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

Novel azabicyclic beta-amino acid derivatives were readily prepared from diexo or diendo norbornene beta-amino acids. The 3-azabicyclo[3.2.1]octane skeleton was obtained by NaIO4-mediated cleavage of the dihydroxylated beta-amino ester intermediates, followed by reductive amination. Lipase-catalyzed enantioselective ring opening of racemic exo-norbornene beta-lactam allowed preparation of the corresponding azabicyclic exo beta-amino acid in enantiopure form.