Acylative Suzuki coupling of amides: acyl-nitrogen activation via synergy of independently modifiable activating groups

Abstract

A highly efficient palladium-catalyzed acylative cross-coupling of carboxylic amides with arylboronic acids has been achieved via synergistic activation of the C(acyl)-N bond by independently modifiable activating groups. Coupling of amides features not only good functional group tolerance but also modifiable reactivities to overcome steric hindrance.

Twisted Amides: From Obscurity to Broadly Useful Transition‐Metal‐Catalyzed Reactions by N−C Amide Bond Activation

“…[47][48][49] From the outset, it was clear that for the amide bond activation concept to be generally useful,m ost crucial is the identification of easily applicable, acyclict wisted amides. The classic work on twisted amides demonstratedt hat amide bond distortion could be used to separate amidicr esonance into aminoketone-like reactivity.In2015, three independent, almost simultaneous publications on the NÀCc ross-coupling were published.…”

“…[47,48,[57][58][59][60][61] The amide bond distortion in N-acyl-tert-butyl-carbamates (Boc) and N-acyl-tosylamides (Ts) has been quantitatively evaluated (Scheme 13). [47,48,[57][58][59][60][61] The amide bond distortion in N-acyl-tert-butyl-carbamates (Boc) and N-acyl-tosylamides (Ts) has been quantitatively evaluated (Scheme 13).…”

“…The cross-coupling of sterically hindered amide substrates was accomplished by using electron-withdrawing aromatic substituents at the amide nitrogen. [48] The methodology allows iterative CÀC/CÀOa mide acyl cross-couplings using the same catalyst system. [72] In the same year,t he Garg group developedt he first Ni-catalyzed Suzuki-cross-coupling of N-Boc/alkyl amides (Scheme 21).…”

Recent Advances in the Metal‐Catalyzed Activation of Amide Bonds

“…In 2015, Li and Zou reportedt he first palladium-catalyzed direct acylative Suzuki cross-coupling reaction of electronically activatedc arboxylic amides through synergistic activation of the C acyl ÀNb ond (Scheme 9). [39] Initial unsuccessfula ttempts at activating the amide bond were performed by employing a non-precious nickel catalyst. Then, after screening ar ange of catalysts, bases, ligands, and solvents, the authors found that a palladium catalystw as effectivef or this transformation.T hus, the reactiono fN-phenyl,N-tosyl-benzamide with various phenylboronic acids in the presence of [Pd(PCy 3 ) 2 Cl 2 ]( 5mol %) and PCy 3 (3 mol %) afforded the corresponding products in 35-98 %y ields.…”

Crystal structure of 3-(4-hydroxy-3-methoxyphenyl)-N-phenylpropanamide, C16H17NO3

“…These compounds serve as starting materials for synthesis of 3-arylpropanols [6], 1,3-diarylpropan-1-ones [7], quinolines [8], β-l lactams [9], 4-aryl-2-quinolinones [10] and 1-indanones [11], as well as ligands in iridium complexes [12]. Despite the wide application of these compounds only few structures have been analyzed by X-ray di raction method: the closest examples include 1,3-di-(3-phenylpropanoylamino)benzene [13], …”