Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 191–193
Efficient microwave induced direct a-halogenation
of carbonyl compounds
Jong Chan Lee,* Jin Young Park, So Young Yoon, Yong Hun Bae
and Seung Jun Lee
Department of Chemistry, Chung-Ang University, Seoul 156-756, South Korea
Received 4 August 2003;revised 10 October 2003;accepted 17 October 2003
Abstract—A novel and direct method for the synthesis of a-halocarbonyl compounds using sequential treatment of carbonyl
compounds with [hydroxy(tosyloxy)iodo]benzene followed by magnesium halides under solvent-free microwave irradiation con-
ditions is described.
ꢀ 2003 Elsevier Ltd. All rights reserved.
a-Haloketones are among the most versatile intermedi-
ates in organic synthesis and their high reactivity makes
them prone to react with large number of nucleophiles
to provide a variety of useful compounds.1 Direct con-
version of carbonyl compounds into a-halocarbonyl
compounds is very important synthetic transformation
that has been received considerable attention. Generally
the direct conversion to a-chloroketones from ketones
can be accomplished by using chlorination agents such
as copper(II) chloride,2 sulfuryl chloride,3 p-toluene-
sulfonyl chloride,4 N-chlorosuccinimide,5 and tetra-
ethylammonium trichloride.6 a-Bromination of ketones
can be achieved using various reagents which include
bromine,7 copper(II) bromide,8 N-bromosuccinimide,5
and tetrabutylammonium tribromide.9 In addition,
a-iodination of ketones is commonly achieved using
iodine–cerium(IV) ammonium nitrate,10 iodine–mercu-
ry(II) chloride,11 and iodine–selenium dioxide.12 How-
ever, these methods suffer from drawbacks such as long
reaction times, use of hazardous chemicals, and cum-
bersome workup procedures. Furthermore, most of
these methods generally employed strongly acidic or
basic conditions, which accompanied by undesirable
formation of a,a-dihalogenated products in significant
amount. Recently a lot of effort has been made to the
development of new efficient reaction conditions on the
a-halogenation reactions of 1,3-dicarbonyl compounds.
For example, combination of magnesium perchlorate
with N-halosuccinimide has been recently demonstrated
to be as effective for a-halogenation of 1,3-dicarbonyl
compounds.13
In the last decade, microwave promoted reactions under
solvent-free conditions have received considerable
attention as a powerful technique to effect various organic
transformations.14 Very recently, microwave induced a-
bromination of ketones achieved under solvent-free
conditions by use of dioxane–dibromide in combination
with silica gel.15 In addition, we recently reported the use
of N-iodosuccinimide and p-toluenesulfonic acid for
facile microwave induced a-iodination of ketones.16
However, to the best of our knowledge, method for a-
chlorination of carbonyl compounds under solvent-free
microwave irradiation conditions has been unprece-
dented to date.
Hypervalent iodine compounds received continuous
attention in organic synthesis and amongst these,
[hydroxy(tosyloxy)iodo]benzene (KoserÕs reagent, HTIB)
has been most commonly employed in numerous organic
transformations.17 In continuation of our research on
application of hypervalent iodine(III) sulfonates to
microwave promoted solvent-free reactions, we now
wish to report the first method that can be generally
applicable to a-chlorination as well as a-bromination
and a-iodination of carbonyl compounds under solvent-
free microwave irradiation conditions, which involves
sequential reaction of the carbonyl compounds with
Keywords: carbonyl compounds;halogenation;hypervalent iodine
sulfonates;magnesium halides;solvent-free microwave heating.
* Corresponding author. Tel.: +82-2-820-5202;fax: +82-2-825-4736;
0040-4039/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.10.133