Synthesis of new silylated sulfur-containing heterocycles through thionation of bis(acylsilanes)

Article abstract of DOI:10.1016/j.tetlet.2003.10.110

The thionation of bis(acylsilanes) with spacers of variable size with hexamethyldisilathiane under cobalt(II) chloride or trimethylsilyl triflate catalysis affords 2,5-bis(trialkylsilyl)-thiophenes, 2,6-bis(trialkylsilyl)-4H- thiopyrans and 2,7-bis(trialkylsilyl)-4,5-dihydrothiepine generally along with a minor amount of the corresponding oxo analogue. The synthesis of both symmetrical and unsymmetrical bis(trialkylsilyl) derivatives was achieved.

Full text of DOI:10.1016/j.tetlet.2003.10.110

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 87–90
Synthesis of new silylated sulfur-containing heterocycles through
thionation of bis(acylsilanes)
Jean-Philippe Bouillon,a Antonella Capperucci,b Charles Portellaa,* and
Alessandro DeglꢀInnocentib,*
aLaboratoire ‘‘Reꢀactions Seꢀlectives et Applications’’, UMR CNRS 6519, Faculteꢀ des Sciences, Universiteꢀ de Reims, B.P. 1039,
F-51687 Reims Cedex 2, France
bDipartimento di Chimica Organica, ICCOM, via della Lastruccia 13, I-50019 Sesto Fiorentino (FI), Italy
Received 24 September 2003; revised 17 October 2003; accepted 21 October 2003
Abstract—The thionation of bis(acylsilanes) with spacers of variable size with hexamethyldisilathiane under cobalt(II) chloride or
trimethylsilyl triflate catalysis affords 2,5-bis(trialkylsilyl)-thiophenes, 2,6-bis(trialkylsilyl)-4H-thiopyrans and 2,7-bis(trialkylsilyl)-
4,5-dihydrothiepine generally along with a minor amount of the corresponding oxo analogue. The synthesis of both symmetrical and
unsymmetrical bis(trialkylsilyl) derivatives was achieved.
Ó 2003 Elsevier Ltd. All rights reserved.
Acylsilanes are well known compounds that have been
shown to be useful intermediates in synthetic organic
chemistry.1 They participate in regio- and stereoselective
processes that allow the synthesis of a number of poly-
functionalized molecules. Preparation of silyl enolethers,
diastereoselective aldol condensations, the synthesis of
b-hydroxysilanes and the stereoselective synthesis of
vinylsilanes are just a few examples of their valuable
reactivity. On the other hand, bis(acylsilanes) have been
less investigated, and only very recently have they been
demonstrated as being very useful compounds,2 able to
participate in a number of interesting reactions, such as
cyclization reactions via intramolecular aldol conden-
sation and cyclodehydration2b;c;3 or formation of elab-
orated silyl organofluorine compounds.4
their structure the high reactivity of the carbon–sulfur
double bond towards nucleophiles, electrophiles and
cycloaddition reactions, together with the peculiar re-
activity of organosilanes, thus leading to various com-
pounds containing the Si–C–S unit.5;6
Enethiolizable thioacylsilanes have been thoroughly in-
vestigated7 and, inter alia, they have been shown to lead
to 2-silyl thiacycloalkenes or Z-a-silyl sulfides, which are
precursors of thioannulated cyclopentenes and thio-
functionalized enones, thus disclosing a general access to
differently silylated sulfur heterocycles of variable ring
size.
In this context, we became interested in the evaluation
of the possibility of devising a general access to a new
class of thioacylsilanes, namely bis(thioacylsilanes),
through direct thionation of bis(acylsilanes), and in this
connection the hexamethyldisilathiane (HMDST)-based
thionation procedure that proved, due to its mildness, to
be quite efficient in thionating labile molecules such as
a,b-unsaturated acylsilanes and stannanes,8 seemed well
suited for such a transformation.
Moreover, the corresponding sulfurated derivatives,
thioacylsilanes, are known as useful building blocks for
polyfunctionalized molecules.5 In fact, besides being
synthetic equivalents of thioaldehydes through a simple
protodesilylation reaction, thioacylsilanes combine in
Thus we reacted 1,5-bis(acylsilane) 1a with HMDST in
the presence of CoCl2Æ6H2O and 2,3-dimethyl-1,3-
butadiene as trapping agent, but no trace of the cyclo-
adduct of the thioacylsilane was evident in the crude
mixture. Nonetheless, a clean reaction was observed,
Keywords: acylsilanes; thionation; thiopirans; dihydrothiepines.
* Corresponding authors. Tel.: +33-3-26-91-32-34; fax: +33-3-26-91-
31-66 (C.P.); tel.: +39-055-4573551; fax: +39-055-4573531 (A.D.);
e-mail: charles.portella@univ-reims.fr; alessandro.deglinnocenti@unifi.it
0040-4039/$ - see front matter Ó 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.110

88
J.-P. Bouillon et al. / Tetrahedron Letters 45 (2004) 87–90
CoCl2.6H2O
MeCN
O
O
+
+
(TMS)2S
Si1
Si 2
Si1
S
Si 2
Si1
O
Si2
1a : Si1=Si2=t-BuMe2Si
2a, 2b
3a, 3b
1b : Si1=Me3Si
Si2=i-Pr3Si
Scheme 1.
affording one main product (63%), which was charac-
terized as 2,6-bis(tert-butyldimethylsilyl)-4H-thiopyran
2a,9 together with a very minor amount (6%) of 2,6-
bis(tert-butyldimethylsilyl)-4H-pyran 3a (Scheme 1).
Compound 3a has already been obtained by treatment
of bis(acylsilane) 1a with acid.3b
Table 1. Thionation of bis(acylsilanes)
Entry
Bis(acylsilane)
Catalyst
Product
Yielda;b (%)
O
O
1
CoCl2Æ6H2O
2a
63c
TBDMS
TBDMS
1a
1b
O
O
2
3
CoCl2Æ6H2O
2b
75d
TMS
TIPS
TMS
O
OR
O
CoCl2Æ6H2O
––
––
TMS
1c (R=H)
1c' (R=Ac)
O
O
4
CoCl2Æ6H2O
4d
61e
TMS
TMS
1d
O
O
5
6
CoCl2Æ6H2O
4e
6f
48f
57
TMS
TIPS
1e
O
TBDMS
TfOTMS
TBDMS
1f
O
O
TIPS
7
TfOTMS
6g
51g
TMS
O
O
1g
O
O
O
8
CoCl2Æ6H2O
TfOTMS
––
––
TMS
a Yield of isolated product.
TMS
1h
b All compounds showed spectroscopic and analytical data consistent with the assigned structure.
c Pyran 3a (6%) was isolated.
d Pyran 3b (2%) was detected.
e Furan 5d (13%) was isolated.
f Furan 5e (43%) was obtained.
g Thiol 7g (27%) was obtained.

J.-P. Bouillon et al. / Tetrahedron Letters 45 (2004) 87–90
89
CoCl2.6H2O
MeCN
O
O
+
+
(TMS)2S
Si2
Si2
Si1
Si1
Si1
Si2
S
O
1d : Si1=Si2=Me3Si
4d, 4e
5d, 5e
1e : Si1=Me3Si
2
i
Si =i-Pr3S
Scheme 2.
O
TfOTMS
MeCN
Si2
SH
Sii-Pr3
+
Me3Si
Si1
+ (TMS)2S
Si 2
S
Si1
S
O
1f : Si1=Si2=t-BuMe2Si
1g : Si1=Me3Si
Si2=i-Pr3Si
6f, 6g
7g
Scheme 3.
This result allows the hypothesis that the formation of
such unreported silylated sulfur heterocycles can be
achieved by intramolecular cyclization of the enethiol
formof the thioacylsilane on the other C @X group
(X ¼ S or O), followed by dehydration or hydrogen
sulfide elimination, and this behavior may be ascribed to
the presence of the silyl group, which favors enethioli-
zation of alkyl thiones bearing a hydrogen atomat the
a-carbon.10
and 5e.3b It is worth noting that the silyl-thiophene 4e
has not previously been described in the literature.
On the other hand, when bis(acylsilanes) with a four-
methylene chain linker, such as the 1,6-bis(acylsilanes)
1f and 1g, were used under the same conditions, the
reaction did not afford the expected thionation or
cyclization derived products, and unreacted starting
compounds were recovered. We therefore used the
stronger catalyst TfOTMS to promote the reaction and
indeed under these conditions the 2,7-bis(tert-butyl-
dimethylsilyl)-4,5-dihydrothiepine 6f was isolated in
good yield by treating 1,6-bis(acylsilane) 1f with
HMDST (Scheme 3).12
With the aimof evaluating the generality of such a re-
action as a potential general route for the synthesis of
sulfurated heterocycles of variable ring size, we tried it
with various bis(acylsilanes) bearing either different
silylated groups or different lengths of carbon chain
between themincluding also
b-hydroxy-substituted
When the unsymmetrical 1,6-bis(acylsilane) 1g was re-
acted under the same conditions, again the related silyl
thiepine 6g was obtained (Scheme 3), together with the
aldol-like intermediate product, 2-triisopropyl-7-tri-
methylsilyl-2,3,4,5-tetrahydro-thiepine-2-thiol 7g (27%),
thus providing a method for synthesizing this kind of
molecule.13
bis(acylsilanes). The results so obtained are summarized
in Table 1. The bis(acylsilanes) reacted smoothly under
the present conditions, and the reaction appears to be
general.
The unsymmetrical substituted bis(acylsilane) 1b led to
2,6-bis(trialkylsilyl)-4H-thiopyran 2b (75%) (Scheme 1).
Also in this case traces (2%) of the corresponding 2,6-
bis(trialkylsilyl)-4H-pyran 3b were detected.3b
Moreover, when 3,4-dihydroxy-1,6-bis(trimethylsilyl)-
acylsilane, protected as the acetonide 1h, was treated
with HMDST and either TfOTMS or CoCl2Æ6H2O, no
formation of the thionated compounds was observed,
the reaction leading only to decomposition of the
starting bis(acylsilane) in the case of triflate, and to an
unidentified mixture of compounds with cobalt(II)
chloride.
In both of the above reactions an aldol-like intermedi-
ate,
2,6-bis(trialkylsilyl)-3,4-dihydro-2H-thiopyran-2-
thiol, was observed in very small amounts (2–3%) after
purification of the crude product.
When the hydroxy-substituted bis(acylsilane) 1c was
treated under the same conditions, only a complex
mixture of unidentified products was obtained. Reaction
of the acetyl protected derivative 1c0 did not afford any
trace of the desired bis(thioacylsilane), even under dif-
ferent experimental conditions.
In conclusion, thionation of bis(acylsilanes) with
HMDST affords a general route to bis-silylated thia-
heterocycles of variable size, with both symmetrical and
unsymmetrical trialkylsilyl substitution being possible.
This type of reaction is not limited to the thionation of
1,5-bis(acylsilanes) but can be efficiently extended to
1,4-bis(acylsilanes) 1d and 1e, allowing in this case the
isolation of 2,5-bis(trialkylsilyl)thiophenes 4d11 and 4e
(Scheme 2), together with 2,5-bis(trialkylsilyl)furans 5d
Acknowledgements
The authors gratefully acknowledge Professor Alfredo
Ricci, University of Bologna, for helpful discussions.

90
J.-P. Bouillon et al. / Tetrahedron Letters 45 (2004) 87–90
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(50 mg, 0.15 mmol) in CH3CN (0.5 mL) were added, under
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TfOTMS (0.012 mL, 0.06 mmol). The mixture was stirred
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CDCl3) d (ppm): 0.10 (12H, s), 0.92 (18H, s), 2.53–2.61
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