; Isobe, R.; Watanabe,
N.; Kobayashi, H. Luminescence 1999, 14, 345–348. (d) Watanabe, W.;
Kobayashi, H.; Azami, M.; Matsumoto, M. Tetrahedron 1999, 55, 6831–
6840. (e) Hoshiya, N.; Fukuda, N.; Watanabe, N.; Matsumoto, M. Tetrahedron
2006, 62, 5808–5820.
CL
to the case of 26, for which λmax was longer than that of
parent 1. Participation of N-Boc carbonyl to the π-electron
system of 25a and oxido anion of 24 presumably causes such
a difference, different from the cases of 1 and 26, for which
emitters are aromatic esters. An MO calculation (B3LYP/
6-31G(d)) supported this idea: energy gaps corresponding to
π*f π emission, ΔE, were estimated to be 3.01 eV for 2,2,
4,4-tetramethyl-3-oxopentyl 3-oxidobenzoate, emitter from
5924 J. Org. Chem. Vol. 75, No. 17, 2010

Watanabe et al.
JOCArticle
and furthermore an N-acyl substituent could decisively affect
the efficiency of singlet-chemiexcitation as observed for the
case of 2b.
[M þ Naþ] 342.1681. Anal. Calcd for C18H25NO4: C, 67.69; H,
7.89; N, 4.39. Found: C, 67.42; H, 8.07; N, 4.36.
2d: colorless amorphous solid (74:26 mixture of conforma-
tional isomers); 1H NMR (500 MHz, CDCl3) δH 0.97 (s, 9H ꢀ
0.74), 0.98 (s, 9H ꢀ 0.26), 1.15 (s, 3H ꢀ 0.26), 1.16 (s, 3H ꢀ 0.74),
1.44 (s, 3H ꢀ 0.26), 1.46 (s, 3H ꢀ 0.74), 1.40-1.63 (m, 6H), 3.21
(d, J = 9.2 Hz, 1H ꢀ 0.74), 3.27 (d, J = 9.2 Hz, 1H ꢀ 0.26),
3.25-3.45 (m, 4H), 4.11 (d, J = 9.2 Hz, 1H ꢀ 0.26), 4.14 (d, J =
9.2 Hz, 1H ꢀ 0.74), 6.41 (s, 1H ꢀ 0.26), 6.52 (dd, J = 8.0 and 2.1
Hz, 1H ꢀ 0.26), 6.65 (dd, J = 8.0 and 2.3 Hz, 1H ꢀ 0.74), 6.69 (d,
J = 7.6 Hz, 1H ꢀ 0.74), 6.70 (s, 1H ꢀ 0.26), 6.80 (s, 1H ꢀ 0.74),
7.08 (dd, J = 8.0 and 7.6 Hz, 1H ꢀ 0.74), 7.14 (dd, J = 8.0 and
7.8 Hz, 1H ꢀ 0.26), 7.25 (s with fine coupling, 1H ꢀ 0.74), 7.45
(d, J = 7.8 Hz, 1H ꢀ 0.26) ppm; 13C NMR (125 MHz, CDCl3)
δC 20.1 and 20.1, 24.3, 25.1 and 25.2, 25.7 and 25.8, 27.0 and
27.1, 37.6, 44.1 and 44.3, 46.2 and 46.3, 62.7, 103.7 and 104.2,
105.4 and 105.6, 113.9 and 117.2, 115.6 and 115.8, 118.0 and
121.3, 128.4 and 128.6, 138.2 and 138.3, 156.0 and 156.4, 160.0,
and 160.0 ppm; IR (KBr) ν~ 3360, 2938, 2862, 1680, 1641, 1592
cm-1; mass (m/z, %) 388 (Mþ, 5), 331 (34), 303 (12), 278 (15),
247 (13), 121 (24), 112 (100), 84 (26), 69 (20), 57 (19); HRMS
(ESI) 411.2216, calcd for C22H32N2O4Na [M þ Naþ] 411.2260.
Experimental Section
Singlet Oxygenation of N-Boc-4-tert-butyl-5-(3-hydroxy-
phenyl)-3,3-dimethyl-2,3-dihydropyrrole (5a). Typical Procedure.
A solution of N-Boc-4-tert-butyl-5-(3-hydroxyphenyl)-3,3-di-
methyl-2,3-dihydropyrrole (5a) (100 mg, 0.29 mmol) and tetra-
phenylporphin (TPP) (1 mg) in CH2Cl2 (10 mL) was irradiated
externally with a 940 W Na lamp under an oxygen atmosphere at
0 °C for 40 min. After the photolysate was concentrated in vacuo,
the residue was chromatographed on silica gel and eluted with
ether-CH2Cl2 (1:4) to give 2-(Boc)-5-tert-butyl-1-(3-hydroxyphe-
nyl)-4,4-dimethyl-2-aza-6,7-dioxabicyclo[3.2.0]heptane (2a) as a
colorless solid (106 mg, 97% yield). Similarly, dihydropyrroles
5b-d, 6, and 7 were transformed to the corresponding dioxe-
tanes 2b-d, 3, and 4 in respective yields of 85%, 92%, 87%, 93%,
and 100%.
2a: colorless amorphous solid (55:45 mixture of conforma-
tional isomers); 1H NMR (500 MHz, CDCl3) δH 1.01 and 1.01
(s, 9H), 1.06-1.13 (m, 12H), 1.37 and 1.40 (s, 3H), 3.63 (d, J =
10.1 Hz, 1H), 4.06 and 4.07 (d, J = 10.1 Hz, 1H), 6.01 (1H ꢀ
0.45), 6.22 (broad s, 1H ꢀ 0.55), 6.78-6.88 (m, 2H), 7.15-7.27
(m, 2H) ppm; 13C NMR (125 MHz, CDCl3) δC 20.6, 25.7 and
25.7, 27.3 and 27.3, 27.7 and 27.8, 37.8 and 37.9, 43.0 and 43.1,
62.9 and 63.0, 81.2 and 81.4, 104.7 and 104.8, 106.2 and 106.5,
114.0 and 116.2, 115.1 and 115.5, 119.3 and 121.1, 128.7 and
128.8, 139.3 and 139.4, 154.5 and 154.9, 155.7, and 155.8 ppm;
IR (KBr) ν~ 3401, 2979, 2931, 1706, 1674, 1604, 1592 cm-1; mass
(m/z, %) 345 (Mþ - 32, 0.3), 278 (29), 264 (14), 220 (62), 192
(23), 121 (100), 57 (46), 56 (20); HRMS (ESI) 400.2071, calcd
for C21H31NO5Na [M þ Naþ] 400.2100. Anal. Calcd for
C21H31NO5: C, 66.82; H, 8.28; N, 3.71. Found: C, 67.14; H,
8.50; N, 3.56.
1
Anal. Calcd for C22H32N2O4 /20CHCl3: C, 67.14; H, 8.19; N,
3
7.10. Found: C, 67.49; H, 8.47; N, 7.11.
3: colorless plates, mp 143.0-143.5 °C dec (from CH2Cl2-
hexane); 1H NMR (400 MHz, CDCl3) δH 0.98 (s, 9H), 1.10 (s,
9H), 1.11 (s, 3H), 1.38 (s, 3H), 3.59 (d, J = 9.9 Hz, 1H), 4.04 (d,
J = 9.9 Hz, 1H), 5.11 (s, 1H), 6.77-6.82 (m, 2H), 7.15-7.20 (m,
1H), 7.51-7.55 (m, 1H) ppm; 13C NMR (125 MHz, CDCl3) δC
20.6, 25.7, 27.2, 27.8, 37.7, 42.9, 62.8, 81.2, 105.1, 105.7, 114.4,
114.9, 128.5, 129.3, 129.8, 154.9, 156.3 ppm; IR (KBr) ν~ 3272,
2979, 2893, 1701, 1666, 1616, 1594 cm-1; mass (m/z, %) 377
(Mþ, trace), 345 (Mþ - 32, 2), 220 (29), 121 (100), 57 (39), 56
(28); HRMS (ESI) 400.2089, calcd for C21H31NO5Na [M þ
Naþ] 400.2100. Anal. Calcd for C21H31NO5 /10H2O: C, 66.50;
1
3
H, 8.29; N, 3.69. Found: C, 66.32; H, 8.41; N, 3.68.
2b: colorless needles, mp 159.5-160.0 °C dec (from CH2Cl2-
hexane) (50:50 mixture of conformational isomers); H NMR
4: Colorless plates, mp 160.5-161.0 °C dec (from CH2Cl2-
hexane) (52:48 mixture of conformational isomers); 1H NMR (400
MHz, CDCl3) δH 1.05 and 1.06 (s, 9H), 1.11 (s, 3H), 1.14 (s, 9H),
1.42 and 1.45 (s, 3H), 3.63 (d, J = 10.0 Hz, 1H), 4.08 and 4.09 (d,
J= 10.0 Hz, 1H), 6.94 (dd, J=8.3and1.7Hz, 1Hꢀ 0.48), 7.10 (d,
J = 1.7 Hz, 1H ꢀ 0.52), 7.35 (dd, J = 8.3 and 1.7 Hz, 1H ꢀ 0.52),
7.39-7.55 (m, 2H), 7.48 (d, J = 1.7 Hz, 1H ꢀ 0.48), 7.64 (d, J =
8.3 Hz, 1H ꢀ 0.48), 7.72 (d, J = 8.3 Hz, 1H ꢀ 0.52), 7.88-7.94 (m,
1H), 7.99 (d, J = 8.3 Hz, 1H), 12.53 (broad s, 1H) ppm; 13C NMR
(125 MHz, CDCl3) δC 20.6 and 20.6, 25.7 and 25.8, 27.3 and 27.4,
27.8 and 27.9, 37.9 and 38.0, 43.1 and 43.2, 62.9 and 63.0, 81.2 and
81.2, 104.1 and 104.3, 106.5, 116.0 and 116.6, 116.6 and 120.1,
118.6 and 118.9, 121.5 and 121.5, 122.2, 125.7 and 125.7, 126.8 and
126.8, 127.2 and 127.6, 132.5 and 132.6, 142.9 and 142.9, 151.7 and
151.8, 154.1 and 154.2, 157.2 and 157.6, 168.6, and 168.8 ppm; IR
(KBr) ν~ 3417, 2978, 2930, 1717, 1630 cm-1; mass (m/z, %) 510
(Mþ, 5), 410 (20), 354 (16), 353 (60), 326 (12), 325 (30), 283 (17),
270 (20), 255 (17), 254 (100), 226 (26), 198 (29), 197 (11), 57 (33), 56
(22); HRMS (ESI) 511.2280, calcd for C28H35N2O5S [M þ Hþ]
511.2267, 533.2084, calcd for C28H34N2O5SNa [M þ Naþ]
533.2086. Anal. Calcd for C28H34N2O5S: C, 65.86; H, 6.71; N,
5.49. Found: C, 65.52; H, 6.73; N, 5.33.
Base-Induced Decomposition of 2-Boc-5-tert-butyl-1-(3-
hydroxyphenyl)-4,4-dimethyl-2-aza-6,7-dioxabicyclo[3.2.0]hep-
tane (2a). Typical Procedure. A solution of 2-Boc-5-tert-butyl-
1-(3-hydroxyphenyl)-4,4-dimethyl-2-aza-6,7-dioxabicyclo[3.2.0]-
heptane (2a) (50.0 mg, 0.13 mmol) in dry DMSO (1 mL) was
added dropwise over 2 min to a solution of TBAF (1 mol/L in
THF) (0.65 mL, 0.65 mmol) in dry DMSO (1 mL) under a
nitrogen atmosphere at room temperature then the mixture was
stirred for 15 min. The reaction mixture was poured into sat. aq
NH4Cl and then extracted with AcOEt. The aqueous layer was
1
(400 MHz, CDCl3) δH 1.00 and 1.01 (s, 9H), 1.13 (s, 3H), 1.48
and 1.52 (s, 3H), 3.84-4.04 (m, 1H), 4.19 and 4.20 (d, J=10.5
Hz, 1H), 5.48 (broad s, 1H ꢀ 0.5), 5.95 (broad s, 1H ꢀ 0.5), 6.51
(d with fine coupling, J = 7.7 Hz, 1H ꢀ 0.5), 6.59 (d with fine
coupling, J = 7.9 Hz, 1H ꢀ 0.5), 6.74 (s, 1H ꢀ 0.5), 6.83-7.09
(m, 1H), 6.87 (d, J = 7.6 Hz, 1H ꢀ 0.5), 7.05 (t, J = 7.9 Hz, 1H ꢀ
0.5), 7.13-7.40 (m, 5.5 H) ppm; 13C NMR (125 MHz, CDCl3)
δC 20.5 and 20.6, 25.7 and 25.7, 27.3, 37.9 and 38.0, 43.5 and
43.7, 64.0 and 64.1, 105.0 and 105.1, 106.0, and 106.2 (broad),
113.7 and 116.8, 115.6 and 115.9, 118.5 and 121.2, 127.4 and
127.5, 128.0 and 128.0, 128.8, 130.0, and 130.3 (broad), 136.2
and 136.4 (broad), 137.5 and 137.9, 155.6 and 155.7, 173.8, and
174.1 ppm; IR (KBr) ν~ 3310, 3006, 2980, 2965, 1650, 1622, 1599
cm-1; mass (m/z, %) 381 (Mþ, 0.4), 349 (Mþ - 32, 1), 278 (7),
204 (24), 176 (11), 122 (31), 121 (19), 105 (100), 77 (37), 57 (12);
HRMS (ESI) 404.1859, calcd for C23H27NO4Na [M þ Naþ]
404.1838. Anal. Calcd for C23H27NO4 1/5CH2Cl2: C, 69.93; H,
3
6.93; N, 3.52. Found: C, 69.98; H, 7.14; N, 3.53.
2c: yellow plates, mp 146.0 °C dec (from CHCl3-hexane)
(50:50 mixture of conformational isomers); 1H NMR (500 MHz,
CDCl3) δH 1.03 and 1.04 (s, 9H), 1.14 (s, 3H), 1.39 (s, 3H), 1.20-
1.60 (m, 3H), 3.70-3.95 (m, 1H), 4.07 (d, J = 8.2 Hz, 1H),
6.76-6.91 (m, 2H), 7.16-7.32 (m, 2H) ppm; 13C NMR (125
MHz, CDCl3) δC 20.8 and 20.9, 24.2 and 24.4, 25.9, 27.2 and
27.2, 37.9 and 37.9, 42.4 (broad), 63.5 and 63.6 (broad), 105.0 and
105.2, 106.9 (broad), 114.0 and 116.8, 116.2, 119.1 and 120.2, 129.4
and 129.5, 137.7 and 137.8, 156.8, 174.5 ppm; IR (KBr) ν~ 3366,
3014, 2965, 2939, 2884, 1642, 1603 cm-1; mass (m/z, %) 319 (Mþ,
0.8), 287 (Mþ - 32, 0.4), 262 (25), 234 (18), 220 (10), 121 (100), 93
(11), 57 (15); HRMS (ESI) 342.1668, calcd for C18H25NO4Na
J. Org. Chem. Vol. 75, No. 17, 2010 5925

Watanabe et al.
JOCArticle
extracted again with AcOEt. The combined organic layer was
washed twice with sat. aq NaCl, dried over MgSO4, and concen-
trated in vacuo. The residue was chromatographed on silica gel
and eluted with hexane-AcOEt (9:1) to give N-Boc-N-(2,2,4,4-
tetramethyl-3-oxopentyl) 3-hydroxybenzamide (22a) as a color-
less oil (46.5 mg, 93% yield).
(s, 9H), 1.37 (s, 6H), 4.09 (s, 2H), 7.26 (dd, J = 8.2 and 1.8 Hz,
1H), 7.33 (d, J = 1.8 Hz, 1H), 7.44 (dd, J = 7.8 and 7.3 Hz, 1H),
7.53 (dd, J=7.8 and 7.3 Hz, 1H), 7.74 (d, J=8.2 Hz, 1H), 7.92 (d,
J=7.8 Hz, 1H), 8.00 (d, J = 7.8 Hz, 1H) ppm; 13C NMR (125
MHz, CDCl3) δC 25.0, 27.4, 28.2, 46.1, 50.7, 52.4, 83.5, 117.1,
118.5, 118.7, 121.6, 122.4, 126.0, 126.9, 128.0, 132.8, 141.6,
151.7, 153.6, 157.6, 168.3, 172.5, 216.3 ppm; IR (KBr) ν~ 2983,
2932, 1733, 1684, 1669, 1566 cm-1; mass (m/z, %) 510 (Mþ, 10),
410 (22), 397 (14), 354 (23), 353 (82), 326 (14), 325 (36), 296 (13),
283 (21), 270 (18), 255 (18), 254 (100), 226 (22), 198 (23), 57 (29);
HRMS (ESI) 511.2295, calcd for C28H35N2O5S [M þ Hþ]
Dioxetanes 2b-d, 3, and 4 were similarly decomposed by
treatment with TBAF/DMSO system to give keto imides 22b-d,
23, and 24 in 99%, 89%, 97%, 94%, and 99% yield.
1
22a: colorless oil; H NMR (500 MHz, CDCl3) δH 1.10 (s,
9H), 1.33 (s, 9H), 1.34 (s, 6H), 4.06 (s, 2H), 6.98 (d with fine coupl-
ing, J = 7.8 Hz, 1H), 7.16-7.20 (m, 2H), 7.24 (t, J=7.8 Hz, 1H),
7.20-7.30 (m, 1H) ppm; 13C NMR (125 MHz, CDCl3) δC 25.0,
27.2, 28.2, 46.3, 51.0, 52.6, 83.2, 114.8, 118.5, 119.7, 129.4, 138.9,
153.9, 156.0, 173.8, 217.7 ppm; IR (liquid film) ν~ 3403, 2978, 2930,
1732, 1677, 1599 cm-1; mass (m/z, %) 320 (Mþ - 57, 10), 264 (20),
236 (11), 221 (11), 220 (68), 192 (24), 163 (11), 121 (100), 57 (44);
HRMS (ESI) 400.2065, calcd for C21H31NO5Na [M þ Naþ]
400.2100.
511.2267. Anal. Calcd for C28H34N2O5S 2.5H2O: C, 60.52; H,
3
7.07; N, 5.04. Found: C, 60.40; H, 6.68; N, 5.24.
Time Course for the Thermal Decomposition of Dioxetanes
2a,b. General Procedure. A solution of dioxetane 2a,b (3-5 mg)
in p-xylene-d10 (0.8 mL) in a 1H NMR sample tube was heated
by means of a liquid paraffin bath thermostated at an appro-
priate temperature of 90-110 °C. After being heated at regular
1
intervals, the samples were subjected to H NMR analysis to
1
22b: colorless oil; H NMR (500 MHz, CDCl3) δH 1.39 (s,
determine the ratio of intact 2a,b to the corresponding keto
imide 22a,b.
9H), 1.41 (s, 6H), 4.30 (s, 2H), 6.65-6.71 (m, 1H), 6.91-7.02 (m,
4H), 7.10 (dd, J = 7.8 and 7.3 Hz, 2H), 7.20 (t, J = 7.8 Hz, 1H),
7.38 (d with fine coupling, J = 7.3 Hz, 2H) ppm; 13C NMR (125
MHz, CDCl3) δC 25.5, 28.2, 46.4, 51.5, 54.8, 115.8, 119.2, 121.1,
128.1, 128.8, 129.6, 131.6, 136.6, 137.8, 155.8, 174.5, 174.7, 217.6
ppm; IR (liquid film) ν~ 3388, 2973, 2930, 2873, 1699, 1679, 1657,
1598 cm-1; mass (m/z, %) 381 (Mþ, 1), 324 (35), 296 (31), 122
(16), 121 (80), 105 (100), 77 (20), 57 (14); HRMS (ESI) 404.1835,
calcd for C23H27NO4Na [M þ Naþ] 404.1838.
Chemiluminescence Measurement and Time Course for the
Charge-Transfer-Induced Decomposition of Dioxetanes. General
Procedure. Chemiluminescence was measured with a JASCO,
FP-750, a FP-6500 spectrometer, and/or a Hamamatsu Photonics
PMA-11 multichannel detector.
A freshly prepared solution (2.0 mL) of TBAF (1.0 ꢀ 10-2
mol dm-3) in DMSO was transferred to a quartz cell (10 ꢀ 10 ꢀ
50 mm3) and the latter was placed in the spectrometer, which
was thermostated with stirring at 25 °C. After 3-5 min, a solu-
tion of the dioxetane 2a,b, 3, or 4 in DMSO (1.0 ꢀ 10-5 mol
dm-3, 1.0 mL) was added by means of a syringe and measure-
ment was started immediately. The time-course of the intensity
of light emission was recorded and processed according to first-
order kinetics. The total light emission was estimated by com-
paring it to that of an adamantylidene-dioxetane, the chemilu-
minescence efficiency ΦCL of which has been reported to be 0.29
and which was used here as a standard.19,20
1
22c: colorless oil; H NMR (500 MHz, CDCl3) δH 1.27 (s,
9H), 1.31 (s, 6H), 2.01 (s, 3H), 4.08 (s, 2H), 7.08 (d, J= 7.8 Hz, 1H),
7.28 (s with fine coupling, 1H), 7.31 (dd, J=7.8 and 1.4 Hz, 1H),
7.34 (t, J=7.8 Hz, 1H), 7.64 (broad s, 1H) ppm; 13C NMR (125
MHz, CDCl3) δC 24.9, 25.8, 28.0, 46.1, 51.0, 53.6, 115.9, 120.7,
121.3, 130.3, 136.3, 156.7, 173.1, 175.0, 217.7 ppm; IR (liquid film)
ν~ 3361, 3055, 2983, 1704, 1666, 1599 cm-1; mass (m/z, %) 319
(Mþ, 1), 262 (26), 234 (17), 220 (10), 121 (100), 93 (11), 57 (17);
HRMS (ESI) 342.1645, calcd for C18H25NO4Na [M þ Naþ]
342.1681.
Fluorescence Measurement of Authentic Emitters 25a-d and
Oxido Anion of 24. A freshly prepared solution of 2.00-2.10 ꢀ
10-5 mol dm-3 of 22a-d or 24, and of 1.0 ꢀ 10-2 mol dm-3 of
TBAF in DMSO was transferred to a quartz cell (10 ꢀ 10 ꢀ 50
mm3) and the latter placed in the spectrometer, which was
thermostated with stirring at 25 °C. Thus, the fluorescence
spectra of 25a-d and oxido anion of 24 were measured and
their fluorescence efficiencies (Φfl) were estimated with fluor-
escein as a standard.
1
22d: colorless oil; H NMR (500 MHz, CDCl3) δH 1.30 (s,
9H), 1.37 (s, 6H), 0.90-1.65 (m, 6H), 2.50-3.57 (m, 4H), 4.05 (s,
2H), 6.93 (dd, J = 8.0 and 2.3 Hz, 1H), 7.07 (d, J = 7.6 Hz, 1H),
7.13 (s with fine coupling, 1H), 7.20 (dd, J = 8.0 and 7.6 Hz, 1H),
7.99 (s, 1H) ppm; 13C NMR (125 MHz, CDCl3) δC 23.7, 24.6
(broad), 28.4, 45.2 (broad), 46.0, 47.6 (broad), 50.8, 54.4, 114.5,
118.8, 119.3, 129.4, 136.2, 156.5, 157.0, 170.5, 217.1 ppm; IR
(liquid film) ν~ 3331, 3055, 2984, 2947, 2862, 1679, 1642, 1597
cm-1; mass (m/z, %) 388 (Mþ, 8), 332 (18), 331 (73), 303 (25),
247 (23), 121 (23), 112 (100), 84 (11); HRMS (ESI) 411.2258,
calcd for C22H32N2O4Na [M þ Naþ] 411.2260.
Acknowledgment. We gratefully acknowledge financial
assistance provided by Grants-in-aid (No. 17550050 and
No. 21550052) for Scientific Research from the Ministry
of Education, Culture, Sports, Science, and Technology,
Japan.
23: colorless viscous oil; 1H NMR (500 MHz, CDCl3) δH 1.16
(s, 9H), 1.33 (s, 9H), 1.35 (s, 6H), 4.08 (s, 2H), 6.77 (d with fine
coupling, J = 8.4 Hz, 2H), 7.57 (d with fine coupling, J = 8.4
Hz, 2H), 7.67 (broad s, 1H) ppm; 13C NMR (125 MHz, CDCl3)
δC 24.9, 27.4, 28.2, 46.3, 51.0, 52.7, 82.9, 115.0, 128.8, 130.7,
154.3, 159.9, 173.7, 218.5 ppm; IR (liquid film) ν~ 3387, 2978,
2933, 1726, 1674, 1607 cm-1; mass (m/z, %) 377 (Mþ, trace), 220
(39), 121 (100), 57 (22); HRMS (ESI) 400.2052, calcd for
C21H31NO5Na [M þ Naþ] 400.2100.
Supporting Information Available: General method for the
Experimental Section, 1H NMR/13C NMR spectra of 2a-d, 3,
4, 5a-d, 6, 7, 8a-d, 9, 10, 11, 13, 14a-d, 15, 17, 18, 20, 21,
22a-d, 23, and 24, and ORTEP views and CIFs for 4 and 14a-
trans. This material is available free of charge via the Internet at
http://pubs.acs.org.
24: colorless plates, mp 162.0-164.0 °C (from CH2Cl2-
hexane); 1H NMR (500 MHz, CDCl3) δH 1.17 (s, 9H), 1.32
5926 J. Org. Chem. Vol. 75, No. 17, 2010