ABSTRACT
Despite being one of the most important and frequently run chemical reactions, the synthesis of amide bonds is accomplished primarily by wasteful methods that proceed by stoichiometric activation of one of the starting materials. We report a nickel-catalyzed procedure that can enable diverse amides to be synthesized from abundant methyl ester starting materials, producing only volatile alcohol as a stoichiometric waste product. In contrast to acid- and base-mediated amidations, the reaction is proposed to proceed by a neutral cross coupling-type mechanism, opening up new opportunities for direct, efficient, chemoselective synthesis.
ABSTRACT
The Suzuki-Miyaura coupling is among the most important C-C bond-forming reactions available due to its reliability, chemoselectivity, and diversity. Aryl halides and pseudohalides such as iodides, bromides, and triflates are traditionally used as the electrophilic coupling partner. The expansion of the reaction scope to nontraditional electrophiles is an ongoing challenge to enable an even greater number of useful products to be made from simple starting materials. Herein, we present how an NHC-based Pd catalyst can enable Suzuki-Miyaura coupling where the C(acyl)-O bond of aryl esters takes on the role of electrophile, allowing the synthesis of various ketone-containing products. This contrasts known reactions of similar esters that provide biaryls via nickel catalysis. The underlying cause of this mechanistic divergence is investigated by DFT calculations, and the robustness of esters compared to more electrophilic acylative coupling partners is analyzed.
