pubs.acs.org/joc
methodology.3 The discovery of the bioactivity of naturally
Versatile and Iodine Atom-Economic
Co-Iodination of Alkenes
occurring organohalogen compounds4 and the continued
use of organoiodo derivatives as drugs and radioactively
labeled diagnostic markers5 provides an incentive for un-
covering new iodination protocols of organic compounds.1c
Unlike chlorination and bromination, iodination of
alkenes is a considerably slower reaction due to the low electro-
philicity of iodine. Activation of elemental iodine for addi-
tion to alkenes, by modifying its electrophilicity, has been
achieved using transition-metal salts6 or oxidizing agents.7
Other electrophilic iodinating agents commonly employed
for iodination of organic molecules include N-iodosuccini-
mide and other N-I compounds,8 bis(pyridinium)iodonium(I)
tetrafluoroborate,9 I2-clays,10 and in situ generated acyl
hypoidoite using a combination of elemental iodine and
hypervalent iodine reagents,11 to name a few. Though these
iodinating agents are excellent sources of Iþ and provide
good to excellent yields of iodinated products, the use of
these reagents produces considerable waste and has no more
than 50% iodine atom economy in the reaction. In keeping
with the green trends in organic synthesis, environmentally
benign and readily available I(III) and I(V) hypervalent
iodine oxidants have also been employed for the facile
oxidation of I2 to in situ generate Iþ for iodohydrin synthesis
in aqueous solvent mixtures.7e,12 In contrast to a few select
reports of in situ generation of Iþ using hypervalent iodine
reagents and I2, Suarez and co-workers have, for nearly two
decades, used a combination of (diacetoxyiodo)benzene
(DAIB, 1) and I2 as reagents to generate anomeric alkoxy
radicals of glycopyrans and glycofurans en route to C1-C2
fragmentataion of the sugar molecules.13 This apparent
dichotomy, where two different reactive intermediates
(Iþ vs I• or other radicals) are produced from a combination
DAIB and I2, caught our attention and we decided to explore
Himabindu Gottam and Thottumkara K. Vinod*
Department of Chemistry, Western Illinois University,
Macomb, Illinois 61455, United States
Received October 18, 2010
Molecular iodine, I2, is readily converted into 2 equiv
of acetyl hypoiodite (CH3CO2I) via oxidation by
(diacetoxyiodo)benzene (DAIB) followed by trapping
of the iodide ion by acetoxyphenyl iodonium ion formed.
The in situ generated CH3CO2I is utilized for the synthesis
of 1,2-iodo-cofunctionalized derivatives of a variety of
alkenes. Conversion of both iodine atoms of I2 to Iþ
sources results in 100% iodine atom economy for the
reported iodo-cofunctionalization of alkenes.
(4) (a) Gribble, G. W. Acc. Chem. Res. 1998, 31, 141. (b) Gribble, G. W.
Chemosphere 2003, 52, 289.
(5) Handbook of Radiopharmaceuticals: Radiochemistry and Applications;
Welch, M. J., Redvanly, C. S., Eds.; Wiley: Chichester, 2003.
Cohalogenation, the simultaneous introduction of a halo-
gen atom and a suitable nucleophile across carbon-carbon
double bonds, is a useful reaction that rapidly generates
valuable synthetic intermediates bearing regio- and stereo-
selectively introduced vicinal functionalities for further syn-
thetic elaborations.1 Bromination or chlorination of alkenes
carried out in the presence of nucleophilic solvents such as
water, alcohols, or carboxylic acids provide ready access to
halohydrins, haloethers, and halocarboxylates, three synthe-
tically versatile intermediates.2 In contrast, the synthesis of
iodohydrins by the addition of I-OH across a carbon-
carbon double bond is a difficult reaction to accomplish
because of the reversibility of this addition process.1a Iodina-
tion of alkenes possessing tethered nucleophilic groups leads
to iodocyclization and represents an important synthetic
(6) For metal-catalyzed co-iodionation of alkenes, see: (a) Barluenga, J.;
Rodriguez, M. A.; Campos, P. J.; Asenio, G. J. Chem. Soc., Chem. Commun.
1987, 1491. (b) Trainor, R. W.; Deacon, G. B.; Jackson, W. R.; Guinta, N.
Aust. J. Chem. 1992, 45, 1265. (c) Mahajan, V. A.; Shinde, P. D.; Gajare,
A. S.; Karthikeyan, M.; Wakharkar, R. D. Green Chem. 2002, 38, 944.
(d) Sansevereino, A. M.; de Mattos, M. C. S. J. Chem. Res. 2004, 638.
(7) For co-iodination of alkenes in the presence of elemental iodine and an
oxidizing agent, see: (a) Ogata, Y.; Aoki, K. J. Org. Chem. 1966, 31, 1625.
(b) Masuda, H.; Takase, K.; Nishio, M.; Hasegawa, A.; Nishiyama, Y.; Ishii,
Y. J. Org. Chem. 1994, 59, 5550. (c) Zupan, M.; Staveber, G. Green Chem.
2005, 7, 100. (d) Kraszkiewicz, L.; Sosnowski, M.; Skuluski, L. Synthesis
2006, 1195. (e) Yusubov, M. S.; Yusubova, R. Y.; Kirschning, A.; Park, J. Y.;
Chi, K.-W. Tetrahedron Lett. 2008, 49, 1506. (f) Yusubov, M. S.; Drygunova,
L. A.; Zhdankin, V. V. Synthesis 2004, 2289.
(8) Virgil, S. C. In Encyclopedia of Reagents for Organic Synthesis;
Paquette, L. A., Ed.; Wiley: Chichester, 1995; Vol. 4.
(9) Barulenga, J. Pure. Appl. Chem 1999, 71, 431 and references cited therein.
(10) Villegas, R. A. S.; de Aguiar, M. R.; de Mattos, M. C. S.; Barbosa,
L. M.; Assumpac-ao, L. C. J. Braz. Chem. Soc. 2004, 15, 150.
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2005, 31, 141. (c) Jareb, M.; Zupan, M. Synthesis 2008, 1487.
(2) (a) Dowle, M. D.; Davies, D. I. Chem. Soc. Rev. 1979, 8, 171.
(b) Bartlett, P. A. Assymetric Synthesis 1984, 3, 411.
(3) (a) Kitagawa, O.; Taguchi, T. Synlett 1999, 1191. (b) Ranganathan, S.;
Muraleedharan, K. M.; Vaish, N. K.; Jayaraman, N. Tetrahedron 2004, 60,
5273. (c) French, A. N.; Bissimere, S.; Wirth, T. Chem. Soc. Rev. 2004, 33, 354.
(11) (a) Goosen, A.; Hoffmann, E.; Taljaard, B. J. Chem. Soc., Perkin
Trans. 1 1994, 41. (b) Fan, R.; Li, W.; Pu, D.; Zhang, L. Org. Lett. 2009, 11,
1425. (c) Li, W.; Gan, J.; Fan, R. Tetrahedron Lett. 2010, 4275.
(12) (a) Kirschning, A.; Plumeier, C.; Rose, L. J. Chem. Soc., Chem.
Commun. 1998, 33. (b) De Corso, A. R.; Panunzi, B.; Tingoli, M. Tetrahedron
Lett. 2001, 42, 7245. (c) Agarwal, M. K.; Adimurthy, S.; Ganguly, B.;
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974 J. Org. Chem. 2011, 76, 974–977
Published on Web 12/30/2010
DOI: 10.1021/jo102051z
r
2010 American Chemical Society