Polymer-Supported Bis(acyloxy)bromate(I)

[256385-96-3]F

(a new polymer-supported oxidant described which performs the oxidation of primary and secondary alcohols into their corresponding carbonyl compounds1)

Physical Data: 2.4 mmol g-1 (based on the amount of bromide attached to the commercial resin, assuming that all bromide ions are transformed into the active species; polymer matrix: copoly(styrene-DVB), 20-50 mesh.

Solubility: insoluble in organic solvents and aqueous solutions.

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

Preparative Methods: a suspension of untreated polymer-bound bromide (e.g. available from Fluka; 1 equiv, 3.2 mmol g-1 resin) and PhI(OAc)2 (1.8 equiv) in dry dichloromethane (3 mL mmol-1 bromide) is shaken under nitrogen at 300 rpm for 8 h at room temperature. The brownish suspension is protected from light. Filtration and washing of the resin with dichloromethane (3×, 20 mL g-1 resin) and drying in vacuo affords the brown title polymer. The weight increase serves as an indicator for efficient ligand transfer onto polymer-bound bromide and gives the most reproducible results (about 85-90% conversion with respect to theoretical bromide). Recycling: a suspension of the used polymer (5 g) in NaOH (2×20 mL, 1 M) is stirred vigorously for 10 min. After washing with distilled water (2×25 mL), the wet resin is treated with HBr (2×25 mL, 2 N). Filtration and washing of the resin with water(dest), (40 ml) absolute methanol (30 mL) and absolute dichloromethane (30 mL) affords the light yellow supported bromide resin, which can be used again after treatment with PhI(OAc)2 without substantial loss of activity.

Handling, Storage, and Precautions: The immobilized bis(acyloxy)bromate(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. A strong smell of acetic acid indicates the decomposition of the active species. This resin is not yet fully tested and should only be used with the usual precautions.

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 has 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 these reagents are used in excess in order to drive the reaction to completion.

Haloate(I) complex 11 is a new member of this class of reagents with diverse chemical properties.3-5

Oxidation of Alcohols1

General Procedure

A mixture of alcohol (1 equiv), resin 1 (3-6 equiv) and catalytic amounts of 2,2,6,6-tetramethyl-l-piperinyloxyl (2 mol%) are shaken at 300 rpm 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. Generally, no further purification by column chromatography is necessary.

Under these conditions primary alcohols are oxidized into aldehydes 2-8 and, importantly, secondary alcohols are converted into ketones 9-15 in excellent yields (yields in parentheses refer to determination by GC).

Considering that a polymer-bound reagent is employed, the reactions proceed rather rapidly (see ref 1). In addition, no over-oxidation to the corresponding carboxylic acids is observed.

Following the general procedure, the products isolated after filtration and evaporation of the solvent are very pure and can be used directly in the next step. In this context, this new oxidation method is well suited for applications in natural product total synthesis because the integrity of a chiral center in the a-position is often a problem during the oxidation process and especially during work-up of the generated carbonyl compound. In fact, the transformation of a chiral alcohol into aldehyde 7 is achieved without any detectable racemization (>95% ee), while the Swern and, to a lesser extent, the Dess-Martin oxidation led to the partly racemized aldehyde 7, either during the reaction or work-up by flash column chromatography.

In comparison with other polymer-supported oxidants, for example, Ley's immobilized perruthenate which is very efficient for oxidizing primary and secondary benzylic alcohols but cannot be employed for secondary alcohols, the title reagent 1 is a powerful tool for the oxidation of all kinds of alcohols. Olefinic double bonds, however, are not tolerated under these conditions.

1,2-Bromoacetoxylation of Alkenes3

General Procedure

A mixture of alkene (1 equiv) and resin 1 (3-7 equiv) is shaken at 300 rpm under light protection 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 (3×20 mL g-1 resin), and the combined organic washings and filtrate are concentrated under reduced pressure. In some cases, purification by column chromatography is necessary.

Similar to the analogous polymer-supported reagents for efficient iodoacetoxylation (see refs 6-8) and iodoazidation9 of alkenes, the title reagent 1 is used to promote the corresponding 1,2-bromoacetoxylations. Following the general procedure, the addition often proceeds with trans selectivity, as demonstrated for cyclohexene and indene transformation products 16 and 17. Reaction of alkoxyallene with resin 1 leads to vinylbromide 18, clearly demonstrating that the relative electron density of the double bond determines the chemoselectivity of the process.

In contrast to iodoacetoxylation6-8 and iodoazidation,9 however, this process often lacks good regio- and stereoselectivity. Two examples are depicted below (eq 1 and 2).

In contrast, the bromoacetoxylation of protected carbohydrate-derived glycals furnishes the corresponding 2-bromo-2-deoxy-glycosyl acetates 27 and 28 in excellent yields.7 In most cases, filtration of the resin and removal of the solvent in vacuo affords the reaction products in high purity.

Furthermore, reaction of vinyl silane 29 with the title reagent 1 also affords the 1,2-addition product 30 in good yield (eq 3).8 Remarkably, desilylation or formation of products derived from desilylation was not observed.


1. Sourkouni-Argirusi, G.; Kirschning, A., Org. Lett. 2000, 2, 3781.
2. Kirschning, A.; Monenschein, H.; Wittenberg, R., Angew. Chem., Int. Ed. Engl. 2001, 40, 650 and Angew. Chem. 2001, 113, 670.
3. Soluble variants of 1 have been employed in: Kirschning, A.; Plumeier, C.; Rose, L., Chem. Commun. 1998, 33.
4. Hashem, M. d. A.; Jung, A.; Ries, M.; Kirschning, A., Synlett 1998, 195.
5. Kirschning, A.; Hashem, M. d. A.; Monenschein, H.; Rose, L.; Schöning, K.-U., J. Org. Chem. 1999, 64, 2720.
6. Monenschein, H.; Sourkouni-Argirusi, G.; Schubothe, K. M.; O'Hare, T.; Kirschning, A., Org. Lett. 1999, 1, 2101.
7. Kirschning, A.; Jesberger, M.; Monenschein, H., Tetrahedron Lett. 1999, 40, 8999.
8. Domann, S.; Sourkouni-Argirusi, G.; Merayo, N.; Schönberger, A.; Kirschning, A., Molecules 2001, 6, 61.
9. Kirschning, A.; Monenschein, H.; Schmeck, C., Angew. Chem., Int. Ed. Engl. 1999, 40, 8999 and Angew. Chem. 1999, 111, 2720.

Andreas Kirschning & Holger Monenschein

Institut für Organische Chemie, Universität Hannover, Germany



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