Asymmetric synthesis of bicyclic α-amino acids by a Diels–Alder reaction to a new chiral α,β-didehydroalanine derivative

Abstract

A new chiral cyclic α,β-didehydroalanine derivative, (6 S)-6-isopropyl-3-methylene-5-phenyl-3,6-dihydro-2 H-1,4-oxazin-2-one, has been prepared by in situ aminomethylation–elimination of a chiral glycine-derived precursor. This oxazin-2-one acts as a reactive dienophile in highly diastereoselective Diels–Alder reactions with cyclopenta- and cyclohexadiene. The major cycloadducts have been isolated and hydrolyzed to afford enantiomerically pure (−)- endo-2-aminobicyclo[2.2.1]heptane-2-carboxylic and exo-2-aminobicyclo[2.2.2]octane-2-carboxylic acids.