Iodine-catalyzed synthesis of β-keto enol ethers

Article abstract of DOI:10.1016/j.tetlet.2004.08.044

The use of iodine, as a catalyst for the synthesis of β-keto enol ethers at room temperature is reported. The use of iodine, as a catalyst for the synthesis of β-keto enol ethers at room temperature is reported.

Full text of DOI:10.1016/j.tetlet.2004.08.044

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 7187–7188
Iodine-catalyzed synthesis of b-keto enol ethers
a
Rajesh S. Bhosale, Sidhanath V. Bhosale, Sheshanath V. Bhosale, Tianyu Wang and
b
b
b
a,
*
P. K. Zubaidha
a
School of Chemical Sciences, SRTM University, Nanded 431606, India
Institute of Chemistry-Organic Chemistry, Freie Universit a¨ t, Takustrassa-3, Berlin-14195, Germany
b
Received 8 June 2004; revised 2 August 2004; accepted 10 August 2004
Available online 24 August 2004
Abstract—The use of iodine, as a catalyst for the synthesis of b-keto enol ethers at room temperature is reported.
Ó 2004 Elsevier Ltd. All rights reserved.
b-Keto enol ethers have been widely used as key inter-
mediates in organic synthesis. For example, they have
been employed for the preparation of enantiomerically
1
–5
5
,6
pure compounds. A literature survey revealed that
several methods have been reported to synthesize b-keto
enol ethers from cyclic b-diketones. The treatment of
cyclic b-diketones with diazomethane yields b-keto enol
Scheme 1.
1
ethers. Etherification of cyclic b-diketones has been re-
ported using an alcohol with p-toluenesulfonic acid
2
monohydrate under reflux, and from 3-chloro-
3
whereas bis-acetals were not obtained (Scheme 1). In
the absence of iodine, the reaction did not proceed even
after 24h.
,4
cycloalk-2-enones with methoxide.
Recently Porta
and co-workers reported conversion of cyclic b-dike-
7
tones to b-keto enol ethers using TiCl in methanol.
4
In recent years, iodine has been used as a versatile
8
Typical experimental procedure: To a stirred solution of
the substrate 1 (0.5g, 44.6mmol) in methanol (10mL),
was added iodine (3mol%). The reaction was monitored
by TLC. After the reaction was complete, the solvent
was removed under reduced pressure. The residue was
extracted with a suitable solvent and washed with aq
sodium thiosulfate solution, and subsequently with
water and brine. The organic layer was dried over mag-
nesium sulfate, filtered and the solvent was removed
under reduced pressure. The product obtained was puri-
–11
reagent for several reactions.
Lewis acid in the dehydration of tertiary alcohols to alk-
Iodine acts as a mild
12
enes. Iodine was also used in the synthesis of mixed
1
3
benzyl–alkyl ethers and was found to serve as an excel-
lent catalyst in the O-isopropylidination of sugars and
1
4
sugar alcohols. Iodine-mediated synthesis of mixed
1
5
ethers under hydrogen (80bar) at 100°C was reported.
In this communication, we describe the etherification of
cyclic b-diketones with different alcohols. At room tem-
perature b-keto enol ethers were obtained cleanly and in
very high yields with iodine as a catalyst (Table 1)
fied by column chromatography on SiO (ethyl acetate/
2
hexane, 1:10) and identified by comparison with an
authentic sample by TLC and H NMR.
1
In summary, the results shown above provide evidence
that excellent yields of the expected products can be ob-
tained in short reaction times. Further investigations
into the scope of iodine-mediated reactions in connec-
tion with acetals are in progress and will be reported
in due course.
Keywords: Etherification; Cyclic-b-diketones; b-Keto enol ethers;
Iodine.
*
Corresponding author. Tel.: +91 2462229242; fax: +91
462229245; e-mail: rsbhosale03@yahoo.co.in
2
0
040-4039/$ - see front matter Ó 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.08.044

7188
R. S. Bhosale et al. / Tetrahedron Letters 45 (2004) 7187–7188
a
Table 1. Iodine-catalyzed etherification of cyclic b-diketones
b
Entry
1
Substrate
Alcohol
MeOH
Product
Time (min)
Yield (%)
94
O
O
3
O
OMe
O
O
O
O
O
O
O
2
3
4
5
6
7
8
9
EtOH
3
3
4
7
5
5
3
3
4
96
95
94
65
91
90
95
96
93
O
OEt
O
O
OH
O
O
OH
O
O
O
OH
O
O
O
OH
Ph
O
O
O
OH
O
O
O
Ph
O
O
MeOH
MeOH
MeOH
O
O
OMe
OMe
O
O
O
O
1
0
OMe
a
Alcohol used as solvent.
Isolated yield.
b
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