A novel recyclable sulfur monoxide transfer reagent

Article abstract of DOI:10.1021/ol016678g

(matrix presented) Trisulfide 2-oxide 11 has been prepared from disulfide 9 via reduction to the corresponding dithiol and subsequent trapping with thionyl chloride. Heating trisulfide oxide 11 in the presence of dienes results in transfer of sulfur monoxide to form cyclic unsaturated sulfoxides 13 in good to excellent yields, along with recovery of disulfide 9. A Pummerer reaction can be used to convert the cyclic sulfoxides into thiophenes.

Full text of DOI:10.1021/ol016678g

ORGANIC
LETTERS
2001
Vol. 3, No. 22
3565-3568
A Novel Recyclable Sulfur Monoxide
Transfer Reagent
Richard S. Grainger,* Alberto Procopio, and Jonathan W. Steed†
Department of Chemistry, King's College London, Strand, London WC2R 2LS, U.K.
richard.grainger@kcl.ac.uk
Received August 31, 2001
ABSTRACT
Trisulfide 2-oxide 11 has been prepared from disulfide 9 via reduction to the corresponding dithiol and subsequent trapping with thionyl
chloride. Heating trisulfide oxide 11 in the presence of dienes results in transfer of sulfur monoxide to form cyclic unsaturated sulfoxides 13
in good to excellent yields, along with recovery of disulfide 9. A Pummerer reaction can be used to convert the cyclic sulfoxides into thiophenes.
The search for an effective source of sulfur monoxide has
proven to be a challenging problem in organic1 and inorganic2
chemistry. Early studies on episulfoxide 13 and thiadiazepin
oxide 24 established that small ring sulfoxides fragment upon
heating to produce alkenes and sulfur monoxide, although
attempts to trap out the SdO released with dienes gave
variable yields of dihydrothiophene-oxide adduct.5 More
recently, Harpp has introduced episulfoxides 3 and 4 as
stable, convenient sources of sulfur monoxide.6 Upon heating
in toluene, 3 and 4 were found to transfer sulfur monoxide
to four different dienes in good yields. The metal complex
5, itself derived from 1, has been shown to transfer sulfur
monoxide to a diene in low yield,7,8 and Simpkins has shown
that rhodium-catalyzed decomposition of stilbene episulfox-
ide provides a means to transfer sulfur monoxide to alkenes,
although this method is restricted to the highly reactive
norbornene and norbornadiene.9 A recent report by Espenson
described the transfer of sulfur monoxide from sultine 6, an
intermediate in the methyltrioxorhenium-catalyzed oxidation
of thioketones with 2 equiv of hydrogen peroxide.10 Yields
of trapped adduct were limited by the incompatibility of
dienes and sulfur monoxide with the strongly oxidizing
conditions under which the trapping experiment was carried
out.
† To whom correspondence regarding crystal structure should be ad-
dressed.
(1) (a) Harpp, D. N. Phosphorus, Sulfur, Silicon 1997, 120/121, 41. (b)
Tardif, S. L.; Rys, A. Z.; Abrams, C. B.; Abu-Yousef, I. A.; Leste´-Lasserre,
P. B. F.; Schultz, E. K. V.; Harpp, D. N. Tetrahedron 1997, 53, 12225.
(2) (a) Schenk, W. A. Angew. Chem., Int. Ed. Engl. 1987, 26, 98. (b)
Huang, R.; Guzei, I. A.; Espenson, J. H. Organometallics 1999, 18, 5420.
(3) (a) Dodson, R. M.; Sauers, R. J. Chem. Soc., Chem. Commun. 1967,
1189. (b) Dodson, R. M.; Nelson, J. P. J. Chem. Soc., Chem. Commun.
1969, 1159. (c) Anastassiou, A. G.; Chao, B. Y.-H. J. Chem. Soc., Chem.
Commun. 1971, 979. (d) Chao, P.; Lemal, D. M. J. Am. Chem. Soc. 1973,
95, 920. (e) Lemal, D. M.; Chao, P. J. Am. Chem. Soc. 1973, 95, 922. (f)
Grigg, R.; Reimer, G. J.; Wade, A. R. J. Chem. Soc., Perkin Trans. 1 1983,
1929.
(4) Chow, Y. L.; Tam, J. N. S.; Blier, J. E. J. Chem. Soc., Chem.
Commun. 1970, 1604. The heterocycle 2 is proposed to close to an
episulfoxide prior to sulfur monoxide extrusion.
(5) For transfer of sulfur monoxide from trans-2,3-diphenylethene
sulfoxide to ylides, see: Bonini, B. F.; Maccagnani, G.; Mazzanti, G.;
Pedrini, P.; Piccinelli, P. J. Chem. Soc., Perkin Trans. 1 1979, 1721.
(6) Abu-Yousef, I. A.; Harpp, D. N. J. Org. Chem. 1997, 62, 8366.
Figure 1. Molecules used to transfer sulfur monoxide to dienes.
10.1021/ol016678g CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/10/2001

In searching for alternative structures that may be capable
of acting as sources of sulfur monoxide, we were drawn to
the unusual reactivity observed in a number of 1,8 (peri)-
substituted naphthalene ring systems.11 In particular, tran-
sannular interactions between two sulfur atoms in cyclic 1,8-
dithiasubstituted naphthalene derivatives have been extensively
studied by Glass12 and Furukawa,13 and in the latter case
this has led to a number of unusual photochemically mediated
extrusion reactions. We chose the peri-fused trisulfide-2-
oxide 11 as our synthetic target.14
provided disulfide 9 in 31% overall yield. Although the yield
is only moderate, this reaction allows the rapid preparation
of gram quantities of disulfide 9. The trisulfide oxide 11 is
a yellow solid that can be stored refrigerated for months
without decomposition.
The X-ray crystal structure of 11 highlights a number of
interesting structural features (Figure 2). A nonplanar
The synthesis of trisulfide-2-oxide 11 is shown in Scheme
1. The known disulfide 9 appeared to be an ideal precursor
Scheme 1. Synthesis of Trisulfide-2-oxide 11
Figure 2. X-ray crystal structure of trisulfide-2-oxide 11.
conformation is adopted by the trithiane ring, whereby the
central sulfur atom S(2) lies out of the mean least-squares
plane of the naphthalene ring and peri-sulfur atoms by
1.1708(14) Å (torsion angles C1-S1-S2-S3, 60.1° and
C8-S3-S2-S1, 64.6°, respectively). The oxygen atom
occupies a pseudoaxial position on the trithiane ring,
probably as a result of stabilization of this conformer through
stereoelectronic effects.20,21
Two factors point to the strain in the system. First, the
enlargement of the expected bond angles at C(1), C(9), and
C(8) (125.7°, 126.6°, and 124.7°) is consistent with the
minimization of steric interactions associated with the close
proximity of substituents at the 1,8-positions of the naph-
thalene ring system.11 Second, whereas S(1) is essentially
coplanar with the naphthalene ring, S(3) lies 0.203(4) Å out
of the mean least-squares plane, on the opposite side to S(2).
The thermal stability of 11 in the absence of dienes was
first investigated. Upon refluxing overnight in chlorobenzene,
clean conversion to disulfide 9 was observed, along with
the formation of elemental sulfur.22 Encouraged by this result,
we investigated the potential of 11 to act as a source of sulfur
monoxide in trapping experiments with dienes and were
delighted to find that refluxing a solution of 11 in chloro-
to 11, despite the somewhat laborious methods previously
employed in its synthesis.15 Indeed, reduction of disulfide 9
with lithium aluminum hydride followed by reaction of the
air-sensitive dithiol (10)16 with thionyl chloride in the
presence of pyridine provided 11 in 65% overall yield after
column chromatography.17 With our subsequent discovery
that 11 does indeed act as a source of sulfur monoxide (vide
infra), we developed a convenient “one-pot” synthesis
disulfide 9 starting from commercially available 1-bromo-
naphthalene 7. Hence, lithium-halogen exchange on 7
followed by directed deprotonation18 and trapping of the
resulting 1,8-dilithionaphthalene (8) with elemental sulfur19
(7) Heyke, O.; Neher, A.; Lorenz, I.-P. Z. Anorg. Allg. Chem. 1992, 23,
608.
(8) For displacement of sulfur monoxide from an iridium complex and
trapping with an orthoquinone, see: Schenk, W. A.; Leissner, J. Z.
Naturforsch., B: Chem. Sci. 1987, 42, 799.
(9) Blake, A. J.; Cooke, P. A.; Kendall, J. D.; Simpkins, N. S.; Westaway,
S. M. J. Chem. Soc., Perkin Trans. 1 2000, 153.
(10) Huang, R.; Espenson, J. H. J. Org. Chem. 1999, 64, 6374.
(11) Balasubramaniyan, V. Chem. ReV. 1966, 66, 567.
(12) Glass, R. S.; Broeker, J. L.; Firouzabadi, H. J. Org. Chem. 1990,
55, 5739.
(19) Meinwald, J.; Dauplaise, D.; Wudl, F.; Hauser, J. J. J. Am. Chem.
Soc. 1977, 99, 255.
(20) Juaristi, E.; Ordon˜ez, M. In Organosulfur Chemistry, Synthetic and
Stereochemical Aspects; Page, P., Ed.; Academic Press: San Diego, CA,
1998; Vol. 2, Chapter 3, pp 63-95.
(21) Pseudoaxial oxygen is also observed in other cyclic trisulfide oxide
derivatives for which the X-ray crystal structures are known (all five-
membered rings): (a) Ghosh, T.; Bartlett, P. D. J. Am. Chem. Soc. 1988,
110, 7499. (b) Watson, W. H.; Krawiec, M.; Ghosh, T.; Bartlett, P. D. Acta
Crystallogr. 1992, C48, 2092. (c) Kimura, T.; Hanzawa, M.; Horn, E.;
Kawii, Y.; Ogawa, S.; Sato, R. Tetrahedron Lett. 1997, 38, 1607.
(22) Presumed to have formed via disproportionation of sulfur monoxide
to SO2 and S2O, which in turn disproportionates to SO2 and S3, a source of
S8.
(13) For a review see: Furukawa, N. Bull. Chem. Soc. Jpn. 1997, 70,
2571.
(14) For a review of trisulfides and their oxides, see: Clennan, E. L.;
Stensaas, K. L. Org. Prep. Proced. Int. 1998, 30, 553
(15) (a) Zweig, A.; Hoffmann, A. K. J. Org. Chem. 1965, 30, 3997. (b)
Gamage, S. A.; Smith, R. A. J. Tetrahedron 1990, 46, 2111.
(16) Yui, K.; Aso, Y.; Otsubo, T.; Ogura, F. Bull. Chem. Soc. Jpn. 1988,
61, 953.
(17) All compounds synthesized exhibited satisfactory spectral data (IR,
1H and 13C NMR, and MS).
(18) (a) Neugebauer, W.; Clark, T.; Schleyer, P. v. R. Chem. Ber. 1983,
116, 3283. (b) Brandsma, L. PreparatiVe Polar Organometallic Chemistry;
Springer-Verlag: Berlin, 1987; Vol. 1, pp 195-196.
3566
Org. Lett., Vol. 3, No. 22, 2001

benzene with excess 2,3-dimethyl butadiene 12a resulted in
quantitatiVe formation of sulfoxide 13a and disulfide 9.23 The
reaction of trisulfide oxide 11 with dienes 12a-d is
summarized in Table 1. Good yields of sulfoxide cycload-
Scheme 2. Thiophene Synthesis
Table 1. Reaction of 11 with Dienes 12a-da
ratio
time sulfoxide/yieldb recovered 9b
entry diene
11:12
(h)
(%)
(%)
1
2
3
4
5
6
7
12a
12b
12c
12c
12d
12d
12d
1:10
1:10
1:2.5
1:1
1:2.5
1:1
14
6
6.5
3
6
13a /100
13b/74
13c/65
13c/50
13d /93
13d /38
13d /84
99
99
The thermal decomposition of acyclic trisulfide-2-oxides
has been investigated in detail by Field and Lacefield.28,29
In contrast to 11, thermolysis of acyclic trisulfide-2-oxides
gives rise to a mixture of trisulfide, disulfide, and sulfur
dioxide (Scheme 3). Interestingly, the proposed mechanism
100
100
100
100
98
6
4.5
2.5:1
a
b
Chlorobenzene, reflux. Isolated yield after column chromatography.
Scheme 3. Thermal Decomposition of Acyclic
Trisulfide-2-oxides
ducts 13 are obtained when the reaction is run with an excess
of diene (entries 1-3 and 5) or an excess of 11 (entry 7).
Poorer yields are obtained when a 1:1 ratio of diene to 11 is
used (compare entries 3 and 4 and 5 and 6). In all cases the
disulfide 9 can be easily recovered in high yield.24
Sulfoxides 13 are potentially useful intermediates in
organic synthesis. For example, dehydration of the myrcene-
derived cycloadduct 13d under Pummerer conditions25 gave
thioperillene 14, a constituent of hop and rose oil (Scheme
2).26 In the case of reaction of 11 with piperine 12e the novel
thiophene 15 was isolated directly from the reaction mix-
ture.27
postulates an initial rearrangement to a disulfide-sulfur
monoxide adduct 17, which rapidly reacts with a second
molecule of trisulfide oxide 16. To determine whether sulfur
monoxide transfer is common to all trisulfide-2-oxides, we
carried out the thermal decomposition of the phenyl deriva-
tive 16 in the presence of 2,3-dimethyl butadiene 12a but
did not observe the formation of any sulfoxide 13a.
In summary, the novel trisulfide oxide 11 has been shown
to be an effective sulfur monoxide transfer reagent in trapping
experiments with dienes. The overall process benefits not
only from a convenient source of sulfur monoxide in thionyl
chloride but also in the generation of a recyclable byproduct
(23) A slower reaction is observed in refluxing toluene; After 26 h a
65% yield of 13a was obtained.
(24) Typical Experimental Procedure. Trisulfide oxide 11 and diene
12 were refluxed in degassed chlorobenzene until TLC analysis showed
complete disappearance of 11. The solvent was removed under reduced
pressure, and the residue was subjected to column chromatography on silica
gel. The nonpolar disulfide 9 eluted first (60-80 pet-ether) followed by
the sulfoxide 13 upon increasing the solvent polarity (ethanol).
(25) de Lucchi, O.; Miotti, U.; Modena, G. Org. React. 1991, 40, 157.
(26) (a) Elvidge, J. A.; Jones, S. P.; Peppard, T. L. J. Chem. Soc., Perkin
Trans. 1 1982, 1089. (b) Araki, S.; Butsugan, Y. Bull. Chem. Soc. Jpn.
1983, 56, 1446. (c) Weyerstahl, P.; Schenk, A.; Marschall, H. Liebigs Ann.
Chem. 1995, 1849.
(27) Thiophene 15 could be formed via in situ dehydration of a sulfur
monoxide adduct (13a), or derived from the reaction of 12e with other
reactive sulfur species (ref 22). For trapping of dienes with S2O, see: (a)
Ishii, A.; Nakabayashi, M.; Nakayama, J. J. Am. Chem. Soc. 1999, 121,
7959. (b) Ishii, A.; Oshida, H.; Nakayama, J. Tetrahedron Lett. 2001, 42,
3117. (c) Ishii, A.; Kawai, T.; Tekura, K.; Oshida, H.; Nakayama, J. Angew.
Chem., Int. Ed. 2001, 40, 1924.
(28) Field, L.; Lacefield, W. B. J. Org. Chem. 1966, 31, 3555.
(29) Flash vacuum pyrolysis (>540 °C) of 1,2,3-benzotrithiole 2-oxide
results in the loss of sulfur monoxide and the formation of benzodithiete:
Breitenstein, M.; Schultz, R.; Schweig, A. J. Org. Chem. 1982, 47, 1979.
Org. Lett., Vol. 3, No. 22, 2001
3567

in disulfide 9. Current efforts include elucidation of the
mechanism of transfer of sulfur monoxide from 11 to dienes
and application of this design principle to the generation of
other reactive intermediates.
Supporting Information Available: X-ray data in CIF
format for compound 11. This material is available free of
charge via the Internet at http://pubs.acs.org. In addition, the
author has deposited X-ray coordinates with the Cambridge
Crystallographic Data Center (CCDC 171805).
Acknowledgment. We thank King’s College London for
funding this work (studentship to A.P.).
OL016678G
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Org. Lett., Vol. 3, No. 22, 2001