5-Methylisoxazole-3-carboxamide-Directed Palladium-Catalyzed γ-C(sp(3))-H Acetoxylation and Application to the Synthesis of γ-Mercapto Amino Acids for Native Chemical Ligation.

Palladium-catalyzed acetoxylation of the primary γ-C(sp(3))-H bonds in the amino acids Val, Thr, and Ile was achieved using a newly discovered 5-methylisoxazole-3-carboxamide directing group. The γ-acetoxylated α-amino acid derivatives could be easily converted to γ-mercapto amino acids, which are useful for native chemical ligation (NCL). The first application of NCL at isoleucine in the semisynthesis of a Xenopus histone H3 protein was also demonstrated.