Pyridylalanine (Pal)-peptide catalyzed enantioselective allenoate additions to N-acyl imines proceed via an atypical "aza-Morita-Baylis-Hillman" mechanism

Org Lett. 2010 Nov 5;12(21):4800-3. doi: 10.1021/ol101947s.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Alanine / chemistry
  • Aza Compounds / chemistry*
  • Catalysis
  • Imines / chemistry*
  • Molecular Structure
  • Peptides / chemistry*
  • Pyridines / chemistry*
  • Stereoisomerism

Substances

  • Aza Compounds
  • Imines
  • Peptides
  • Pyridines
  • pyridine
  • Alanine