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.