Thermal rearrangements of bis-allenyl thiosulfonates. Synthesis of novel thienothiophene and thieno-oxathiine derivatives

Article abstract of DOI:10.1016/S0040-4039(02)02409-7

The synthesis and thermal rearrangement of bis-allenyl thiosulfonates are described. Bis-γ,γ-disubstituted allenyl thiosulfonates have been prepared by disproportionation of the corresponding allenesulfinic acids. On heating, these compounds unexpectedly rearrange to a mixture of 1H,3H-thieno[3,4-d][1,2]oxathiine-3-oxide 8, 1H,3H-thieno[3,4-c]thiophene-2,2-dioxide 9, and 3-alkyl-4-alkenylthiophene 10. A tentative reaction mechanism involving sequential sigmatropic rearrangements and cyclizations is suggested.

Full text of DOI:10.1016/S0040-4039(02)02409-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9615–9619
Thermal rearrangements of bis-allenyl thiosulfonates. Synthesis
of novel thienothiophene and thieno-oxathiine derivatives
Mihail L. Birsa, Marina Cherkinsky and Samuel Braverman*
Department of Chemistry, Bar-Ilan University, Ramat-Gan 52900, Israel
Received 12 September 2002; revised 15 October 2002; accepted 24 October 2002
Abstract—The synthesis and thermal rearrangement of bis-allenyl thiosulfonates are described. Bis-g,g-disubstituted allenyl
thiosulfonates have been prepared by disproportionation of the corresponding allenesulfinic acids. On heating, these compounds
unexpectedly rearrange to a mixture of 1H,3H-thieno[3,4-d][1,2]oxathiine-3-oxide 8, 1H,3H-thieno[3,4-c]thiophene-2,2-dioxide 9,
and 3-alkyl-4-alkenylthiophene 10. A tentative reaction mechanism involving sequential sigmatropic rearrangements and cycliza-
tions is suggested. © 2002 Elsevier Science Ltd. All rights reserved.
The [2,3]-sigmatropic rearrangements of propargylic
sulfenates and sulfinates to allenic sulfoxides and sul-
fones, respectively, were discovered by us during the
mid sixties and have received extensive application in
organic synthesis since then.1–4 In one such application
from our own laboratory, a combination of two [2,3]-
sigmatropic rearrangements was used to prepare bis-
g,g-dimethylallenyl sulfone 1. This sulfone undergoes a
facile cyclization on heating to the thiophene-1,1-diox-
ide 2 via a 2,2%-bisallyl type diradical intermediate
(Scheme 1).5
examine which of the above two reaction modes such
compounds would follow. In general, thiosulfonates
exhibit interesting properties. They are powerful
sulfenylating agents,7–10 with antimicrobial and fungici-
dal activities,11,12 and with some industrial applications
both in polymer production and in photographic
processes.13
Although many synthetic approaches are known for the
preparation of symmetrical and unsymmetrical thiosul-
fonates in general,10,14 their application for the prepara-
tion of allenic thiosulfonates is limited by the lack of
appropriate starting materials. The synthesis of bis-g,g-
dimethyl- and bis-g-cyclohexylallenyl thiosulfonates, 7a
and 7b, respectively, has been reported to take place by
disproportionation of the corresponding sulfinic acids,
which are produced in situ by hydrolysis of allenyl
sulfinamides (yields 11–34%).15 However, we have
found it more convenient to use a somewhat different
approach. Thus, sodium g,g-disubstituted allenesulfi-
nates 6a,b were prepared by hydrolysis of the corre-
Subsequently, we also investigated the rearrangements
of diheteroatom bridged bisallenes. Thus, bisallenyl
disulfide 3 was found to undergo a tandem [3,3]-sigma-
tropic rearrangement and a double intramolecular
Michael addition to give the bicyclic compound 4
(Scheme 2).6
Prompted by these results, we decided to incorporate a
thiosulfonate moiety as a bisallenic bridge in order to
Scheme 1.
Keywords: allenes; sulfinates; thiosulfonates; rearrangements.
* Corresponding author. Tel.: +972-3-5318322; fax: +972-3-5351250; e-mail: bravers@mail.biu.ac.il
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02409-7

9616
M. L. Birsa et al. / Tetrahedron Letters 43 (2002) 9615–9619
sponding sulfinate esters 5a,b under basic conditions
(Scheme 3). The latter are readily available from the
reaction of sulfur dichloride with the appropriately
substituted propargylic alcohols (Scheme 1). Sodium
allenesulfinates 6a,b were isolated in 80–85% yields as
white solids (mp >300°C), which were sensitive to
atmospheric moisture.16 Treatment of 6a,b with an
excess of methanesulfonic acid in DMSO generated the
corresponding sulfinic acids whose well known
disproportionation17 afforded thiosulfonates 7a,b
(Scheme 3). DMSO was found to be the best solvent for
the above transformation. Using methanol or biphasic
systems such as diethyl ether–water, large amounts of
a,b-unsaturated g-sultines18–20 were obtained as by-
products. In a typical procedure, sodium allenesulfinate
(5 mmol) was slowly added to a cooled solution (10°C)
of CH3SO3H (1 mL) in DMSO (5 mL). After 3 h under
vigorous stirring the reaction mixture was diluted with
CH2Cl2, followed by usual work-up. Thiosulfonates
7a,b were then purified by chromatography (silica gel,
ether–hexane 2:3).
Previously, it was reported that bis-g,g-dimethylallenyl
thiosulfonate 7a is unstable at room temperature.15
However, we have found that thiosulfonates 7a,b under
heating, undergo a series of rearrangement and cycliza-
tion reactions. Moreover, reaction rates and product
ratios are quite dependent on the nature of solvent and
temperature, respectively. Thus, we found that on heat-
ing in chloroform 7a afforded a mixture of 1,1,4,4-tet-
ramethyl-1H,3H-thieno[3,4-d][1,2]oxathiine-3-oxide 8a,
1,1,3,3-tetramethyl-1H,3H-thieno[3,4-c]thiophene-2,2-
dioxide 9a and 3-isopropyl-4-isopropenylthiophene 10a
(Scheme 4, Table 1, entry 1). When bis-g,g-dimethyl-
allenyl thiosulfonate 7a was heated below 40°C only
the first two products were formed (Table 1, entries
3 and 4). Furthermore, the reaction times decrease
with increasing polarity of the solvents. For example,
Scheme 2.
Scheme 3.
Scheme 4.
Table 1. Rearrangement products of bis-allenyl thiosulfonates 7a,b
Entry
Compd
Solvent
T (°C)
Time (h)
Products (ratio, %)
Yield (%)a
1
2
3
4
5
6
7a
7a
7a
7a
7b
7b
CHCl3
Me2CO
CHCl3
DMSO
CHCl3
DMSO
55
55
40
40
40
40
12
10
120
12
120
60
8a (47)
8a (66)
8a (91)
8a (72)
8b (40)
8b (42)
9a (6)
9a (8)
9a (9)
9a (28)
9b (8)
9b (17)
10a (47)
10a (26)
–
50
75
60
80
80
85
–
10b (52)
10b (41)
a Total yield for isolated products.

M. L. Birsa et al. / Tetrahedron Letters 43 (2002) 9615–9619
9617
changing the solvent from CHCl3 to DMSO decreases
the reaction time by a factor of ten. Bis-g-cyclohexyl-
allenyl thiosulfonate 7b rearranged in a similar manner
to 7a (Scheme 4). Structure assignments of reaction
products have unequivocally been determined by 2D
NMR analysis.21
product 8 (Scheme 5). Alternatively, a [1,3]-sulfinate
migration of 12 via path b leads to formation of
intermediate 14, which on cyclization can afford both 8
and 9. The experimental data shows that in all cases
greater amounts of 8 are formed than 9. The ambident
character of the sulfinate anion is well known.23–25
Thus, the ring closure in intermediate 14 can proceed
by either sulfur or oxygen nucleophilic attack.
Although, the former is usually the more favored route
with neutral electrophiles the latter is the more domi-
nant with positively charged electrophiles. This, as well
as the formation of 8 via both mechanistic paths, may
account for the higher percentages of this product
relative to 9.
Although no experimental evidence in support of a
detailed reaction mechanism for the formation of the
various products is available, the effect of solvent
polarity on reaction rates seems to favour an ionic
mechanism. A tentative mechanism for the thermal
rearrangement of bis-allenyl thiosulfonates is shown in
Scheme 5. We assume that first, thiosulfonates 7a,b
undergo a [3,3]-sigmatropic rearrangement to give
intermediate 11. However, instead of rotation around
the central CꢀC s bond and cyclization similar to that
observed for bis-allenyl disulfides (Scheme 2),6 this
intermediate reacts by a different route. Intermediate 11
contains a sulfene moiety, which is well known for its
electrophilicity.22 Thus, an intramolecular nucleophilic
attack by the thioaldehyde sulfur atom on the sulfene
carbon atom generates the zwitterionic intermediate 12,
which has both a five-membered sulfonium ring and a
sulfinate anion moiety.
Thieno[3,4-d][1,2]oxathiine-3-oxides 8a,b were found to
be unexpectedly stable under thermal conditions. Even
at 160°C they do not undergo isomerization to com-
pounds 9a,b or lose sulfur dioxide. In view of the
above, the formation of thiophene derivatives 10a,b,
most likely takes place via sulfur dioxide extrusion from
intermediate 11. The carbene formation from sulfene by
loss of sulfur dioxide has been previously reported.26
Expulsion of sulfur dioxide from sulfene 11 generates a
carbene which undergoes an addition reaction to the
thioaldehyde sulfur atom to give 15 (Scheme 6). The
latter rearranges via a radical mechanism to thiophene
derivatives 10, similar to the cyclization of 1 to 2
(Scheme 1).
We suggest that subsequent cyclizations of 12 proceed
by two routes. [2,3]-Sigmatropic rearrangement of this
intermediate via path a leads to the formation of 13,
which then undergoes cycloaromatization to give
Scheme 5.

9618
M. L. Birsa et al. / Tetrahedron Letters 43 (2002) 9615–9619
Scheme 6.
Acknowledgements
THF (25 mL), an aqueous solution of NaOH (15%, 9.3
mmol) was added. The reaction mixture was stirred at rt
until a homogeneous solution was obtained (ca. 2 h).
Then, THF and water were evaporated under vacuum at
rt and the residue was washed a few times with acetone,
filtered and dried in a dessicator to give 6a as a white
solid; yield: 1.14 g (80%); mp >300°C; IR (KBr): 3441,
The financial support of this study by the Israel Science
Foundations is gratefully acknowledged.
1985, 1654, 1224, 1130, 1048, 631 cm−1 1H NMR (300
;
References
MHz, D2O): l 1.79 (d, J=2.9 Hz, 6H, CH3), 5.70 (sept.,
J=2.9 Hz, 1H); 13C NMR (75 MHz, D2O): l 19.5 (CH3),
103.8 (Cq), 105.9 (CH), 198.9 (Cq). Anal. calcd for
C5H7NaO2S (154.16): C, 38.95; H, 4.58; S, 20.80. Found:
C, 38.73; H, 4.45; S, 20.52%.
1. Braverman, S. In The Chemistry of Sulfones and Sulfox-
ides; Patai, S.; Rappoport, Z.; Stirling, C. J. M., Eds.;
Wiley: New York, 1988; pp. 665–716 and 717–757.
2. Braverman, S. In The Chemistry of Double-Bonded Func-
tional Groups. Supplement A2; Patai, S., Ed.; Wiley:
Chichester, 1989; pp. 963–1060.
3. Braverman, S. In The Chemistry of Sulfinic Acids, Esters
and their Derivatives; Patai, S., Ed.; Wiley: New York,
1990; pp. 297–349.
4. Braverman, S. In The Chemistry of Sulfenic Acids and
their Derivatives; Patai, S., Ed.; Wiley: New York, 1990;
pp. 311–359.
5. Braverman, S.; Segev, D. J. Am. Chem. Soc. 1974, 96,
1245–1247.
17. Oae, S. Organic Chemistry of Sulfur; Plenum: New York,
1977; p. 614.
18. Braverman, S.; Reisman, D. J. Am. Chem. Soc. 1977, 99,
605–607.
19. Braverman, S.; Reisman, D. Tetrahedron Lett. 1977, 18,
1753–1756.
20. Braverman, S.; Duar, Y. J. Am. Chem. Soc. 1983, 105,
1061–1063.
21. All new compounds gave satisfactory analytical and spec-
tral data in accordance with their structures. Selected
analytical and spectral data:
6. Braverman, S.; Freund, M. Tetrahedron 1990, 46, 5759–
5776.
7. Parsons, T. F.; Buckman, J. D.; Pearson, D. E.; Field, L.
Compound 8a: white crystals (PTLC, CH2Cl2–hexane
3:1, Rf=0.25), mp=87–88°C; IR (KBr): 3072, 2935,
2854, 1745, 1462, 1365, 1258, 1128, 1111, 923, 844 cm−1
;
J. Org. Chem. 1965, 30, 1923–1926.
1H NMR (600 MHz, CDCl3): l 1.45 (s, 3H, CH3), 1.64
(s, 3H, CH3), 1.67 (s, 3H, CH3), 1.82 (s, 3H, CH3), 7.07
(d, J=3.2 Hz, 1H, H-5), 7.22 (d, J=3.2 Hz, 1H, H-7);
13C NMR (75 MHz, CDCl3): l 22.2 (CH3), 25.8 (CH3),
33.56 (CH3), 34.0 (CH3), 57.6 (Cq), 82.7 (Cq), 120.1
(CH), 122.3 (CH), 135.7 (Cq), 139.1 (Cq). Anal. calcd for
C10H14O2S2 (230.35): C, 52.14; H, 6.13; S, 27.84. Found:
C, 51.98; H, 5.94; S, 27.59%.
8. Palumbo, G.; Ferreri, C.; D’Ambrocio, C.; Caputo, R.
Phosphorus Sulfur Silicon 1984, 19, 235–238.
9. Fujiki, K.; Yoshida, E. Y. Synth. Commun. 1999, 29,
3289–3294.
10. Fujiki, K.; Akieda, S.; Yasuda, H.; Sasaki, Y. Synthesis
2001, 7, 1035–1042.
11. Weidner, J. P.; Block, S. S. J. Med. Chem. 1964, 7,
671–673.
Compound 9a: white crystals (PTLC, CH2Cl2–hexane
3:1, Rf=0.37), mp=72–73°C; IR (KBr): 3056, 2962,
12. Block, S. S.; Weidner, J. P. Mech. React. Sulfur Compd.
1967, 2, 235–236.
13. Zefirov, N. S.; Zyk, N. V.; Beloglazkina, E. K.;
Kutateladze, A. G. Sulfur Rep. 1993, 14, 223–240.
14. Hogg, D. R. In Comprehensive Organic Chemistry; Jones,
D. N., Ed.; Pergamon Press: Oxford, 1979; Vol. 3, pp.
299–302.
15. Baudin, J.-B.; Julia, S. A.; Ruel, O.; Toupet, L.; Wang,
Y. Bull. Soc. Chim. Fr. 1995, 132, 79–85.
16. Sodium k,k%-dimethylallenyl sulfinate 6a: typical procedure:
To a solution of sulfinate ester 5a (1.84 g, 9.3 mmol) in
2853, 1730, 1454, 1365, 1282, 1118, 1094, 1027, 807 cm−1
;
1H NMR (600 MHz, CDCl3): l 1.69 (s, 12H, 4CH3), 7.16
(s, 2H, H-4+H-6); 13C NMR (75 MHz, CDCl3): l 25.6
(CH3), 62.7 (Cq), 118.9 (CH), 141.6 (Cq). Anal. calcd for
C10H14O2S2 (230.35): C, 52.14; H, 6.13; S, 27.84. Found:
C, 52.02; H, 5.98; S, 27.55%.
Compound 10b: colorless oil (PTLC, CH2Cl2–hexane 3:1,
Rf=0.8); IR (neat): 2924, 2851, 1446, 1267, 923, 786
1
cm−1; H NMR (300 MHz, CDCl3): l 1.34 (m, 4H), 1.74

M. L. Birsa et al. / Tetrahedron Letters 43 (2002) 9615–9619
9619
(m, 8H), 1.95 (m, 2H), 2.18 (m, 2H), 2.25 (m, 2H), 2.63 (m,
1H), 5.67 (m, 1H), 6.91 (d, J=3.3 Hz, 1H), 6.94 (d, J=3.3
Hz, 1H); 13C NMR (75 MHz, CDCl3): l 22.1 (CH2), 23.2
(CH2), 25.6 (CH2), 26.3 (CH2), 27.0 (CH2), 30.5 (CH2), 34.7
(CH2), 38.2 (CH), 118.8 (CH), 120.8 (CH), 126.2 (CH),
134.3 (Cq), 145.2 (Cq), 147.4 (Cq). HRMS calcd for
C16H22S: 246.144223. Found: 246.144269.
Z., Eds.; Wiley: Chichester, 1991; pp. 720–734.
23. Stirling, C. J. M. Int. J. Sulfur Chem. Part B 1971, 6,
277–320.
24. Kobayashi, M.; Toriyabe, K. Sulfur Lett. 1985, 3, 117–
122.
25. Hambley, T. W.; Harsanyi, M. C.; Norris, R. K. J. Org.
Chem. 1988, 53, 3104–3108.
26. Sarver, B. E.; Jones, M., Jr.; van Leusen, A. M. J. Am.
22. King, J. F.; Rathone, R. In The Chemistry of Sulfonic
Acids, Esters and their Derivatives; Patai, S.; Rappoport,
Chem. Soc. 1975, 97, 4771–4772.