Brønsted Acid Catalyzed Enantioselective Indole Aza-Claisen Rearrangement Mediated by an Arene CH–O Interaction

Although the aromatic aza-Claisen
rearrangement is a general strategy
for accessing substituted aromatic amines, there are no highly enantioselective
examples of this process. We report the first Brønsted acid catalyzed
enantioselective indole aza-Claisen rearrangement for the synthesis
of chiral 3-amino-2-substituted indoles. We present evidence for an
arene CH–O interaction as a source of activation and stereoinduction,
which is an unprecedented phenomenon in enantioselective Brønsted
acid catalysis. The products of this reaction can be transformed into
3-aminooxindoles, which are prevalent in many biologically active
small molecules.