The indium(III) chloride-catalysed hydrolysis and in situ Mukaiyama-type reaction of arylmethyl ketone derived silyl enol ethers under solvent-free conditions

Article abstract of DOI:10.1016/S0040-4039(03)01350-9

Treatment of trimethylsilyl enol ethers of arylmethyl ketones with catalytic amounts of indium(III) chloride under solvent-free conditions leads to a remarkably efficient process of in situ hydrolysis and Mukaiyama-type addition to the resulting ketones.

Full text of DOI:10.1016/S0040-4039(03)01350-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 5683–5685
The indium(III) chloride-catalysed hydrolysis and in situ
Mukaiyama-type reaction of arylmethyl ketone derived silyl enol
ethers under solvent-free conditions
Sirirat Chancharunee,a,b Patrick Perlmuttera,* and Maya Stattona
aSchool of Chemistry and the Centre for Green Chemistry, Monash University, PO Box 23, Victoria 3800, Australia
bDepartment of Chemistry, Naresuan University, Phitsanulok, Thailand
Received 14 March 2003; revised 23 May 2003; accepted 30 May 2003
This paper is dedicated with respect and admiration to Professor Teruaki Mukaiyama
Abstract—Treatment of trimethylsilyl enol ethers of arylmethyl ketones with catalytic amounts of indium(III) chloride under
solvent-free conditions leads to a remarkably efficient process of in situ hydrolysis and Mukaiyama-type addition to the resulting
ketones.
© 2003 Elsevier Ltd. All rights reserved.
As part of a program directed towards the development
of new nucleophilic addition ring closure [NARC]-
based synthetic protocols,1 we had occasion to examine
solvent-free2 InCl3-catalysed Mukaiyama aldol reac-
tions.3,4 In the case of the reaction of the trimethylsilyl
enol ether of acetophenone (1a) with benzaldehyde,
which was expected to generate 3, the consistent forma-
tion of a by-product (4a, Scheme 1) was observed.
In this work it was found that simply mixing a TMS
enol ether, such as 1a, with a catalytic amount of InCl3
generated the corresponding adduct 4a. Scheme 2 pro-
vides a balanced equation for this process.9
The amount of water present in these reactions appears
to be critical to the success of the reaction. We found
that the combination of the use of flame-dried appara-
tus and the passage of moist air across the catalyst
surface for several minutes prior to addition of the silyl
enol ether led to smooth conversion to the correspond-
ing adduct 4 (Table 1, entries 1–6). Under these con-
trolled conditions hydrolysis is apparently sufficiently
slow to enable the aldol-like addition to occur. The
remaining silyl enol ether essentially ‘traps’ the ketone
as it is formed. In order to minimise hydrolysis of the
product silyl ethers it was important to remove the
InCl3 prior to chromatography or other manipulations.
Hence the crude product was suspended in ethyl acetate
and immediately washed with aqueous potassium car-
bonate. However, in two cases some alcohol was still
generated after chromatography (entries 5 and 6).
Adduct 4a appeared to be the result of addition of enol
ether 1a to acetophenone rather than to benzaldehyde.
As there were several interesting aspects to this discov-
ery a more systematic investigation of the origin and
limitations of the process was carried out the results of
which are reported here.5
Mukaiyama-type additions of ketone silyl enol ethers to
simple ketones have been reported using metallic
iodide-activated bismuth(III) chloride,6 titanium and
zirconium triflates7 and electrogenerated acid catalysis.8
Scheme 1. Mukaiyama coupling of silyl enol ethers to alde-
hydes under neat conditions.
Scheme 2. Balanced equation for the reaction of arylsilyl enol
* Corresponding author.
ethers under InCl3 catalysis.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01350-9

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S. Chancharunee et al. / Tetrahedron Letters 44 (2003) 5683–5685
Table 1. InCl3-promoted self-coupling aldol reactions
Attempts to apply this procedure to b-substituted enol
ethers such as cyclohexanone and propiophenone TMS
enol ethers were unsuccessful leading only to hydrolysis
of the starting material.
From Table 1 the process appears to be relatively
insensitive to the presence of either electron-withdraw-
ing or electron-donating substituents on the aromatic
ring. In addition, catalyst concentrations as low as 1
mol% still gave modest conversion albeit after much
longer reaction times (compare entries 2 and 3). Cata-
lyst loadings ranging from 10 to 20 mol% appeared to
provide the best conversion.
Remarkably, several of the relatively simple b-hydroxy-
ketone derivatives described here, such as 4b, 4d and 4e,
have not been reported previously in the open litera-
ture. Some of the adducts were crystalline and the
X-ray structure of one of these, 4b, is shown in Figure
1.10
Figure 1. X-Ray crystal structure of adduct 4b.

S. Chancharunee et al. / Tetrahedron Letters 44 (2003) 5683–5685
5685
No. 315) and Dr. Gary D. Fallon for solving the X-ray
crystal structure of 4b. S.C. is grateful to the Australian
Government for the award of
Fellowship.
a Thai–Australia
References
1. Perlmutter, P. In Topics in Current Chemistry; Metz, P.,
Ed.; Springer: Heidelberg, 1997; Vol. 190, p. 87.
2. For a recent review on solvent free reactions, see:
Tanaka, K.; Toda, F. Chem. Rev. 2000, 100, 1025.
3. Mukaiyama, T. Org. React. 1982, 28, 203.
Scheme 3. InCl3-catalysed cross-coupling of silyl enol ethers
with simple ketones under neat conditions.
4. Kobayashi, S.; Busujima, T.; Nagayama, S. Tetrahedron
Lett. 1998, 39, 1579. See also: Loh, T.-P.; Huang, J.-M.;
Goh, S.-H.; Vittal, J. J. Org. Lett. 2000, 2, 1291.
5. For a review of the applications of InCl3 in synthesis, see:
Babu, G.; Perumal, P. T. Aldrichim. Acta 2000, 33, 16.
6. Le Roux, C.; Gaspard-Iloughmane, H.; Dubac, J. J. Org.
Chem. 1993, 58, 1835.
It was also of interest to establish whether or not this
process could be diverted to enable other ketones to
react with silyl enol ethers such as 1a or 1c. Indeed
employing an excess of acetone (5a) or 2-butanone (5b),
gave the corresponding Mukaiyama-type adducts, 6, in
reasonable (although not optimised) yields (Scheme 3).
Adducts 6a and 6b were obtained as mixtures of TMS
ethers (R¦=TMS) and free alcohols (R¦=H) whereas
for 6c only the TMS ether was isolated. In these cases
no prior passage of moist air was necessary as there was
apparently sufficient water in each of the ketones. Only
traces of the ‘self-coupled’ products, 4a or 4c, were
observed.
7. Hollis, T. K.; Robinson, N. P.; Bosnich, B. Tetrahedron
Lett. 1992, 33, 6423.
8. Torii, S.; Inokuchi, T.; Takagishi, S.; Horike, H.;
Kuroda, H.; Uneyama, K. Bull. Chem. Soc. Jpn. 1987,
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9. For examples and discussion of InCl3-catalysed
Mukaiyama reactions in water, see: Loh, T.-P.; Pei, J.;
Cao, G.-Q. J. Chem. Soc., Chem. Commun. 1996, 1819.
See also: Loh, T.-P.; Pei, J.; Koh, K. S.-V.; Coao, G.-
Q.; Li, X.-R. Tetrahedron Lett. 1997, 38, 3465 and Ref.
4.
10. Crystallographic data (excluding structure factors) for the
structures in this paper, have been deposited with the
Cambridge Crystallographic Data Centre as supplemen-
tary publication number CCDC 195029. Copies of the
data can be obtained, free of charge, on application to
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK (fax:
+44(0)-1223-336033 or e-mail: deposit@ccdc.cam.ac.uk).
In conclusion, we have discovered a new, operationally
simple, mild, solvent-free catalytic process for convert-
ing trimethylsilyl enol ethers of arylmethyl ketones into
the corresponding b-silyloxyketones of general struc-
tures 4 and 6.
Acknowledgements
We thank the Centre for Green Chemistry, Monash
University for financial support for this research (Grant