Stereoselective synthesis of dipeptide β-turn mimetics: 7-Benzyl and 8-phenyl substituted azabicyclo[4.3.0]nonane amino acid esters

A stereoselective method has been developed for the synthesis of 7- and 8-substituted dipeptide β-turn mimetic azabicyclo[4.3.0]nonane amino acid esters. The allyl groups were introduced in high diastereoselectivity, controlled by 3-phenyl or 4-benzyl groups in pyroglutamic acid derivatives 3 or 9, respectively. The precursors, dehydroamino acids 7 and 13 derived from 5 or 11, underwent asymmetric hydrogenations with Burk's DuPHOS Rh(I)-based catalysts to furnish α-amino acid derivatives in high stereoselectivity. The resulting amino acids 8 and 14 were converted to the β-turn mimetics 6,5-bicyclic lactams 1a-d in high yields.