Palladium/NHC (NHC = N-Heterocyclic Carbene)-Catalyzed B-Alkyl Suzuki Cross-Coupling of Amides by Selective N-C Bond Cleavage.

A highly chemoselective, palladium-NHC (NHC = N-heterocyclic carbene)-catalyzed, direct cross-coupling between B-sp3-alkyl reagents and activated amides by N-C(O) cleavage is reported. Palladium-NHC precatalysts promote chemoselective alkylations of amides that are inaccessible by applying strong organometallic reagents. Various amides, including challenging primary amides after direct and site-selective N, N-di-Boc activation, are compatible with this method. The potential of this mild protocol is demonstrated in sequential C(sp2)-C(sp2)/C(sp2)-C(sp3) cross-couplings deploying a di-Boc amide derived from a common primary amide bond. The method provides a rare example of air- and moisture-stable, well-defined, and highly reactive Pd-NHC precatalysts in B-alkyl-Suzuki cross-couplings.