Construction of an All-Carbon Quaternary Stereocenter by the Peptide-Catalyzed Asymmetric Michael Addition of Nitromethane to β-Disubstituted α,β-Unsaturated Aldehydes

摘要

Recently, considerable attention has been devoted to the synthesis of chiral γ-amino acid derivatives because of their biological activity in relation to γ-aminobutyric acid (GABA), a major inhibitory neurotransmitter in central nervous system. γ-Arnino acids are also of great value as non-proteinogenic amino acid components involved in biologically active short peptides such as pepstatin,' hapalosin, and dolastatin 10. Among the diverse structural variants of chiral γ-amino acids, those with a substitueht at the p-position are an important class of pharmaceuticals, which includes baclofen, pregabalin, and phenibut. ' Whereas a variety of methods have been developed for the synthesis of chiral β-monosubstituted γ-amino acids, there are only limited examples for the preparation of β-disubstituted derivatives. Furthermore, the reported reaction scope is confined to those having two alkyl groups on the β-carbon of γ-amino acids, and catalytic enantioselective construction of an all-carbqn-sub-stituted quaternary stereocenter at the β-position has not yet been achieved.