The use of (−)-8-phenylisoneomenthol and (−)-8-phenylmenthol in the enantioselective synthesis of 3-functionalized 2-azabicyclo[2.2.1]heptane derivatives via aza-Diels–Alder reaction

Abstract

The asymmetric aza-Diels–Alder reaction of the (1 R)-8-phenylmenthyl or (1 R)-8-phenylisoneomenthyl glyoxylate-derived N-benzylimine with cyclopentadiene resulted in the enantioselective synthesis of the corresponding pure [(1 S,3- exo)-2-benzyl-2-azabicyclo[2.2.1]hept-5-ene]-3-carboxylates (80 or 69% yield, respectively). Reduction of these cycloadducts with LiAlH 4 afforded pure (−)-[(1 S,3- exo)-2-benzyl-2-azabicyclo[2.2.1]hept-5-en-3-yl]methanol. Furthermore, a reaction sequence based on Barbier–Wieland degradation of both (1 S,3- exo)-adducts afforded pure (+)-(1 R)-2-benzoyl-2-azabicyclo[2.2.1]heptan-3-one. In the course of the two transformation sequences referred, the chiral auxiliaries were recovered in a virtually quantitative way.