Carbenylative Buchwald-Hartwig Coupling of Aryl Halides, N-Tosylhydrazones, and Anilines

A Pd/Cu cocatalyzed synthesis of N-benzhydryl amines from aryl halides (electrophiles), N-tosylhydrazones (carbene equivalents), and anilines (nucleophiles) has been developed. The reaction operates under mild conditions and exhibits broad substrate scope and excellent functional group tolerance. The synthetic utility of this approach is highlighted by the concise preparation of various drug molecules and their analogues, as well as its integration into downstream derivatizations. The essential role of Cu complexes is unusual for Pd-catalyzed C–N cross-coupling reactions, which usually do not require a cocatalyst for ligand exchange. We propose that this dual catalysis strategy is necessary to control the timing of Pd amido complex formation.