Highly stereoselective aziridine ring-opening with phenylselenide anion and selective intramolecular aldol closure for the enantiopure synthesis of γ-aminocyclopentene derivatives

Abstract

A practical and enantiopure synthesis for the preparation of key intermediates of conformationally locked γ-amino acid and nucleoside analogues is described. First, a highly stereoselective aziridine ring-opening reaction with phenylselenide anion was employed for the stereoselective synthesis of the chiral aminoselenide (1 S,2 S,1′ S)- 8, which after N-benzylation was transformed into the corresponding allyl amine (1 S,1′ S)- 7 by oxidation with H 2O 2. Then, dihydroxylation–dehomologation of (1 S,1′ S)- 7 with (OsO 4/NMO, NaIO 4) selectively afforded the desired γ-aminocyclopentene aldehyde ( S)- 1 and its corresponding γ-amino acid ( S)- 2 via an intramolecular selective aldol-condensation catalyzed by an internal base.