Exploring the pivotal role of silver(I) additives in palladium-catalyzed NH2-directed C(sp3)-H arylation reactions

Combined theoretical and experimental studies have explained the mechanism of Pd-catalyzed delta-C(sp(3))-H arylation of primary amines. Instead of the monomeric Pd mechanism, our research unveils that all steps including C-H activation, oxidative addition, and reductive elimination take place via the heterodimeric Pd-Ag intermediates and transition states. Experimentally, the active heterodimeric Pd-Ag species were detected by mass spectrometry, which further confirms the proposed heterodimeric mechanism. Insight gained through this study reveals the synergistic manner of palladium catalysis and silver(I) additives in native NH2-directed C-H activation and C-C coupling reactions. (C) 2021 Published by Elsevier B.V. on behalf of Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences.

Automated summary

The mechanism of Pd-catalyzed delta-C(sp(3))-H arylation of primary amines was explained through combined theoretical and experimental studies. It was found that all steps occur via heterodimeric Pd-Ag intermediates and transition states, instead of the monomeric Pd mechanism. Experimental detection of active heterodimeric Pd-Ag species confirmed the proposed mechanism.