Nucleophilic Addition to Coordinated Ligands

Introduction

In transition metal chemistry, ligands bound to a metal center can undergo nucleophilic attack, a fundamental reaction that plays a key role in catalytic cycles, organic synthesis, and industrial processes. This reactivity is influenced by the metal’s oxidation state, coordination environment, and the electronic nature of the ligand. The ligand will be activated by a metal. This allows for a nucleophile to attack the ligand without needing to first bind to the metal. The nucleophile will be covalently bonded with the ligand. 

Key Principles

1. Activation of Ligands Toward Nucleophiles

   • Coordination of a ligand to a transition metal can polarize its electron density, making it more susceptible to nucleophilic attack. For example, carbonyl (CO) ligands in metal complexes are electrophilic at carbon due to backbonding from the metal, allowing nucleophiles (e.g., hydrides, amines, or alkoxides) to attack the carbonyl carbon (Collman et al.).

   • Similarly, η²-coordinated alkenes and alkynes become electrophilic upon binding to electron-deficient metals, facilitating nucleophilic addition (Hegedus).

2. Mechanistic Pathways

   • Direct Nucleophilic Attack: The nucleophile targets an electrophilic site on the ligand (e.g., carbene or nitrosyl ligands).

   • Migratory Insertion: A nucleophilic ligand (e.g., alkyl or hydride) migrates to an adjacent electrophilic ligand (e.g., CO or alkene), followed by reductive elimination (Norton).

   • Electron-Transfer Mechanisms: In some cases, nucleophilic attack is facilitated by redox-active metals that modulate ligand electrophilicity (Finke).

3. Influence of Metal Center

   • The metal’s oxidation state and ligand field effects alter the reactivity of coordinated ligands. For instance, low-valent metals (e.g., Rh(I) or Pd(0)) enhance backdonation, making π-acceptor ligands (like CO or CNR) more nucleophilic at the metal but more electrophilic at the ligand.

Applications

• Hydroformylation: Nucleophilic attack on coordinated CO by hydride ligands is a key step in the conversion of alkenes to aldehydes.

• Hydrocyanation: Ni(0)-catalyzed addition of HCN to alkenes proceeds via nucleophilic attack on a metal-alkene intermediate (Hegedus).

• Carbene Transfer Reactions: Nucleophilic attack on Fischer carbene complexes (e.g., Cr(CO)₅=C(OMe)R) enables C–C bond formation in organic synthesis (Collman).

Conclusion

Understanding nucleophilic attack on ligands provides critical insights into designing efficient catalytic systems and synthesizing complex molecules.