Simplifying the Synthesis of Nonproteinogenic Amino Acids via Palladium-Catalyzed δ-Methyl C–H Olefination of Aliphatic Amines and Amino Acids

Abstract

Transition metal-catalyzed directing group assisted C− H functionalizations provide a straightforward access to a wide variety of nonproteinogenic amino acids. While altering the side chain of an existing natural amino acids is one way, introducing a functional group to an aliphatic amine to synthesize versatile unnatural amino acids is another exciting avenue. In this work, we explore both the possibilities by the palladium-catalyzed δ-C(sp 3 )−H olefination of aliphatic amines and amino acids. A diverse substrate scope including sequential difunctionalizations followed by post synthetic transformations were achieved to understand the applicability of the current protocol. An indepth mechanistic study was carried out to learn the mode of the reaction pathway.