From pyrrolidin-2-ones to 3-aza-2-oxobicyclo[3.2.0]heptanes. Synthesis of both enantiomers of cis-2-aminomethylcyclobutane carboxylic acid, a conformationally restricted analogue of GABA

By changing the cyclisation conditions (NaH in THF or NaOEt in EtOH), an enantiopure malonamide containing an enoate acceptor afforded either diastereomeric pyrrolidin-2-one 3 or 4 as the major product of the intramolecular conjugate addition. After separation, both diastereomers were converted through simple steps into the corresponding 3-aza-2- oxobicyclo[3.2.0] heptane which eventually led to each enantiomer of cis-2- aminomethylcyclobutanecarboxylic acid, 1, a conformationally restricted analogue of GABA, in both enantiomerically pure form.