Nickel-catalysed Suzuki–Miyaura coupling of amides

The Suzuki–Miyaura coupling has become one of the most important and prevalent methods for the construction of C–C bonds. Although palladium catalysis has historically dominated the field, the use of nickel catalysis has become increasingly widespread because of its unique ability to cleave carbon–heteroatom bonds that are unreactive towards other transition metals. We report the first nickel-catalysed Suzuki–Miyaura coupling of amides, which proceeds by an uncommon cleavage of the amide C–N bond after N - tert -butoxycarbonyl activation. The methodology is mild, functional-group tolerant and can be strategically employed in sequential transition-metal-catalysed cross-coupling sequences to unite heterocyclic fragments. These studies demonstrate that amides, despite classically considered inert substrates, can be harnessed as synthons for use in reactions that form C–C bonds through cleavage of the C–N bond using non-precious metal catalysis. Amides have historically been considered stable and unreactive functional groups because of resonance stabilization. Here, it is demonstrated that Boc-activated amides can be employed in Suzuki–Miyaura couplings using non-precious-metal catalysis. The overall reaction is complementary to the widely employed Weinreb ketone synthesis.