Tripeptides of the type H-D-Pro-Pro-Xaa-NH2 as catalysts for asymmetric 1,4-addition reactions: structural requirements for high catalytic efficiency.
Analysis of the structural and functional requirements within the asymmetric peptidic catalyst H-D-Pro-Pro-Asp-NH(2) led to the development of the closely related peptide H-D-Pro-Pro-Glu-NH(2) as an even more efficient catalyst for asymmetric conjugate addition reactions of aldehydes to nitroolefins. In the presence of as little as 1 mol % of H-D-Pro-Pro-Glu-NH(2), a broad range of aldehydes and nitroolefins react readily with each other. The resulting gamma-nitroaldehydes were obtained in excellent yields and stereoselectivities at room temperature. Within the structure of the peptidic catalysts, the D-Pro-Pro motif is the major contributor to the high stereoselectivities. The C-terminal amide and the spacer to the carboxylic acid in the side-chain of the C-terminal amino acid are responsible for the fine-tuning of the stereoselectivity. The peptidic catalysts not only allow for highly effective asymmetric catalysis under mild conditions, but also function in the absence of additives.
Wiesner
Markus
M
Department of Chemistry, University of Basel, St. Johanns-Ring 19, 4056 Basel, Switzerland.
Neuburger
Markus
M
Wennemers
Helma
H
D000447:Aldehydes / Q000737:chemistry*; D000595:Amino Acid Sequence; D002384:Catalysis; D018698:Glutamic Acid / Q000737:chemistry; D008968:Molecular Conformation; D009574:Nitro Compounds / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D010446:Peptide Fragments; D011392:Proline / Q000737:chemistry*; D013237:Stereoisomerism
D000447:Aldehydes; D009574:Nitro Compounds; D009842:Oligopeptides; D010446:Peptide Fragments; D018698:Glutamic Acid; D011392:Proline