New insight into the reaction of singlet oxygen with sulfur-containing cyclic alkenes: Dye-sensitized photooxygenation of 5,6-dihydro-1,4-dithiins

Article abstract of DOI:10.1021/jo701983v

(Chemical Equation Presented) The reaction of 3-methyl-5,6-dihydro-1,4- dithiins with singlet oxygen affords dicarbonyl compounds and/or ring-contracted ketosulfoxides, the latter regio- and stereoselectively, depending on the nature of the substituent at C-2 and on the reaction conditions. In competition with normal fragmentation, the intermediate dioxetanes, derived from [2 + 2] cycloaddition of singlet oxygen to the double bond, undergo an intramolecular oxygen transfer to the sulfur-1 atom, leading to labile epoxide intermediates. The latter convert to cis- and trans-ketosulfoxides through a non-concerted S-4 migration. This pathway is promoted by the electron-withdrawing group at C-2 and, for monosubstituted amide, by the solvent basicity. S-Oxidation of dithiins is insignificant, except for the monosubstituted amide derivative or in the presence of protic species, and occurs selectively at the S-1 atom.

Full text of DOI:10.1021/jo701983v

New Insight into the Reaction of Singlet Oxygen with
Sulfur-Containing Cyclic Alkenes: Dye-Sensitized Photooxygenation
of 5,6-Dihydro-1,4-dithiins
Flavio Cermola,† Annalisa Guaragna,† Maria Rosaria Iesce,*,† Giovanni Palumbo,†
Raffaella Purcaro,† Maria Rubino,† and Angela Tuzi‡
Dipartimento di Chimica Organica e Biochimica and Dipartimento di Chimica, UniVersita` degli Studi di
Napoli Federico II, Complesso UniVersitario Monte Sant’ Angelo, Via Cinthia, I-80126, Napoli, Italy
iesce@unina.it
ReceiVed September 10, 2007
The reaction of 3-methyl-5,6-dihydro-1,4-dithiins with singlet oxygen affords dicarbonyl compounds
and/or ring-contracted ketosulfoxides, the latter regio- and stereoselectively, depending on the nature of
the substituent at C-2 and on the reaction conditions. In competition with normal fragmentation, the
intermediate dioxetanes, derived from [2 + 2] cycloaddition of singlet oxygen to the double bond, undergo
an intramolecular oxygen transfer to the sulfur-1 atom, leading to labile epoxide intermediates. The latter
convert to cis- and trans-ketosulfoxides through a non-concerted S-4 migration. This pathway is promoted
by the electron-withdrawing group at C-2 and, for monosubstituted amide, by the solvent basicity.
S-Oxidation of dithiins is insignificant, except for the monosubstituted amide derivative or in the presence
of protic species, and occurs selectively at the S-1 atom.
Introduction
that it is subject to decomposition to sulfide and ground-state
oxygen (physical quenching)4 and to chemical processes.
Although sulfoxide formation is its main reaction, persulfoxide
undergoes a myriad of inter- and intramolecular reactions
strongly depending on the substituents or on the reaction
conditions (nature of solvent, presence of acid traces, temper-
ature, etc.).5 Among the others, recently it has been reported
that the presence of R-hydrogens may favor the oxidation
capability of a sulfide and induce the breakage of the sulfur-
R-carbon bond.6
The reaction of sulfides with singlet oxygen has received great
attention due to the many important roles of sulfur-containing
substances in key positions of proteins, enzymes, etc. or as
antioxidants in polymers or rubbers.1 Studies have been
particularly devoted to the question of the identities of the
reactive intermediates.2 Persulfoxide (R2S+-OO- T R2S•-OO•)
is accepted as the first formed intermediate.3 It is well-known
* Corresponding author. Fax: +39 081 674 392.
† Dipartimento di Chimica Organica e Biochimica.
‡ Dipartimento di Chimica.
(4) Liang, J.-J.; Gu, C.-L.; Kacher, M. L.; Foote, C. S. J. Am. Chem.
Soc. 1983, 105, 4717.
(5) (a) Akasaka, T.; Ando, W. In Organic Peroxides; Ando, W., Ed.; J.
Wiley and Sons: New York, 1992; p 599. (b) Clennan, E. L.; Pace, A.
Tetrahedron 2005, 61, 6665. (c) Iesce, M. R.; Cermola, F.; Rubino, M.
Curr. Org. Chem. 2007, 11, 1053.
(1) For some reviews: (a) Clennan, E. L. Sulfur Rep. 1996, 19, 171. (b)
Jensen, F. In AdVances in Oxygenated Processes; Baumstark, A. L., Ed.;
JAI Press: Greenwich, CT, 1995; Vol. 4, pp 1-48. (c) Ando, W.; Takata,
T. In Singlet Oxygen; Frimer, A. A., Ed.; CRC Press: Boca Raton, FL,
1985; Vol. III, part 2.
(2) For some recent reports: Clennan, E. L.; Hightower, S. E.; Greer,
A. J. Am. Chem. Soc. 2005, 127, 11819.
(3) Nahm, K.; Foote, C. S. J. Am. Chem. Soc. 1989, 111, 1909.
(6) (a) Takata, T.; Tamura, Y.; Ando, W. Tetrahedron 1985, 41, 2133.
(b) Bonesi, S. M.; Torriani, R.; Mella, M.; Albini, A. Eur. J. Org. Chem.
1999, 1723.
10.1021/jo701983v CCC: $37.00 © 2007 American Chemical Society
Published on Web 11/30/2007
J. Org. Chem. 2007, 72, 10075-10080
10075

Cermola et al.
SCHEME 1. Oxygenation Products
FIGURE 1. 2,3-Disubstituted dithiins.
Sulfur oxidation goes to a lesser extent in the singlet oxygen
reaction of cyclic and acyclic vinyl sulfides so that the [2 + 2]
cycloaddition of singlet oxygen to the double bond, or the ene-
mode reaction in the presence of allylic hydrogens, becomes
the preferential pathway.1 In this context, we recently found
that the reaction of 5,6-dihydro-1,4-oxathiins with singlet oxygen
led to the corresponding dioxetanes almost exclusively.7 The
presence of a sulfur atom influences the behavior of the bicyclic
peroxides, which bear an electron-withdrawing group, promoting
the formation of unusual ring-contracted ketosulfoxides instead
of the usual O-O and C-C bond breakage products.7 To gain
further information on the role of sulfur in the singlet oxygen
reaction of sulfur-substituted cycloalkenes, we have devoted our
attention to the 5,6-dihydro-1,4-dithiin system. In particular, we
have examined the dye-sensitized photooxygenation8 of deriva-
tives 1a-d with a substituent pattern suitable to study the
substituent effect (Figure 1).9 The reactions were carried out in
CH2Cl2 but also in protic media, known to favor the oxidation
of sulfides (e.g., trifluroethanol (TFE)10a or methanol,4,10b the
latter also capable of trapping ionic intermediates in the
oxygenation of electron-rich alkenes10c). Further experiments
were also carried out in CH3CN and acetone, which could have
a role, as hydrogen bond acceptors, in the presence of an amidic
hydrogen (e.g., 1c).
compound 2a and diketone 3a (Table 1, entry 1). Dicarbonyl
compound 2c was a minor product in the reaction of amide 1c,
which led mainly to sulfoxide 4c (Table 1, entry 8). Ester 1b
and N-methyl amide 1d gave ketoesters cis-6b,d besides small
amounts of their trans-isomers (Table 1, entries 4 and 13,
respectively).
Concentration or solvent change (from CH2Cl2 to acetone or
to more polar CH3CN) showed no significant effects except for
1c. In this case, a serious change of the 2c/4c ratio was found
by using a more diluted solution [8:2 in 10-2 M (Table 1, entry
8) and 4:6 in 10-3 M (Table 1, entry 9)]. The basic nature of
the solvent was also significant. Indeed, the 1H NMR spectrum
of the reaction mixture in CH3CN showed, in addition to 2c
and 4c and trans-6c, the presence of cis-6c as a labile compound
that converted to trans-6c (Table 1, entry 11). A similar result,
but with a higher amount of the labile compound, was obtained
using acetone as the solvent (Table 1, entry 12). TLC gave only
trans-6c (35% in CH3CN and 61% in acetone). Ketothioketal
7c was also found in both solvents.
For all series, a drastic change in product distribution was
observed in MeOH or by adding 10-100 equiv of trifluoroet-
hanol (TFE)10a in CH2Cl2. Under these conditions, S-oxides
4b-d were selectively formed (Table 1, entries 5, 6, 10, 14,
and 15). Methyl phenyl dithiin 1a led to both sulfoxides 4a
and 5a. Moreover, ketosulfoxide 6a was found besides a small
amount of ketothioketals 7a and 8a (Table 1, entries 2 and 3).
Identification of Products. All compounds were character-
ized on the basis of analytical and/or spectroscopic data. The
stereochemistry of cis- and trans-6b,d and trans-6c was assigned
by X-ray analysis. The crystallographic determination also
accounted for the upfield value of Me-CO protons (δ 1.54) in
the 1H NMR of cis-6d. It shows that the methyl group is above
the ring current of phenyl and is, hence, affected by its strong
diamagnetic effect, as previously reported for similar com-
pounds.7 NMR data for the labile cis-6c were deduced from
the reaction mixture in acetone, by performing the spectra in
acetone-d6, in which the conversion to trans-6c occurred slowly.
The close similarity of the data with those of trans-6c allowed
us to tentatively assign the structure cis-6c. In particular, the
13C spectrum exhibited two signals as triplets at δ 35.8 and 58.3,
which were correlated to a complex proton pattern in the δ range
of 3.80-4.46 due to the SCH2CH2SO system. In addition to
the amide carbon signal (δ 166.3), two quaternary carbons at δ
95.2 and 199.8 due to the quaternary carbon linked to two
heteroatoms and to the carbonyl carbon, respectively, were
observed.
Results and Discussion
Photooxygenation of 1a-d (0.02 M solution) was carried out
at -20 °C using tetraphenylporphine (in CH2Cl2) or methylene
blue (in MeOH, CH3CN, and acetone) as sensitizers. The
reaction products that were generally isolated by TLC are shown
in Scheme 1. Table 1 reports the relative amounts of the products
1
that were spectroscopically deduced by H NMR of the crude
reaction mixtures, as well as the yields of pure isolated
compounds. Isolated yields were lower than those estimated by
1H NMR spectra of the crude mixtures since all products
underwent partial chromatographic alteration.
As shown in Table 1, product distribution depends on the
nature of the substituents at the double bond and on the solvent
used. In CH2Cl2, methyl aryl dithiin 1a gives dicarbonyl
(7) (a) Cermola, F.; Iesce, M. R. J. Org. Chem. 2002, 67, 4937. (b)
Cermola, F.; De Lorenzo, F.; Giordano, F.; Graziano, M. L.; Iesce, M. R.;
Palumbo, G. Org. Lett. 2000, 2, 1205.
(8) The use of a dye, visible light, and molecular oxygen is one of the
most common and efficient procedures to produce singlet oxygen. Foote,
C. S.; Clennan, E. L. In ActiVe Oxygen in Chemistry; Foote, C. S., Valentine,
J. S., Greenberg, A., Liebman, J. F., Eds.; Chapman and Hall: London,
1995; p 105.
(9) A symmetrically substituted dithiin (2,3-diphenyl derivative) was
previously photooxygenated giving the corresponding dicarbonyl compound
and benzyl: Handley, R. S.; Stern, A. J.; Schaap, A. P. Tetrahedron Lett.
1985, 26, 3183.
(10) (a) Bonesi, S. M.; Mella, M.; d’Alessandro, N.; Aloisi, G. G.;
Vanissi, M.; Albini, A. J. Org. Chem. 1998, 63, 9945. (b) Clennan, E. L.;
Greer, A. J. Org. Chem. 1996, 61, 4793. (c) Gorman, A. A.; Gould, I. R.;
Hamblett, I. J. Am. Chem. Soc. 1982, 104, 7098.
Compounds 4 and 5 showed typical sulfoxide bands at 1020-
1010 cm-1 in the IR spectra as well as the downfield shift of
one triplet signal in the δ range of 42-43 due to the CH2SO
carbon in the 13C spectra. Structures 4 were assigned on the
10076 J. Org. Chem., Vol. 72, No. 26, 2007

Photooxygenation of 5,6-Dihydro-1,4-dithiins
TABLE 1. Dye-Sensitized Photooxygenation of 1a-da
product distributionb
entry
dithiin
solvent
2
3
4 [5]
(trace)
21(13)[10(6)]
15(8)[9(4)]
(<2)
70(39)
26(19)
34(23)
80(58)
35(28)
68(50)
41(38)
15(7)
cis-6
trans-6
7
8
c
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
1a
CH2Cl2
50(35)
19(15)
25(20)
50(55)
34(24)
38(29)
c
CH2Cl2 /TFEd,e
12(7)f
8(4)f
4(2)
2(<2)
(trace)
3(2)
MeOHg
c
1b
1c
CH2Cl2
90(62)
30(20)
67(51)
63(48)
10(8)
(trace)
7(3)
3(<2)
(trace)
(trace)
3(<2)
17j(35)
25j(61)
5(2)
c
CH2Cl2 /TFEd,e
MeOHg
MeOHg/-50 °C
c
CH2Cl2
CH2Cl2
20(15)
50(34)
20(16)
11(9)
(trace)
15(10)
9(6)
c,h
MeOHg
CH3CNg
acetoneg
28i
3(<2)
10(4)
3(<2)
47i
c
1d
CH2Cl2
(trace)
89(31)
56(25)
95(58)
11(3)
44(25)
c
CH2Cl2 /TFEd,e
MeOHg
1
a 0.02 M solution at -20 °C except otherwise stated. b Product ratios that have been determined by H NMR spectra of crude reaction mixtures are an
average of two or three determinations. In parentheses, yields of pure products that have been isolated by preparative TLC are reported. They are lower than
those deduced spectroscopically due to the partial decomposition during chromatographic separation. c Tetraphenylporphine (TPP) as the sensitizer. d 1:
trifluoroethanol (TFE) ) 1:100. e Under these conditions, the low chromatographic yield is due to the presence of unidentified material. f Stereochemistry
not assigned. g Methylene blue as the sensitizer. h 10-3 M solution. i This value diminishes in time since the product converted to trans-6c. j This value
increases in time at the expense of that of cis-6c.
SCHEME 2
basis of the 2-D spectra (HMBC), which showed a correlation
between the Me protons and the CH2S carbon (δ range of 23-
24) through J4 coupling.
Intermediates. Attempts to detect labile intermediates at low
temperatures failed except for 1a. In this case, when the reaction
was carried out at -70 °C in CDCl3/CFCl3, NMR analysis at
this temperature showed the presence of the dioxetane 9a.11 This
compound exhibited a Me singlet at δ 1.40, as linked to a
saturated carbon in the proton spectrum and, in the 13C spectrum,
two characteristic dioxetane carbons at δ 98.2 and 102.5. On
raising the temperature, dioxetane 9a converted mainly to
dicarbonyl compounds 2a and 3a.
The peroxidic nature of dioxetane 9a was proven by treatment
at low temperature with pre-cooled Et2S. The sulfoxide Et2SO
was rapidly formed in addition to ketothioketals 7a and 8a. As
reported,1c dioxetane reduction by phosphorus or sulfide com-
pounds involves the intermediacy of an epoxide. It is therefore
possible that epoxide 10a is formed but, as it is thermodynami-
cally unstable as observed for similar condensed compounds,7,12
quickly rearranges by 1,2-migration of the sulfur atom.
SCHEME 3
Mechanistic Interpretation. On the basis of these results
and previous data,7 it can be assumed that the reaction of dithiins
with singlet oxygen13 occurs mainly via [2 + 2] cycloaddition
leading to dioxetanes 9. The usual fragmentation of these
peroxides gives dicarbonyl compounds 2, while R,R′-diketones
3 should derive from 9 via cleavage of both C-S bonds, as
reported for 2,3-diphenyl-1,4-dithiin9 and thioethylene deriva-
tives14 (Scheme 3). These pathways compete with the formation
of ketosulfoxides 6 in the presence of an electron-withdrawing
group. As reported for oxathiins,7 the increased electron demand
by the peroxide O-O bond induces an intramolecular nucleo-
philic attack, by one of the neighboring sulfurs to the peroxidic
oxygen, leading to ketosulfoxides 6 likely via the undetected
labile epoxides 11. Structures 6b-d clearly indicate that the
attack occurs by S-1 rather than S-4. The latter is, instead,
involved in the migration step (Scheme 3). As suggested by
the mixture of stereoisomers, migration should occur in a non-
(11) The lower stability of electron-withdrawing substituted dioxetanes
than that of alkyl- or aryl-substituted analogues has already been observed
in the oxathiin systems.7a
(12) Rearrangements of labile epoxides to carbonyl compounds are well-
documented. See, for example: (a) Adam, W.; Hadjiarapoglou, L.; Wang,
X. Tetrahedron Lett. 1991, 32, 1295. (b) Baylon, C.; Hanna, I. Tetrahedron
Lett. 1995, 36, 6475. (c) Katritzky, A. R.; Xie, L.; Serdyuk, L. J. Org.
Chem. 1996, 61, 7564.
(13) We confirmed the occurrence of singlet oxygen by carrying out the
photooxygenation of dithiins 1 either in the absence of the dye or in the
presence of 1,4-diazabicyclo[2.2.2]octane (DABCO), a well known quencher
of singlet oxygen.8 In both cases, dithiins were recovered unchanged even
after prolonged irradiation times.
(14) See, for example: (a) Adam, W.; Liu, J.-C. J. Am. Chem. Soc. 1972,
94, 1206. (b) Ando, W.; Watanabe, K.; Migita, T. Tetrahedron Lett. 1975,
47, 4130.
J. Org. Chem, Vol. 72, No. 26, 2007 10077

Cermola et al.
SCHEME 5
FIGURE 2.
SCHEME 6
SCHEME 7
FIGURE 3. Theoretical calculations.
SCHEME 4
TABLE 2. HOMO Energy Valuesa of 1a-d versus
Tetrasubstituted Olefin
(or 5). These compounds are significant only in the presence
of a protic species (TFE) or in MeOH as the solvent. According
to the accepted mechanism, the initial persulfoxide 13, when
stabilized by hydrogen bonding (or via an intermediate 14), does
not quench but transfers oxygen to a second molecule of dithiin
to give two molecules of sulfoxides 4 (Scheme 5). The formation
of sulfoxide 4c, even in CH2Cl2 (Table 1, entry 8), should be
due to the stabilization of the persulfoxide intermediate through
intermolecular NH hydrogen bonding. This hypothesis is
supported by the significant decrease of sulfoxide 4c in more
diluted solutions (10-3 M, Table 1, entry 9) and in acetone
(Table 1, entry 12), where NH bonding is preferentially formed
with the basic solvent.
Oxidation occurs selectively at the S-1 atom, with the
formation of sulfoxides 4b-d, due to the presence of the
electron-withdrawing group that decreases the nucleophilicity
of the S-4 atom (Scheme 6).16 For series a, both S-1 and S-4
oxidation can occur. Moreover, intermediates 13a and 13a′ can
give inter- or intramolecular O-transfer to the electron-rich
double bond with the formation of ketothioketals 7a and 8a
and of ketosulfoxide 6a, likely by means of a labile epoxide
intermediate (Scheme 7).17
1a
1b
1c
1d
HOMO (eV)
-7.83
-8.11
-8.29
-8.12
-9.0
a Calculated by Hyperchem 6.0 with AM1 force field.
concerted manner (e.g., via the charged species 12 that may
decay to both cis-6 and, to a lesser extent, trans-6).
The anomalous results in the oxygenation of amide 1c where
ketosulfoxides 6c are not found (Table 1, entries 8-10), except
in CH3CN (Table 1, entry 11) and acetone (Table 1, entry 12),
can be explained assuming that the sulfur attack to peroxide
oxygen may be difficult due to the H-bonding between NH and
S, as shown in Figure 2. In basic solvents, instead NH bonding
occurs with the solvent, and ketosulfoxides 6c can be formed.
The conversion of cis-6c to the more thermodynamically
stable trans-6c could be ascribed to the kinetic-thermodynamic
control through the species 12c (Scheme 4). Indeed, a MM+
conformational analysis assigned a lower energy to the trans-
isomer of ca. 4 kcal/mol than to the cis-isomer 6c (Figure 3),
likely due to intramolecular hydrogen bonding.
In all cases examined, no ene products were ever found
despite the presence of allylic hydrogens. This should be due
to the high nucleophilicity of the double bond as shown by
HOMO values, which are higher than that of tetramethyleth-
ylene, a well-known singlet oxygen reactant15 (Table 2). Hence,
the electrophilic singlet oxygen attacks preferentially the
electron-rich double bond.
Conclusion
As found for the oxathiin system,7 the presence of two
heteroatoms in the dithiin system makes the double bond highly
reactive toward singlet oxygen, promoting the dioxetane mode.
(16) It is interesting to note that the oxidation of 1b with MCPBA showed
the same chemoselectivity affording sulfoxide 4b: unpublished results from
G. Palumbo and A. Guaragna.
The high HOMO values and the reversibility of sulfur
oxidation account for the low, if any, amount of sulfoxides 4
(17) Trapping of persulfoxides by alkenes with formation of epoxides
is reported: Akasaka, T.; Sakurai, A.; Ando, W. J. Am. Chem. Soc. 1991,
113, 2696.
(15) Schaap, A. P.; Zaklika, K. A. In Singlet Oxygen; Wasserman, H.
H., Murray, R. W., Eds.; Academic Press: New York, 1979; p 234.
10078 J. Org. Chem., Vol. 72, No. 26, 2007

Photooxygenation of 5,6-Dihydro-1,4-dithiins
(CHCl3) 1673, 1025 cm-1; MS m/z 224 (M+), 180, 59; 1H NMR δ
1.98 (s, 3H, Me), 2.78 (t, J ) 13.8 Hz, 1H), 2.95 (dd, J ) 12.2 Hz,
1H), 3.58 (d, J ) 12.2 Hz, 1H), 3.72 (t, J ) 13.8 Hz, 1H), 7.20-
7.45 (m, 5H); 13C NMR δ 16.8 (q), 22.0 (t), 44.4 (t), 128.6 (d),
128.7 (d), 129.0 (d), 133.1 (s), 137.2 (s), 138.8 (s). Anal. calcd for
C11H12OS2: C, 58.89; H, 5.39; S, 28.58. Found: C, 59.10; H, 5.37;
S, 28.69. 5a: oil; IR (CHCl3) 1020 cm-1; MS m/z 224 (M+), 195,
178, 163, 121; 1H NMR δ 2.13 (s, 3H), 2.80-3.05 (m, 2H), 3.45-
3.60 (m, 2H), 7.20-7.45 (m, 5H); 13C NMR δ 18.1 (t), 19.3 (q),
45.3 (t), 126.8 (s), 128.6 (d), 128.7 (d), 129.0 (d), 131.1 (s), 137.4
(s). Anal. calcd for C11H12OS2: C, 58.89; H, 5.39; S, 28.58.
Found: C, 59.12; H, 5.41; S, 28.70. 6a (stereochemistry not
assigned): oil; IR (CHCl3) 1711, 1062 cm-1; MS m/z 240 (M+),
Once more, the electron-poor substituent makes the geminal
peroxidic oxygen an electrophile that can easily react with the
sulfur-1 atom. However, according to the migratory aptitude S
. S+-O- > O, the undetected epoxide intermediate undergoes
exclusively a S-migration,18 and this occurs through a charged
intermediate that should be favored by the easy cleavage of the
C-S bond.19
In both systems (oxathiins and dithiins), the oxidation of ring
sulfur is a secondary reaction. It takes place only under certain
conditions (low temperature and protic media) and gives
sulfoxides. Despite the presence of R-hydrogens, no sulfones
nor C-S bond breaking products are found likely due to the
low acidity of these hydrogens20 or to geometrical factors that
make the intramolecular abstraction of the R-proton difficult to
form the hydroperoxy sulfonium ylide.21
1
197, 163, 121; H NMR δ 2.24 (s, 3H), 2.70 (ddd, J) 13.6, 9.6,
8.3 Hz, 1H), 3.14 (ddd, J) 13.6, 6.8, 2.4 Hz, 1H), 3.41 (ddd, J)
13.6, 8.3, 2.4 Hz, 1H), 3.92 (ddd, J) 13.6, 9.6, 6.8 Hz, 1H), 7.40-
7.80 (m, 5H); 13C NMR δ 29.7 (q), 32.0 (t), 50.8 (t), 96.8 (s), 127.5
(d), 129.5 (d), 129.8 (d), 132.0 (s), 198.3 (s). Anal. calcd for
C11H12O2S2: C, 54.97; H, 5.03; S, 26.68. Found: C, 54.75; H, 5.01;
S, 26.57. 7a (with a purity of 86%): GC-MS m/z 181 (M - 43)+,
Experimental Section
Compounds 1a,22 1b,23 and 1c [mp 100-101 °C (lit.24 100-
102 °C)] were prepared by N-bromosuccinimide-promoted
ring expansion of the related 1,3-dithiolanes; the latter were
synthetized in good yields by refluxing the corresponding carb-
onyl compounds and 1,2-ethanedithiol in the presence of PPh3/
I2.25
1
121, 77; H NMR δ 2.14 (s, 3H), 3.30-3.45 (m, 4H), 7.30-7.60
(m, 5H); 13C NMR δ 21.9 (q), 39.8 (two overlapping t), 80.5 (s),
127.1 (d), 128.9 (d), 128.8 (d), 137.8 (s), 198.0 (s). 8a (with a purity
of 75%): GC-MS m/z 224, 119 (base peak), 105, 77, 59; 1H NMR
δ 2.06 (s, 3H), 3.38 (m, 2H), 3.44 (m, 2H), 7.35-7.45 (m, 3H),
7.95 (d, J ) 7.1 Hz, 2H); 13C NMR δ 28.9 (q), 40.3 (two
overlapping t), 72.0 (s), 127.9 (d), 129.4 (d), 131.7 (d), 133.5 (s),
195.2 (s).
General Procedure of Photooxygenation. Each 0.02 M solution
of 1a-d (0.5 mmol) in dry solvent (for Table 1, entry 9: 0.001
M) in the presence of the sensitizer (2 × 10-3 mmol) (tetraphe-
nylporphine in CH2Cl2; methylene blue in the other solvents)
was irradiated at -20 °C with a halogen lamp (650 W). During
irradiation, dry oxygen was bubbled through the solution.
From 1b: oxygenation in CH2Cl2 and TLC chromatography
(Et2O) led, with decreasing Rf values: cis-6b (62%): mp 79-80 °C;
IR (CHCl3) 1734, 1065 cm-1; MS m/z 163 (M+ - 59), 59,
1
43 (base peak); H NMR δ 2.49 (s, 3H), 3.40 (ddd, J) 12.5, 4.5,
1
When the reaction was complete (2-3 h, H NMR), removal of
2.0 Hz, 1H), 3.55-3.65 (m, 2H), 3.78 (s, 3H), 4.10 (dt, J ) 4.5,
11.3 Hz, 1H); 13C NMR δ 30.3 (q), 35.4 (t), 53.7 (q), 57.4 (t), 90.1
(s), 167.6 (s), 197.1 (s). Anal. calcd for C7H10O4S2: C, 37.82; H,
4.53; S, 28.85. Found: C, 37.95; H, 4.51; S, 28.96. trans-6b (8%):
the solvent gave a residue that was carefully analyzed by 1H NMR.
Then, the residue was chromatographed on TLC. Table 1
reports the various conditions used as well as the product distribu-
tion.
mp 74-75 °C; IR (CHCl3) 1736, 1053 cm-1; MS m/z 179 (M+
-
From 1a: oxygenation in CH2Cl2 led to a mixture composed of
2a, 3a, and an unidentified polymeric material. TLC chromatog-
raphy [light petroleum/Et2O (1:3)] gave, with decreasing Rf
values: 2a (35%): IR 1691, 1662 cm-1; MS m/z 240 (M+), 165,
105 (base peak), 77, 43; 1H NMR (CDCl3) δ 2.36 (s, 3H), 3.16 (t,
J ) 6.3 Hz, 2H), 3.26 (t, J ) 6.3 Hz, 2H), 7.40-7.60 (m, 3H),
7.96 (d, J ) 8.1 Hz, 2H); 13C NMR δ 28.8 (t), 29.1 (t), 30.6 (q),
127.3 (d), 128.6 (d), 133.6 (d), 136.1 (s), 191.2 (s), 195.2 (s); Anal.
calcd for C11H12O2S2: C, 54.97; H, 5.03; S, 26.68. Found: C, 54.76;
H, 5.01; S, 26.78. 3a (55%): identified by comparison with the
commercially available product. 4a (trace): identified by compari-
son with an authentic sample. Photooxygenation in methanol and
successive TLCs of the residue carried out as stated previously led
to 2a (20%), 3a (29%), 7a (<2% with a purity of 86%), 8a (2%
with a purity of 85%), 6a (4%), 4a (8%), and 5a (4%). 4a: oil; IR
43) 163 (M+ - 59), 59 (CO2Me), 43 (base peak); 1H NMR δ 2.28
(s, 3H), 3.25-3.35 (m, 2H), 3.55 (m, 1H), 3.87 (m, 1H), 3.94 (s,
3H); 13C NMR δ 26.1 (q), 34.4 (t), 54.6 (q), 58.6 (t), 93.5 (s),
163.5 (s), 197.1 (s); Anal. calcd for C7H10O4S2: C, 37.82; H, 4.53;
S, 28.85. Found: C, 37.97; H, 4.55; S, 28.74. 4b (trace): identified
by comparison with authentic sample. Oxygenation in methanol
and TLC chromatography of the residue carried out as stated
previously led, with decreasing Rf values, to cis-6b (51%), trans-
6b (3%), and 4b (19%). 4b: viscous; IR (CHCl3) 1716, 1029 cm-1
;
MS m/z 206 (M+), 190, 175, 162, 59 (base peak); 1H NMR δ 2.48
[overlapping s and dt (J ) 13.9, 2.3 Hz), 4H], 2.87 (ddd, J ) 13.9,
5.0, 2.3 Hz, 1H), 3.44 (ddd, J ) 13.9, 5.0, 2.2 Hz, 1H), 3.67 (dt,
J ) 13.9, 2.2 Hz, 1H), 3.80 (s, 3H); 13C NMR δ 16.9 (q), 25.5 (t),
41.5 (t), 52.2 (q), 123.0 (s), 160.5 (s) 163.1 (s); Anal. calcd for
C7H10O3S2: C, 40.76; H, 4.89; S, 31.09. Found: C, 40.61; H, 4.87;
S, 31.20.
(18) In the oxygenation of oxathiins, the related epoxide rearranges via
both O-migration and SO-migration, and the latter is the relevant mode.7
In the dithiin series, sulphur migration overcomes completely the sulfoxide-
migration.
(19) Yao, X.-Q.; Hou, X.-J.; Xiang, H.-W.; Li, Y.-W. J. Phys. Chem. A
2003, 107, 9991.
(20) (a) Takata, T.; Ishibashi, K.; Ando, W. Tetrahedron Lett. 1985, 26,
4609. (b) Barbarella, G.; Garbesi, A.; Fava, A. HelV. Chim. Acta 1971, 51,
2297.
(21) McGlinchey, M. J.; Sayer, B. G.; Onuska, F. I.; Comba, M. E. J.
Chem. Soc., Perkin Trans. 2 1978, 1267.
(22) Caputo, R.; Ferreri, C.; Isita, P.; Longobardo, L.; Mastroianni, D.;
Palumbo, G. Synth. Commun. 1992, 22, 1345.
(23) Nevalainen, V.; Vainiotalo, P. Org. Mass Spectrom. 1987, 22,
586.
(24) Lee, W. S.; Lee, K.; Nam, K. D.; Ki, Y. J. Tetrahedron 1991, 47,
8091.
Low Temperature Photooxygenation of 1a-d. A solution of
1a (0.15 mmol) in CDCl3/CFCl3 (2:1, 5 mL) was photooxy
genated as stated previously at -70 °C. After 3 h, NMR analysis
of a sample recorded at this temperature showed the presence,
in addition to small amounts of 2a and 3a, of 6-methyl-1-phenyl-
1
7,8-dioxa-2,5-dithiabicyclo[4.2.0]octane (9a) [selected signals H
NMR (500 MHz, CDCl3/CFCl3) δ 1.43 (s, 3H), 3.20 (m, 2H), 3.75
(m, 2H), 7.20-7.60 (m, 5H); 13C NMR δ 24.4 (t), 25.2 (q),
26.0 (t), 98.2 (s), 102.5 (s), 128.6 (d), 128.8 (d), 129.3 (d), 133.1
(s)]. On raising the temperature, the signals of this transient
disappeared, and the final spectrum was similar to that obtained
by oxygenation at -20 °C. A precooled solution of Et2S (0.3
mmol) in CDCl3 (1 mL) was added to the remainder of the mixture,
which then was examined by NMR at -70 °C. In addition to the
signals of 2a and 3a, the signals of Et2SO, 7a and 8a, were also
detected.
(25) Caputo, R.; Guaragna, A.; Palumbo, G.; Pedatella, S. J. Org. Chem.
1997, 62, 9369.
J. Org. Chem, Vol. 72, No. 26, 2007 10079

Cermola et al.
When dithiins 1b-d were photooxygenated in CDCl3/CFCl3 at
-70 °C as 1a, after completion of the reactions, NMR analysis of
each solution at -70 °C showed no transient, and the spectrum
was similar to that obtained from the reaction at -20 °C.
di Metodologie Chimico-Fisiche-Universita` degli Studi di Napoli
Federico II.
Supporting Information Available: Detailed experimental
procedures, analytical data, and X-ray crystallographic data. This
materialisavailablefreeofchargeviatheInternetathttp://pubs.acs.org.
Acknowledgment. NMR spectra were run and crystal-
lographic work was undertaken at the Centro Interdipartimentale
JO701983V
10080 J. Org. Chem., Vol. 72, No. 26, 2007