Stereoselective Synthesis of β-Alkylated α-Amino Acids via Palladium-Catalyzed Alkylation of Unactivated Methylene C(sp3)-H Bonds with Primary Alkyl Halides

We report a new set of reactions based on the Pd-catalyzed alkylation of methylene C(sp(3))-H bonds of aliphatic quinolyl carboxamides with alpha-haloacetate and methyl iodide and applications in the stereoselective synthesis of various beta-alkylated alpha-amino acids. These reactions represent the first generally applicable method for the catalytic alkylation of unconstrained and unactivated methylene C-H bonds with high synthetic relevance. When applied with simple isotope-enriched reagents, they also provide a convenient and powerful means to site-selectively incorporate isotopes into the carbon scaffolds of amino acid compounds.