Stereoselective synthesis of β-alkylated α-amino acids via palladium-catalyzed alkylation of unactivated methylene C(sp3)-H bonds with primary alkyl halides

J Am Chem Soc. 2013 Aug 14;135(32):12135-41. doi: 10.1021/ja406484v. Epub 2013 Aug 6.

Abstract

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 α-haloacetate and methyl iodide and applications in the stereoselective synthesis of various β-alkylated α-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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetates / chemistry
  • Alkylation
  • Amides / chemistry
  • Amino Acids / chemical synthesis*
  • Amino Acids / chemistry
  • Catalysis
  • Halogens / chemistry
  • Hydrocarbons, Iodinated / chemistry
  • Palladium / chemistry*
  • Stereoisomerism

Substances

  • Acetates
  • Amides
  • Amino Acids
  • Halogens
  • Hydrocarbons, Iodinated
  • Palladium
  • methyl iodide