Synthesis of sulfanyl-, sulfinyl-, and sulfonyl-substituted bicyclic dioxetanes and their base-induced chemiluminescence

Article abstract of DOI:10.1021/jo902477n

(Chemical Equation Presented) The singlet oxygenation of 4-tert-butyl-3,3-dimethyl-5-(3-oxyphenyl)-2,3-dihydrothiophenes 5c-e bearing an acetoxy or methoxy group at the 2-position exclusively gave the corresponding sulfanylsubstituted bicyclic dioxetanes 2c-e, while that of 5a without 2-substituent mainly gave sulfoxide 11 alongwith a small amount of dioxetane 2a. These dioxetanes were sufficiently stable thermally to permit handling at room temperature. Sulfanyl-substituted dioxetanes, 2c and 2e, were further oxidized with m-chloroperbenzoic acid to afford the corresponding sulfinyl-substituted dioxetanes 3c, 3e and sulfonylsubstituted dioxetanes 4c, 4e. X-ray single crystallographic analysis was performed for 2c and 4e. Baseinduced decomposition of the dioxetanes in DMSO gave light with a maximum wavelength λ_max^CL at 554 nmfor 2a and 565 nmfor 2e in moderate light yields,while sulfinyl-derivative 3e gaveweak light with λ_max^CL = 795 nm and sulfonyl-derivative 4e gave very weak light with λ_max^CL = 848 nm. 2010 American Chemical Society.

Full text of DOI:10.1021/jo902477n

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Synthesis of Sulfanyl-, Sulfinyl-, and Sulfonyl-Substituted Bicyclic
Dioxetanes and Their Base-Induced Chemiluminescence
Nobuko Watanabe, Masato Kikuchi, Yuusuke Maniwa, Hisako K. Ijuin, and
Masakatsu Matsumoto*
Department of Chemistry, Kanagawa University, Tsuchiya, Hiratsuka, Kanagawa 259-1293, Japan
matsumo-chem@kanagawa-u.ac.jp
Received November 19, 2009
The singlet oxygenation of 4-tert-butyl-3,3-dimethyl-5-(3-oxyphenyl)-2,3-dihydrothiophenes 5c-e
bearing an acetoxy or methoxy group at the 2-position exclusively gave the corresponding sulfanyl-
substituted bicyclic dioxetanes 2c-e, while that of 5a without 2-substituent mainly gave sulfoxide 11
along with a small amount of dioxetane 2a. These dioxetanes were sufficiently stable thermally to permit
handling at room temperature. Sulfanyl-substituted dioxetanes, 2c and 2e, were further oxidized with
m-chloroperbenzoic acid to afford the corresponding sulfinyl-substituted dioxetanes 3c, 3eand sulfonyl-
substituted dioxetanes 4c, 4e. X-ray single crystallographic analysis was performed for 2c and 4e. Base-
induced decomposition of the dioxetanes in DMSO gave light with a maximum wavelength λmaxCL at
554 nm for2aand 565nm for2e in moderate light yields, while sulfinyl-derivative 3e gave weak light with
λmaxCL = 795 nm and sulfonyl-derivative 4e gave very weak light with λmaxCL = 848 nm.
Introduction
luminescence substrates.3-8 Sulfur-analogues, e.g. sulfany-
lethylenes, also smoothly undergo the 1,2-addition of sing-
let oxygen.9,10 However, the resulting sulfanyl-substituted
Enolethersreadily undergosingletoxygenationtogiveoxy-
substituted dioxetanes, which at room temperature have
half-lives (t1/2TD: TD = thermal decomposition) that range
from shorter than a second to hundreds of years.1,2 Thus,
such dioxetanes, especially those bearing an easily oxidized
aryl group, have been developed as high-performance chemi-
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Photochem. Photobiol. 1995, 62, 35–43. (f) Adam, W.; Bronstein, I.; Edwards,
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Singlet Oxygen; Wasserman, H. H., Murray, R. W., Eds.; Academic Press:
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Kricka, L. J., Stanley, P. E., Eds.; Wiley: Chichester, UK, 1994; pp 56-59.
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DOI: 10.1021/jo902477n
r
Published on Web 01/14/2010
J. Org. Chem. 2010, 75, 879–884 879
2010 American Chemical Society

Watanabe et al.
JOCArticle
CHART 1. Oxy-Substituted Dioxetane 1-O and Sulfanyl-Sub-
stituted Dioxetane 1-S
Methylene Blue (MB)18 in CH2Cl2 under an oxygen atmo-
sphere at 0 °C for 2.5 h, singlet oxygenation took place
smoothly. 1H NMR analysis of the photolysate showed
that dioxetane 2c was selectively produced, while there was
no S-oxygenation product. Chromatographic purification
of the photolysate (silica gel/CH2Cl2-hexane) gave 2c as
pale yellow columnar crystals (from ether-hexane, mp
98.5-99.5 °C dec). Dioxetane 2c gave satisfactory 1H
NMR, 13C NMR, IR, mass spectral data, and elemental
analysis. The stereochemistry of an acetoxy group of 2c
was finally determined to be trans relative to the dioxetane
O-O based on X-ray single crystallographic analysis, and
the ORTEP view of 2c is shown in the Supporting Informa-
tion. The stereoisomer 2c-cis (Chart 2) was not observed even
in the crude photolysate of 5c. This shows that singlet oxygen
exclusively attacked the π-face from the less-hindred site
for 5c. Upon heating in toluene-d8, 2c decomposed following
first-order kinetics to quantitatively give keto thioate 10c
(Chart 3). Thus, the time-course of the thermolysis of 2c
was examined at 60-80 °C in toluene-d8 and the thermo-
dynamic parameters and half-life were estimated from
dioxetanes are ingeneral quiteunstable, incontrast to theoxy-
analogues, except for polyfluoroalkylsulfanyl-substituted di-
oxetanes.11 For instance, a dioxetane fused with a tetrahy-
drothiophene ring, such as 1,5-dimethyl-6,7-dioxa-2-thiabi-
cyclo[3.2.0]heptane (1-S) has small activation free energy
ΔGq = 95 kJ mol-1, which is much lower (about 25 kJ mol-1
than its oxy-analogue 1-O for thermolysis (Chart 1).12,13
)
We found that the introduction of bulky substituents in
place of two methyls at the 1- and 5-positions and further
substitution at the 3- and 4-positions in 1-S led to sulfanyl-
substituted dioxetanes 2 with sufficient thermal stability to
permit handling at room temperature (Charts 1 and 2).14,15
In addition, we synthesized unprecedented sulfinyl- and
sulfonyl-substituted dioxetanes, 3 and 4, and investigated
the chemiluminescent decomposition of the thus-realized
dioxetanes bearing a sulfur with various oxidation states.
Arrhenius plots: ΔGq=113 kJ mol-1, ΔHq=111 kJ mol-1
,
ΔSq = -5.7 kJ mol-1, and t1/2TD at 25 °C = 210 d.
Singlet oxygenation took place at CdC of the dihy-
drothiophene ring also for 5d and 5e but not at sulfur to
selectively give the corresponding dioxetanes 2d and 2e
without their stereoisomers. The stereochemistry of 2d and
2e was tentatively assigned to be trans, as with 2c, based on
the presumption that the π-face selectivity of 1O2 was similar
to that for 5c. In contrast to 5c-e, dihydrothiophene analo-
gue 5a with no substituent at the 2-position underwent
singlet oxygenation to predominantly give sulfoxide 11
(93%) along with a small amount of expected dioxetane 2a
(6%). Singlet oxygen also attacked preferentially the sulfur
of methoxyphenyl-analogue 5b to give 9, though dioxetane
2b could not be isolated because of its instability but decom-
position product 10b was produced. These results show that
a 2-oxy substituent in 2,3-dihydrothiophenes 5 decisively
influences the chemoselectivity to determine whether singlet
oxygen preferentially attacks a CdC double bond or sulfur
atom. An MO calculation showed for dihydrothiophenes 5a,
5c, and 5d that HOMO electron density at the sulfur de-
creased and that on the CdC inversely increased when an
oxy-substituent was introduced at the adjacent position of
the sulfur (Supporting Information). Thus, in addition to the
steric effect described above, the 2-oxy substituent is sug-
gested to decrease the reactivity of the sulfur relative to the
CdC toward electrophilic 1O2.
Results and Discussion
1. Synthesis of Sulfanyl-Substituted Bicyclic Dioxetanes
and Their Thermal Stability. The synthesis of sulfanyl-sub-
stituted dioxetanes 2 was based on the singlet oxygena-
tion of the precursor dihydrothiophenes 5, the preparation
of which included the LDA-mediated cyclization of 7-(3-
methoxyphenyl)-6-thiaheptan-3-one 7 into 3-hydroxytetra-
hydrothiophene 8 as a key step, as shown in Scheme 1.
Thiaheptanone 7 was synthesized by condensation of 3-
methoxybenzyl chloride with 2,2,4,4-tetramethyl-1-sulfanyl-
pentan-3-ol, prepared from tosylate 6, and successive oxida-
tion of the condensation product with Ac2O/DMSO.16 The
thus-synthesized 8 was dehydrated with SOCl2 to give dihy-
drothiophene 5b in high yield. Oxidation of 5b with sodium
periodate in aq MeOH gave sulfoxide 9, the Pummerer
rearrangement17 of which was attained with Ac2O in hot
toluene to give 2-acetoxydihydrothiophene 5c. 2-Methoxy-
derivative 5d was prepared from 5c through its hydrolysis
giving hydroxy-derivative 5f. Deprotection of 5b and 5d was
carried out with EtSNa in hot DMF to give 5a and 5g,
respectively. Esterification of 5g with Ac2O gave acetate 5e.
When 2-acetoxy-2,3-dihydrothiophene 5c was irradiated
with a Na-lamp in the presence of a catalytic amount of
Thermolysis of 2a and 2c-e exclusively gave the corre-
sponding keto thioates 10a and 10c-e in toluene-d8. The
experimental thermodynamic parameters for the thermolysis
of 2a and 2c-e are summarized in Table 1. They show that
an electron-withdrawing group, e.g., acetoxy group, at the
2-position of the tetrahydrothiophene ring apparently acts to
improve the thermal stability of bicyclic sulfanyl-substituted
dioxetanes 2.
2. Synthesis of Sulfinyl- and Sulfonyl-Substituted Bicyclic
Dioxetanes and Their Thermal Stability. In contrast to
sulfanylethylenes (CdCSR), sulfinylethylenes [CdCS(O)R]
and sulfonylethylenes [CdCS(O2)R] are too electron-defi-
cient to undergo 1,2-addition of electrophilic 1O2 to a
carbon-carbon double bond, and thus there are no known
(11) Akhavan-Tafti, H.; Eickholt, R. A.; Arghavani, Z.; Schaap, A. P.
J. Am. Chem. Soc. 1997, 119, 245–246.
(12) Adam, A.; Griesbeck, G. A.; Gollnick, K.; Knutzen-Mies, K. J. Org.
Chem. 1988, 53, 1492–1495.
(13) Gollnick, K.; Knutzen-Mies, K. J. Org. Chem. 1991, 56, 4027–4031.
(14) A similar structural modification of 1-O has been reported to lead to
1-aryl-5-tert-butyl-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptanes with marked
thermal stability.15
(15) (a) Matsumoto, M.; Watanabe, N.; Kasuga, N. C.; Hamada, F.;
Tadokoro, K. Tetrahedron Lett. 1997, 38, 2863–2866. (b) Matsumoto, M.;
Murakami, H.; Watanabe, N. Chem. Commun. 1998, 2319–2320.
(16) (a) Albright, J. D.; Goldman, L. J. Am. Chem. Soc. 1967, 89, 2416–
2423. (b) Tidwell, T. T. Org. React. 1990, 39, 297–572.
(17) (a) Pummerer, R. Ber. Dtsch. Chem. Ges. 1910, 43, 1401–1412. (b) De
Lucchi, O.; Miott, U.; Modena, G. Org. React. 1991, 40, 157–405.
(18) Among various sensitizers, such as TPP, perfluoroTPP, and Rose
Bengal, MB gave the desired dioxetanes with the least byproduct.
880 J. Org. Chem. Vol. 75, No. 3, 2010

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CHART 2. S-Substituted Dioxetanes 2, SO-Substituted Dioxetanes 3, and SO2-Substituted Dioxetanes 4
SCHEME 1. Synthetic Pathway of Key Intermediates 5 Leading to Sulfanyl-Substituted Dioxetanes 2
CHART 3. Keto Thioates 10, 12, and 13 and Dihydrothiophene
S-Oxide 11
TABLE 1. Thermodynamic Parameters for the Thermolysis of Dioxe-
tanes 2, 3, and 4a
ΔHq/kJ mol-1 ΔSq/J mol-1 ΔGq/kJ mol-1 t1/2 at 25 °C/day
2a
2c
2d
2e
3c
3e
4c
4e
107
111
112
116
107
91
-6.1
-5.7
9.9
21
26
-25
-56
-37
109
113
109
110
99
98
115
113
50
210
54
65
0.8
0.6
470
190
98
102
aThermolysis of 2, 3, and 4 was carried out in toluene-d8 at 50-80 °C.
temperature, sulfinyl-substituted dioxetane 3c was formed
selectively. Dioxetane 3c could only barely be isolated
by column chromatography, although its purity was not
satisfactory, since it was unstable and decomposed gradually
at room temperature. On the other hand, sulfonyl-substi-
tuted dioxetane 4c was thermally stable and obtained by
the oxidation of 2c with >2 equiv of MCPBA (Chart 2).
13C NMR chemical shifts, as a characteristic index of
dioxetane ring carbons, were observed in CDCl3 at δ
(ppm) 104.9 and 109.4 for 2c, 102.0 and 104.2 for 3c, and
100.2 and 101.2 for 4c. Dioxetane 2e was similarly oxidized
with MCPBA to give 3e and 4e: 4e was obtained as stable
examples of dioxetanes bearing a sulfinyl or sulfonyl
group.1,2 In fact, attempts at the singlet oxygenation of
dihydrothiophene S-oxides 9 and 11 only resulted in recov-
ery of the intact substrates. Thus, we planned to oxidize
sulfanyl-substituted dioxetanes and selected 2c and 2e as
representative substrates. When 2c was treated with 1 equiv
of m-chloroperbenzoic acid (MCPBA) in CH2Cl2 at room
J. Org. Chem. Vol. 75, No. 3, 2010 881

Watanabe et al.
JOCArticle
crystals that allowed X-ray single crystallographic analysis
(Supporting Information).
TABLE 2. Base-Induced Chemiluminescent Decomposition of Dioxe-
tanes Bearing a Sulfanyl-, Sulfinyl-, or Sulfonyl Group in a TBAF/DMSO
Systema
1H NMR showed that, on heating in toluene-d8, 4c decom-
posed to give a rather simple product assigned as 13c,
although it could not be isolatedbut rather gave a degradation
product, 3-methoxybenzoic acid, in high yield (94%), during
isolation. Thermolysis of 3c gave a complex mixture instead of
the expected product 12c (Chart 3). However, during the early
stage of thermolysis, dioxetanes 3c and 4c both disappeared
following first-order kinetics. The behaviors of 3e and 4e on
heating were similar to those of 3c and 4c. Thus, the formal
activation parameters of thermolysis for 3c, 3e and 4c, 4e were
estimated to be similar to those in the case of 2. As shown in
Table 1, thermal stability increased in the order sulfinyl-
substituted dioxetane 3 , sulfanyl-substituted dioxetane 2
< sulfonyl-substituted dioxetane 4.
CL
λmax
R
Y
H
/nm
ΦCLb
kCTID/s-1 t1/2CTID/s
2a
H
S
S
554
565
795
848
7.9 ꢀ 10-3 4.3 ꢀ 10-2
12
4.9
2e OMe Ac
3e OMe Ac SO
4e OMe Ac SO2
aAll reactions were carried out at 25 °C. bΦCL values were estimated
based on the value reported for 3-adamantylidene-4-methoxy-4-(3-
siloxyphenyl)-1,2-dioxetane.22
3.0 ꢀ 10-3 1.4 ꢀ 10-1
2.2 ꢀ 10-7 3.3
0.2
3. Base-Induced Chemiluminescent Decomposition of Sul-
fanyl-, Sulfinyl-, and Sulfonyl-Substituted Dioxetanes. De-
protonation or deprotection of a dioxetane substituted
with a phenolic group gives unstable dioxetane bearing an
oxidophenyl anion, which undergoes intramolecular charge-
transfer-induced decomposition (CTID)19 with the accom-
panying emission of light.3-8 Thus, we investigated the
CTID of the present dioxetanes 2e-4e bearing a 3-acetox-
yphenyl group and dioxetane 2a bearing a 3-hydroxyphenyl
group. When a solution of 2e in DMSO (1.0 ꢀ 10-5 M, 1 mL)
was added to a tetrabutylammonium fluoride (TBAF)20,21
solution in DMSO (1.0 ꢀ 10-2, 2 mL) at 25 °C, 2e
FIGURE 1. Chemiluminescence spectra of sulfanyl-2a, 2e, sulfinyl-
3e, and sulfonyl-substituted dioxetane 4e.
decomposed following pseudo-first-order kinetics (kCTID
,
Table 2) to emit yellow light, the spectrum of which is
shown in Figure 1. The chemiluminescence properties were
as follows: maximum wavelength λmaxCL=565 nm, chemi-
SCHEME 2. TBAF-Induced Chemiluminescent Decomposition
of Dioxetanes Bearing a Sulfanyl-, Sulfinyl-, or Sulfonyl Group
luminescence efficiency ΦCL=3.0 ꢀ 10-3 22,23
,
and half-life
of decomposition t1/2CTID = 4.9 s (Table 2). Although a
neutral form of 14e could not be isolated from the spent
reaction mixture presumably because of its instability under
the basic conditions, the CTID of 2e should give excited 14e,
inferring from various CTIDs of hydroxyaryl-substituted
dioxetanes reported (Scheme 2).8 The decomposition of 2a
was similarly induced with TBAF to give chemiluminescence
(Figure 1 and Table 2). Notably, sulfanyl-substituted dioxe-
CL
tanes 2a and 2e displayed chemiluminescence with λmax
that was considerably longer than that for a related oxy-
467 nm),24 and the substituent R at the 3-position of 2
influenced the chemiluminescence spectrum, as illustrated
in Figure 1.
substituted dioxetane such as 5-tert-butyl-1-(3-hydroxy-
CL
phenyl)-4,4-dimethyl-2,6,7-trioxabicyclo[3.2.0]heptane (λmax
=
Next, we attempted to investigate the base-induced de-
composition of sulfonyl-substituted dioxetane 4e. When
treated with a large excess of TBAF in DMSO, 4e decom-
posed to give very weak dark-red light (λmaxCL = 848 nm),
the spectrum of which is shown in Figure 1. As shown in
Table 2, ΦCL was only 1/14000 of that for sulfanyl-substi-
tuted dioxetane 2e. Although 3e was unstable as described
(19) The chemiluminescent (CL) decomposition of hydroxyphenyl-sub-
stituted dioxetanes has been proposed to proceed by the CIEEL8 (chemically
initiated electron exchange luminescence) mechanism, where an initially
formed radical ion pair annihilates by back electron transfer (BET) to afford
excited aromatic ester. However, the question as to whether such a CL
reaction includes BET as a fundamental process is still being argued and
remains unclear. Therefore, we have recently been using the term CTID,
which includes the CIEEL and other CT-induced mechanisms.
(20) TBAF has been known to effectively act as a base for hydrolysis of
esters and amides.21
above, we tried to examine the TBAF-induced decomposi-
CL
tion of 3e. As a result, 3e gave very weak light with λmax
=
795 nm (Figure 1), and neither ΦCL nor kCTID was estimated.
The tendency for the present dioxetanes to decrease
emission energy as increasing oxidation state of the sulfur
is apparently elucidated by an MO calculation (B3LYP/
6-31G(d)): the energy gap (ΔE = ELUMO - EHOMO) of
model emitters, ArCO-X-Me (Ar = m-oxidophenyl),
decreased in the order of X = O (ΔE = 3.17 eV) > X = S
(2.85 eV) > X = SO (2.42 eV) > X = SO2 (2.27 eV).
(21) (a) Namikoshi, M.; Kundu, B.; Rinehart, K. L. J. Org. Chem. 1991,
56, 5464–5466. (b) Choe, Y. S.; Katzenellenbogen, J. A. Tetrahedron Lett.
1993, 34, 1579–1580. (c) Kita, Y.; Maeda, H.; Takahashi, F.; Fujii, S.;
Ogawa, T.; Hatayama, K. Chem. Pharm. Bull. 1994, 42, 147–150.
(22) ΦCL was estimated based on the value of 0.29 for chemiluminescent
decomposition of 3-adamantylidene-4-methoxy-4-(3-oxidophenyl)-1,2-di-
oxetane in the TBAF/DMSO system.23
(23) Trofimov, A. V.; Mielke, K.; Vasil’ev, R. F.; Adam, W. Photochem.
Photobiol. 1996, 63, 463–467.
(24) Matsumoto, M.; Yamada, K.; Ishikawa, H.; Hoshiya, N.; Watanabe,
N.; Ijuin, H. K. Tetrahedron Lett. 2006, 47, 8407–8411.
882 J. Org. Chem. Vol. 75, No. 3, 2010

Watanabe et al.
JOCArticle
Conclusions
Singlet Oxygenation of 4-tert-Butyl-5-(3-hydroxyphenyl)-3,3-
dimethyl-2,3-dihydrothiophene (5a). A solution of 4-tert-butyl-
5-(3-hydroxyphenyl)-3,3-dimethyl-2,3-dihydrothiophene (5a)
(252 mg, 0.960 mmol) and TPP (1.0 mg) in CH2Cl2 (20 mL)
was irradiated externally with a 940 W Na lamp for 20 min under
an oxygen atmosphere at 0 °C. The photolysate was concen-
trated in vacuo and the residue was chromatographed on silica
gel and eluted with CH2Cl2 to give dioxetane 2a as a pale yellow
solid (16 mg, 6% yield). Further elution gave sulfoxide 11 as a
colorless solid (249 mg, 93% yield). Sulfoxide 11 was synthe-
sized independently by the oxidation of 5a with sodium period-
ate in H2O/MeOH.
The sulfanyl-substituted bicyclic dioxetanes 2 reported
here were found to be sufficiently stable thermally to permit
handling at room temperature. Among them, 2a and 2e
underwent TBAF-induced decomposition in DMSO to
give yellow light with moderate chemiluminescence yields
(ΦCL = 3.0 ꢀ 10-3 to 7.9 ꢀ 10-3). The oxidation of 2c and 2e
with 1 equiv of MCPBA gave the corresponding sulfinyl-
substituted dioxetanes 3c and 3e, while their oxidation
with >2 equiv of MCPBA gave the corresponding sulfo-
nyl-substituted dioxetanes 4c and 4e. Both 3e and 4e were
also found to undergo TBAF-induced decomposition to give
very weak light with λmaxCL values longer than those for 2.
2a: yellow granules ,mp 96.0-97.5 °C dec (from ether-
1
hexane). H NMR (400 MHz, CDCl3): δH 1.04 (s, 9H), 1.26
(s, 3H), 1.50 (s, 3H), 2.55 (d, J = 11.6 Hz, 1H), 3.95 (d with fine
coupling, J = 11.6 Hz, 1H), 4.86 (br s, 1H), 6.79 (dd, J = 8.9 and
2.4 Hz, 1H), 7.08-7.28 (m, 3H) ppm. 13C NMR (125 MHz,
CDCl3): δC 22.7, 24.9, 27.7, 38.5, 47.4, 52.2, 106.7, 112.4, 114.9
(br), 115.6, 120.4 (br), 128.9, 139.5, 155.1 ppm. IR (KBr):
ν~ 3433, 3064, 2985, 2964, 1601 cm-1. Mass (m/z, %): 294
(Mþ, 0.9), 262 (Mþ - 32, 0.8), 238 (25), 209 (11), 121 (100).
HRMS (ESI): 317.1185, calcd for C16H22O3SNa [M þ Naþ]
317.1187. Anal. Calcd for C16H22O3S: C, 65.27; H, 7.53. Found:
C, 65.23; H, 7.62.
Experimental Section
Singlet Oxygenation of 2-Acetoxy-4-tert-butyl-5-(3-methoxy-
phenyl)-3,3-dimethyl-2,3-dihydrothiophene (5c): Typical Proce-
dure. A solution of 2-acetoxy-4-tert-butyl-5-(3-methoxyphenyl)-
3,3-dimethyl-2,3-dihydrothiophene (5c) (265 mg, 0.792 mmol)
and MB (5.0 mg) in dry CH2Cl2 (25 mL) was irradiated externally
with a 940 W Na lamp for 2.5 h under an oxygen atmosphere
at 0 °C. The photolysate was concentrated in vacuo. The residue
was chromatographed on silica gel and eluted with CH2Cl2-
hexane (1:2) to give 3-acetoxy-5-tert-butyl-1-(3-methoxyphenyl)-
4,4-dimethyl-6,7-dioxa-2-thiabicyclo[3.2.0]heptane (2c) as a pale
yellow solid (256 mg, 88% yield).
11: colorless granules, mp 174.0-175.0 °C (from THF-
1
hexane). H NMR (400 MHz, CDCl3): δH 1.15 (s, 9H), 1.47
(s, 3H), 1.64 (s, 3H), 2.96 (d, J = 12.7 Hz, 1H), 3.29 (d, J = 12.7
Hz, 1H), 6.66-6.72 (m, 2H), 6.76 (br s, 1H), 7.14 (td, J = 7.8 and
2.2 Hz, 1H) ppm. 13C NMR (100 MHz, CDCl3): δC 30.0, 30.5,
32.1, 37.3, 51.2, 66.4, 115.7, 117.1 (br), 120.5 (br), 129.1, 135.1,
Dihydrothiophenes 5d and 5e were similarly oxygenated with
singlet oxygen to give the coresponding dioxetanes 2d and 2e
both in 85% yields, respectively.
142.7, 156.9, 159.5 ppm. IR (KBr): ν~ 3152, 2965, 1588 cm-1
.
Mass (m/z, %): 278 (Mþ, 22), 262 (61), 247 (100), 191 (70), 159
(53), 121 (27). HRMS (ESI): 279.1417, calcd for C16H23O2S
[M þ Hþ] 279.1419, and 301.1217, calcd for C16H22O2SNa
[MþNaþ] 301.1238. Anal. Calcd for C16H22O2S: C, 69.02; H,
7.96. Found: C, 68.97; H, 8.14.
2c: pale yellow columns, mp 98.5-99.5 °C dec (from
ether-hexane). 1H NMR (400 MHz, CDCl3): δH 1.09 (s, 9H),
1.16 (s, 3H), 1.41 (s, 3H), 2.19 (s, 3H), 3.81 (s, 3H), 6.69 (s, 1H),
6.86 (d with fine coupling, J = 8.2 Hz, 1H), 7.08-7.30 (m, 3H)
ppm. 13C NMR (125 MHz, CDCl3): δC 18.3, 20.0, 20.8, 27.8,
39.2, 53.7, 55.3, 83.1, 104.9, 109.4, 113.7 (br), 114.1, 120.4 (br),
Oxidation of 3-Acetoxy-5-tert-butyl-1-(3-methoxyphenyl)-
4,4-dimethyl-6,7-dioxa-2-thiabicyclo[3.2.0]heptane (2c) with m-
Chloroperbenzoic Acid (MCPBA): Typical Procedure. MCPBA
(65.0%, 135 mg, 0.508 mmol) was added to a solution of 3-
acetoxy-5-tert-butyl-1-(3-methoxyphenyl)-4,4-dimethyl-6,7-di-
oxa-2-thiabicyclo[3.2.0]heptane (2c) (200 mg, 0.546 mmol) in
dry CH2Cl2 (4.0 mL) and stirred at room temperature for 1.5 h.
The reaction mixture was chromatographed on NH silica gel
and eluted with CH2Cl2 to remove m-chlorobenzoic acid and
intact MCPBA. The solid 3-acetoxy-5-tert-butyl-1-(3-methoxy-
phenyl)-4,4-dimethyl-6,7-dioxa-2-thiabicyclo[3.2.0]heptane 2-oxide
(3c) was recrystallized from ether-hexane to give 3c as a pale
yellow granules (181 mg, 87% yield).
When 4 equiv of MCPMA was used to oxidize 2c (100 mg)
under similar conditions as described above, 3-acetoxy-5-tert-
butyl-1-(3-methoxyphenyl)-4,4-dimethyl-6,7-dioxa-2-thiabicy-
clo[3.2.0]heptane 2,2-dioxide (4c) was produced. The reaction
mixture was chromatographed on NH silica gel and eluted with
CH2Cl2 to give 4c as a pale yellow solid (84% yield).
128.7, 138.3, 159.0, 169.6 ppm. IR (KBr): ν~ 3009, 1762 cm-1
.
Mass (m/z, %): 366 (Mþ, trace), 334 (Mþ - 32, 3), 136 (11), 135
(100). HRMS (ESI): 389.1385, calcd for C19H26O5SNa [M þ
Naþ] 389.1399. Anal. Calcd for C19H26O5S: C, 62.27; H, 7.15.
Found: C, 61.88; H, 7.19.
2d: pale yellow columns, mp 86.0-87.5 °C dec (from ether-
1
hexane). H NMR (400 MHz, CDCl3): δH 1.07 (s, 9H), 1.20
(s, 3H), 1.32 (s, 3H), 3.59 (s, 3H), 3.81 (s, 3H), 5.61 (s, 1H), 6.85
(d with fine coupling, J = 8.2 Hz, 1H), 7.04-7.32 (m, 2H),
7.26 (dd, J=8.2 and 7.8 Hz, 1H) ppm. 13C NMR (125 MHz,
CDCl3): δC 17.6, 20.1, 27.9, 39.2, 54.0, 55.3, 60.8, 94.8, 105.9,
108.5, 113.4 (br), 114.0, 120.7 (br), 128.6, 139.2, 158.9 ppm. IR
(KBr): ν~ 2988, 2933, 2832, 1607, 1581 cm-1. Mass (m/z, %):
338 (Mþ, trace), 306 (Mþ - 32, 1), 171 (30), 136 (11), 135 (100),
107 (10). HRMS (ESI): 361.1441, calcd for C18H26O4SNa [M þ
Naþ] 361.1450. Anal. Calcd for C18H26O4S: C, 63.87; H, 7.74.
Found: C, 63.79; H, 7.87.
2e: pale yellow granules, mp 98.5-100.5 °C dec (from ether-
Similar oxidation was applied to 1-(3-acetoxyphenyl)-5-tert-
butyl-3-methoxy-4,4-dimethyl-6,7-dioxa-2-thiabicyclo[3.2.0]he-
ptane (2e) to give 1-(3-acetoxyphenyl)-5-tert-butyl-3-methoxy-
4,4-dimethyl-6,7-dioxa-2-thiabicyclo[3.2.0]heptane 2-oxide (3e)
(31%) or 1-(3-acetoxyphenyl)-5-tert-butyl-3-methoxy-4,4-dime-
thyl-6,7-dioxa-2-thiabicyclo[3.2.0]heptane 2,2-dioxide (4e) (84%).
3c: pale yellow granules, mp 72.5-74.5 °C dec (from ether-
1
hexane). H NMR (400 MHz, CDCl3): δH 1.06 (s, 9H), 1.20
(s, 3H), 1.31 (s, 3H), 2.30 (s, 3H), 3.59 (s, 3H), 5.61 (s, 1H), 7.06
(ddd, J =8.1, 2.2, and 0.7 Hz, 1H), 7.30-7.40 (m, 1H), 7.35
(t, J = 8.1 Hz, 1H), 7.42-7.51 (m, 1H) ppm. 13C NMR (125
MHz, CDCl3) δC 17.6, 20.0, 21.0, 27.7, 39.2, 53.9, 60.7, 94.9,
105.9, 108.0, 120.8 (br), 121.7, 124.2, and 125.9 (br), 128.5,
139.3, 150.0, 169.0 ppm. IR (KBr): ν~ 2981, 2935, 1766, 1589
cm-1. Mass (m/z, %, 20 eV): 366 (Mþ, 3), 334 (Mþ - 32, 9), 281
(39), 250 (12), 171 (56), 164 (12), 163 (100), 152 (13), 136 (10), 128
(36). HRMS (ESI, 30 eV): 389.1400, calcd for C19H26O5SNa
[M þ Naþ] 389.1399. Anal. Calcd for C19H26O5S: C, 62.27; H,
7.15. Found: C, 62.26; H, 7.32.
1
hexane). H NMR (400 MHz, CDCl3): δH 1.10 (s, 3H), 1.11
(s, 9H), 1.40 (s, 3H), 2.30 (s, 3H), 3.83 (s, 3H), 6.84-7.30 (m,
4H), 7.37 (t, J = 8.2 Hz, 1H) ppm. 13C NMR (125 MHz,
CDCl3): δC 19.8, 20.5, 20.8, 27.3, 40.0, 48.4, 55.3, 92.7, 102.0,
104.2, 113.2 (br), 115.0, 118.2, and 119.7 (br), 129.7, 135.0,
159.7, 169.2 ppm. IR (KBr): ν~ 2976, 1764, 1688, 1584 cm-1
.
J. Org. Chem. Vol. 75, No. 3, 2010 883

Watanabe et al.
JOCArticle
Mass (m/z, %, 20 eV): 382 (Mþ, 0.5), 286 (39), 152 (33), 135 (74),
85 (77), 57 (100). HRMS (ESI): 405.1342, calcd for C19H26O6S-
Na [M þ Naþ] 405.1348, and 787.2822, calcd for C38H52O12S2-
Na [2M þ Naþ] 787.2798.
10c: colorless needles melted at 94.0-94.5 °C (from ether-
1
hexane). H NMR (400 MHz, CDCl3): δH 1.29 (s, 9H), 1.41
(s, 3H), 1.42 (s, 3H), 2.05 (s, 3H), 3.85 (s, 3H), 7.12 (ddd, J = 8.3,
2.6, and 1.0 Hz, 1H), 7.12 (s, 1H), 7.35 (dd, J = 8.3 and 7.6 Hz,
1H), 7.48 (dd, J = 2.6 and 1.7 Hz, 1H), 7.58 (ddd, J = 7.6, 1.7,
and 1.0 Hz, 1H) ppm. 13C NMR (125 MHz, CDCl3): δC 20.9,
22.5, 22.7, 28.3, 45.9, 54.1, 55.5, 81.8, 111.5, 120.2, 120.5, 129.6,
137.5, 159.7, 168.7, 188.8, 214.8 ppm. IR (KBr): ν~ 2974, 1753,
1680, 1580 cm-1. Mass (m/z, %): 366 (Mþ, trace), 252 (4), 222
(7), 136 (11), 135 (100), 107 (10). HRMS (ESI): 389.1390, calcd
for C19H26O5SNa [M þ Naþ] 389.1399. Anal. Calcd for
C19H26O5S: C, 62.27; H, 7.15. Found: C, 62.15; H, 7.22.
Time Course for Thermal Decomposition of Dioxetanes 2:
General Procedure. A solution of dioxetane 2 (3-5 mg) in
toluene-d8 (0.8 mL) in an NMR sample tube was heated by
means of a liquid paraffin bath thermostated at an appropriate
temperature range of 50-80 °C. After heating at regular inter-
vals, 1H NMR analysis was conducted on the samples to
determine the ratio of the intact 2 vs. the corresponding keto
thioester 10.
Chemiluminescence Measurement: General Procedure. A
freshly prepared solution (2 mL) of TBAF (1.0 ꢀ 10-2 mol/L)
in DMSO was transferred to a quartz cell (10 ꢀ 10 ꢀ 50 mm) and
the latter placed in the spectrometer, which was thermostated
with stirring at 25 °C. After 3-5 min, a solution of the sulfanyl-
substituted dioxetane 2a or 2e in DMSO (1.0 ꢀ 10-5 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 adamantylidene dioxetane, whose chemiluminescent effi-
ciency ΦCL has been reported to be 0.29 and was used here
as a standard.22 For chemiluminescent decomposition of sulfi-
nyl-substituted dioxetane 3e, a solution of the dioxetane in
DMSO (1.0 ꢀ 10-4 mol/L, 1 mL) was used, while for sulfonyl-
substituted dioxetane 4e, a solution of the dioxetane in DMSO
(1.0 ꢀ 10-3 mol/L, 1 mL) and TBAF (0.1 mol/L) in DMSO were
used.
4c: pale yellow granules, mp 120.0-123.0 °C dec (from
ether-hexane). 1H NMR (400 MHz, CDCl3): δH 1.16 (s, 9H),
1.18 (s, 3H), 1.51 (s, 3H), 2.35 (s, 3H), 3.83 (s, 3H), 6.67 (s, 1H),
7.00 (d with fine coupling, J = 8.3 Hz, 1H), 7.10 (s with fine
coupling, 1H), 7.16 (ddd, J = 7.8, 1.7, and 0.9 Hz, 1H), 7.37 (dd,
J = 8.3 and 7.8 Hz, 1H) ppm. 13C NMR (125 MHz, CDCl3): δC
18.1, 20.4, 21.0, 27.7, 40.7, 46.2, 55.3, 85.1, 100.2, 101.2, 112.7,
and 115.0 (br), 115.7, 119.6, and 121.2 (br), 127.6, 128.7, and
129.5 (br), 158.6 and 159.6 (br), 168.8 ppm. IR (KBr): ν~ 2975,
1769, 1607, 1582 cm-1. Mass (m/z, %, 20 eV): 398 (Mþ, 0.3), 277
(11), 199 (13), 152 (37), 135 (50), 128 (17), 85 (62), 57 (100).
HRMS (ESI): 421.1300, calcd for C19H26O7SNa [M þ Naþ]
421.1297, and 819.2687, calcd for C38H52O14S2Na [2M þ Naþ]
819.2696. Anal. Calcd for C19H26O7S: C, 57.27; H, 6.58. Found:
C, 57.22; H, 6.58.
3e: pale yellow plates, mp 93.3-95.0 °C dec (from ether-
1
hexane). H NMR (400 MHz, CDCl3): δH 1.09 (s, 9H), 1.20
(s, 3H), 1.33 (s, 3H), 2.31 (s, 3H), 3.86 (s, 3H), 5.27 (s, 1H),
7.04-7.55 (m, 2H), 7.15 (d with fine coupling, J = 7.9 Hz, 1H),
7.45 (t, J = 7.9 Hz, 1H) ppm. 13C NMR (125 MHz, CDCl3): δC
19.3, 20.8, 21.0, 27.3, 40.0, 49.3, 61.1, 102.3, 103.7, 104.2, 122.7,
129.5 (br), 135.6, 150.7 (br), 168.9 ppm. IR (KBr): ν~ 2976, 1764,
1206, 1030 cm-1. Mass(m/z, %, 20 eV): 318 (Mþ - 64, 2), 303(2),
212 (18), 171 (51), 163 (48), 138 (10), 86 (33), 85 (100). HRMS
(ESI): 405.1340, calcd for C19H26O6SNa [M þ Naþ] 405.1348.
4e: pale yellow plates, mp 100.0-102.0 °C dec (from AcOEt-
1
hexane). H NMR (400 MHz, CDCl3): δH 1.13 (s, 9H), 1.24
(s, 3H), 1.41 (s, 3H), 2.31 (s, 3H), 3.89 (s, 3H), 5.13 (s, 1H),
C
7.19-7.24 (m, 1H), 7.30 (br s, 1H), 7.40-7.50 (m, 2H) ppm. 13
NMR (125 MHz, CDCl3): δC 17.3, 21.0, 21.3, 27.6, 40.6, 46.7,
61.5, 96.5, 99.6, 101.5, 120.7, and 122.5 (br), 123.1, 124.3, and
126.2 (br), 128.1, 128.4, and 129.3 (br), 149.5 and 150.7 (br), 168.9
ppm. IR (KBr): ν~ 2981, 2940, 1769, 1589 cm-1. Mass (m/z, %,
20 eV): 180 (AcOC6H4CO2H, 10), 171 (11), 163 (43), 152 (15), 138
(46), 128 (12), 86 (27), 85 (69), 57 (100). HRMS (ESI): 421.1280,
calcd for C19H26O7SNa [M þ Naþ] 421.1297. Anal. Calcd for
C19H26O7S: C, 57.27; H, 6.58. Found: C, 56.89; H, 6.67.
Acknowledgment. The authors 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.
Thermal Decomposition of 3-Acetoxy-5-tert-butyl-1-(3-methoxy-
phenyl)-4,4-dimethyl-6,7-dioxa-2-thiabicyclo[3.2.0]heptane (2c): Typi-
calProcedure. Dioxetane 2c (54.6 mg, 0.149 mmol) was stirred in
toluene (1.0 mL) for 1 h under a N2 atmosphere at 110 °C. After
the concentration in vacuo, the reaction mixture was chromato-
graphed on silica gel and eluted with AcOEt-hexane (1:9) to
give S-1-acetoxy-2,2,4,4-tetramethyl-3-oxopentyl 3-methoxy-
benzenethioate (10c) as a colorless solid (47.6 mg, 87% yield).
The other dioxetanes 2a, 2d, and 2e were similarly decomposed
in hot toluene to give the corresponding arylthioate 10a, 10d,
and 10e in 75-92% isolated yield.
Supporting Information Available: General method for the
Experimental Section, 1H NMR/13C NMR spectra of 2c-e, 2a,
3c, 3e, 4c, 4e, 5a-g, 7OH, 7, 8-cis, 8-trans, 9, 10a, 10c-e, and 11,
and crystallographic information files for 2c and 4e. This
material is available free of charge via the Internet at http://
pubs.acs.org.
884 J. Org. Chem. Vol. 75, No. 3, 2010