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-NH2 led to the development of the closely related peptide H-d-Pro- Pro-Glu-NH2 as an even more efficient catalyst for asymmetric conjugate addi- tion reactions of aldehydes to nitroolefins. In the presence of as little as 1 mol % of H-d-Pro-Pro-Glu-NH2, a broad range of aldehydes and nitroolefins react readily with each other. The resulting g-nitroaldehydes were ob- tained in excellent yields and stereose- lectivities at room temperature. Within the structure of the peptidic catalysts, the d-Pro-Pro motif is the major con- tributor 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 re- sponsible for the fine-tuning of the stereoselectivity. The peptidic catalysts not only allow for highly effective asymmetric catalysis under mild condi- tions, but also function in the absence of additives.