Steric effects on the isomer equilibrium of amides N-terminal to proline can be explored with 5-alkylprolines having bulky 5-position substituents. Enantiopure 5-tert-butylprolines were thus synthesized from glutamic acid via an acylation/diastereoselective reductive amination sequence. Double deprotonation of γ-methyl N-(PhF) glutamate (2) with LiN (SiMe3) 2 and C-acylation with pivaloyl chloride provided β-keto ester 3, which upon γ-ester hydrolysis ...
