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.
Bibliographical noteKAUST Repository Item: Exported on 2023-07-24
Acknowledgements: We thank Rutgers University, the NSF (CAREER CHE-1650766), and the NIH (R35GM133326) for generous financial support. Supplement funding for this project was provided by the Rutgers University – Newark Chancellor’s Research Office. The 500 MHz spectrometer used in this study was supported by the NSF-MRI grant (CHE-1229030). A.P. is a Serra Húnter Fellow and ICREA Academia Prize 2019, and thanks the Spanish Ministerio de Ciencia e Innovación for a project PID2021-127423NB-I00 and the Generalitat de Catalunya for project 2021SGR623. S.P.N. thanks the BOF research fund, as well as the SBO projects CO2perate and D2M, for financial support. C.S.J.C. (G0C5423N) and S.P.N. (G0A6823N) thank the FWO for support. Y.L. thanks the CSC for a Ph.D. fellowship.
ASJC Scopus subject areas
- Organic Chemistry