Mechanochemical Solvent‐Free Suzuki–Miyaura Cross‐Coupling of Amides via Highly Chemoselective N−C Cleavage

Abstract

Although cross-coupling reactions of amides by selective NÀ C cleavage are one of the most powerful and burgeoning areas in organic synthesis due to the ubiquity of amide bonds, the development of mechanochemical, solidstate methods remains a major challenge. Herein, we report the first mechanochemical strategy for highly chemoselective, solvent-free palladium-catalyzed cross-coupling of amides by NÀ C bond activation. The method is conducted in the absence of external heating, for short reaction time and shows excellent chemoselectivity for σ NÀ C bond activation. The reaction shows excellent functional group tolerance and can be applied to late-stage functionalization of complex APIs and sequential orthogonal cross-couplings exploiting double solventless solid-state methods. The results extend mechanochemical reaction environments to advance the chemical repertoire of NÀ C bond interconversions to solid-state environmentally friendly mechanochemical methods.

Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus

“…28 It has also been utilized to modify and enhance the activity of natural products and pharmaceuticals in late stages to achieve better yields and chemoselectivity. [29][30][31] Our research team employed SMC coupling to synthesize carboxamides and carboxylate derivatives, which were then tested for their in-vitro anti-bacterial properties against WHO-listed extremely resistant bacterial strains, aiming to identify potential therapeutic candidates. [32][33][34][35] In the present study, both the ESBL producing E. coli and MRSA were resistant to commonly used antibiotics including penicillins, cephalosporins, and beta-lactam inhibitors.…”