An Enantioselective Approach to 4-Substituted Proline Scaffolds: Synthesis of ()-5-(-Butoxy Carbonyl)-5-Azaspiro[2.4]heptane-6-Carboxylic Acid.

A catalytic and enantioselective preparation of the ()-4-methyleneproline scaffold is described. The key reaction is a one-pot double allylic alkylation of an imine analogue of glycine in the presence of a chinchonidine-derived catalyst under phase transfer conditions. These 4-methylene substituted proline derivatives are versatile starting materials often used in medicinal chemistry.