A short diastereoselective synthesis of enantiopure highly substituted tetrahydroepoxyisoindolines

Diastereoselective intramolecular Diels-Alder reaction on 3-allyl-2-furyl- or 3-furfuryl-2-vinyl-substituted chiral perhydro-1,3-benzoxazines derived from (-)-aminomenthol is described. The [4 + 2] cycloaddition is highly ste reo- and regioselective leading to the thermodynamic adducts as major produ cts. Reduction of the N,O-acetal, followed by elimination of the menthol ap pendage, allows both enantiomers of disubstituted epoxy tetrahydroisoindoli nes to be prepared. Nucleophilic ring opening of the N,O-moiety in the addu cts by magnesium or aluminum derivatives, followed by elimination of the me nthol, leads to the synthesis of enantiopure regioisomeric trisubstituted e poxy tetrahydroisoindolines with up to five stereocenters.