What Makes for a Good Catalytic Cycle? A Theoretical Study of the Role of an Anionic Palladium(0) Complex in the Cross-Coupling of an Aryl Halide with an Anionic Nucleophile

Abstract

The cross-coupling reaction Ar-X + Nu -f Ar-Nu + X -, catalyzed by Pd(0) complexes, was studied theoretically by means of DFT calculations; Ph-Cl was used as a substrate and HS -as the nucleophile. The studied catalysts are the pristine Pd(0) complexes Pd 0 -(PR 3 ) 2 (1 R ; R ) H, vinyl, Ph), the corresponding anionic complexes Pd 0 (PR 3 ) 2 Cl -(1 R,Cl ), proposed by two of us (C.A. and A.J.), and the chelated complexes with diphosphine ligands PH 2 (CH 2 ) n PH 2 (2 H,n ; n ) 2-6). The full catalytic cycles were studied for 1 H , 1 H,Cl , 2 H,3 , and 2 H,6 . The efficiency of a catalytic cycle under turnover conditions is determined by the energetic span, the energy difference between the summit and trough of the cycle; the smaller the energy span, the higher the turnover frequency of the cycle. In this sense, the best Pd(0) catalyst was found to be the anionic 1 H,Cl species. The DFT analysis shows that the anionic catalyst so formed is superior to the pristine species, since it "flattens" the energy landscape of the catalytic cycle by stabilizing the transition state for oxidative addition, the summit of the cycle, and at the same time "destabilizing" the nucleophilic addition product, the deepest point of the cycle. This is precisely the role deduced initially from experimental evidence. Thus, during substrate activation, the Cl -ion keeps a small P-Pd-P angle, which is a prerequisite for a low activation barrier to oxidative addition. During nucleophilic substitution, the Cl -additive is displaced by the nucleophile, and hence the stabilizing advantage is lost, thereby raising the substitution product complex relative to the onset of the reactants. After product release, Cl -returns to regenerate the anionic catalyst, Pd 0 (PR 3 ) 2 Cl -, which in turn binds the substrate and prevents its diffusive escape, thereby ensuring an efficient restart of the cycle.

Halide-Enhanced Catalytic Activity of Palladium Nanoparticles Comes at the Expense of Catalyst Recovery

“…Aerobic oxidation followed by hydrolysis then reforms the Pd 2+ species. In Scheme 3, we have shown the catalytic cycle involving palladium dihalide species, but these may also be monohalide species, in line with literature reports [4][5][6] of such monoanionic species playing a key role in cross-coupling reactions. The formation of HOOB(OH) 2 , which goes on the form H 2 O 2 , is supported by the observed formation of phenol as a side product in the reaction.…”

“…This rate-retarding effect has been attributed to the formation of unreactive halo-palladium complexes [3]. The effects of added chloride can be more complicated [4,5] including as a result of leveling the energy profile around the catalytic cycle [6]. The ability to study the transmetallation step in the absence of the halide-releasing oxidative addition step thus offers opportunities for improved mechanistic understanding.…”

Insights into Sonogashira Cross‐Coupling by High‐Throughput Kinetics and Descriptor Modeling

“…Despite this excellent correlation, one should remember that activation parameters can vary, depending on the ring size of the chelating phosphines. [92] Nonetheless, this is strong evidence for the oxidative addition being the rate-limiting step in the Sonogashira coupling of aryl chlorides.…”

A theoretical investigation of the oxidation states of palladium complexes and their role in the carbonylation reaction

“…Kinetic studies carried out by Amatore [11] and coworkers for Pd(OAc) 2 /PPh 3 mixtures show that the rate-limiting step is an intramolecular process that affords a Pd(0) species, which is unstable in the absence of a ligand excess. This species is characterized by two different 13 P NMR signals and reacts with iodobenzene. These authors have carried out additive oxidation of iodobenzene [12] to Pd(0) complexes together with cyclic voltammetry experiments (that allow to ascertain the amount of Pd(0) species) to establish the oxidation state (i.e.…”

“…This study should outline in details the mechanistic changes with respect to the Pd(II)-based carbonylation of a similar system and permits the understanding of the effect of the oxidation state change [53]. Pd(0) species are considered in many cases to be the active catalytic species [13,[63][64][65][66][67][68][69][70], so a systematic study comparing both oxidation states will be very insightful. It is worth to mention that here a more realistic model-system including triphenylphosphine ligands instead of simple PH 3 units (as done in previous papers) is considered.…”