Asymmetric synthesis of aminocyclooctenecarbonitriles: Cyclooctene β-lactam and hydroxyaminocyclooctene carboxylic precursors

Abstract Enantiopure β-aminocyclooctenenitriles, as precursors of β-amino acids and β-lactams, were synthesized from a readily available chloroalkene nitrile and ( S )-methylbenzylamine via a straightforward substitution reaction and purified by crystallization. Acidic hydrolysis of the nitrile groups to their corresponding amides followed by DCC assisted carbonyl group activation gave novel α,β-unsaturated lactams. The treatment of 3-bromo-8-chlorocyclooctenecarbonitrile with ( S )-methylbenzylamine furnished a diastereomeric mixture of bromoaminocyclooctenecarbonitriles via an S N 2′ pathway rather than bromide substitution via an S N 2 pathway. The diastereomeric mixture of bromoaminocyclooctanecarbonitriles provided two novel aziridines upon heating. TFA catalyzed aziridine ring opening gave γ-hydroxyl-β-aminocyclooctenecarbonitriles and γ-amino-β-hydroxycyclooctenecarbonitriles.