Investigation of the Role of Ag salts in Pd-Catalysed Direct Arylation Reactions

Ag(I) salts are common additives in Pd-catalysed C–H functionalization reactions resulting in enhanced rates and yields compared to other metal salts. This was largely attributed to the ability of Ag(I) to act as halide scavengers. However, recent evidence has shown that Ag(I) salts can mediate the C–H bond activation step within reactions (Chapter 1). This thesis details the investigation of the role of Ag(I) salt in the C–H direct arylation reaction of iodoarenes with fluoroarenes catalysed by Pd complexes in the presence of phosphine ligands. The stability of the Ag–P bond was determined by the choice of ligand.
Reaction of Ag2CO3 with C6F5H and PPh3 resulted in the formation of the an AgC6F5(PPh3)n complex. The Ag–PPh3 bond was highly labile at room-temperature, thus no 107Ag/109Ag coupling information could be determined by NMR spectroscopy due to rapid phosphine-exchange, making it problematic for mechanistic investigation. Analysis by low-temperature NMR spectroscopy revealed complex speciation due to phosphine-exchange and binding modes with carbonate ligand (Chapter 2).
When the ligand was changed to Xphos, several reaction products could be isolated and characterised as single species in solution. Ag-intermediates were readily identified in solution by NMR spectroscopy, as the NMR active 107Ag and 109Ag provided diagnostic Ag–X coupling patterns. Key observations: a) Ag2CO3 and Xphos react with C6F5H to form the C–H bond activation product Ag(C6F5)(XPhos), b) cross-coupling reaction between Ag(C6F5)(XPhos) and PdI(Ph)(XPhos) produced Ph-C6F5 at room-temperature. c) successful cross-coupling was accomplished using catalytic amounts of Ag salts as the sole silver source. A Pd/Ag co-catalytic mechanism was proposed wherein Ag mediates C–H bond activation and Pd performs cross-coupling (Chapter 3).
Further reaction optimisation was conducted and the haloarene and fluoroarene scope was explored. Strong dependence on the dialkylbiarylphosphine was noted, with Xphos being the optimal ligand (Chapter 4).