Chiral Pyridine-Catalyzed HN₃-Addition to Ketenes

Significance

Catalytic enantioselective addition of hydrazoic acid to unsymmetric ketenes 1 followed by thermally induced Curtius rearrangement of initially formed acid azides 4 gives rise to optically enriched protected amines of the general form 3. Moderate steric congestion and electron-rich aromatic groups on the ketene proved beneficial. Unhindered phenyl ethyl ketene furnished almost racemic product. Catalyst (+)-2, a planar-chiral pyridine derivative, structurally related to the well-established DMAP motifs (see review below), was found to effectively mediate the addition step. According to their mechanistic proposal, protonated (+)-2 acts as a chiral Brønsted acid achieving the enantioselective protonation of achiral enolate 5.