Ligand Substitution

Introduction

Reactions in which coordinated ligands are replaced are known as ligand substitution reactions as shown by the following equation:

MLx + nL' ↔ MLx-n L'n + nL

Ligand substitution is often the first step and sometimes the rate determining steps in both stoichiometric and catalytic processes involving transition metal organometallic complexes. Experiments suggest that the site of a coordinative unsaturation may be the most important property of a homogenous catalyst.

The mechanism for substation in organometallic chemistry is quite similar to that of carbon-centered substitution reactions, SN1 and SN2. In both organic and inorganic cases, substitution mechanisms can follow two fundamental pathways: associative and dissociate. The term “limiting” refers to the extreme bases of these mechanisms. For two electron pathways, if bond formation occurs leading to an intermediate or transition state with an increased coordination number, the mechanism is called associative (A) or SN2 (limiting). Conversely when only bond breaking occurs during the formation of an intermediate of decreased coordination number, the mechanism is called dissociative (D) or SN1 (limiting). The mechanism by which an organometallic complex undergoes ligand substitution depends largely on whether it is coordinatively saturated. Coordinatively saturated 18-electron complexes generally undergo substitution by the dissociative two-electron pathways, whereas coordinatively unsaturated 16-electron complexes (d8 complexes of Ni, Pd, and Pt) tend to undergo associative two-electron pathways

Associative reaction: Incoming ligand forms a bond to the metal and creates and intermediate of higher coordination number. Then the departing ligand takes its lone pair and leaves. This is common for 16 electron complexes (like d8 complexes of Ni Pd, and Pt)

Dissociative: Ligand departs and a new complex with lower coordination n number forms. Then, a new ligand associates with complex in the second step.

Examples and Mechanism: Coordinatively Unsaturated Complexes

  • 16-Electron Complexes:

Ligand substitution reactions in 16-electron square planar d⁸ complexes—such as Pt(II), Pd(II), Ni(II), Au(III), Rh(I), and Ir(I)—represent one of the most investigated classes of substitution reactions in coordination chemistry. These processes are examples of associatively activated substitutions, where the coordinative unsaturation of the metal center plays a key role. The classic case involves ligand exchange in square planar Pt(II) complexes (figure 1), which typically (though not always) proceeds with retention of stereochemistry at the metal center. The kinetics often follow a two-term rate law, such as in the replacement of NHEt₂ by ¹⁴C-labeled NHEt₂ in PtLCl₂(NHEt₂), where the observed rate constant (kobs = k₁ + k₂[NHEt₂]) reflects contributions from both solvent-assisted substitution (k₁) and direct nucleophilic attack (k₂).

Several factors influence the substitution rates in these systems. The nucleophile dependence for soft, polarizable Pt(II) follows the trend PR₃ > py ≈ NH₃ > Cl⁻ > H₂O > OH⁻, spanning a rate range of approximately 10⁵. The leaving group ability, as observed in Pt(dien)X⁺ + py reactions, decreases in the order NO₃⁻ > H₂O > Cl⁻ > Br⁻ > I⁻ > N₃⁻ > SCN⁻ > NO₂⁻ > CN⁻, reflecting the stability of the five-coordinate intermediate formed upon nucleophilic attack. Additionally, the metal ion itself significantly impacts reactivity, with rates decreasing in the order Ni(II) > Pd(II) ≫ Pt(II), a trend attributed to the varying ease of forming 18-electron five-coordinate intermediates. In some cases, these five-coordinate species have been isolated and structurally characterized; they are often highly fluxional, undergoing rapid ligand exchange via pseudorotation. While they can participate in cis/trans isomerization, stereochemical retention is more common, though recent studies suggest that loss of configuration may occur more frequently than previously assumed.

The trans influence and trans effect are fundamental concepts in these systems. The trans influence refers to the thermodynamic weakening of the metal-ligand bond trans to a given ligand, while the trans effect describes the kinetic acceleration of substitution at the trans position, incorporating both ground-state and transition-state effects. The trans influence series spans a broad range of ligands, with strong σ-donors (e.g., R₃Si⁻, H⁻) and π-acceptors (e.g., CO, olefins) exerting the greatest effects: R₃Si⁻ > H⁻ ≈ CH₃⁻ ≈ CN⁻ ≈ olefin/CO > PR₃ > NO₂⁻ ≈ I⁻ ≈ SCN⁻ > Br⁻ > Cl⁻ > RNH₂ ≈ NH₃ > OH⁻ > NO₃⁻ ≈ H₂O.

Although associative mechanisms dominate, dissociative pathways have been observed in certain 16-electron complexes. For example, in cis-PtPh₂(Me₂SO)₂, the weakly coordinated DMSO ligands (trans to high-trans-influence phenyl groups) exchange via a dissociative mechanism, possibly involving an η²-DMSO intermediate. Similarly, six-coordinate Mo(II) alkyne complexes such as Mo(CO)(RC≡CR')(S₂CNMe₂)₂ undergo CO dissociation rather than associative alkyne exchange, highlighting the role of π-donor ligands in facilitating unusual mechanistic pathways. These exceptions demonstrate that even in unsaturated systems, dissociative processes can compete under the right conditions.

 

  • 17-Electron Complexes:

Transition metal complexes with 17 electrons are significantly more reactive than their 18-electron counterparts, exhibiting much faster ligand substitution rates. For instance, the 17-electron complex V(CO)₆ substitutes ligands with PPh₃ at -70°C in just 90 minutes, while its 18-electron analog [V(CO)₆]⁻ remains inert even in molten PPh₃. Such reactivity differences can span 10³ to 10¹⁰ times, highlighting the dramatic lability of 17-electron species. Initially, it was believed that 17-electron complexes like V(CO)₆ or Mn(CO)₅ would follow dissociative pathways, losing a CO ligand to form 15-electron intermediates rather than undergoing associative substitution. However, molecular orbital theory provides a clearer explanation: when a 17-electron complex binds an incoming ligand to form a 19-electron intermediate, the bonding interaction is favorable because two electrons occupy a bonding orbital while only one enters an antibonding orbital. This insight, first proposed by Poe in 1975, helps explain why some stable 19-electron complexes exist—typically cases where the extra electron resides in a ligand-based orbital, effectively making them 18-electron complexes with a radical anion ligand.

Experimental studies on 17-electron intermediates, generated through photolysis, oxidation, or other methods, have reinforced the associative substitution mechanism. Poe's work demonstrated that steric effects play a key role with bulky phosphines like P(i-Pr)₃, whereas harder Lewis bases (e.g., pyridine or THF) often induce disproportionation. Further evidence comes from studies on persistent radicals like Mn(CO)₃L₂ (where L is a bulky phosphine) and electrochemically generated [MeCpMn(CO)₂L]⁺, all supporting associative pathways. Thus, unlike 18-electron complexes, which typically undergo dissociative substitution, 17-electron species favor associative mechanisms due to their inherent electronic structure and bonding interactions.

 

  • 18-Electron Complexes

Ligand substitution reactions in 18-electron, coordinatively saturated complexes proceed much more slowly than in their 16-electron counterparts. An example is the dramatic rate difference observed between Rh(acac)(ethylene)₂, a 16-electron complex that undergoes rapid associative ethylene exchange (~4×10⁻¹⁰ sec⁻¹ at 25°C), and 18-electron complexes like Ni(CO)₄, CpRh(ethylene)₂, and Cr(CO)₆. These saturated complexes require substantial activation energies approaching their metal-ligand bond dissociation energies (25±2, 31, and 37±2 kcal/mol, respectively), necessitating elevated temperatures (0-30°C, ≥100°C, and 80-140°C) for observable substitution rates.

The poor reactivity of 18-electron complexes can be overcome through various activation strategies. Photochemical irradiation, Lewis base catalysis (e.g., R₃P=O), redox processes, acid/base assistance, and radical chain initiation (as with HRe(CO)₅) all provide pathways to accelerate substitution. These competing mechanisms exhibit remarkable sensitivity to reaction conditions - minor variations can dramatically alter reactivity. For instance, PBu₃ substitution in HRe(CO)₅ proceeds within minutes under photolysis but shows no reaction after two months in the dark with ultra-pure reagents. Similarly, while highly purified Fe(CO)₅ resists substitution below 90°C, less stringent conditions permit reactions at 60°C. The notorious irreproducibility of Mo(CO)₄(amine) substitutions with PPh₃ further illustrates how trace impurities (like Ph₃P=O) can dominate reactivity patterns. These examples underscore the delicate balance of factors governing substitution in saturated complexes, where subtle changes can activate latent reaction pathways.

18-Electron Complexes

Eighteen-electron complexes are coordinatively saturated and generally stable, leading to much slower ligand substitution rates compared to 16-electron complexes. For example, the 16-electron Rh(acac)(ethylene)₂ undergoes associative ethylene exchange at ≥10⁴ sec⁻¹ (25°C), while the 18-electron CpRh(ethylene)₂ dissociates ethylene over 10¹⁴ times slower (~4×10⁻¹⁰ sec⁻¹). The high activation barriers (approaching M-L bond energies of 25-37 kcal/mol) in 18-electron complexes like Ni(CO)₄, CpRh(ethylene)₂, and Cr(CO)₆ require elevated temperatures (0-140°C) for observable substitution. While normally inert, their reactivity can be accelerated by photolysis, Lewis bases, redox processes, or radical initiators - though these pathways are highly condition-dependent, as seen in HRe(CO)₅ (minutes with light vs. months without) or Fe(CO)₅ (unreactive below 90°C when pure). Substitution mechanisms may follow dissociative ligand substitution with competing associative pathways, substation reactions by polyhapto ligands, or associative ligand substitution.

 

Catalyzed and Assisted Ligand Substitution Reactions

Catalyzed and assisted ligand substitution reactions have been widely investigated, with particular emphasis on catalytic pathways that offer efficient and selective transformation of coordination complexes. Among these, electron transfer catalysis stands out as a fundamentally important mechanism, operating through single-electron transfer processes that can be initiated either electrochemically or via chemical reagents. The electrochemical approach provides particularly clear insight into the core principles of this catalytic system. These reactions are systematically classified into four distinct mechanistic pathways based on their activation mode (oxidative O or reductive R) and the nature of the participating reagent (nucleophile N or electrophile E): SON2, SOE1, SRE2, and SRN1, each following the generalized catalytic cycle illustrated in Figure 1.

 

Radical chain mechanisms constitute another significant category of substitution processes, first identified during studies of disubstituted HRe(CO)₃L₂ formation. This radical-based pathway successfully explains several characteristic experimental observations, including the exclusive production of disubstituted products, complete reaction suppression under rigorously light-free conditions with ultrapure reagents (showing no conversion even after 60 days at 25°C), distinctive kinetic irreproducibility, observable induction periods, unusual product accumulation profiles, significant rate enhancement by photogenerated Re(CO)₅ radicals, and pronounced oxygen inhibition effects. The complete radical chain mechanism accounting for these phenomena is detailed in Scheme 2.

Beyond these primary pathways, researchers have developed additional assisted substitution strategies including Brønsted and Lewis acid catalysis, employment of specialized nucleophiles such as R₃NO, R₃PO, MeO⁻ or halide ions, sonochemical activation methods, and the well-established photochemical dissociation of ligands - particularly carbonyl groups. Each of these approaches offers unique advantages and demonstrates the remarkable versatility of modern ligand substitution chemistry in manipulating coordination complexes under controlled conditions. The choice of method depends on specific reaction requirements, with factors such as selectivity, efficiency, and mildness of conditions often determining the optimal pathway for a given transformation.