Synthesis of conformationally constrained, orthogonally protected 3-azabicyclo[3.2.1]octane β-amino esters

Abstract

Novel azabicyclic β-amino acid derivatives were readily prepared from diexo or diendo norbornene β-amino acids. The 3-azabicyclo[3.2.1]octane skeleton was obtained by NaIO4mediated cleavage of the dihydroxylated β-amino ester intermediates, followed by reductive amination. Lipase-catalyzed enantioselective ring opening of racemic exo-norbornene β-lactam allowed preparation of the corresponding azabicyclic exo β-amino acid in enantiopure form.