Nickel-Catalyzed Diaryl Ketone Synthesis by N–C Cleavage: Direct Negishi Cross-Coupling of Primary Amides by Site-Selective <i>N</i>,<i>N</i>‑Di-Boc Activation

A general Negishi acylation of primary amides enabled by a combination of site-selective <i>N</i>,<i>N</i>-di-Boc activation and nickel catalysis is reported for the first time. The reaction is promoted by a bench-stable, inexpensive Ni catalyst. The reaction shows excellent functional group compatibility, affording functionalized diaryl ketones by selective N–C cleavage. Most notably, this protocol represents the first amide cross-coupling by direct metal insertion of simple and readily available primary amides. The overall strategy by <i>N</i>,<i>N</i>-di-Boc activation/metal insertion is suitable for a broad range of coupling protocols via acylmetals. Mechanistic experiments suggest high reactivity of <i>N</i>,<i>N</i>-di-Boc activated 1° amides in direct amide C–N cross-couplings