Poly[4-(diacetoxyiodo)styrene]

 · (C12H13IO4)n  · (MW 348.12)n

(polystyrene-supported derivative of (diacetoxyiodo)benzene used in the oxidation of aniline,1,2 oxidation of hydroquinones,3-5 oxidative spirocyclization,4 phenolic oxidative coupling,6,7 oxidation of alcohols,4,8 oxidative cleavage of diols,1 a-hydroxylation and a-acetoxylation of ketones,3-5 oxidative 1,2-aryl migrations of alkyl aryl ketones,3,9 generation of carbonyls from hydrazones and oximes,5 oxidation of sulfides3,5 and thiols,5 iodination of aromatic rings,3,9 preparation of heterocycles,10,11 preparation of diaryliodonium salts,12,13 and the oxidation of triphenylphosphine,5 organotellurium compounds5 and organoselenides14)

Alternate Name: PS-I(OAc)2, poly[styrene(iodosoacetate)], polymer-supported (diacetoxyiodo)benzene, PSDIB, polymer-supported phenyliodine diacetate, poly-p-iodosostyryldiacetate.

Physical Data: loading ca. 2.0-3.5 mmol g-1.4,5,10,11

Solubility: some solubility in organic solvents such as CH2Cl2 (DCM), EtOAc, and CHCl3; insoluble in Et2O and MeOH.

Analysis of Reagent Purity: iodometry and elemental analysis.3-5,9-11

Preparative Methods: a solution of polystyrene (32 g, 0.31 mol), diiodine (32 g, 0.25 mol), iodine pentoxide (12 g, 0.04 mol), carbon tetrachloride (40 mL) and 50% sulfuric acid (60 mL) in nitrobenzene (400 mL) was kept at 90 °C for 39 h. The reaction mixture was cooled, diluted with chloroform (200 mL) and precipitated with methanol. Filtration gave poly(4-iodostyrene) (65 g) as a pale yellow powder. A mixture of poly(4-iodostyrene) (5 g) and peracetic acid solution [prepared from 30% hydrogen peroxide (25 mL) and acetic anhydride (90 mL)] was kept at 30-40 °C overnight. Precipitation with diethyl ether and filtration gave poly[4-(diacetoxyiodo)styrene] (5.7 g) as a white powder.1,12 The loading is determined by iodometry or elemental analysis.3-5,9-11

Handling, Storage, and Precautions: resin is best stored protected from direct sunlight and in a refrigerator, although no appreciable decomposition was observed at room temperature.4,10

Introduction

(Diacetoxyiodo)benzene and bis(trifluoroacetoxy)iodobenzene have been widely used in a range of oxidative procedures.15 The polymer-supported reagent, poly[4-(diacetoxyiodo)styrene], was first prepared by Okawara1 in 1961 but its chemistry was not well studied until almost 40 years later. This reagent offers advantages over PhI(OAc)2 in that the polymer-supported by-product, poly(4-iodostyrene), is easily isolated after the reaction (by filtration) and the reagent can be regenerated and reused with no loss in activity. In some cases, as highlighted below, the reactivity of the polymer-supported reagent differs from that of PhI(OAc)2 itself.

Regeneration and Re-use of Reagent2,3,7,9

Poly(4-iodostyrene) is recovered from reactions by filtration (following prior precipitation with diethyl ether if necessary) and elemental analysis indicates that the loading of iodine is the same as in the initially prepared polymer. This product is then reoxidized with peracetic acid as in the original preparation. Up to five recycles of the regenerated PS-I(OAc)2 have been reported with little or no loss in activity.2,5

Oxidation of Aniline

The first example of the use of PS-I(OAc)2 was the oxidation of aniline to the corresponding azo compound in 73% yield (1).1 A later investigation of this reaction demonstrated that the reagent could be regenerated and reused with minimal loss in activity. During five recycles, yields in the range of 81-87% were obtained.2

Oxidation of Hydroquinones

A number of substituted o- and p-hydroquinones have been oxidized to the corresponding quinones using PS-I(OAc)2 in MeOH or dichloromethane in good-to-excellent yield (63-100%) (2).3-5

Oxidative Spirocyclization of Tyrosine Derivatives

Oxidative spirocyclizations of tyrosine derivatives with hypervalent iodine compounds have previously been reported to yield spirodienones diastereoselectively,16 but the reported yields vary from 18-83%, indicating the capricious nature of the reaction. Using PS-I(OAc)2, consistent yields of 75-96% were obtained with products being greater than 90% pure by NMR spectroscopy and LC-MS (3).4

Phenolic Oxidative Coupling

As part of an orchestrated multi-step sequence using solid-supported reagents, PS-I(OAc)2 has been used to effect a para-para phenolic oxidative coupling (4) during a racemic synthesis of oxomaritidine.6 No other products were detected by LC-MS after filtration and evaporation of the reaction mixture.

Non-phenolic oxidative biaryl coupling has also been achieved with phenolic ethers and PS-I(OAc)2 in the presence of BF3·Et2O (5).7 The reaction has been shown to work in both inter- and intra-molecular modes. Good yields (75-78%) are obtained in most cases, although some substrates gave surprising results. The closely related polymer-supported bis(trifluoroacetoxyiodo)benzene (vide infra) appears to be a more efficient and general reagent in this case.7

Oxidation of Alcohols

The clean quantitative oxidation of a range of benzylic alcohols to benzaldehydes has been demonstrated using an excess of oxidizing agent (6).4

However, when the oxidation is performed in water in the presence of catalytic KBr, primary alcohols are oxidized to carboxylic acids in >90% yield (7). Under the same conditions, secondary alcohols are readily oxidized to ketones in yields >86%.8

Oxidative Cleavage of Diols

Two examples of the oxidative cleavage of diols have been reported using PS-I(OAc)2 in benzene at 80 °C giving ketones in 26-43% yields (8).1

a-Hydroxylation and a-Acetoxylation of Ketones

Aryl methyl ketones are hydroxylated in modest yield with PS-I(OAc)2 under basic conditions (NaOH, MeOH). This is accompanied by the formation of small amounts of the corresponding 2,2-dimethoxy acetals. Yields are generally inferior to those obtained with (diacetoxyiodo)benzene, although there are exceptions.3 However, treatment of aryl methyl ketones with an excess of PS-I(OAc)2 under acidic conditions affords quantitative yields of hydroxy ketones (9).4

Treatment of acetophenone with PS-I(OAc)2 in a mixture of acetic anhydride and acetic acid results in a-acetoxylation in 52% yield.5

Oxidative 1,2-Aryl Migration of Alkyl Aryl Ketones

The 1,2-aryl migration of propiophenones occurs in good yield with PS-I(OAc)2 in the presence of trimethyl orthoformate under acidic conditions and results compare favourably with those obtained using (diacetoxyiodo)benzene (10).3,9

In a similar manner, 3-benzoylpropionic acid reacts to give dimethyl 2-phenylsuccinate in excellent yield, again comparing favourably with results obtained using (diacetoxyiodo)benzene (11).9

Carbonyls from Hydrazones and Oximes

Treatment of hydrazones and oximes with PS-I(OAc)2 results in the formation of the corresponding carbonyl compounds (12).5 The reactions are carried out under very mild conditions (stirring at room temperature) and yields are in the range of 71-78%.

Oxidation of Sulfides and Thiols

Dialkyl sulfides are oxidized to sulfoxides with PS-I(OAc)2 in wet chloroform in excellent yields. Aryl-substituted sulfides afford sulfones as the major product with PS-I(OAc)2, whereas sulfoxides are obtained with (diacetoxyiodo)benzene (13).3 It is presumed that the sulfoxide is held on to the solid-supported oxidizing agent for a longer time period due to weak p-p interactions between the aryl substituents and the polystyrene skeleton, allowing the further oxidation to occur.

Performing the reaction in dichloromethane at reflux over a shorter reaction time (4 h) results in the oxidation of ditolylsulfide to ditolylsulfoxide in 71% yield with no formation of the sulfone witnessed.5

In addition, PS-I(OAc)2 has also been used to oxidize thiols to disulfides in excellent yield, even after recycling the reagent five times5 (14).

Iodination of Aromatic Compounds

Aromatic compounds are iodinated in variable yields (41-99%) with iodine and PS-I(OAc)2 and mixtures of mono- and di-iodinated compounds may be obtained. Ratios of mono- and di-iodination can differ significantly from those obtained with (diacetoxyiodo)benzene (15).3,9

Preparation of Heterocycles

1,3,4-Oxadiazoles have been prepared from aldehyde N-acylhydrazones in the presence of PS-I(OAc)2 and sodium acetate·trihydrate (16).10 Yields are variable, in the range of 24-68%, but generally compare well to those obtained with (diacetoxyiodo)benzene.17

A number of pyrazoline derivatives have been prepared from aldehyde phenylhydrazones in the presence of PS-I(OAc)2 in acrylonitrile (17).11 Yields in the range of 58-69% compare extremely well with those obtained when (diacetoxyiodo)benzene was used in the reaction.

Miscellaneous

Polymer-supported diaryliodonium salts have been prepared from PS-I(OAc)2 by stirring with the appropriate arene and an acid. For example, phenyl polystyryliodonium bisulfate is prepared by reaction with benzene and sulfuric acid (18).12,13

PS-I(OAc)2 has been used to oxidize triphenylphosphine to triphenylphosphine oxide in 72% yield,5 as well as to oxidatively cleave diphenylditelluride to form a benzenetellurinic mixed anhydride and for the oxidation of ditolyltelluride to ditolyltellurium diacetate.5 In the presence of sodium phosphonates and PS-I(OAc)2, diphenyl diselenide is converted into O,O-dialkyl phosphonoselenoates14 (19).

Related Reagents.

Polymer-supported bis(trifluoroacetoxyiodo)benzene, PS-I(OCOCF3), has been prepared by heating PS-I(OAc)2 in trifluoroacetic acid or by oxidation of poly(4-iodostyrene) with hydrogen peroxide/trifluoroacetic anhydride.7 This reagent shows greater solubility in dichloromethane than PS-I(OAc)2 and proves superior in effecting biaryl coupling of phenolic ethers. It has also been used in an example of phenolic oxidative coupling showing comparable results to PS-I(OAc)2.6 Alumina-supported (diacetoxyiodo)benzene has been used to oxidize a range a benzylic alcohols to aldehydes and ketones under solventless, microwave-promoted conditions in yields of 86-96%.18 This rapid procedure (1-3 min) also avoids over-oxidation of alcohols to carboxylic acids. Oxidation of hydroquinones to quinones occurs in lower yield (43-69%). (Polystyrylmethyl)trimethylammonium iodoacetate has also been developed and used in the iodoacetoxylation of alkenes19 and glycals20 (20) in good-to-excellent yields (57-98%). The iodoacetoxylation is trans-selective. This reagent also transforms terminal alkynes to 1-iodoalkynes in 70-83% yields and generates vinyl iodides from alkoxyallenes.19 Treatment of PS-I(OAc)2 with p-toluenesulfonic acid monohydrate in CHCl321 or DCM22 affords PS-I(OH)OTs. This reagent has subsequently been used to prepare a-tosyloxyketones in 33-94% yields,21 superior in some cases to yields obtained with PhI(OAc)2 and to prepare polymer-supported alkynylphenyl iodonium salts.22 Preparation of 5-benzoyldihydrofuran-2-ones is achieved in 55-73% yields when treating 4-benzoylbutyric acids with PS-I(OH)OTs in DCM at reflux. These yields are reproducible when using recycled reagent.23 Aminomethylpolystyrene-supported (diacetoxyiodo)benzene has been used to oxidise hydroquinones to quinones in yields of 52-100%, comparable to those obtained with PS-I(OAc)2. Oxidation of phenols to quinones is acheived in variable yield (24-81%) as are oxidative spirocyclisations (yields of 24-82%).24 indent The synthesis of p-quinones from phenol ether derivatives has been accomplished with PS-I(OCOCF3)2 in water in yields of 71-95%, comparable to those obtained with PhI(OCOCF3)2 even after three cycles using recovered and regenerated reagent.25 Furthermore, PS-I(OCOCF3)2 has been used to generate carbonyl functionality from hydrazones, oximes and semicarbazones.26


1. Okawara, M.; Mizuta, K., J. Chem. Soc. (Japan) 1961, 64, 232.
2. Hallensleben, M. L., Angew. Makromol. Chem. 1972, 27, 223.
3. Togo, H.; Abe, S.; Nogami, G.; Yokoyama, M., Bull. Chem. Soc. Jpn 1999, 72, 2351.
4. Ley, S. V.; Thomas, A. W.; Finch, H., J. Chem. Soc., Perkin Trans. 1 1999, 669.
5. Wang, G.-P.; Chen, Z.-C., Synth Commun. 1999, 29, 2859.
6. Ley, S. V.; Schuct, O.; Thomas, A. W.; Murray, P. J., J. Chem. Soc., Perkin Trans. 1 1999, 1251.
7. Tohma, H.; Morioka, H.; Takizawa, S.; Arisawa, M.; Kita, Y., Tetrahedron 2001, 57, 345.
8. Tohma, H.; Takizawa, S.; Maegawa, T.; Kita, Y., Angew. Chem., Int. Ed. Engl. 2000, 39, 1306.
9. Togo, H.; Nogami, G.; Yokoyama, M., Synlett 1998, 534.
10. Huang, X.; Zhu, Q., J. Chem. Res. (S) 2000, 300.
11. Huang, X.; Zhu, Q., Synth. Commun. 2001, 31, 111.
12. Yamada, Y.; Okawara, M., Makromol. Chem. 1972, 152, 153.
13. Chen, D.-J.; Chen, Z.-C., Synlett 2000, 1175.
14. Chen, D.-J.; Chen, Z.-C., Synth. Commun. 2001, 31, 421.
15. (a) Moriaraty, R. M.; Prakash, O., Acc. Chem. Res. 1986, 19, 244. (b) Varvoglis, A.; Spyroudis, S., Synlett 1998, 221. (c) Wirth, T.; Hirt, U. H., Synthesis 1999, 1271.
16. (a) McKillop, A.; McLaren, L.; Taylor, R. J. K.; Watson, R. J.; Lewis, N. J., Synlett 1992, 201. (b) McKillop, A.; McLaren, L.; Taylor, R. J. K.; Watson, R. J.; Lewis, N. J., J. Chem. Soc., Perkin Trans. 1 1996, 1385.
17. Yang, R.-Y.; Dai, L.-X., J. Org. Chem. 1993, 58, 3381.
18. Varma, R. S.; Dahiya, R.; Saini, R. K., Tetrahedron Lett. 1997, 38, 7029.
19. Monenschein, H.; Sourkouni-Argirusi, G.; Schubothe, K. M.; O'Hare, T.; Kirschning, A., Org. Lett. 1999, 1, 2101.
20. Kirschning, A.; Jesberger, M.; Monenschein, H., Tetrahedron Lett. 1999, 40, 8999.
21. Abe, S.; Sakuratani, K.; Togo, H., Synlett. 2001, 22.
22. Huang, X.; Zhu, Q., Tetrahedron Lett. 2001, 42, 6373.
23. Huang, X.; Zhu, Q., Zhang, J., J. Chem. Res. (S) 2001, 480.
24. Ficht, S.; Mulbaier, M.; Giannis, A., Tetrahedron. 2001, 57, 4863.
25. Tohma, H.; Morioka, H.; Harayama, Y.; Hashizume, M.; Kita, Y., Tetrahedron Lett. 2001 42, 6899.
26. Chen, D.-J.; Cheng, D.-P.; Chen, Z.-C., Synth. Commun. 2001, 31, 3847.

Richard J. K. Taylor & Matthew S. Addie

University of York, York, UK



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