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.
Saunders
Lindsey B
LB
Department of Chemistry, Yale University, P.O. Box 208107, New Haven, Connecticut 06520, United States.
Cowen
Bryan J
BJ
Miller
Scott J
SJ
D000409:Alanine / Q000737:chemistry; D001372:Aza Compounds / Q000737:chemistry*; D002384:Catalysis; D007097:Imines / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D013237:Stereoisomerism
D001372:Aza Compounds; D007097:Imines; D010455:Peptides; D011725:Pyridines; C023666:pyridine; D000409:Alanine