Thioepoxide formation by ring closure of allylthiyl radicals - A novel rearrangement of allylic thionitrites

Article abstract of DOI:10.1039/b207252c

Tertiary allylic thionitrites undergo thermal rearrangement to α,β-episulfide nitroso dimers via ring closure of allylthiyl radicals.

Full text of DOI:10.1039/b207252c

Thioepoxide formation by ring closure of allylthiyl radicals—a novel
rearrangement of allylic thionitrites
Marta Cavero,a William B. Motherwell,*a Pierre Potierb and Jean-Marc Weibela
a University College London, Christopher Ingold Laboratories, 20 Gordon Street, London, UK WC1H 0AJ.
E-mail: w.b.motherwell@ucl.ac.uk; Fax: +44 20 7679 7524; Tel: +44 20 7679 7533
b Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, Cedex,
France
Received (in Cambridge, UK) 24th July 2002, Accepted 22nd August 2002
First published as an Advance Article on the web 18th September 2002
Tertiary allylic thionitrites undergo thermal rearrangement
to a,b-episulfide nitroso dimers via ring closure of allylthiyl
radicals.
and mass spectrometry but decomposed slowly if allowed to
stand at room temperature for prolonged periods.
In order to study their thermal behaviour, thionitrites were
simply dissolved in benzene or dichloromethane and the
resulting solutions were then heated at 40 °C until total
disappearance of their characteristic green colour (usually after
6–7 h). Separation of the reaction mixtures by flash chromatog-
raphy allowed isolation and characterisation of the major
products as the unusual episulfide nitroso dimers of general
formula 8 which were accompanied in some instances by a
second minor product 9, which formally resulted from thermo-
dynamically favourable allylic transposition and dimerisation to
the corresponding disulfide (Scheme 3). The yields of the
products obtained are shown in Table 1.
From a stereochemical viewpoint it was of particular interest
to note that the nitroso dimers 8 isolated from thionitrites 3–6
were formed as single diastereoisomers in each case whilst
those from thionitrites 2 and 7 were formed as mixtures. The
centrosymmetric structure of the dimer from thionitrite 3 was
unequivocally revealed by an X-ray crystallographic analysis
(Fig. 1). However, because of crystal decomposition, refine-
Within the last decade, the endogenously generated free radical,
nitric oxide, has been implicated in an increasing number of
fundamentally important biological processes, including con-
trol of blood pressure, cytotoxicity, and neurotransmission.1 As
a direct consequence, the chemistry of nitric oxide derivatives,
and in particular of thionitrites (S-nitrosothiols) has become an
area of considerable current research interest.2 The vital role
played by these intermediates for the storage, transport and
release of nitric oxide in vivo has been clearly recognised3 and,
to some extent, effectively mirrors their simple thermal
decomposition to give disulfide with concomitant liberation of
nitric oxide. This latter reaction is generally considered to
involve the intermediacy of thiyl radicals and can also be
brought about by irradiation or in the presence of certain metal
salts.2
As part of our ongoing interest in the homolytic reactivity of
thionitrites,4 we have previously shown that the capture of nitric
oxide from a thionitrite by a carbon centered radical can be a
very effective step in a free radical chain reaction, presumably
via a propagative addition–elimination mechanism. With this
observation in mind, and also given the rapid and reversible
addition of thiyl radicals to alkenes, we were especially
intrigued by the potential behaviour of tertiary allylic thioni-
trites (1) since the location of the internal alkene trap would then
allow us, in principle, to access the thiyl analogue of the well
known oxiranyl carbinyl–allyloxy radical rearrangement5 as
implied in Scheme 1. We now wish to report the results of our
preliminary study in this area.
The required tertiary allylic thionitrites were readily prepared
by the general route shown in Scheme 2. Thus, two carbon
homologation of commercially available lactones via Wads-
worth–Horner–Emmons olefination to their a,b-unsaturated
esters and subsequent lithium aluminium hydride reduction
gave allylic alcohols which were then transformed into
dithiocarbonates using the well established [3,3] sigmatropic
shift6 of the corresponding allylic xanthates. Aminolysis of the
dithiocarbonates was most effectively achieved using neat
2-aminoethanol and the resultant tertiary allylic thiols were then
nitrosated with sodium nitrite in acetic acid. The desired tertiary
allylic thionitrites prepared by this sequence are shown in
Scheme 2 and were isolated as green oils. They proved to be
sufficiently stable to allow purification by filtration through
silica gel and full characterisation by 1H and 13C NMR, IR, UV
Scheme 2 Reagents and conditions: (i) (EtO)2POCH2CO2Et (for R3 = H)
or (EtO)2PO(CH3)CO2Et (for R3 = CH3), NaH, THF, 0 °C to r.t., 2 h,
95–99%; (ii) LiAlH4, Et2O, 0 °C, 45 min, r.t., 1 h, 70–92%; (iii) a) NaH,
THF, 0 °C to r.t., 1 h; b) CS2, reflux, 1 h; c) MeI; (iv) reflux, 7 h, 45–60%;
(v) 2-aminoethanol, r.t., 2 h, 55–85%; (vi) NaNO2, AcOH, r.t., 2 h,
45–85%.
Scheme 1
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CHEM. COMMUN., 2002, 2394–2395
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We gratefully acknowledge financial support from the CNRS
(Gif-sur-Yvette, France) for the provision of a postgraduate
studentship to M. C., and the European Community for the
award of a Fellowship to J.-M. W. We also wish to thank Dr. A.
M. Z. Slawin for the X-ray crystallographic determination.
Notes and references
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Scheme 3
Table 1 Thermal rearrangement of thionitrites
Product yield (%)
Disulfide 9
Thionitrite
Solventa
Nitroso dimer 8
2
3
4
5
6
7
A
21
52b
A (B)
A (B)
A (B)
A (B)
A
16 (18)
0 (0)
30 (17)
0 (0)
0
39 ,(65)
43 (73)
30 (65)
65 (72)
58
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Fig. 1
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electrophilic addition of a nitrosonium cation to the double bond
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tetrafluoroborate to thionitrite led to extensive decomposition.
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intramolecular homolytic displacement leading to epoxide
formation from allylic peroxy derivatives,7 the well known lack
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described herein represents, to the best of our knowledge, the
first preparative example involving the sulfur congener.
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