Palladium-catalyzed Suzuki-Miyaura coupling of amides by carbon-nitrogen cleavage: General strategy for amide N-C bond activation

Guangrong Meng, Michal Szostak

Research output: Contribution to journalArticlepeer-review

111 Scopus citations

Abstract

The first palladium-catalyzed Suzuki-Miyaura cross-coupling of amides with boronic acids for the synthesis of ketones by sterically-controlled N-C bond activation is reported. The transformation is characterized by operational simplicity using bench-stable, commercial reagents and catalysts, and a broad substrate scope, including substrates with electron-donating and withdrawing groups on both coupling partners, steric-hindrance, heterocycles, halides, esters and ketones. The scope and limitations are presented in the synthesis of >60 functionalized ketones. Mechanistic studies provide insight into the catalytic cycle of the cross-coupling, including the first experimental evidence for Pd insertion into the amide N-C bond. The synthetic utility is showcased by a gram-scale cross-coupling and cross-coupling at room temperature. Most importantly, this process provides a blueprint for the development of a plethora of metal catalyzed reactions of typically inert amide bonds via acyl-metal intermediates. A unified strategy for amide bond activation to enable metal insertion into N-C amide bond is outlined (Scheme 1).

Original languageEnglish (US)
Pages (from-to)5690-5707
Number of pages18
JournalOrganic and Biomolecular Chemistry
Volume14
Issue number24
DOIs
StatePublished - Jan 1 2016

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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