We report the Pd-catalyzed acyl and the Ni-catalyzed biaryl Suzuki–Miyaura cross-coupling of N-acetyl-amides with arylboronic acids by selective N–C(O) cleavage. Activation of the amide bond by N-acylation provides electronically destabilized,… Click to show full abstract
We report the Pd-catalyzed acyl and the Ni-catalyzed biaryl Suzuki–Miyaura cross-coupling of N-acetyl-amides with arylboronic acids by selective N–C(O) cleavage. Activation of the amide bond by N-acylation provides electronically destabilized, acyclic, nonplanar amide, which readily undergoes cross-coupling with a wide range of boronic acids to produce biaryl ketones or biaryls in a highly efficient manner. Most crucially, the presented results introduce N-acetyl-amides as reactive acyclic amides in the emerging manifold of transition-metal-catalyzed amide cross-coupling. The scope and origin of high selectivity are discussed. Mechanistic studies point to remodeling of amidic resonance and amide bond twist as selectivity determining features in a unified strategy for cross-coupling of acyclic amides. Structural studies, mechanistic investigations as well as beneficial effects of the N-acyl substitution on cross-coupling of amides are reported.
               
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