Organocatalytic Asymmetric Transferhydrogenation of β-Nitroacrylates:Accessing β~2-Amino Acids

摘要

Pioneered by Seebach et al. and Gellmann et al., β-peptides recently emerged as a new class of peptidomimetics with potentially widespread biological and medicinal applications. As a consequence, the synthesis of β-amino acids has attracted considerable attention. While β~3-amino acids, which are branched in the β-position, are now commercially available with most natural substituents, the analogous β~2-amino acids, branched in the a-posi-tion, although particularly promising, are more difficult to obtain. Very recently, Gellmann et al. reported an elegant organocatalytic Mannich reaction that furnishes β-amino aldehydes in high yields and enantioselectivities. The products of this reaction can be readily converted into β~2-amino acids. Here we report an alternative approach that relies on a catalytic asymmetric Hantzsch ester mediated conjugate reduction of readily available β-nitroacrylates to the corresponding β-nitroesters, which themselves are easily converted into β~2-amino acids via hydrogenation.