Pyridylalanine (Pal)-Peptide Catalyzed Enantioselective Allenoate Additions to N-Acyl Imines Proceed via an Atypical aza-Morita-Baylis-Hillman Mechanism

Mechanistic experiments, including kinetics and hydrogen/deuterium kinetic isotope effects, reveal an atypical rate-determining step in a pyridylalanine-peptide catalyzed enantioselective coupling of allenoates and N-acyl imines. Typically, acrylates participate in both the aldehyde-based Morita-Baylis-Hillman (MBH) reaction and the imine-based variant (the aza-MBH) through similar mechanisms, with proton transfer/catalyst regeneration often rate-determining. In contrast, the title reaction exhibits kinetics wherein proton transfer is kinetically silent.