Polymer-Supported Carbonate

Physical Data: loading 3.5 mmol g-1.

Solubility: the reagent is insoluble in all common aqueous and organic solvents.

Form Supplied in: white and brown beads, commercially available, containing 20% water. Commercial supplier: Fluka.

Purification: the polymer should be washed in dichloromethane and dried in vacuo prior to use.

Handling, Storage, and Precautions: powdered resin is harmful if inhaled or ingested. Stable at room temperature.

Polymer-supported carbonate (PS-carbonate), first described in 1981,1 is a weakly basic reagent with several applications for organic synthesis, notably for the neutralization of acidic solutions, as a source of nucleophilic carbonate, and for mediating various functional group interconversions and deprotections.

The earliest application of carbonate resin was for the conversion of primary alkyl halides to alcohols under mild conditions in excellent yields (eq 1), although secondary halides gave some elimination products under the same conditions.1 The order of reactivity was determined as I- Br- Cl-.

This reagent has also been applied to the formation of triols from a-iodo carbonates.2 The reaction proceeds via an epoxide intermediate which is only hydrolysed in the presence of a proximal hydroxyl group (eq 2). This reaction elegantly overcomes the usual problematic aqueous work-up encountered due to the high solubility of the triol products in water.

More recently, the synthesis of several heterocyclic systems has been achieved using PS-carbonate. Oxazoles were formed cleanly from a-iodotrichloroacetamides in high yield (eq 3),3 and oxazolidin-2-ones were synthesized stereoselectively from b-iodo a-hydroxyammonium salts (eq 4).4 The latter reaction involves insertion of carbon dioxide and proceeds via an a-epoxycarbamate intermediate.

The formation of oxazolidin-2-ones has also been elegantly accomplished in one pot from enantiopure allylic amine salts using iodine adsorbed onto PS-carbonate as a supported source of both iodine for the iodolactonization and carbon dioxide for the carbamate formation (eq 5).5 Selectivity for the E product increased upon benzyl protection of the ammonium salt.

PS-carbonate has recently been used in several multi-step organic syntheses in conjunction with other polymeric reagents. Ley et al. reported the synthesis of (±)-oxomaritidine and some elaborated analogs,6 in which carbonate resin was used in the final step to remove a trifluoroacetate protecting group and mediate an intramolecular 1,4-addition to cleanly furnish the target molecule (eq 6).

The same group has also reported the use of this reagent in the formation of a cyclic hemiacetal from a-bromoketones and catechol.7 Aminomethylpolystyrene was added to remove any remaining a-bromoketone to give the desired product in high purity as a mixture of open and closed chain forms (eq 7).

A further application of this reagent is the neutralization of ammonium salts. Treatment of several salts with PS-carbonate in refluxing methanol yielded the free amines in clean fashion (eq 8).3 This principle has been applied to the purification of a range of bicyclo[2.2.2]octane derivatives following an intermolecular cycloaddition step.8 Polymer-supported thiol and diisopropylethylamine (DIPEA) were used to remove unreacted cyclohexenone and the resultant ammonium salts were neutralized with the carbonate resin to afford the desired product after simple filtration and evaporation (eq 9).

1. Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S., Synthesis 1981, 793.
2. Bongini, A.; Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S., J. Org. Chem. 1982, 47, 4626.
3. Cardillo, G.; Orena, M.; Porzi, G.; Sandri, S., J. Chem. Soc. Chem. Commun. 1982, 1309.
4. Cardillo, G.; Orena, M.; Sandri, S.; Tomasini, C., Tetrahedron 1985, 41, 163.
5. Cardillo, G.; Orena, M.; Sandri, S., J. Org. Chem. 1986, 51, 713.
6. Ley, S. V.; Murray, P. J.; Schucht, O.; Thomas, A. W., J. Chem. Soc., Perkin Trans. 1. 1999, 1251.
7. Habermann, J.; Ley, S. V.; Scicinski, J. J.; Scott, J. S.; Smits, R.; Thomas, A. W., J. Chem. Soc., Perkin Trans. 1 1999, 2425.
8. Ley, S. V.; Massi, A., J. Comb. Chem. 2000, 2, 104.

Steven V. Ley & Robert N. Bream

University of Cambridge, Cambridge, UK

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.