Solvent-free reactions with hypervalent iodine reagents

Article abstract of DOI:10.1021/ol047363e

(Chemical Equation Presented) We describe solvent-free reactions for the synthesis of hypervalent iodine reagents and their use in solid-state reactions. Improved yields and higher purities of the products are observed.

Full text of DOI:10.1021/ol047363e

ORGANIC
LETTERS
2005
Vol. 7, No. 3
519-521
Solvent-Free Reactions with Hypervalent
Iodine Reagents
Mekhman S. Yusubov*,† and Thomas Wirth*,‡
Department of Chemistry, Siberian State Medical UniVersity, MoskoVski trakt, 2,
634050 Tomsk, Russia, Department of Organic Chemistry, Tomsk Polytechnic
UniVersity, 30 Lenin st., 634050 Tomsk, Russia, and School of Chemistry,
Cardiff UniVersity, P.O. Box 912, Cardiff CF10 3TB, UK
yusuboV@mail.ru; wirth@cf.ac.uk
Received December 22, 2004
ABSTRACT
We describe solvent-free reactions for the synthesis of hypervalent iodine reagents and their use in solid-state reactions. Improved yields and
higher purities of the products are observed.
Hypervalent iodine reagents have found broad application
in organic chemistry and are nowadays frequently used in
synthesis.1 It is of great interest to investigate their ability
as highly selective oxidants, their electrophilic properties and
to develop new reactions using hypervalent iodine com-
pounds. Because these are nonmetallic oxidation reagents,
they avoid the issues of toxicity of many transition metals
commonly involved in such processes. Therefore, hyperva-
lent iodine compounds bear a high potential for the improve-
ment of known reactions not only from the environmental
and pharmaceutical point of view, but also as interesting
reagents for the development of completely new synthetic
transformations. The continued need for efficient transforma-
tions led to the development of solvent-free reactions which
we describe here. Solvent-free reactions have many advan-
tages and important aspects are reduced pollution, lower costs
and the simplicity of the processes involved.2 Because many
organic solvents are ecologically harmful, strategies for their
minimized usage and developments toward benign chemical
technologies are highly sought after.3 Because many hyper-
valent iodine reagents have low solubilities in most organic
solvents, the development of solvent-free reactions is a big
step forward and should lead to an increased use of this
chemistry. Only iodine(III) compounds should be considered
for these reactions, because some iodine(V) compounds are
known to be shock and pressure sensitive.4 The iodine(III)
compounds described here have been safely used on a
millimolar scale.
For our initial investigations, we used (diacetoxyiodo)
benzene 1a (Ar ) Ph) as a hypervalent iodine reagent, which
is commercially available and can also easily be prepared.5
Ligand exchange reactions on this compound are known and
have been used frequently to prepare other hypervalent iodine
reagents.6 The reaction of 1a (Ar ) Ph) with p-toluene-
sulfonic acid monohydrate 2a (R ) p-Ts) results in the
formation of (hydroxytosyloxyiodo)benzene 3a (Koser’s
reagent) but has only been carried out in an organic solvent
such as dichloromethane or acetonitrile.7 We find similar or
even better yields in the solid-state reaction just by grinding
the two reaction partners 1 and 2 for several minutes and
evaporating the acetic acid liberated in the ligand exchange
reaction.
† Siberian State Medical University and Tomsk Polytechnic University.
‡ Cardiff University.
(1) (a) HyperValent Iodine in Organic Synthesis; Varvoglis A., Ed.
Academic Press: Oxford, 1997. (b) Wirth, T.; Hirt, U. H. Synthesis 1999,
1271. (c) Zhdankin, V. V.; Stang, P. J. Chem. ReV. 2002, 102, 2523. (d)
Wirth, T., Ed. HyperValent Iodine Chemistry, Top. Curr. Chem. 2003, 224.
(2) (a) Tanaka, K.; Toda, F. Chem. ReV. 2000, 100, 1025. (b) Cave, G.
W. V.; Raston, C. L.; Scott, J. L. Chem. Commun. 2001, 2159. (c) Metzger,
J. O. In Organic Synthesis Highlights V; Schmalz, H.-G., Wirth, T., Eds.;
Wiley-VCH: Weinheim, 2003; p 82.
(3) Eissen, M.; Metzger, J. O.; Schmidt, E.; Schneidewind, U. Angew.
Chem., Int. Ed. 2002, 41, 414.
(4) Plumb, J. B.; Harper, D. J. Chem. Eng. News 1990, 68, 8 (29), 3.
(5) Sharefkin, J. G.; Saltzman, H. Org. Synth. 1963, 43, 62.
(6) Koser, G. F.; Wettach, R. H. J. Org. Chem. 1980, 45, 1542.
(7) Koser, G. F.; Wettach, R. H.; Troup, J. M.; Frenz, B. A. J. Org.
Chem. 1976, 41, 3609.
10.1021/ol047363e CCC: $30.25
© 2005 American Chemical Society
Published on Web 01/13/2005

The same products, 6a and 6b, can be obtained by a
solvent-free reaction of 1 and 2 with 2-iodobenzoic acid 5.
The results are summarized in Table 2.
Scheme 1. Solvent-Free Reactions of (Diacetoxyiodo)Arenes
1 and Sulfonic Acids 2
Table 2. Solvent-Free Reactions to IBA Derivatives 6
entry
starting materials
2: R
product 6 (yield)
The reactions investigated usually were complete within
several minutes on a millimolar scale.8 The products are very
clean as judged by the NMR spectra of the crude reaction
mixtures and only evaporation of acetic acid on high vacuum
was necessary. Only for some reactions the removal of excess
sulfonic acid by washing with diethyl ether was necessary
to obtain pure products. The results are summarized in Table
1. Some of these reactions can be enhanced just by adding
a drop of acetic acid to the mixture of the two solid reactants.
1
2
3
4
4
4
2a: p-Ts
2b: Ms
2a: p-Ts
2b: Ms
6a (91%)
6b (86%)
6a (86%)
6b (80%)
1a (Ar ) Ph), 5 (1:1)
1a (Ar ) Ph), 5 (1:1)
In the reaction with 5, an intermediate formation of a
reagent of type 3 is likely to take place. As reagents such as
3 can react with a variety of different substrates, we
investigated the solid-state reaction of a mixture of 1a (Ar
) Ph) and 2 together with a range of substrates 7. Several
of these reactions have already been performed in solution,
but the yields are generally higher when performed under
solvent-free conditions as shown in Table 3.
Table 1. Solvent-Free Reactions of (Diacetoxyiodo)arenes 1
and Sulfonic Acids 2
entry
1: Ar
2: R
product 3 (yield) lit. yield
The sulfonylations of 1,3-diketones take place in a few
minutes to give the products 8 in reasonable yields (Table
3, entries 1-4). The sulfonylation of ketones in R-position
with reagents of type 3 is known as well and the yields
obtained are still comparable to reactions carried out in
1
2
3
4
5
6
1a: Ph
1a: Ph
1a: Ph
1b: 1-naphthyl 2c: Cs
1c: 2-naphthyl 2a: p-Ts
1c: 2-naphthyl 2c: Cs
2a: p-Tsa
2b: Msa
2c: Csa
3a (93%)
3b (98%)
3c (91%)
3d (94%)
3e (77%)
3f (80%)
93%; ref 9
87%; ref 10
b; ref 11
this work
b; ref 6
this work
a p-Ts, 4-Me-C6H4SO2; Ms, MeSO2; Cs, (1R)-10-camphorylsulfonyl.
Table 3. Solvent-Free Reactions of 1a (Ar ) Ph), 2, and
Different Substrates 7
b No yield reported.
Also other acids can be used, the solvent-free reaction of
1 (Ar ) Ph) with 2.2 equiv of trifluoroacetic acid led in a
very clean reaction to the formation of [bis(trifluoroactoxy)-
iodo] benzene in 95% yield.12 This hypervalent iodine
reagent, [bis(trifluoroactoxy)iodo] benzene, can be used with
similar efficiency in the solid-state ligand exchange reaction
with p-toluenesulfonic acid monohydrate 2a (R ) p-Ts) to
give 3a in 97% yield.
Ligand exchange reactions are also possible using iodosyl
benzoic acid (IBA) 4. Treatment with sulfonic acids led to
the formation of the corresponding IBA derivatives 613 in
good yields as shown in Scheme 2. These IBA derivatives
6 can be used advantageously for the iodination of aromatic
rings14 or for iodotosylations of alkynes.15
Scheme 2. Solvent-Free Reactions to IBA Derivatives 6
a Reaction performed without addition of 2.
520
Org. Lett., Vol. 7, No. 3, 2005

solutions (Table 3, entries 5 and 6). The formation of
products resulting from a ligand-exchange with dimedone
are known, in the solid-state these reactions proceed with
very high efficiency as shown in Table 3 (Table 3, entries 7
and 8). If (diacetoxyiodo) benzene is used as reagent without
addition of a sulfonic acid 2, the corresponding hypervalent
iodine derivatives with one acetate moiety exchanged to the
diketone are obtained (Table 3, entries 9 and 10). The
reaction with aryl-substituted alkenes is known to proceed
via rearrangements at high concentrations as the aryl moiety
stabilizes a positive charge by formation of phenonium ion
intermediates.16 As the concentration in solvent-free reactions
is at its maximum, the products are the expected ones and
are formed in higher yields than in solution (Table 3, entries
11-13).
In conclusion, by using solvent-free reaction conditions
for the synthesis of hypervalent iodine reagents of type 3
and an in situ generation of these reagents for reactions with
different substrates we were able to improve the yields and
purities of the reaction products considerably. These reaction
conditions are contributing to the development of sustainable
techniques in organic synthesis and to the simplicity of
reactions with hypervalent iodine compounds.
Acknowledgment. We thank Maria A. Arrica for the
synthesis of 1 (R ) 1-naphthyl, 2-naphthyl) and 4. M.S.Y.
thanks the Ministry of Education (grant 546-05) and RFFI
(grant 05-03-32459-a) for support.
(8) Typical Procedure. A mixture of (diacetoxyiodo)benzene 1 (Ar )
Ph, 184 mg, 0.571 mmol) and p-TsOH‚H2O (111 mg, 0.584 mmol) was
gently blended in an agate mortar. The resulting homogeneous mixture was
then ground for 10 min. The formation of acetic acid and wetting of the
reaction mixture was observed. The solid residue was washed with diethyl
ether (5 mL) and dried under high vacuum to afford 3a (218 mg, 97%),
mp 134-136 °C.
(9) Koser, G. F.; Wettach, R. H. J. Org. Chem. 1977, 42, 1476.
(10) Lodaya, J. S.; Koser, G. F. J. Org. Chem. 1988, 53, 210.
(11) Goff, J. M.; Justik, M. W.; Koser, G. F. Tetrahedron Lett. 2001,
42, 5597.
Supporting Information Available: Experimental de-
tails. This material is available free of charge via the Internet
at http://pubs.acs.org.
OL047363E
(12) Loudon, G. M.; Radhakrishna, A. S.; Almond, M. R.; Blodgett, J.
K.; Boutin, R. H. J. Org. Chem. 1984, 49, 4272.
(13) (a) Zhdankin, V. V.; Kuehl, C. J.; Bolz, J. T.; Formaneck, M. S.;
Simonsen, A. J. Tetrahedron Lett. 1994, 35, 7323. (b) Zhdankin, V. V.;
Kuehl, C. J.; Krasutsky, A. P.; Bolz, J. T.; Simonsen, A. J. J. Org. Chem.
1996, 61, 6547.
(14) Muraki, T.; Togo, H.; Yokoyama, M. Synlett 1998, 286.
(15) Muraki, T.; Togo, H.; Yokoyama, M. J. Org. Chem. 1999, 64, 2883.
(16) Boye, A. C.; Meyer, D.; Ingison, C. K.; French, A. N.; Wirth, T.
Org. Lett. 2003, 5, 2157.
(17) Koser, G. F.; Relenyi, A. G.; Kalos, A. N.; Rebrovic, L.; Wettach,
R. H. J. Org. Chem. 1982, 47, 2487.
(18) Varma, R. S.; Kumar, D. Catal. Lett. 1998, 53, 225.
(19) (a) Koser, G. F.; Rebrovic, L.; Wettach, R. H. J. Org. Chem. 1981,
46, 4324. (b) Biland, A. S.; Altermann, S.; Wirth, T. ARKIVOC 2003, 6,
164.
(20) Yusubov, M. S.; Zholobova, G. A. Russ. J. Org. Chem. 2001, 37,
1179.
Org. Lett., Vol. 7, No. 3, 2005
521