Pd-PEPPSI: Pd-NHC Precatalyst for Suzuki-Miyaura Cross-Coupling Reactions of Amides

Pd-PEPPSI-IPr serves as a highly reactive precatalyst in the direct Suzuki-Miyaura cross-coupling of amides. An array of amides can be cross-coupled with a range of arylboronic acids in very good yields using a single, operationally simple protocol. The studies described represent the first use of versatile PEPPSI type of Pd-NHC complexes as catalysts for the cross-coupling of amides by N-C bond activation. The method is user-friendly, since it employs a commercially available, air- and moisture-stable Pd-PEPPSI-IPr complex. Pd-PEPPSI-IPr provides a significant improvement over all current Pd/phosphane catalysts for amide N-C bond activation. Mechanistic studies provide insight into the reaction rates of Pd-NHC-catalyzed cross-coupling of different amides, with Pd-PEPPSI-IPr being particularly effective for the cross-coupling of N-Boc carbamates under the developed conditions.