Suzuki–Miyaura Cross-Coupling of Amides by N–C Cleavage Mediated by Air-Stable, Well-Defined [Pd(NHC)(sulfide)Cl2] Catalysts: Reaction Development, Scope, and Mechanism

Shiyi Yang, Xiang Yu, Yaxu Liu, Michele Tomasini, Lucia Caporaso, Albert Poater, Luigi Cavallo, Catherine S. J. Cazin, Steven P. Nolan, Michal Szostak

Research output: Contribution to journalArticlepeer-review

Abstract

The Suzuki–Miyaura cross-coupling of amides by selective N–C acyl bond cleavage represents a powerful tool for constructing biaryl ketones from historically inert amide bonds. These amide bond activation reactions hinge upon efficient oxidative addition of the N–C acyl bond to Pd(0). However, in contrast to the well-researched activation of aryl halides by C(sp2)–X oxidative addition, very few studies on the mechanism of C(acyl)–N bond oxidative addition and catalyst effect have been reported. Herein, we report a study on [Pd(NHC)(sulfide)Cl2] catalysts in amide N–C bond activation. These readily prepared, well-defined, air- and moisture-stable Pd(II)–NHC catalysts feature SMe2 (DMS = dimethylsulfide) or S(CH2CH2)2 (THT = tetrahydrothiophene) as ancillary ligands. The reaction development, kinetic studies, and reaction scope are presented. Extensive DFT studies were conducted to gain insight into the mechanism of C(acyl)–N bond oxidative addition and catalyst activation. We expect that [Pd(NHC)(sulfide)Cl2] precatalysts featuring sulfides as well-defined, readily accessible ancillary ligands will find application in C(acyl)–X bond activation in organic synthesis and catalysis.
Original languageEnglish (US)
JournalThe Journal of Organic Chemistry
DOIs
StatePublished - Jul 19 2023

ASJC Scopus subject areas

  • Organic Chemistry

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