title: Solid-phase asymmetric synthesis using a polymer-supported chiral Evans'-type oxazolidin-2-one.
abstract: This protocol describes the synthesis of (S)-4-(4-hydroxybenzyl)-oxazolidin-2-one, its attachment to a Merrifield-Cl resin and its use for asymmetric synthesis. The chiral auxiliary is prepared in four steps from N-Boc-L-tyrosine on a multigram scale in high yield and attached to Merrifield-Cl resin via its phenolic group to afford a solid-supported chiral auxiliary for asymmetric synthesis that takes ∼7 d to prepare. A procedure for its N-acylation is reported and a method for carrying out diastereoselective solid-supported Evans' syn-aldol reactions is described, with aldol products being cleaved from the polymer by either hydrolysis or reduction. The use of the supported auxiliary for two sequential 'on-bead' reactions has been demonstrated for the synthesis of a chiral cyclopropane aldol and a γ-lactone in a >95:5 diastereomeric ratio. These polymer-supported reactions are carried out in IRORI Kan resin capsules to protect the polymer support from mechanical degradation, thus allowing multiple on-bead reactions to be performed.
authors.affiliation: Department of Chemistry, University of Bath, Bath, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Green
authors.forename: Jennifer
authors.initials: J
authors.lastname: Peed
authors.forename: James E
authors.initials: JE
authors.lastname: Taylor
authors.forename: Richard A R
authors.initials: RA
authors.lastname: Blackburn
authors.forename: Steven D
authors.initials: SD
authors.lastname: Bull
mesh_terms: D023303:Oxazolidinones / Q000138:chemical synthesis* / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D060327:Solid-Phase Synthesis Techniques
chemical_list: C095039:Merrifield resin; D023303:Oxazolidinones; D011108:Polymers; D011137:Polystyrenes
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