Forming All-Carbon Quaternary Stereocenters by Organocatalytic Aminomethylation: Concise Access to β2,2 -Amino Acids

Abstract

The asymmetric synthesis of β^2,2 -amino acids remains a formidable challenge in organic synthesis. Here a novel organocatalytic enantioselective aminomethylation of ketenes with stable and readily available N,O-acetals is reported, providing β^2,2 -amino esters bearing an all-carbon quaternary stereogenic center in high enantiomeric ratios with a catalytic amount of chiral phosphoric acid. Typically, this transformation probably proceeds through an asymmetric counter-anion-directed catalysis. As a result, a concise, practical, and atom-economic protocol toward rapidly access to β^2,2 -amino acids has been developed.

Keywords: N,O-acetals; amino acids; ketenes; organocatalysis; phosphoric acid.