α-Iodination of enaminones using the modified Johnson's procedure: The use of I2 and Et3N

Article abstract of DOI:10.1016/S0040-4039(03)01518-1

Facile synthesis of α-iodo enaminones 2 was carried out by the use of iodine and triethylamine in methylene chloride in short time in excellent yields.

Full text of DOI:10.1016/S0040-4039(03)01518-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6317–6318
a-Iodination of enaminones using the modified Johnson’s
procedure: the use of I2 and Et3N
Jeong Mi Kim, Jeong Eun Na and Jae Nyoung Kim*
Department of Chemistry and Institute of Basic Science, Chonnam National University, Kwangju 500-757, Republic of Korea
Received 7 May 2003; revised 7 June 2003; accepted 13 June 2003
Abstract—Facile synthesis of a-iodo enaminones 2 was carried out by the use of iodine and triethylamine in methylene chloride
in short time in excellent yields.
© 2003 Elsevier Ltd. All rights reserved.
tional use of DMAP).8 We presumed that the Johnson’s
conditions could also be applied to the enaminone
system. Thus, we examined the reaction of enaminone
1a and iodine in the presence of pyridine, DMAP
(4-dimethylaminopyridine), or Et3N. The best results
(95%) were observed when we used Et3N.9
Iodination of enaminones at the a-position is important
in organic chemistry.1–6 a-Iodo enaminones could be
used as important starting materials for the synthesis of
heterobicyclic enones1 as well as for the preparation of
biologically active heterocyclic compounds.4,5b In these
respects, many papers have been reported for the syn-
thesis of these compounds.2–6 Campos et al. used
bis(pyridine)iodonium(I) tetrafluoroborate in methylene
chloride.2 Benzyltrimethylammonium dichloroiodate
(BTMAICl2) has been reported by Matsuo and co-
workers to be an efficient a-iodinating agent for the
secondary enaminones.3 Kordik and Reitz have
reported unexpected a-chlorination of tertiary enam-
inones by using the same reagent.4 N-Iodosuccinimide
has been used successfully for the iodination of tricy-
clodecenyl enaminones.5 Indirect method for the syn-
thesis of a-iodo enaminones involving thermal
decomposition of trifluoroethyliodonium salts has been
developed.6 However, most of the reported methods
suffer from moderate yields or the need of special
reagents. Thus, development of more cheaper and eas-
ily available reagent for the a-iodination of enaminones
would be beneficial.
As shown in Scheme 1 and in Table 1, various kinds of
enaminones 1a–h can be iodinated at the a-position in
excellent yields instantaneously (within 5 min) to give
a-iodo enaminones 2a–h. Pyridine or DMAP can also
be used (see entry 1) in the reaction with similar results.
We could isolate the desired products by column chro-
matography without aqueous workup process. Unfor-
tunately, enaminones derived from secondary amine
(namely, tertiary enaminone) did not give the corre-
sponding a-iodo products (as an example, see entry 9).
The reason is unclear at this point.
Experimental procedure for the synthesis of 2a is typi-
cal. To a stirred solution of 1a (374 mg, 2 mmol)10 and
iodine (508 mg, 2 mmol) in dichloromethane (5 mL)
was added triethylamine (202 mg, 2 mmol) at room
temperature. After 5 min at room temperature solvent
was removed under reduced pressure. The residue was
a-Iodination of a,b-unsaturated carbonyl compounds
can be carried out most conveniently by the Johnson’s
conditions, which used iodine in CCl4–pyridine sol-
vent.7 The original Johnson’s method was used fre-
quently in the sequences of total synthesis of many
natural products by slightly modified version (e.g. addi-
Keywords: iodination; enaminones; iodine; triethylamine; Johnson’s
procedure.
* Corresponding author. Fax: +82-62-530-3381; e-mail: kimjn@
chonnam.chonnam.ac.kr
Scheme 1.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01518-1

6318
J. M. Kim et al. / Tetrahedron Letters 44 (2003) 6317–6318
Table 1. Synthesis of a-iodo enaminones 2
separated by silica gel column chromatography (CH2Cl2
followed by hexane/ethyl acetate, 1:1) to give the desired
a-iodo enaminone 2a as a light tan solid, 595 mg (95%).
The postulated reaction mechanism is shown in Scheme
2.11 a-Iodo iminium salt (I) could be formed via direct
attack of iodine at the a-position of 1a. Or, (I) could be
generated via an SN2% type reaction of the initially formed
N-iodonium salt (II).5,12 Following abstraction of a-pro-
ton from (I) by triethylamine gave the product 2a.
In summary, we report herein the facile synthesis of
a-iodo enaminones by the use of iodine and triethylamine
in short time in excellent yields.
Acknowledgements
This work was supported by Korea Research Founda-
tion Grant (KRF-2002-015-CP0215).
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Scheme 2.
11. The reaction mechanism in Figure 1 was suggested by one
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Figure 1.