Palladium-catalyzed Sonogashira coupling of amides: access to ynones via C–N bond cleavage

Abstract

The first palladium-catalyzed Sonogashira coupling of amides has been developed, which proceeds via a selective cleavage of the N-acylsaccharin C-N bond. Notably, the new approach employs N-acylsaccharins as coupling partners to give ynones in good to excellent yield. This protocol can be efficiently utilized in the synthesis of a broad array of ynones under low catalyst loading and Cu-free conditions.

Recent Advances in the Metal‐Catalyzed Activation of Amide Bonds

“…Zeng and co-workersdescribed a[Pd(PPh 3 ) 3 Cl 2 ]-catalyzed Sonogashirac ross-coupling reactiono fe lectronically activated Nacylsaccharins with terminal alkynes to give ynones through CÀNc leavage (Scheme 28). [66] Previously reported sterically and electronically active amides did not exhibit any reactivity in this Sonogashira cross-couplingr eaction. Moreover,t he use of Weinreb amides (N-OMe,N-Me) and distorted cyclic imides were also unsuccessful in this transformation.T herefore, the authors utilized the unique structural properties of N-acylsaccharin, N-benzoylsacchrin, and other derivatives.…”

Decarbonylative Phosphorylation of Amides by Palladium and Nickel Catalysis: The Hirao Cross‐Coupling of Amide Derivatives

“…[28,29] Theo bserved selectivity of the amide coupling in the presence of ArÀCl or ArÀ CN bonds is consistent with the facility of metal insertion into the resonance destabilized amides. [26][27][28][29][30][31][32][33] Notably,t his transformation is tolerant to functional groups that are prone to metal-catalyzed CÀOc leavage, such as aryl ester and aryl sulfonate (Scheme 2), highlighting the potential to achieve high selectivity using amide electrophiles under orthogonal cross-coupling conditions.…”

“…Amide bond cross-coupling has recently emerged as apowerful tool for the construction of organic molecules. [21][22][23][24] As amply demonstrated [25][26][27][28][29][30][31][32][33] aunique amide bond activation mode utilizing amide bond n N to p* C=O resonance destabilization [34] can be successfully deployed to accomplish direct metal insertion into the typically inert N À C(O) moiety. [21] To date,the ability to utilize amides as precursors to form C À O, CÀN, CÀC, CÀB, and CÀHbonds with high predictability and chemoselectivity via acyl and decarbonylative pathways has been demonstrated.…”

Acyl Sonogashira Cross-Coupling: State of the Art and Application to the Synthesis of Heterocyclic Compounds

“…Very recently Zeng and co-workers [35] described the first example of acyl Sonogashira reactions between a terminal acetylene and an amide as a coupling partner instead of classic acid chloride. The reactions required 1 mol % PdCl 2 (PPh 3 ) 2 and were performed under copper free conditions.…”

“…The authors tested electronically and sterically different amides, but only N-benzoylsaccarine was found to be suitable ( Figure 2), affording alkynones in good to excellent yields (51%-98%). Very recently Zeng and co-workers [35] described the first example of acyl Sonogashira reactions between a terminal acetylene and an amide as a coupling partner instead of classic acid chloride. The reactions required 1 mol % PdCl2(PPh3)2 and were performed under copper free conditions.…”