Acyl and Decarbonylative Suzuki Coupling of N-Acetyl Amides: Electronic Tuning of Twisted, Acyclic Amides in Catalytic Carbon–Nitrogen Bond Cleavage

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.

Recent Advances in Acyl Suzuki Cross-Coupling

“…More recently, we have reported "mono-twisted" N-Ac-amides as highly reactive acyclic amides in acyl Suzuki cross-coupling (Scheme 23E) [81]. In this work, it was demonstrated that catalyst selection dictates an acyl or decarbonylative mechanism.…”

Recent Advances in the Metal‐Catalyzed Activation of Amide Bonds

“…[65] In 2018, Szostak and co-workers reported ap alladium-catalyzed cross-coupling reaction of N-Ph,N-acyl amides with arylboronic acids and an ickel-catalyzed decarbonylative Suzuki-Miyaura cross-coupling reactiono fN-acetyl amides with arylboronic acids through NÀCa ctivation (Scheme 37). [75] Common planar amides were converted into twisted (acyclic) amides, Scheme33. Nickel-catalyzed cross-coupling reaction of aryl halides with amidesthrough NÀCa ctivation.…”

N-Acylphthalimides: Efficient Acyl Coupling Reagents in Suzuki–Miyaura Cross-Coupling by N–C Cleavage Catalyzed by Pd–PEPPSI Precatalysts

“…To date, a wide range of amides and amide-based reagents, including the most reactive N-acyl-glutarimides [13] as well as anilides [14], N-Boc-carbamates [15], N-Ts-sulfonamides [16], N, N-di-Boc amides [17], N-acyl-saccharins [18,19], N-Ms-sulfonamides [20], N-acyl-pyrroles [21], N-Me-pyrimidines [22], N-acyl-succinimides [23][24][25], and N-Ac-amides [26] have been successfully engaged as electrophilic cross-coupling partners by N-C activation. In all examples described to date, the reactivity has been controlled by a ground-state destabilization mechanism of the amide bond [12].…”