Indium(III)-catalysed highly regioselective addition of thiolacetic acid to non-activated olefins

Article abstract of DOI:10.1016/j.tetlet.2005.11.030

Indium(III) chloride and indium(III) trifluoromethanesulfonate were found to be excellent catalysts for the addition of thiolacetic acid to non-activated olefins. The reaction is highly regioselective and can be run in the presence of 1 mol % of catalyst.

Full text of DOI:10.1016/j.tetlet.2005.11.030

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 287–289
Indium(III)-catalysed highly regioselective addition
of thiolacetic acid to non-activated olefins
Michel We¨ıwera and Elisabet Dunacha,b,
*
˜
a
ˆ
`
´
Laboratoire Aromes, Syntheses et Interactions, Universite de Nice-Sophia Antipolis, Parc Valrose, 06108 Nice cedex 2, France
bLaboratoire de Chimie Bio-Organique, CNRS, UMR 6001, Universite´ de Nice-Sophia Antipolis, Parc Valrose,
06108 Nice cedex 2, France
Received 3 October 2005; revised 28 October 2005; accepted 4 November 2005
Available online 22 November 2005
Abstract—Indium(III) chloride and indium(III) trifluoromethanesulfonate were found to be excellent catalysts for the addition of
thiolacetic acid to non-activated olefins. The reaction is highly regioselective and can be run in the presence of 1 mol % of catalyst.
Ó 2005 Elsevier Ltd. All rights reserved.
In the last few years, indium derivatives and particularly
indium(III) chloride and trifluoromethanesulfonate
have found successful applications as catalysts in syn-
thetic organic chemistry, for example, in ring opening
of epoxides and aziridines,1 Mukaiyama-type reactions,2
intramolecular Prins-type cyclisations,3 Diels–Alder
cycloadditions,4 reductive Friedel–Crafts alkylations5
or thioacetalisation of aldehydes and ketones.6 More-
over, InCl3 and In(OTf)3 are stable under air and in
water and constitute interesting catalysts for clean and
green chemistry, due to the possibility of recovery
and recycling.7
synthesis usually involves the functionalisation of an ole-
fin with hydrogen sulfide or thiolacetic acid, followed by
the thioester reduction to the thiol. The olefin addition is
generally carried out in the presence of a radical initiator
such as AIBN,10 UV irradiation,11 or an oxidising agent12
promoting the formation of sulfur centered radicals and
anti-Markovnikov-type adducts. It can also be carried
out in acidic media and an heterogeneous system based
on Montmorillonite K10 clay has been reported for the
addition of thiobenzoic acid to olefins.13 Although sev-
eral examples report the addition of thiolacetic acid to
conjugated olefins in a Michael-type reaction in basic
media,14 to our knowledge, there is no example of a cat-
alytic system involving the use of Lewis acids to effect the
addition of thiolacetic acid to non-activated olefins.
Sulfur compounds constitute an interesting family of nat-
ural compounds in particular in the field of flavour and
fragrance chemistry.8 Although present in trace amounts,
they often play an important role in the overall aroma of
coffee, meat, vegetables and fruits.9 Thiols are known to
be among the most powerful sulfur compounds from
the point of view of their organoleptic properties. Their
In the aim to develop a new system involving Lewis acid
catalysis for the functionalisation of alkenes, we exam-
ined the indium(III)-catalysed addition of thiolacetic
acid to non-activated olefins (Scheme 1).
R1
R2
R3
R3
R1
R2
R3
R1
R2
In(III) 5 mol%
AcSH
+
+
SAc
SAc
1
2
3
Scheme 1.
Keywords: Indium chloride; Indium triflate; Markovnikov-type addition; Thiolacetic acid; Non-activated olefins.
*
Corresponding author. Tel.: +33 (0)492076142; fax: +33 (0)492076151; e-mail: dunach@unice.fr
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.11.030

288
M. Weı¨wer, E. Dun˜ach / Tetrahedron Letters 47 (2006) 287–289
The efficiency of several metallic triflates was tested for
the addition of AcSH to citronellyl methyl ether 1a
(See Table 1) chosen as the model compound.
Several trisubstituted olefins 1a–c (entries 1–3) were
selectively converted into the corresponding thioace-
tates 2 (Markovnikov product) in almost quantitative
yields. 2,2-Disubstituted alkene 1d afforded regiospecifi-
cally the AcS– addition into the 2-position of the dou-
ble bond to afford 2d as the single isomer in 86%
isolated yield (entry 4). Conjugated diene 1e (entry 5)
was also regioselectively converted into the mono-
thioacetate 2e. Only one AcS– group was incorporated
into the 1,3-diene, regardless of the excess of thiolacetic
acid.
The use of strong Lewis acids such as Al(OTf)3 or
Sc(OTf)3 in 5 mol % ratio led regioselectively to 2a
though in a slow reaction (10 h in refluxing 1,2-dichloro-
ethane). In contrast, InCl3 or In(OTf)3 showed high
catalytic activity with the clean and regiospecific forma-
tion of thioacetate 2a in less than 1 h. The reaction
could also be run in the presence of 1 mol % In(III)
catalyst without solvent and 2a was obtained in 92%
yield after 24 h. Under the different conditions, either
In(OTf)3 or InCl3 afforded regiospecifically the thioacid
addition on the most substituted site of the olefin, in a
Markovnikov-type addition. It is noteworthy that the
regiochemical outcome is the opposite to that obtained
by the more classical radical-type addition with
AIBN.10
For mono- and 1,2-disubstituted olefins 1f–i (entries 6–
9), indium(III) chloride was less efficient and afforded
low conversions. However, In(OTf)3 showed a good
catalytic activity for the addition of AcSH to these less
substituted double bonds, in particular in refluxing
nitromethane (entries 7 and 8), a more polar and
higher boiling point solvent. For terminal olefin 1f,
the expected thioacetate issued from the addition of
the AcS– moiety to the internal olefinic carbon did
not occur. Instead, the reaction led cleanly to 2f in
91% isolated yield. Thioacetate 2f results from a first
The In(III)-catalysed selective functionalisation of C–C
double bonds was further extended to other differently
substituted olefins. The results are summarised in Table 1.
Table 1. In(III)-catalysed thioacetylation of olefins15
Entry Substrate
Conditions
Product
% Yield regioselectivity (2/3)
OMe
AcS
OMe
1
InCl3 (5 mol %) ClCH2CH2Cl 80 °C, 1 h
87 (100/—)
1a
2a
AcS
CO2Et
SAc
CO2Et
SAc
2
3
InCl3 (5 mol %) ClCH2CH2Cl 80 °C, 1 h
InCl3 (5 mol %) ClCH2CH2Cl 80 °C, 1 h
InCl3 (5 mol %) ClCH2CH2Cl 80 °C, 0.5 h
92 (100/—)
93 (100/—)
86 (100/—)
1b
2b
2c
AcS
1c
AcS
4
1d
2d
SAc
5
InCl3 (5 mol %) ClCH2CH2Cl 80 °C, 0.25 h
92 (100/—)
1e
2e
SAc
6
In(OTf)3 (5 mol %) ClCH2CH2Cl 80 °C, 2 h
In(OTf)3 (5 mol %) CH3NO2 100 °C, 15 h
91
72
1f
2f
SAc
C4H9
C4H9
7
1g
2g and isomers
SAc
8
9
In(OTf)3 (5 mol %) CH3NO2 100 °C, 2 h
In(OTf)3 (1 mol %) no solvent 80 °C, 48 h
70
67
1h
2h
SAc
1i
2i

M. Weı¨wer, E. Dun˜ach / Tetrahedron Letters 47 (2006) 287–289
289
isomerisation of the double bond followed by the addi-
tion of thiolacetic acid on the tertiary carbon. For
comparison, with the use of 5 mol % InCl3, 2f was also
formed as the only product, but in 60% yield after
72 h. A strong counter-ion effect was observed for this
reaction.
isomerisation of C–C double bonds to more substituted
olefins occurred in some cases.
References and notes
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R. New J. Chem. 2001, 25, 221; (b) Yadav, J. S.; Reddy, B.
V. S.; Kumar, G. M.; Murthy, Ch. V. S. R. Synth.
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2. Chancharunee, S.; Perlmutter, P.; Statton, M. Tetrahedron
Lett. 2003, 44, 5683.
3. Chan, K.-P.; Loh, T.-P. Tetrahedron Lett. 2004, 45, 8387.
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Tetrahedron Lett. 2000, 41, 10333; (b) Ali, T.; Chauhan,
K. K.; Frost, C. G. Tetrahedron Lett. 1999, 40, 5621.
5. Miyai, T.; Onishi, Y.; Baba, A. Tetrahedron Lett. 1998, 39,
6291.
For linear alkene 1g, an isomerisation of the double
bond through the alkyl chain occurred and a mixture
of the four thioacetate isomers was obtained in 72%
overall yield. Thioacetylation of cyclooctene 1h and
cyclohexene 1i was efficiently catalysed by In(OTf)3 to
afford the corresponding derivatives 2h and 2i, respec-
tively. The functionalisation of 1i could be run without
solvent in the presence of 1 mol % In(OTf)3, affording
cyclohexanyl thioacetate 2i in 67% yield.
6. Muthusamy, S.; Babu, S. A.; Gunanathan, C. Tetrahedron
2002, 58, 7897.
7. (a) Prajapati, D.; Laskar, D. D.; Sandhu, J. S. Tetrahedron
Lett. 2000, 41, 8639; (b) Ghosh, R.; Maiti, S.; Chakra-
borty, A.; Halder, R. J. Mol. Catal. A, Chem. 2004, 215, 49.
8. Goeke, A. Sulfur Rep. 2002, 23, 243.
9. Jameson, S. B. In Chemistry and Technology of Flavors and
Fragrances; Rowe, D. J., Ed.; Blackwell Publishing Ltd:
Oxford, UK, 2005.
10. Pinkney, P. S. (E. I. du Pont de Nemours & Co.), U.S.
2551813, 1951.
11. Bordwell, F. G.; Hewett, W. A. J. Am. Chem. Soc. 1957,
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13. Kanagasabapathy, S.; Sudalai, A.; Benicewicz, B. C.
Tetrahedron Lett. 2001, 42, 3791.
14. Coster, M. J.; De Voss, J. J. Org. Lett. 2002, 4, 3047.
15. General procedure for the In(III)-catalysed addition of
thiolacetic acid to olefins: to a mixture of olefin (5 mmol)
and InCl3 or In(OTf)3 (5 mol %) in distilled 1,2-dichloro-
ethane (5 mL) was slowly added thiolacetic acid
(5.5 mmol). The temperature was increased to 80 °C and
the progress of the reaction was monitored by GC analysis.
On completion of the reaction, the mixture was quenched
with HCl 1 M and extracted with Et2O. The organic layer
was washed with saturated aqueous NaHCO3 and dried
with MgSO4. The solvent was evaporated and the products
were purified and analysed by 1H and 13C NMR and mass
spectrometry.
The observed Markovnikov-type regioselectivity as well
as the isomerisation of the double bond for substrates 1f
and 1g indicated that the mechanism most probably
involves a protic pathway. Moreover, a reaction with
olefin 1d under the conditions of entry 4 with added
2,6-di-tert-butyl-4-methylpyridine (DTBMP, 5 mol %)
as a hindered base led to no thioacid addition after
0.5 h. After 10 h, some addition occurred with com-
pletely reversed regioselectivity, in an anti-Markovnikov
reaction, most probably due to a slow radical-type reac-
tion with light. We propose that the In(III) catalyst
forms an In(III) thioacetate and liberates H+, responsi-
ble for the catalytic activity. The formation of an inter-
mediate In(III) thioacetate may enhance the acidity of
AcSH as well as the nucleophilicity of the thioacetate
moiety. This catalytic system constitutes a novel exam-
ple of the newly reported Lewis acid-assisted Brønsted
acid catalysed process.16
In conclusion, InCl3 and In(OTf)3 were shown for the
first time to be very efficient catalysts for the regiospec-
ific Markovnikov-type addition of thiolacetic acid to
non-activated olefins. The reaction was carried out with-
out solvent and in the presence of 1 mol % In(III) for the
functionalisation of substrates 1a and 1i. InCl3 is an effi-
cient catalyst for the addition of thiolacetic acid to tri-
substituted olefins, and the use of more active
In(OTf)3 is required for the addition to mono- and
disubstituted olefins. The In(III)-catalysed selective
16. Yamamoto, H.; Futatsugi, K. Angew. Chem., Int. Ed.
2005, 44, 1924.