Pyridylalanine (Pal)-Peptide Catalyzed Enantioselective Allenoate Additions to N-Acyl Imines

An amine-catalyzed reaction has been discovered that couples a-allenic esters with N-acyl imines in good to excellent yields (up to 88%). Extension of this methodology from the study of achiral pyridine-based catalysis to chiral peptide-based scaffolds is presented. The approach culminated in the identification of a tetrameric peptide sequence containing an embedded pyridylalanine (Pat) residue as an efficient asymmetric catalyst for enantioselective coupling reactions. The unique allenic products are obtained with enantiomer ratios of up to similar to 95:5 (up to >98:2 following recrystallization).