Preparation of N-(Boc)-Allylglycine Methyl Ester Using a Zinc-Mediated, Palladium-Catalyzed Cross-Coupling Reaction

In the context of our research in peptide mimicry, we required an efficient, atom economical route to enantiomerically pure allylglycine analogues. Building on the established precedent of zinc-mediated, palladium-catalyzed crosscoupling reactions of commercially available and inexpensive tert-butyl (R)-1-(methoxycarbonyl)-2-iodoethylcarbamate, this extension employs vinyl bromide to give effective access to allylglycine in enantiomerically pure form on multi-gram scale. Negishi cross coupling of the alininyl zinc intermediate with vinyl bromide is effectively mediated by Pd2(dba)3 and tri-(o-tolyl)phosphine and has been examined at lower temperature to give the N-(Boc)-allylglycine methyl ester with improved yield. Keywords: N-(Boc)-Allylglycine methyl ester; tert-Butyl (S)-1-(methoxycarbonyl)but-3-enylcarbamate; tert-Butyl (R)-1-(methoxycarbonyl)-2-iodoethylcarbamate; Dichloromethane; Triphenylphosphine; Zinc-mediated palladium-catalyzed cross-coupling reaction