Palladium-catalyzed acetoxylation of the primary γ-C(sp3)–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.
5-Methylisoxazole-3-carboxamide-Directed Palladium-Catalyzed γ-C(sp3)–H Acetoxylation and Application to the Synthesis of γ-Mercapto Amino Acids for Native Chemical Ligation
School of Biological Sciences, Nanyang Technological University, Singapore 637551
Org. Lett., 2016, 18 (11), pp 2696–2699
Publication Date (Web): May 24, 2016
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