Premium
Adapting to Substrate Challenges: Peptides as Catalysts for Conjugate Addition Reactions of Aldehydes to α,β‐Disubstituted Nitroolefins
Author(s) -
Duschmalé Jörg,
Wennemers Helma
Publication year - 2012
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201102484
Subject(s) - stereocenter , conjugate , chemoselectivity , catalysis , chemistry , aldol reaction , stereoselectivity , reactivity (psychology) , combinatorial chemistry , amino acid , organic chemistry , substrate (aquarium) , enantioselective synthesis , biochemistry , medicine , mathematical analysis , oceanography , alternative medicine , mathematics , pathology , geology
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.