Organic Process Research & Development 2002, 6, 190−191
A Simple and Efficient Iodination of Alcohols on Polymer-Supported
Triphenylphosphine
Gopinathan Anilkumar, Hisanori Nambu, and Yasuyuki Kita*
Graduate School of Pharmaceutical Sciences, Osaka UniVersity, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan
Abstract:
other drawbacks such as low yields,14 long reaction times,15
drastic reaction conditions and tedious work-up13 procedure.
Moreover, in all these reports, the product has to be purified
by column chromatography. The most recent reports in these
lines are also not devoid of limitations such as long reaction
time, refluxing temperature (CH3CN), or chromatographic
purification of the product.16,17 Although some scant reports
using polymer-supported triphenyl phosphine-iodine com-
plex18 have been reported for the conversion of some
R-amino acids19 and sugars20 into the corresponding iodides,
no work directed towards the synthesis of organic iodides
from alcohols using the Ph3P-I2 complex on polymer support
has been reported.21 We now investigated a novel iodination
method using iodine, imidazole, and polymer-supported
triphenylphosphine in anhydrous dichloromethane, which
transforms the alcohols into iodides. We first tried this
reagent system on benzyl alcohol, which afforded benzyl
iodide in 97% yield within 15 min at room temperature.
Subsequent scrutiny showed that the reagent system is
suitable for a variety of alcohols and culminated into a simple
and mild procedure for the conversion of alcohols into
iodides; the latter was obtained in pure form by simple
filtration.22 Thus, benzylic, allylic, and primary alcohols
undergo smooth transformation to the corresponding iodides
in excellent yields at room temperature.23
A simple, mild, and high-yielding procedure for the iodination
of allylic, benzylic, and other primary alcohols using a combi-
nation of iodine and imidazole on polymer-supported triphenyl
phosphine is described.
Organic halides are indispensable intermediates in organic
synthesis, and their transformations to useful compounds are
well documented in the literature.1 Both organic bromides
and iodides are often used in the carbon-carbon bond
formation via radical or substitution reactions. In addition,
they serve as intermediates in a wide variety of reactions
and rearrangements. Thus, the conversion of alcohols into
the corresponding halides is a very important transformation.
The most common precursors to alkyl halides are alcohols,
and therefore the conversion of alcohols into halides is the
frequently encountered transformation in organic synthesis.2
Among the halides, iodides are the most reactive, and in some
cases, iodides show unique reactivity.3
In continuation of our studies on the C-C bond-forming
radical reactions of halides,4 we were in need of a variety of
organic halides, especially iodides. A number of methods
for the transformation of alcohols into alkyl iodides using a
variety of reagent systems such as BF3-Et2O/NaI,5,6 P4/I2,7
Cl2SO-DMF/KI,8 MgI2,9 HI,10 ClSiMe3/NaI,11 R3PI2-Et2O,
or C6H6/HMPA12 and gas-phase reactions using KI in the
presence of phase-transfer catalysts13 are reported in the
literature. The reported procedures suffer from one or the
Among the various solvents tried, dichloromethane was
found to be the solvent of choice.24 The products were
isolated after filtration of the polymer-bound phosphine oxide
* Author for correspondence. Fax: +81-6-6879-8229. E-mail: kita@
phs.osaka-u.ac.jp.
(13) Tundo, P.; Venturello, P. Synthesis 1979, 952.
(1) Chambers, R. D.; James, S. R In ComprehensiVe Organic Chemistry;
Barton, D. H. R., Ollis, W. D., Ed.; Pergamon Press: Oxford, 1979; Vol
1, p 493; Bohlmann, R. In ComprehensiVe Organic Synthesis; Trost, B.
M., Fleming, I., Ed.; Pergamon Press: Oxford, 1991; Vol 6, p 203;
Hudlicky, M.; Hudlicky, T. In Chemistry of Functional Groups, Supplement
D; Patai, S., Rappoport, Z., Ed.; Wiley: New York, 1983; p 1021.
(2) Marsden, S. P. Contemp. Org. Synth. 1996, 4, 118.
(3) Villieras, J.; Bacquet, C.; Normant, J. F. Bull. Chem. Soc. Fr. 1975, 1797.
(4) Kita, Y.; Gotanda, K.; Sano, A.; Oka, M.; Murata, K.; Suemura, M.;
Matsugi, M. Tetrahedron Lett. 1997, 48, 8345; Kita, Y.; Sano, A.;
Yamaguchi, T.; Oka, M.; Gotanda, K.; Matsugi, M. Tetrahedron Lett. 1997,
38, 3549; Kita, Y.; Sano, A.; Yamaguchi, T.; Oka, M.; Gotanda, K.;
Matsugi, M. J. Org. Chem., 1999, 64, 675; Kita, Y.; Nambu, H.; Ramesh,
N. G.; Anilkumar, G.; Matsugi, M. Org. Lett. 2001, 3, 1157; Kita, Y.;
Matsugi, M. In Radicals in Organic Synthesis; Renaud, P., Sibi, M. P.,
Ed.; Wiley-VCH: Weinheim, 2001; Vol.1, p 1.
(5) Mandal, A. K.; Mahajan, S. W. Tetrahedron Lett. 1985, 26, 3863.
(6) Vankar, Y. D.; Rao, C. T. Tetrahedron Lett. 1985, 26, 2717.
(7) Jung, M. E.; Ornstein, P. L. Tetrahedron Lett. 1977, 31, 2659.
(8) Fernandez, I.; Garcia, B.; Munoz, S.; Pedro, J. R.; Salud, R. Synlett 1993,
489.
(9) Martinez, A. G.; Alvarez, R. M.; Vilar, E. T.; Fraile, A. G.; Barnica, J. O.;
Hanack, M.; Subramanian, L. R. Tetrahedron Lett. 1987, 28, 6441.
(10) Stone, H.; Shechter, H. Org. Synth. 1963, 4, 323.
(14) Joseph, R.; Pallan, P.; Sudalai, A.; Ravindranathan, T. Tetrahedron Lett.
1995, 36, 609.
(15) Garegg, P. J.; Johansson, R.; Ortega, C.; Samuelsson, G. J. Chem. Soc.,
Perkin Trans 1 1982, 681.
(16) Deo, M. D.; Marcantoni, E.; Torregiani, E.; Bartolli, G.; Bellucci, M. C.;
Bosco, M.; Sambri, L. J. Org. Chem. 2000, 65, 2830.
(17) Bandgar, B. P.; Sadavarte, V. S.; Uppalla, L. S. Tetrahedron Lett. 2001,
42, 951.
(18) Polymer-bound Ph3P-I complex has also been used in coupling reactions
in peptide synthesis and in other reactions. See Caputo, R.; Cassano, E.;
Longobardo, L.; Mastroianni, D.; Palumbo, G. Synthesis 1995, 141 and
references cited therein.
(19) Caputo, R.; Cassano, E.; Longobardo, L.; Palumbo, G. Tetrahedron 1995,
51, 12337.
(20) Caputa, R.; Kunz, H.; Mastroianni, D.; Palumbo, G.; Pedatella, S.; Solla,
F. Eur. J. Org. Chem., 1999, 3147; Classon, B.; Liu, Z.; Samuelsson, B. J.
Org. Chem., 1988, 53, 6126.
(21) Some reports on the preparation of iodide derivatives of steroids and
carbohydrates using unsupported triphenyl phosphine are known. Lange,
G. L.; Gottardo, C. Synth. Commun. 1990, 1437; Garegg, P. J.; Samuelsson,
B. J. Chem. Soc., Perkin Trans. 1 1980, 2866; Hanessian, S.; Ponpipom,
M. M.; Lavellee, P. Carbohydr. Res. 1972, 24, 45.
(22) In the case of certain aliphatic alcohols (entries 15 and 16) showing low
reactivity, filtration of the reaction mixture through a small plug of silicagel
was necessary to get pure product. The purity of the products was
(11) Olah, G. A.; Narang, S. C.; Gupta, B. G. B.; Malhotra, R. J. Org. Chem.,
1979, 44, 1247.
1
determined by H NMR or GC analysis and was found to be greater than
(12) Haynes, R. K.; Holden, M. Aust. J. Chem., 1982, 35, 517.
95%.
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Vol. 6, No. 2, 2002 / Organic Process Research & Development
10.1021/op010094c CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/25/2002