Double diastereoselection in asymmetric [2+3] cycloaddition of chiral oxazoline N-oxides: application to the kinetic resolution of a racemic alpha,beta-unsaturated delta-lactone

The asymmetric [2+3] cycloaddition reaction between chiral oxazoline N-oxid e 1 and alpha,beta-unsaturated lactone 2 was studied. A double diastereosel ection was observed, (1R)-1 and (R)-2 gave a mismatched pair with almost no cycloadduct obtained. A transition state model is proposed, accounting for the destabilization of transition state in the cycloaddition reaction. Thi s result has led to kinetic resolution studies, in which both enantiomers o f 1 were reacted with racemic lactone 2. The enantiomeric excess of the rec overed lactone 2 was determined to be up to 70% ee, by C-13-{H-1} NMR analy sis in a chiral liquid crystalline solvent. The experimental results are in agreement with predicted enantiomeric excesses and consistent with the tra nsition state models. (C) 1999 Elsevier Science Ltd. All rights reserved.