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Protecting-Group-Free Amidation of Amino Acids using Lewis Acid Catalysts
Marco T Sabatini1, Valerija Karaluka1, Rachel M Lanigan1
1Department of Chemistry, University College London, Christopher Ingold Laboratories, 20 Gordon Street, London, WC1H 0AJ, UK.
Abstract:
Amidation of unprotected amino acids has been investigated using a variety of 'classical" coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions.
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