Direct Evidence for Competitive C-H Activation by a Well-Defined Silver XPhos Complex in Palladium-Catalyzed C-H Functionalization

Increasing evidence indicates that silver salts can play a role in the C-H activation step of palladium-catalyzed C-H functionalization. Here we isolate a silver(I) complex by C-H bond activation and demonstrate its catalytic competence for C-H functionalization. We demonstrate how silver carbonate, a common but highly insoluble additive, reacts with pentafluorobenzene in the presence of a bulky phosphine, XPhos, to form the C-H bond activation product Ag(C6F5)(XPhos). By isolating and fully characterizing this complex and the related carbonate and iodide complexes, [Ag(XPhos)]2(μ-κ2,κ2-CO3) and [AgI(XPhos)]2, we show how well-defined Ag(I) complexes can operate in conjunction with palladium complexes to achieve C-H functionalization even at ambient temperature. Reactions are tested against the standard cross-coupling of C6F5H with 4-iodotoluene, catalyzed by palladium acetate at 60 °C in the presence of silver carbonate and Xphos. Key observations are that (a) PdI(C6H5)(XPhos) reacts stoichiometrically with Ag(C6F5)(XPhos) to form Ph-C6F5 instantly at room temperature; (b) catalytic cross coupling can be achieved using 5% Ag(C6F5)(XPhos) as the sole silver source; and (c) palladium acetate (typical precatalyst) can be replaced for catalytic cross coupling by the expected oxidative addition compound PdI(C6H5)(XPhos). These investigations lead to a catalytic cycle in which Ag(I) plays the C-H bond activation role and palladium plays the coupling role. Moreover, we show how the phosphine can be exchanged between silver complexes, ensuring that it is recycled even though silver carbonate is consumed during catalytic cross-coupling

Opening a Pandora’s Flask on a Prototype Catalytic Direct Arylation Reaction of Pentafluorobenzene : The Ag2CO3/Pd(OAc)2/PPh3 System

Direct C-H functionalization reactions have opened new avenues in catalysis, removing the need for prefunctionalization of at least one of the substrates. Although C-H functionalization catalyzed by palladium complexes in the presence of a base is generally considered to proceed by the CMD/AMLA-6 mechanism, recent research has shown that silver(I) salts, frequently used as bases, can function as C-H bond activators instead of (or in addition to) palladium(II). In this study, we examine the coupling of pentafluorobenzene 1 to 4-iodotoluene 2a (and its analogues) to form 4-(pentafluorophenyl)toluene 3a catalyzed by palladium(II) acetate with the commonplace PPh3 ligand, silver carbonate as base, and DMF as solvent. By studying the reaction of 1 with Ag2CO3/PPh3 and with isolated silver (triphenylphosphine) carbonate complexes, we show the formation of C-H activation products containing the Ag(C6F5)(PPh3)n unit. However, analysis is complicated by the lability of the Ag-PPh3 bond and the presence of multiple species in the solution. The speciation of palladium(II) is investigated by high-resolution-MAS NMR (chosen for its suitability for suspensions) with a substoichiometric catalyst, demonstrating the formation of an equilibrium mixture of Pd(Ar)(κ1-OAc)(PPh3)2 and [Pd(Ar)(μ-OAc)(PPh3)]2 as resting states (Ar = Ph, 4-tolyl). These two complexes react stoichiometrically with 1 to form coupling products. The catalytic reaction kinetics is investigated by in situ IR spectroscopy revealing a two-term rate law and dependence on [Pdtot/nPPh3]0.5 consistent with the dissociation of an off-cycle palladium dimer. The first term is independent of [1], whereas the second term is first order in [1]. The observed rates are very similar with Pd(PPh3)4, Pd(Ph)(κ1-OAc)(PPh3)2, and [Pd(Ph)(μ-OAc)(PPh3)]2 catalysts. The kinetic isotope effect varied significantly according to conditions. The multiple speciation of both AgI and PdII acts as a warning against specifying the catalytic cycles in detail. Moreover, the rapid dynamic interconversion of AgI species creates a level of complexity that has not been appreciated previously

The iron-catalysed Suzuki coupling of aryl chlorides

The very widely exploited Suzuki biaryl coupling reaction typically requires catalysts based on palladium, but there is an increasing desire to replace this metal with a more sustainable, less expensive alternative, with catalysts based on iron being a particularly attractive target. Here we show that a simple iron-based catalyst with an N-heterocyclic carbene ligand can be used to excellent effect in the Suzuki biaryl coupling of aryl chloride substrates with aryl boronic esters activated by an organolithium reagent. Mechanistic studies suggest the possible involvement of Fe(I) as the lowest oxidation state on the catalytic manifold and show that the challenging step is not activation of the aryl chloride substrate, but rather the transmetallation step. These findings are likely to lead to a renaissance of iron-catalysed carbon–carbon bond-forming transformations with soft nucleophilic coupling partners

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)

Comment on room temperature colossal superparamagnetic order in aminoferrocene–graphene molecular magnets

A re-examination of recent claims of room temperature colossal superparamagnetic behaviour of a material based on graphene oxide (GO) modified by well-known aminoferrocene has been undertaken. The synthetic claims of the well-known and commercially available aminoferrocene do not bear scrutiny, neither from new data obtained nor from the data presented in the original paper. The density functional theory-derived model developed to describe the apparent magnetic properties of the material is based on an artefact that occurs through poor choice of the starting model for the GO

The iron-catalysed Suzuki coupling of aryl chlorides

A simple iron-based catalyst with an N-heterocyclic carbene ligand can be used to excellent effect in the previously unknown Suzuki biaryl coupling of aryl chloride substrates with aryl boronic esters activated by an organolithium reagent. Mechanistic studies suggest the possible involvement of Fe(I) as the lowest oxidation state on the catalytic manifold and show that the challenging step is not activation of the aryl chloride substrate, but rather the transmetallation step. These findings are likely to pave the way for a renaissance of iron-catalysed carbon-carbon bond-forming transformations with ‘soft’ nucleophilic coupling partners

Manganese-Mediated C–H Bond Activation of Fluorinated Aromatics and the ortho-Fluorine Effect : Kinetic Analysis by In Situ Infrared Spectroscopic Analysis and Time-Resolved Methods

Insights into the factors controlling the site selectivity of transition metal-catalyzed C–H bond functionalization reactions are vital to their successful implementation in the synthesis of complex target molecules. The introduction of fluorine atoms into substrates has the potential to deliver this selectivity. In this study, we employ spectroscopic and computational methods to demonstrate how the “ortho-fluorine effect” influences the kinetic and thermodynamic control of C–H bond activation in manganese(I)-mediated reactions. The C–H bond activation of fluorinated N,N-dimethylbenzylamines and fluorinated 2-phenylpyridines by benzyl manganese(I) pentacarbonyl BnMn(CO)5 leads to the formation of cyclomanganated tetracarbonyl complexes (2a–b and 4a–e), which all exhibit C–H bond activation ortho-to-fluorine. Corroboration of the experimental findings with density functional theory methods confirms that a kinetically controlled irreversible σ-complex-assisted metathesis mechanism is operative in these reactions. The addition of benzoic acid results in a mechanistic switch, so that cyclomanganation proceeds through a reversible AMLA-6 mechanism (kinetically and thermodynamically controlled). These stoichiometric findings are critical to catalysis, particularly subsequent insertion of a suitable acceptor substrate into the C–Mn bond of the regioisomeric cyclomanganated tetracarbonyl complex intermediates. The employment of time-resolved infrared spectroscopic analysis allowed for correlation of the rates of terminal acetylene insertion into the C–Mn bond with the relative thermodynamic stability of the regioisomeric complexes. Thus, more stable manganacycles, imparted by an ortho-fluorine substituent, exhibit a slower rate of terminal acetylene insertion, whereas a para-fluorine atom accelerates this step. A critical factor in governing C–H bond site selectivity under catalytic conditions is the generation of the regioisomeric cyclomanganated intermediates, rather than their subsequent reactivity toward alkyne insertion