reagents and has afforded resins that react with equal
efficiency.
a more convenient oxidation method. Since dioxirane oxida-
tion was effective, it was decided to test the in situ generated
4
f,g
6
Recently, we reported the preparation and oxidative
properties of N-(2-iodyl-phenyl)-acylamides 1, which are
soluble and stable IBX analogues having pseudo benzio-
dioxiranes as oxidizing agents. However, these procedures
-
1
yielded a lower resin activity of 0.08-0.14 mmol g . The
7
a
reaction with potassium monopersulfate triple salt (oxone)
5
3c
doxazine structure (Figure 1). These investigations, being
and sodium hypochlorite in aqueous medium also failed,
resulting in a resin which exhibited virtually no oxidative
activity.
Scheme 1. Preparation of Polymeric Reagent 5
Figure 1. Amides of 2-iodoxybenzoic acid and N-(2-iodyl-phenyl)-
acylamides (NIPA).
a logical extension of previous work on IBX amides, revealed
that compounds 1 are able to oxidize either alcohols or
sulfides, with their reactivity depending largely on the
substitution pattern on the amide group adjacent to the iodyl
moiety. In the context of these findings, we considered
developing a polymer-supported N-(2-iodyl-phenyl)-acyl-
amide reagent. Here we present the facile synthesis of such
a hypervalent iodine derivative and show that it is a potent
oxidant toward a broad range of alcohols.
To furnish a pseudo benziodoxazine scaffold and to ensure
proper immobilization to the resin through an amide function,
the carbamoylbutanoic acid moiety was chosen as a linker.
Commercially available 2-iodoaniline 2 was reacted with
glutaric anhydride to give acid 3, which was subsequently
coupled to aminomethylpolystyrene with HOBt/DIC to give
resin 4. To block any possible free amino groups, the resin
was subsequently treated with an excess of acetic anhydride
and pyridine.
Finally, the oxidation with an equimolar mixture of
tetrabutylammonium oxone with methanesulfonic acid (5.0
7b
4
c-g
equiv, CH Cl , rt, 6 h)
2
2
afforded the NIPA resin 5 with
-
1
high loading levels (0.70-0.80 mmol g ). IR analysis of
the prepared resin matched perfectly with the IR spectra of
the resin 5 obtained by the 3,3-dimethyldioxirane oxidation.
To avoid the supplementary preparation of tetrabutylammo-
nium oxone, we have examined the oxidation of the polymer
4 in a CH Cl -H O biphasic system using oxone, Bu -
The loading of the resin 4 was determined by elemental
analysis and corresponded to 82% conversion when the mass
increase is taken into account. Oxidation of 4 to NIPA resin
5
was initially performed with 3,3-dimethyldioxirane as was
5
described for a solution-phase synthesis. The obtained resin
was characterized by IR spectroscopy and elemental analysis.
Oxidizing activity of NIPA resin 5 was measured by GC-
MS analysis with an excess of benzyl alcohol as a test
substrate [1,2-dichloroethane (DCE), reflux, 60 min] and was
2
2
2
4
NHSO , and CH SO H.
4
3
3
This modified protocol gave resin 5 with essentially the
same loading levels and IR characteristics. As indicated by
elemental analysis of resin 5, only minor iodine loss (5-
-
1
2
found to be 0.31 mmol g with respect to IO groups.
7
% with respect to the initial iodine content) was observed
Moderate loading levels and utilization of unstable and not
readily available 3,3-dimethyldioxirane prompted us to seek
8,9
under the strongly acidic reaction conditions.
The oxidative properties of reagent 5 were evaluated by
the reaction with various benzylic, allylic, primary and
secondary alcohols, as well as a diol (Table 1). All employed
alcohols were commercially available, as well as the respec-
tive carbonyl compounds. Reactions were performed in DCE
under reflux (30-60 min) since at room temperature long
(4) For a review on polymer-supported hypervalent iodine reagents,
see: (a) Togo, H.; Sakuratani, H. Synlett 2002, 1966. (b) M u¨ lbaier, M.;
Giannis, A. Angew. Chem., Int. Ed. 2001, 40, 4393. (c) Sorg, G.; Mengel,
A.; Jung, G.; Rademann, J. Angew. Chem., Int. Ed. 2001, 40, 4395. (d)
Reed, N. N.; Delgado, M.; Hereford, K.; Clapham, B.; Janda, K. D. Bioorg.
Med. Chem. Lett. 2002, 12, 2047. (e) Lei, Z.; Denecker, C.; Jegasothy, S.;
Sherrington, D. C.; Slater, N. K. H.; Sutherland, A. J. Tetrahedron Lett.
2
2
2
003, 44, 1635. (f) Chung, W.-J.; Kim, D.-K.; Lee, Y.-S. Tetrahedron Lett.
003, 44, 9251. (g) Chung, W.-J.; Kim, D.-K.; Lee, Y.-S. Synlett 2005,
175.
(6) (a) Frohn, M.; Wang, Z.-X.; Shi, Y. J. Org. Chem. 1998, 63, 6425.
(b) Grocock, E.; Marples, B. A.; Toon, R. C. Tetrahedron 2000, 56, 989.
(7) (a) Frigerio, M.; Santagostino, M.; Sputore, J. J. Org. Chem. 1999,
64, 4537. (b) Trost, B. M.; Braslau, R. J. Org. Chem. 1988, 53, 532.
(5) Ladziata, U.; Koposov, A. Y.; Lo, K. Y.; Willging, J.; Nemykin, V.
N.; Zhdankin, V. V. Angew. Chem., Int. Ed. 2005, 44, 7127.
168
Org. Lett., Vol. 8, No. 1, 2006