Ligand Substitution

Introduction

Ligand substitution reactions involve the replacement of coordinated ligands in transition metal complexes as shown by figure 1. These reactions are fundamental in both stoichiometric and catalytic processes, often serving as the rate-determining step. They are usually an essential first step.

ML_x+ nL'   ⇌  ML_x-n L’_n + nL

Figure 1: General ligand substitution reaction scheme: L is the leaving ligand and L' is the incoming ligand.

Mechanisms of Ligand Substitution

Substitution mechanisms in organometallic chemistry resemble organic SN₁ and SN₂ reactions, following two primary pathways:

1. Associative (A or SN₂ like)

   • The incoming ligand binds first, forming a higher-coordinate intermediate.

   • Common in 16-electron complexes (e.g., square planar d⁸ complexes of Ni(II), Pd(II), Pt(II)).

   • Classic associative ligand substitution reaction with second order kinetics, characteric of 16-electron transition metal complexes (Figure 2).

Figure 2: Second-order kinetics in the associative substitution of (η⁵-carbocycle)Rh(CO)₂ with PPh₃, following the rate law: d[product]/dt = k₂[(η⁵-carbocycle)Rh(CO)₂][PPh₃]

1. Dissociative (D or SN₁ like)

   • A ligand dissociates first, creating a lower-coordinate intermediate before the new ligand binds.

   • Typical for 18-electron complexes, which must lose a ligand to become reactive.

   • Classic example of dissociative substitution in 18-electron, tetrahedral d¹⁰ complexes (Figure 3).

Figure 3. Ligand substitution in tetrahedral Ni(CO)₄ proceeds through a dissociative mechanism, with CO dissociation as the rate-determining step, as evidenced by first-order kinetics (−d[Ni(CO)₄]/dt = *k*₁[Ni(CO)₄]) independent of incoming ligand. The transient Ni(CO)₃ intermediate rapidly reacts with incoming ligands (L = CO, PR₃) or undergoes isotopic exchange with *Ni(¹³CO)₄ in the gas phase. While recombination with CO faces minimal barriers, solvent coordination and steric effects of bulky ligands can significantly alter the reaction pathway energetics.

Substitution in Different Electron Configurations

1. 16-Electron Complexes (e.g., Pt(II), Pd(II), Ni(II))

• Undergo associative substitution due to coordinative unsaturation.

• Factors influencing rates:

  • Nucleophile dependence: nucleophile dependence for soft, polarizable Pt(II) follows the trend PR₃ > py ≈ NH₃ > Cl⁻ > H₂O > OH⁻, spanning a rate range of approximately 10⁵.

  • Leaving group ability: 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

  • Metal reactivity trend: 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

  • Trans Influence (Thermodynamic Effect)

Definition: The ability of a ligand to weaken the metal-ligand bond trans to itself in the ground state (static effect).

Cause: Strong σ-donation or π-backbonding from the ligand reduces electron density along the trans axis.

Trend:
R₃Si⁻ > H⁻ ≈ CH₃⁻ ≈ CN⁻ ≈ CO/olefins > PR₃ > NO₂⁻ ≈ I⁻ ≈ SCN⁻ > Br⁻ > Cl⁻ > NH₃ ≈ H₂O

Strong σ-donors (H⁻, CH₃⁻) and π-acceptors (CO, C₂H₄) have the greatest trans influence.

• • Trans Effect (Kinetic Effect)

Definition: The ability of a ligand to accelerate substitution of the ligand trans to itself.

Cause:Ligands that are strong σ-donors and π-acceptors (CO, CN⁻, H⁻) show the strongest trans effect.

• • • σ-donation: Weakens the trans M–L bond in the transition state.

    • π-acceptance: Stabilizes the 5-coordinate intermediate by delocalizing electron densityTrend:
      CN⁻ ≈ CO ≈ C₂H₄ ≈ H⁻ > PR₃ > NO₂⁻ > I⁻ > Br⁻ > Cl⁻ > NH₃ > H₂O

      Ligands that are strong σ-donors and π-acceptors (CO, CN⁻, H⁻) show the strongest trans effect.

      Trend:
      CN⁻ ≈ CO ≈ C₂H₄ ≈ H⁻ > PR₃ > NO₂⁻ > I⁻ > Br⁻ > Cl⁻ > NH₃ > H₂O

2. 17-Electron Complexes: Hyper-Reactive Radical Intermediates

• 17-electron complexes exhibit dramatically faster ligand substitution rates than their 18-electron counterparts due to their open-shell radical character.

• Key Features:

• • Extreme Lability: Substitution occurs up to 10³–10¹⁰ times faster than in 18e⁻ complexes.

    • Example: V(CO)₆ substitutes CO with PPh₃ at –70°C in 90 min, while [V(CO)₆]⁻ (18e⁻) is inert even in molten PPh₃.
      

  • Mechanism: Initially, a dissociative pathway (loss of CO to form a 15e⁻ intermediate) was assumed. However, molecular orbital theory explains why associative substitution dominates:

    • Incoming ligand forms a 19e⁻ intermediate.

    • Net stabilization: 2 electrons fill a bonding orbital, while only 1 enters an antibonding orbital.

    • Some stable 19e⁻ complexes exist (e.g., [CpFe(CO)₂]•) if the extra electron resides on a ligand.

  • Experimental Evidence:

    • Steric effects: Bulky ligands (e.g., P(i-Pr)₃) slow substitution.

    • Hard bases (pyridine, THF) often cause disproportionation instead of substitution.

    • Persistent radicals like Mn(CO)₃(PR₃)₂ confirm associative pathways.

3. 18-Electron Complexes: Hyper-Reactive Radical Intermediates

• 18e⁻ complexes are coordinatively saturated and substitution requires breaking strong M–L bonds.

• Challenges:

  • High Activation Energy: (25–37 kcal/mol, close to M–L bond energies).

  • Extremely slow rates: CpRh(C₂H₄)₂ exchanges ethylene ~10¹⁴× slower than 16e⁻ Rh(acac)(C₂H₄)₂.

Activation Strategies

Catalyzed Substitution Pathways

A. Electorn Transfer Catalysis

• Four mechanisms (SON₁ , SOE₁ , SRE₂ , SRN₁ ) via electrochemical/chemical redox.

B. Radical Chain Mechanisms

• Observed in HRe(CO)₅ → HRe(CO)₃L₂:

  • Exclusive disubstitution (no mono-substituted product).

  • Oxygen inhibition (quenches radicals).

  • Photocatalyzed by Re(CO)₅•.

C. Other Assisted Pathways

Key Takeaways

1. 16e⁻ complexes: Fast, associative, controlled by trans effects

2. 17e⁻ complexes: Radical-driven, extremely labile

3. 18e⁻ complexes: Require activation (light, redox, catalysts)

4. Design principles: Electron count and conditions dictate mechanism