Stereoselective syntheses of tri- and tetrapeptide analogues by dynamic resolution of α-halo amides in nucleophilic substitution

Dynamic resolution of α-bromo and α-chloro acetamides in nucleophilic substitution with amine nucleophiles in the presence of TBAI has been investigated for stereoselective syntheses of tri- and tetrapeptide analogues. Mechanistic investigations suggest that primary pathway of the asymmetric induction is a dynamic kinetic resolution and real intermediate for the substitution is α-iodo acetamides. Also, application of this mild and simple methodology to stereoselective preparations of N-carboxyalkyl, N-aminoalkyl and N-hydroxyalkyl peptide analogues is demonstrated.