A General Stereocontrolled Synthesis of Opines through Asymmetric Pd-Catalyzed N-Allylation of Amino Acid Esters

Article abstract of DOI:10.1002/ejoc.202100259

A stereo-divergent synthesis of natural and unnatural opines in stereochemically pure form is based on the direct palladium-catalyzed N-allylation of α-amino acid esters (up to 97 % ee or 99 : 1 d.r.) using methyl (E)-2-penten-4-yl carbonate in the presence of only 1 mol% of a catalyst, prepared in-situ from the C₂-symmetric diphosphine iPr-MediPhos and [Pd(allyl)Cl]₂. Selected target compounds (incl. a derivative of the drug enalapril) were efficiently obtained from the N-allylated intermediates by oxidative cleavage (ozonolysis) of the allylic C=C bond under temporary N-Boc-protection.