N-Pyrrolidine-based α/β-peptides incorporating ABOC, a constrained bicyclic β-amino acid, for asymmetric aldol reaction catalysis

Article abstract of DOI:10.1016/j.tet.2016.02.027

A series of N-pyrrolidine-based α,β-peptide catalysts incorporating a constrained 2-aminobicyclo[2.2.2]octane carboxylic acid (ABOC) residue were synthesized and evaluated in the asymmetric aldol reaction from acetone and some p-substituted benzaldehydes. Their catalytic properties were shown to be highly dependent on the amino acid sequences and on the absolute configuration of the ABOC residue that played a determinant role. Among the peptides tested, the heterochiral tripeptide H-Pro-(R)-ABOC-Asp-OCH₃ 13, that adopts a turn conformation in the solid state, proved to be the most efficient catalyst affording β-hydroxy ketones in high yields and good enantioselectivities (up to 87%).