Indium(III) chloride as an efficient, convenient catalyst for thioacetalization and its chemoselectivity

Article abstract of DOI:10.1016/S0040-4039(00)01966-3

An efficient method for the preparation of 1,3-dithiolanes from aldehydes and ketones with 1,2-ethanedithiol in the presence of a catalytic amount of anhydrous indium(III) chloride is reported. A mild and highly chemoselective thioacetalization of carbony

Full text of DOI:10.1016/S0040-4039(00)01966-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 359–362
Indium(III) chloride as an efficient, convenient catalyst for
thioacetalization and its chemoselectivity
Sengodagounder Muthusamy,* Srinivasarao Arulananda Babu and Chidambaram Gunanathan
Silicates and Catalysis Discipline, Central Salt and Marine Chemicals Research Institute, Bhavnagar 364 002, India
Received 30 October 2000; accepted 7 November 2000
Abstract—An efficient method for the preparation of 1,3-dithiolanes from aldehydes and ketones with 1,2-ethanedithiol in the
presence of a catalytic amount of anhydrous indium(III) chloride is reported. A mild and highly chemoselective thioacetalization
of carbonyl compounds using indium(III) chloride as the catalyst is also described. The desired products were obtained in 71–95%
yield. © 2000 Elsevier Science Ltd. All rights reserved.
When a solution of p-methoxybenzaldehyde, 1.1 equiv-
alents of 1,2-ethanedithiol and 0.3 equivalents of anhy-
drous indium(III) chloride in dry dichloromethane was
stirred at 25°C under an argon atmosphere for 15 min,
thioacetal 1 was produced12 and isolated in 92% yield
after extractive workup and chromatography on silica
gel. The reaction is clean and the workup procedure is
very simple.
Since the introduction of 1,3-dithianes as nucleophilic
acylating reagents by Corey and Seebach,1 dithioacetals
have become widely used tools for the formation of
CꢀC bonds. In addition, the stability exhibited by 1,3-
dithiolanes under acidic or basic conditions has led to
their synthetic utility as carbonyl protecting groups2
and as intermediates in the conversion of a carbonyl
function to a hydrocarbon derivative.3 For their prepa-
ration from carbonyl compounds, acid catalysts such as
concentrated HCl, ZnCl2 or BF3·Et2O have invariably
been used.2 Numerous other methods that are reported
for this conversion include the use of a Nafion-H4
catalyst, titanium tetrachloride,5 magnesium or zinc
triflates,6 and anhydrous lanthanum chloride.7 Yet, de-
spite their importance and necessity in synthesis,
chemoselectivity between aldehydes and ketones has
only been reported with catalysts like silica gel treated
with thionyl chloride,8 an Amberlyst-15 catalyst9 and
ceric ammonium nitrate.10 So far in the literature, no
Lewis acid has been reported to show chemoselectivity
for the carbonyl compound. In view of the recent surge
in activity on the use of indium(III) chloride as a mild
Lewis acid catalyst for various organic transforma-
tions,11 we wish to report a new and efficient synthesis
of 1,3-dithiolanes, as well as the chemoselective protec-
tion of various carbonyl compounds using indium(III)
chloride as the catalyst.
Encouraged by this result, we carried out further inves-
tigations on p-nitrobenzaldehyde and p-hydroxyben-
zaldehyde which were also converted to the
corresponding 1,3-dithiolanes 2 and 3 in very good
yields (see Table 1)13–16 using indium(III) chloride as
the catalyst. Enolizable ketones like ethyl acetoacetate
under the same reaction conditions with indium(III)
chloride as the catalyst for 5 hours were converted to
the corresponding thioacetal, e.g. 4, in 74% yield. With
our continuing interest in the synthesis17 of oxa-poly-
cyclic compounds, even an oxa-bridged compound was
converted into the corresponding 1,3-dithiolane deriva-
tive 5 in good yield. Alicyclic ketones like 2-carbethoxy-
2-methylcyclohexanone, ethyl 2-(2-oxocyclohexane)-
acetate; a,b-unsaturated ketones like benzylidene tetra-
lone and (E)-4-phenyl-3-buten-2-one in the presence of
1,2-ethanedithiol with indium(III) chloride as a catalyst
were converted to the corresponding dithiolanes 6–9 in
good yields, respectively.
We observed that the reaction with aldehydes takes
place rapidly in the presence of indium(III) chloride
when compared to the rate with ketones (see Table 1).
The difference in reactivity of the indium(III) chloride
catalyst towards aldehydes and ketones gave us impetus
to study chemoselective reactions.
Keywords: aldehydes; ketones; indium(III) chloride; 1,2-ethanedithiol;
1,3-dithiolanes.
* Corresponding author. Tel.: +91 278 567760; fax: +91 278 567562;
e-mail: salt@csir.res.in
0040-4039/01/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)01966-3

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S. Muthusamy et al. / Tetrahedron Letters 42 (2001) 359–362
Towards this objective, we carried out initial experi-
ments with equimolar mixtures of an aldehyde and a
ketone (Scheme 1). When an equimolar (1.5 mmol)
mixture of p-hydroxybenzaldehyde and acetophenone
was allowed to react with 1.5 mmol of 1,2-ethanedithiol
and a catalytic amount of indium(III) chloride in dry
methanol at ambient temperature, a high yield (93%) of
3 was obtained and the unchanged acetophenone was
recovered. A similar result was obtained when the
experiment was performed on a mixture of p-hydroxy-
Table 1. Preparation of 1,3-dithiolanes13 using anhydrous indium(III) chloride

S. Muthusamy et al. / Tetrahedron Letters 42 (2001) 359–362
361
Scheme 1.
References
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12. Typical experimental procedure: To a freshly distilled
dichloromethane (dried over phosphorous pentoxide) so-
lution of the appropriate carbonyl compound (1 mmol)
and 1,2-ethanedithiol (1.1 mmol) was added anhydrous
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Scheme 2.
benzaldehyde
and
ethyl
3-(2-oxocyclohexane)-
propionate. Further, we studied thioacetalization of the
keto-aldehydes 1218 (Scheme 2) which also exhibited
splendid selectivity towards the formyl group. When
4-acetylbenzaldehyde
(12a)
reacted
with
1,2-
ethanedithiol under the usual conditions, only the alde-
hyde group reacted and afforded the corresponding
product 13a in 87% yield. Repetition of this reaction
with 12b furnished the dithiolane 13b in 89% yield.
There was no evidence that the ketonic carbonyl group
reacted to any measurable extent.
In summary, mild conditions coupled with an exceed-
ingly simple protocol for the protection of aldehydes or
ketones as dithiolanes using indium(III) chloride as a
catalyst is reported. Furthermore, the relatively slow
reaction rate of ketones allows for chemoselective pro-
tection of aldehydes in the presence of ketones, making
this is an important tool in synthetic organic chemistry.
The notable advantages of this method are its chemose-
lectivity and the requirement for minimum amounts of
catalyst.
Acknowledgements
This research was supported by CSIR [Young Scientist
Scheme] and the Department of Science and Technol-
ogy, New Delhi. We thank Dr. P. K. Ghosh, Director
and R. V. Jasra, Head of the Division, for their encour-
agement of this work. S.A.B. and C.G. thank CSIR,
13. All new compounds gave satisfactory spectral data in
accordance to their proposed structures.
New Delhi, for a Fellowship.
.

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