Polymer-Supported Bis(acyloxy)iodate(I)

[68574-12-9]F

(a new electrophilic polymer-supported reagent which efficiently promotes iodo acetoxylations of alkenes as well as iodination of terminal alkynes1)

Physical Data: Loading 2.1 mmol g-1 (based on the amount of iodide attached to the commercial resin, assuming that all iodide ions are transformed into the active species); polymer matrix: copoly(styrene-DVB), 20-50 mesh.

Solubility: insoluble in most organic and aqueous solvents.

Form Supplied in: macroscopic, light yellow resin beads; readily available by following the procedure provided below.

Preparative Methods: a suspension of polymer-bound iodide (available from Fluka; 1 equiv, 2.9 mmol g-1 resin) and PhI(OAc)2 (1.8 equiv) in dry dichloromethane (3 mL mmol-1 iodide) under nitrogen is shaken at 300 rpm for 6 h at room temperature. The brownish suspension was protected from light. Filtration and washing of the resin with dichloromethane (3×, 25 mL g-1 resin) and drying in vacuo affords the light yellow title polymer. The weight increase serves as an indicator for efficient ligand transfer onto polymer-bound iodide and gives most reproducible results (about 90% conversion with respect to theoretical iodide). Recycling: a suspension of the used polymer (18 g) in concentrated HI (25 mL, 67%) is stirred vigorously for 10 min. After addition of another 10 mL of distilled water, the suspension is stirred for an additional 30 min. Filtration and washing of the resin with water(dest) (500 mL), absolute methanol, (400 mL) and absolute dichloromethane (300 mL) affords the dark brown supported iodide resin which can be used again after treatment with PhI(OAc)2 without substantial loss of activity.

Handling, Storage, and Precautions: The bis(acyloxy)iodate(I) resin can be prepared on a 100 g scale. It is the most labile resin (thermally and photochemically) among resin-bound haloates, including the bis(azido)iodate(I) resin and the bis(acyloxy)iodate(I) resin described so far. It can be stored below -15°C and protected from light for at least 1 week, but preferentially should be used shortly after its preparation. Because of its sensitivity to air and moisture, the resin should be stored under nitrogen. A strong smell of acetic acid indicates the decomposition of the active species. This resin is not yet fully tested and should be used only with the usual precautions.

Background

The development and use of polymer-supported reagents has seen a dramatic increase over the past 5 years, although the basic principles of this technique have been known for at least 30 years.2 The advantage of this hybrid solid-solution-phase technique lies in the simple work-up and isolation of the reaction products, even if these reagents are used in excess in order to drive the reaction to completion. Haloate(I) complex 1 is a new electrophilic member of this class of reagents with diverse chemical properties1,3-6 as is briefly depicted below.

1,2-Iodoacetoxylations of alkenes1,3-5

General Procedure

A mixture of alkene or alkyne (1 equiv) and resin (3-4 equiv) is shaken at 300 rpm under protection from light in dry dichloromethane (1.5 mL mmol-1) at room temperature. Completion of the reaction is monitored by TLC. Filtration terminates the reaction. The resin is washed with dichloromethane (3×40 mL g-1 resin), and the combined organic washings and filtrate are concentrated under reduced pressure. In some cases, further purification by column chromatography is necessary.

Following this general procedure (see also reference 1), in most cases, 1,2-functionalization of alkenes affords single iodoacetoxylation products 2-5.

The addition proceeds with trans selectivity, as demonstrated for cyclohexene- and indene-transformation products 6 and 7. The transformation of alkoxyallenes into the corresponding vinyliodides 8 and 9 demonstrates that inductive effects of the double bond substituents determine the chemoselectivity of the process.

Halogenated substrates react very sluggishly at room temperature; at 80°C complete consumption of alkenes is achieved. Under these conditions 4-bromostyrene gives the desired 1,2-addition product 10 in moderate yield, while 3-chloro-1-phenylprop-1-ene yields iodoacetoxylation product 11 in low yield. In contrast, allyl chloride undergoes nucleophilic substitution to furnish allyl acetate 12 as the major product.

Importantly, hydroxy groups are tolerated under the reaction conditions but can be converted to derivatives. Allyl alcohol 13 affords acetate 15 in excellent yield, indicating that the expected addition to give 14 is followed by an acyl migration to the terminal alcohol group (eq 1). In contrast, the corresponding homoallyl alcohol gives an intermediate cation which is trapped in an intramolecular mode by the hydroxy group to furnish tetrahydofuran 16.

Likewise, partially, and even fully, unprotected glycals can, in the presence of reagent 1, undergo a 1,2-functionalization as summarized for glycosyl acetates 22, 24 and 17. In addition, the iodoacetoxylation of protected carbohydrate-derived glycals is carried out in different solvents (see ref 3) with excellent yields of the corresponding 2-deoxy-2-iodo-glycosyl acetates (18-21, 23). In most cases, filtration of the resin and removal of the solvent in vacuo affords the reaction products with high purity.

Furthermore, the title reagent 1 promotes transformation of vinyl and allyl silanes and, instead of the expected desilylation, the 1,2-addition products 25-29 are formed as major products (see ref 5).

All transformations are achieved using an excess of the immobilized reagent 1. This may be rationalized by assuming that only the most accessible haloate(I) anions are involved in the cohalogenation process. If acylated, hypohalites are the active species after release from the polymer, their degradation prior to the reaction with alkenes may also contribute to the need for a formal excess of reagent.

When comparing this polymer-supported technique with the solution variant7-9 using tetraethylammonium iodide and (diacetoxyiodo)benzene for the in situ preparation of Et4NI(OAc)2 (see refs 7 and 8) and subsequent iodoacetoxylation, the isolated yields for the acetates that are derived from the solution variant are reduced due to their lability during the recommended reductive aqueous work-up.

Iodination of alkynes1

A second set of experiments using terminal alkynes for the transformation with the title reagent 1 affords alkynyl iodides 30-33, presumably generated by electrophilic attack of the iodonium ion and formation of an intermediate vinyl cation followed by deprotonation. Remarkably, the nitrile functionality in 32 is tolerated.

The formation of the unusual cyclization product 34, generated from the corresponding acyclic terminal alkyne, may be rationalized by electrophilic attack of a second equivalent of the iodonium ion onto the triple bond in the corresponding intermediate iodoalkyne and subsequent cyclization.

It is noteworthy that, unlike classical reagents for the acetoxyiodination of alkenes, the use of the title reagent 1 does not require glacial acetic acid or heavy metals. More specific features and advantages of this reagent are: (1) the polymer is readily available, (2) the preparation is short and straightforward, (3) the work-up of the reaction products is simple filtration and concentration, (4) the reaction mixture is free of iodobenzene, which is the common by-product when hypervalent reagents like the starting diacetoxyiodobenzene are employed, (5) the reagent is storable to some extent, (6) the reagent is generated and can be applied in different organic solvents, and (7) the reagent is recyclable.


1. Monenschein, H.; Sourkouni-Argirusi, G.; Schubothe, K. M.; O'Hare, T.; Kirschning, A., Org. Lett. 1999, 1, 2101.
2. a) Kirschning, A.; Monenschein, H.; Wittenberg, R., Angew. Chem., Int. Ed. Engl. 2001, 40, 650 and Angew. Chem. 2001, 113, 670. (b) Ley, S. V.; Baxendale, I. R.; Bream, R. N.; Jackson, P. S.; Leach, A. G.; Longbottom, D. A.; Nesi, M.; Scott, J. S.; Storer, R. I.; Taylor, S. J.; J. Chem. Soc., Perkin Trans. I 2000, 3815. (c) Drewry, D. H.; Coe, D. M.; Poon, S., Med. Res. Rev. 1999, 19, 97.
3. Kirschning, A.; Jesberger, M.; Monenschein, H., Tetrahedron Lett. 1999, 40, 8999.
4. Sourkouni-Argirusi, G.; Kirschning, A., Org. Lett. 2000, 2, 3781.
5. Domann, S.; Sourkouni-Argirusi, G.; Merayo, N.; Schönberger, A.; Kirschning, A., Molecules 2001, 6, 61.
6. Kirschning, A.; Monenschein, H.; Schmeck, C., Angew. Chem., Int. Ed. Engl. 1999, 38, 8999 and Angew. Chem. 1999, 111, 2720.
7. Soluble variants of 1 have been employed in: Kirschning, A.; Plumeier, C.; Rose, L., Chem. Commun. 1998, 33.
8. Hashem, Md. A.; Jung, A.; Ries, M.; Kirschning, A., Synlett 1998, 195.
9. Kirschning, A.; Hashem, M.d. A.; Monenschein, H.; Rose, L.; Schöning, K.-U., J. Org. Chem. 1999, 64, 2720.

Andreas Kirschning & Holger Monenschein

Institut für Organische Chemie, Universität Hannover, Germany



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