Synthesis of?,?-unsaturated amino acids via ester enolate Claisen rearrangement of chelated allylic esters

Abstract

Deprotonation ofN-protected amino acid allylic esters with LDA at -78°C and subsequent addition of a metal salt presumably results in the formation of a chelated metal enolate which undergoes Claisen rearrangement upon warming up to room temperature, giving rise to unsaturated amino acid. Many different metal salts can be used for chelation, but in general the best results are obtained with zinc chloride. Due to the fixed enolate geometry, as a result of chelate formation, and a strong preference for thechair like transition state, the rearrangement proceeds with a high degree of diastereoselectivity. This methodology can be applied to acyclic as well as to cyclic substrates, and even to peptides, and allows for the synthesis of amino acids containing quaternary carbon centers.