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 stereo- and regioselective leading to the thermodynamic adducts as major products. Reduction of the N,O-acetal, followed by elimination of the menthol appendage, allows both enantiomers of disubstituted epoxy tetrahydroisoindolines to be prepared. Nucleophilic ring opening of the N,O-moiety in the adducts by magnesium or aluminum derivatives, followed by elimination of the menthol, leads to the synthesis of enantiopure regioisomeric trisubstituted epoxy tetrahydroisoindolines with up to five stereocenters.