title: Adapting to substrate challenges: peptides as catalysts for conjugate addition reactions of aldehydes to α,β-disubstituted nitroolefins.
abstract: Conjugate addition reactions of aldehydes to α,β-disubstituted nitroolefins are important because they provide synthetically useful γ-nitroaldehydes bearing three consecutive stereogenic centers. Such reactions are challenging due to the drastically lower reactivity of α,β-disubstituted nitroolefins compared to, for example, β-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 α,β-disubstituted nitroolefins react readily with each other providing γ-nitroaldehydes in good yields and diastereoselectivities as well as excellent enantioselectivities. Chiral pyrrolidines as well as fully substituted γ-butyrolactams and γ-amino acids are easily accessible from the γ-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.
authors.affiliation: Department of Chemistry, University of Basel, St. Johanns-Ring 19, CH-4056 Basel, Switzerland.
authors.forename: Jörg
authors.initials: J
authors.lastname: Duschmalé
authors.forename: Helma
authors.initials: H
authors.lastname: Wennemers
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000475:Alkenes / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D009574:Nitro Compounds / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000447:Aldehydes; D000475:Alkenes; D009574:Nitro Compounds; D010455:Peptides