Polymer-Supported Bis(azido)iodate(I)

(a new polymer-supported source for iodo azide which efficiently promotes azido iodinations of alkenes1)

Physical Data: loading: 2.3 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: not soluble in most organic and aqueous solutions.

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

Preparative Methods: a suspension of untreated polymer-bound iodide (available from Fluka; 1 equiv, 2.9 mmol iodide g-1 resin) and PhI(OAc)2 (1.8 equiv) in dry CH2Cl2 (3 mL mmol-1 iodide) is shaken under nitrogen at 300 rpm for 6 h at room temperature. The brownish suspension is protected from light. Filtration and washing of the light yellow resin with dichloromethane (three times, 30 mL g-1 resin) and drying in vacuo affords the polymer-bound bis(acyloxy)iodate(I) (2) complex. A suspension of this polymer (1 equiv with respect to the starting material) is protected from light, suspended in dry dichloromethane (4 mL mmol-1), treated with trimethylsilylazide (2.6 equiv) and shaken at 300 rpm under nitrogen for an additional 6 h. During this time the organic phase turns to red. Filtration and washing of the resin with dichloromethane (three times, 30 mL g-1 resin) and drying in vacuo affords the orange title polymer (3). The weight increase serves as an indicator for efficient functionalization and gives the most reproducible results (about 90% conversion with respect to theoretical iodide). The IR spectrum of the new polymer shows a pair of strong bands at n = 2010 and 1943 cm-1 which indicates the presence of azido groups.

Recycling: A suspension of the used polymer (18 g) in HI (25 ml, 67%) is stirred vigorously for 10 min. After the addition of a portion of 10 mL of distilled water the mixture is stirred for an additional 30 min. Filtration and washing of the resin with distilled water (0.5 L), absolute methanol (0.4 L), and absolute dichloromethane (0.3 L) affords the dark brown resin loaded with iodide anions, which can be used again, after treatment with PhI(OAc)2 followed by TMSN3 without substantial loss of activity.

Handling, Storage, and Precautions: The immobilized bis(azido)iodate(I) complex can be prepared on a 100 g scale. Protected from light, it can be stored below -15 °C for weeks without loss of activity. Because of its sensitivity to air and moisture, it should be stored under argon. Small amounts of the reagent do not tend to explode under mechanical stress or by heat (280 °C) or in the presence of open flames if it is generated properly and all traces of azide have been washed off. This resin is not yet fully tested and should be used only with the usual precautions.

Caution! During the recycling process, HN3 is released which is highly toxic. Therefore, a well ventilated fume hood is absolutely necessary.

Background

Since the beginning of modern synthetic organic chemistry, the goal of chemists has been to produce single compounds in as pure form as possible. In this context, the development and applications of polymer-supported reagents have seen a dramatic increase in interest lately.2 The advantage of this hybrid solid-solution-phase technique lies in the simple work-up and isolation of the reaction products, even if reagents are used in excess in order to drive the reaction to completion.

Polymer-bound reagent 31 is a new member of this class of reagents3-6 with diverse chemical properties. It is the first example of a stable synthetic equivalent for iodine azide immobilized on a solid support. Reagent 3 is prepared from polystyrene-bound iodide (1) by treatment with (diacetoxyiodo)benzene which presumably leads to the immobilized bis(acyloxy)iodate(I) complex (2). The subsequent ligand-exchange reaction using trimethylsilylazide furnishes the title reagent (3) (1).

1,2-Iodoazidation of Alkenes1,3,5

General Procedure

Under protection from light, a mixture of alkene (1 equiv) and resin (3-8 equiv) in dry dichloromethane (2 mL mmol-1) are shaken at 300 rpm at room temperature. Completion of the reaction is monitored by TLC. Filtration terminates the reaction. The resin is washed with dichloromethane (three times 20 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.

Under these conditions, 1,2-functionalization of alkenes typically affords a single azidoiodination product in good yield (4)-(10) (2). The yields in parentheses refer to isolated products.

The addition proceeds with trans selectivity as demonstrated for the indene addition product (13). The regioselectivity of the 1,2-addition is governed by the more stable intermediate carbenium ion formed after electrophilic attack of the iodonium species. When alkyl-substituted alkenes are employed, small amounts (5%) of the formal anti-Markovnikov addition products are formed along with the desired products (14 and 15). Transformation of the alkoxyallene into the corresponding vinyliodide (10) clearly demonstrates that the nucleophilic character of the double bond determines the chemoselectivity of the process.

Importantly, hydroxy groups are tolerated under the reaction conditions employed and products 11 and 12 were isolated in excellent yields.

In addition, the azidoiodination of protected carbohydrate-derived glycals is efficiently achieved to yield the corresponding 2-deoxy-2-iodoglycosyl azides 17 and 18. In both cases, filtration of the resin and removal of the solvent in vacuo provides the reaction products in high purity.

All transformations are achieved using an excess of the polymer-bound reagent 3. This may be rationalized by assuming that only those polymer-bound haloate(I) anions are involved which are most exposed to the solution or that the iodine azide is the active species and is slowly released from the polymeric surface. Substantial decomposition under the reaction conditions could be responsible for the necessity of employing an excess of immobilized reagent 3. In addition, prolonged reaction may time lead to by-products 19, 21, and 22 when electron-rich styrene derivatives are used as starting alkenes.

The polymer-assisted process is substantially more effective than the solution variants using tetraethylammonium iodide, (diacetoxyiodo)benzene and trimethylsilylazide for the in situ preparation of Et4NI(N3)2.7 In fact, the latter procedure leads to reduced isolated yields which can be ascribed to the sensitivity of 2-iodo azides to hydrolytic work-up conditions.

Specific advantages of this hybrid solid-solution-phase technique in comparison to the solution phase counterpart are: (a) the polymer is readily available, (b) simple work-up of the reaction products, (c) the reaction products are not contaminated with iodobenzene, (d) the reagent is stable and can be stored for months without loss of activity, (e) it is non explosive, (f) it can be generated and applied in different organic solvents, and (g) it can conveniently be recycled using HI.


1. Kirschning, A.; Monenschein, H.; Schmeck, C., Angew. Chem., Int. Ed. Engl. 1999, 38, 2594; Angew. Chem. 1999, 111, 2720.
2. (a) Kirschning, A.; Monenschein, H.; Wittenberg, R., Angew. Chem., Int. Ed. Engl. 2001, 40, 650; 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. Monenschein, H.; Sourkouni-Argirusi, G.; Schubothe, K. M.; O'Hare, T.; Kirschning, A., Org. Lett. 1999, 1, 2101.
5. Domann, S.; Sourkouni-Argirusi, G.; Merayo, N.; Schönberger, A.; Kirschning, A., Molecules 2001, 6, 61.
6. Sourkouni-Argirusi, G.; Kirschning, A., Org. Lett. 2000, 2, 3781.
7. Kirschning, A.; Hashem, Md. A.; Monenschein, H.; Rose, L.; Schöning, K.-U., J. Org. Chem. 1999, 64, 6522.

Andreas Kirschning & Holger Monenschein

Institut für Organische Chemie, Universität Hannover, Hannover, Germany



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