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

An amine-catalyzed reaction has been discovered that couples α-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 (Pal) residue as an efficient asymmetric catalyst for enantioselective coupling reactions. The unique allenic products are obtained with enantiomer ratios of up to ∼95:5 (up to >98:2 following recrystallization).