Asymmetric Formation of Allylic Amines with N-Substituted Quaternary Stereocenters by Pd~(II)-Cataryzed Aza-Claisen Rearrangements

摘要

Enantiomerically pure allylic amines are valuable building blocks, as they possess two highly versatile functional groups. Two widely used methods for their preparation are the transition-metal-catalyzed allylic substitution and the aza-Claisen rearrangement of trihaloacetimidates (Overman rearrangement). A longstanding problem is the catalytic enantioselective formation of quaternary stereocenters by either of these methodologies. Since quaternary carbon atoms bearing a nitrogen substituent are a widespread structural motif for bioactive natural and non-natural compounds, the asymmetric construction of those stereocenters by means of asymmetric catalysis is an important challenge. Enantiopure allylic amines possessing a quaternary N-substituted stereo-center are particularly attractive for the synthesis of quaternary amino acids, which are important targets owing to their ability to induce helical peptide structures and owing to the fact that peptides incorporating quaternary amino acid residues possess enhanced stability toward proteases.