Palladium(0)-catalyzed regioselective synthesis of α-dehydro-β-amino esters from amines and allyl acetates: synthesis of a α-dehydro-β-amino acid derived cyclic peptide as a constrained β-turn mimic

Abstract

Acetates derived from the adducts of the Baylis-Hillman reaction can be reacted in a regioselective manner with amines in the presence of palladium(0) catalyst to afford a-dehydro-β-amino esters (2 and 3) in good yields. The regioselectivity of the reaction can be controlled by temperature and reaction medium leading to the synthesis of regioisomers 2 or 3. The a-dehydro-β-amino acid 3 is a turn inducer, and the dipeptides 6 derived from it show the presence of an eight-membered intramolecular hydrogen bond. Also, cobalt(II) chloride catalyzes the cleavage of epoxy peptides with α-dehydro-β-amino acid derivative 3b to afford the corresponding dipeptide derivatives 8, which exhibit an intramolecular hydrogen bond and thus mimic a β-turn. This intramolecular hydrogen bonding preorganizes the corresponding diallylated peptide 8c for cyclization via ring-closing metathesis to afford the cyclic peptide 9 as a constrained mimic of a β-turn.