Adapting to Substrate Challenges: Peptides as Catalysts for Conjugate Addition Reactions of Aldehydes to alpha,beta-Disubstituted Nitroolefins

作者：Duschmale Joerg; Wennemers Helma^*

来源：Chemistry - A European Journal, 2012, 18(4): 1111-1120.

DOI：10.1002/chem.201102484

• addition reactions
• asymmetric catalysis
• nitroolefins
• peptides
• proline

Conjugate addition reactions of aldehydes to a,beta-disubstituted nitroolefins are important because they provide synthetically useful ?-nitroaldehydes bearing three consecutive stereogenic centers. Such reactions are challenging due to the drastically lower reactivity of a,beta-disubstituted nitroolefins compared to, for example, beta-monosubstituted nitroolefins. The testing of a small collection of peptides of the type Pro-Pro-Xaa (Xaa=acidic amino acid) led to the identification of H-Pro-Pro-D-Gln-OH and H-Pro-Pro-Asn-OH as excellent stereoselective catalysts for this transformation. In the presence of 5 mol?% of these peptides different combinations of aldehydes and a,beta-disubstituted nitroolefins react readily with each other providing gamma-nitroaldehydes in good yields and diastereoselectivities as well as excellent enantioselectivities. Chiral pyrrolidines as well as fully substituted gamma-butyrolactams and gamma-amino acids are easily accessible from the gamma-nitroaldehydes. Mechanistic studies demonstrate that the configuration at all three stereogenic centers is induced by the peptidic catalysts. Only a minimal amount of products from homo-aldol reactions is observed demonstrating the high chemoselectivity of the peptidic catalysts.

• 出版日期2012-1