TETRAHEDRON: ASYMMETRY Tetrahedron: Asymmetry 13 (2002) 333–337 Pergamon A soluble polymer-bound Evans’ chiral auxiliary: synthesis, characterization and use in cycloaddition reactio GiovanniDesimoni, a Giuseppe Faita, a, * Alessandro Galbiati, b Dario Pasini, a, * Paolo Quadrelli a and Fabio Rancati a a Department of Organic Chemistry, University of Pavia-Viale Taramelli, 10 -I -27100 Pavia,Italy b NPT s.r.l.-Viale Zanotti, 90 -I -27027 Gropello Cairoli ( PV ) , Italy Received 13 February 2002; accepted 6 March 2002 Abstract—The synthesis of novel soluble polymer-supported optically-active oxazolidinone (Evans’ chiral auxiliary) with chiral monomer/styrene ratios is described. The polymer was obtained in high yields and then functionalized with trans- anhydrideto givea high loading polymer(2.42 mmol/g). The reactivity wastested in the1,3-dipolarcycloaddition with diphenylnitrone under catalyzed and uncatalyzed conditions. The cycloadducts could be obtained in high purities and fair yields after reductive cleavage. The stereoselectivity is parallelto that obtained with the model substrate under classicalsolution conditions. © 2002 Elsevier Science Ltd. All rights reserved. Crosslinked,insolublepolymersupportsfor organic synthesis have recently witnessed a resurgence of inter- est for applications in combinatorial chemistry. 1 Most recently,a variety of catalystsfor enantioselective organic synthesis on insoluble supports have appeared in the literature. 2 Tuning of the reactivity of the sup- ported organic compounds in the unavoidably hetero- geneous-phase reactions, as well as the detection and analysis of the functionalized, supported products can, however,be extremelyproblematic.Severalgroups have recently explored the use of soluble linear poly- meric, 3 dendritic 4 and precipiton 5 supports. The advan- tagesof solid-phase synthesis are retained,since the macromolecular supportis easily removed from the reaction mixture via precipitation from an appropriate solvent,but the synthetic pathway can be carried out undermore convenient homogeneous solution condi- tions, with easiercharacterization ofthe covalently bound substrates. Chiral 3-substituted1,3-oxazolidin-2-ones, originally introduced by Evans, 6a act as chiralauxiliaries in sev- eral CC bond forming reactions as well as in metal- catalyzed cycloaddition reactions between a variety of 1,3-dipoles and dienes, with good control of diastereo- and enantioselectivity. 6 Typically, the catalyticpro- cesses involve the dissolution in organic solvents of the metalsalts (added as a heterogeneous solid) as a result of coordination ofthe metalcation to the 1,3-dicar- bonylmoiety in the chiralauxiliary.Grafting of this chiral auxiliary to Merrifield and Wang resins has already been achieved by us 7 and other groups, 8 but the metal-catalyzed reactions of these resin-supported aux- iliaries have shown some differences in stereoselectivity in comparison to the solution-phase reactions. 7a A car- rier for the cation was found to be necessary in solid- phase chemistry to allow interaction of the Lewis acid with the grafted coordinating substrate and to simulate classical catalysis conditions in solution, with the Wang supportshowing highersensitivity to saltconcentra- tions than the Merrifield resin-supported auxiliary. 7b Herein, we communicate the synthesis, characteriza- tion, and functionalization of a novel, soluble polymer- supported optically-active oxazolidinone. Since the two most common support strategies developed for soluble macromolecular supportsare polyethylene glycol and polystyrene-based, 3c we chosethe latter in order to avoid competitiveinteractionsbetweenthe oxygen atoms of the polymer chains and the Lewis acidic metal cation. Furthermore, polystyrene supports are removed by precipitation in polar organic solvents in which all the excess reagents should remain soluble. Preliminary investigations on the reactivity of the soluble polymer- * Correspondingauthors. Tel.: +39-0382-507866; fax: +39-0382- 507323; (G.F.) tel.: +39-0382-507312; fax: 39-0382-507323 (D.P.); e-mail: faita@chifis.unipv.it; pasini@chifis.unipv.it 0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved. PII: S 0 9 5 7 - 4 1 6 6 ( 0 2 ) 0 0 1 1 7 - 9