Direct α-iodination of ketones using iodine/SeO2

Article abstract of DOI:10.1016/S0040-4039(00)00310-5

A satisfactory yield one-pot synthesis of various α-mono iodoketones 2 was achieved by iodination under oxidative conditions of ketones 1. The monoiodination of different aliphatic or cyclic ketones (1-tetralones) showed the quite general applicability of

Full text of DOI:10.1016/S0040-4039(00)00310-5

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 41 (2000) 2903–2905
Direct α-iodination of ketones using iodine/SeO2
Alain Bekaert,∗ Olivier Barberan, Marina Gervais and Jean-Daniel Brion
Laboratoire de Chimie Thérapeutique, associé au CNRS BioCIS, Faculté de Pharmacie Université de Paris XI,
rue Jean-Baptiste Clément F 92296 Châtenay-Malabry France
Received 27 December 1999; accepted 18 February 2000
Abstract
A satisfactory yield one-pot synthesis of various α-mono iodoketones 2 was achieved by iodination under
oxidative conditions of ketones 1. The monoiodination of different aliphatic or cyclic ketones (1-tetralones) showed
the quite general applicability of the method. © 2000 Elsevier Science Ltd. All rights reserved.
During the last few years, methods were reported for the synthesis of α-iodoketones1 from olefins,2a
epoxides,2b or ketones and derivatives (enol esters and enol ethers). Although some of them permitted
significant advances,3,4 the use of highly toxic reagents (thallium acetate) or difficulties in the synthesis
and purification of enol silylethers represented serious disadvantages. Generally, enol acetates or enol
silylethers were treated with silver acetate/iodine followed by triethylammonium fluoride,5 or copper(II)
nitrate.5 Horiuchi et al. reported the direct α-iodination of ketones with iodine–copper(II) acetate or
iodine–cerium(IV) ammonium nitrate in acetic acid.6
New efficient syntheses of α-iodoketones, in particular of 2-iodoindanones and 2-iodotetralones,7 are
still desirable in view of the possible involvement of these cyclic compounds in inter(intra)molecular
radical reactions.8 This paper reports a rapid (3 h) and convenient one-pot synthesis of α-iodoketones
from the corresponding ketones with iodine and selenium dioxide under neutral or acidic conditions
(Scheme 1).
Scheme 1.
Treatment of ketones (1a–f) with 0.55 molar equivalent of iodine in acetic acid (or acetonitrile)
and 0.55 molar equivalent of powdered SeO2 afforded the corresponding α-monoiodoketones (2a–f)
∗
Corresponding author. Fax: +33 01 46 83 58 28; e-mail: jean-daniel.brion@cep.u-psud.fr
0040-4039/00/$ - see front matter © 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)00310-5
tetl 16590

2904
in satisfactory yields9 (Table 1). A catalytic amount of oxidant (0.1 mol) gave no significant results.
The reaction was carried out successfully for 3-iodochroman-4-one (2g) in moderate yield. In the case
of unsymmetrical aliphatic ketones (1h), two monoiodinated regioisomers (2h–2h0) were obtained and
separated by chromatography. This method failed for 1-iodo-2-tetralones, leading to by-products.
Table 1
α-Iodoketones
Concerning the reaction mechanism, D’Auria et al. reported that iodonium ions could be the reacting
species after oxidation of iodine.10 Direct treatment of ketones 1 with iodine without any oxidant did
not afford any iodoketone. In contrast, in the conditions described above, anisole was iodinated into 4-
iodoanisole (yield=39%). Thus, selenium dioxide was supposed to act as a Lewis acid catalyst (with
possibly formation of selenious enol ester) and as oxidant of iodide into the iodonium ion.
In conclusion, the main interest of the process is that it allows us to dispense with the enol silylated
ether intermediate, the purification of which was tedious according to the literature, especially for 6-
methoxy-1-tetralone. Iodination of ketones with selenium dioxide and iodine represents a convenient pro-
cedure for α-monoiodination of 1-tetralones, due to the simple conditions and satisfactory yields.
References
1. De Kimpe, N.; Verhe, R. In The chemistry of α-haloketones, α-haloaldehydes and α-haloimines; Patai, S.; Rappoport, Z.,
Eds.; John Wiley Interscience: New York, 1988; pp. 36–37.
2. Wade, L. G. Compendium of Organic Synthetic Methods, John Wiley & Sons: New York, 1984; Vol. 5, p. 508; (b) Cardillo,
G., Shimizu, M. J. Org. Chem. 1977, 42, 4268–4270.
3. (a) Motohashi, S.; Satomi, M.; Fujimoto, Y.; Tatsuno, T. Synthesis 1982, 1021–1023; (b) Sha, C.-K.; Young, J.-J.; Jean, T.-S.
J. Org. Chem. 1987, 52, 3919–3920.
4. Cort, A. D. J. Org. Chem. 1991, 56, 6708–6709.
5. Rubottom, G. M.; Mott, R. C. J. Org. Chem. 1979, 44, 1731–1734.
6. (a) Horiuchi, C. A.; Satoh, J. Y. Synthesis 1981, 312–314; (b) Horiuchi, C. A. Kiji, S. Chem. Lett. 1988, 31–34.

2905
7. Sket, B.; Zupan, M. Bull. Chem. Soc. Jpn. 1987, 60, 4489–4491.
8. Curran, D. P. Synthesis 1988, 417–439; (b) Sha, C.-K.; Jean, T.-S.; Wang, D.-C. Tetrahedron Lett. 1990, 31, 3745–3748.
9. General procedure for the preparation of 2: To a solution of 1 (0.1 mol) in 50 mL of solvent, finely powdered SeO2 (6.10 g,
55 mmol) and iodine (13.97 g, 55 mmol) were added. The mixture was warmed (see Table 1). After filtration over a short
SiO2 column for removing the red precipitate (selenium), the dark solution was diluted with 200 mL of H2O and extracted
with CH2Cl2. The organic phase was extracted with 100 mL of 10% Na2S2O3 solution and then with H2O. After drying, the
solvents were removed and the residue purified by column chromatography or crystallization to yield 2 (light sensitive).
10. D’Auria, M.; D’Onofrio, F.; Piancatelli, G.; Scettri, A. Synth. Commun. 1982, 12, 1127–1138.
11. Yield is expressed in analytically pure iodoketone (after purification by chromatography or crystallization).
12. Townsend, J. M.; Spencer, T. A. Tetrahedron Lett. 1971, 137–140.
13. 2-Iodo-7-methoxytetralone: m.p.=44–45°C (CH2Cl2/petroleum ether); IR (KBr): 1679 cm−1; 1H NMR (200 MHz, δ ppm):
7.53 (d, J=2.7 Hz, 1H, H8); 7.18 (d, J=8.6 Hz, 1H, H5); 7.08 (dd, J=8.6 Hz and 2.7 Hz, 1H, H6); 4.99 (t, J=3.4 Hz, 1H, H2);
3.82 (s, 3H, OMe); 3.02 (m, 1H, H4); 2.78 (dt, J=16.5 Hz and 4.0 Hz, 1H, H4); 2.16 (m, 2H, H3).
14. 3-Iodochroman-4-one: m.p.=70°C (CH2Cl2/petroleum ether); IR (KBr): 1673 cm−1; 1H NMR (200 MHz, δ pp): 7.94 (dd,
J=7.8 Hz and 1.6 Hz, 1H, H5); 7.54 (td, J=7.6 Hz and 1.6 Hz, 1H, H7); 7.09 (t, J=7.8 Hz, 1H, H6); 7.05 (d, J=7.6 Hz, 1H,
H8); 4.90 (dd, J=4.2 Hz, and 3.0 Hz, 1H, H3); 4.50 (dd, J=12.0 Hz and 4,2 Hz, 1H, H2); 4.45 (dd, J=12.0 Hz and 3.0 Hz,
1H, H2).
15. 2-Iodo-6-methoxytetralone: m.p.=90–91°C (CH2Cl2/petroleum ether); IR (KBr): 1661 cm−1; 1H NMR (200 MHz, δ ppm):
8.40 (d, J=8.7 Hz, 1H, H8); 6.85 (dd, J=8.7 Hz and 2.5 Hz, 1H, H7); 6.71 (d, J=2,5 Hz, 1H, H5); 4.96 (t, J=3.0 Hz, 1H, H2);
3.86 (s, 3H, OMe); 3.11 (m, 1H, H4); 2.82 (dt, J=17.0 and 3.8 Hz, 1H, H4); 2.15 (m, 2H, H3).
16. Ryglowski, A.; Kafarski, P. Tetrahedron 1996, 52, 10685–10692. The ratio 2h:2h0(1:1) was measured after separation by
chromatography.