The chlorination of arenes via electrophilic aromatic substitution (S_EAr) reactions is an important example of C–H functionalization. This strategy is particularly useful in drug design, because the introduction of a chlorine substituent to a medicinally active compound can be used to tune its pharmacokinetic properties. Iodobenzene dichloride (PhICl₂) is an easy-to-handle solid that acts as a chlorinating agent. It could be a promising alternative to chlorine gas in S_EAr reactions. However, it is a weaker oxidizing agent than Cl₂.

Tiffany Poynder, Sevan Houston, and Jason Dutton, La Trobe University, Melbourne, Australia, have found that the activity of PhICl₂ can be enhanced using readily accessible [Ag]₂[B₁₂Cl₁₂] as a catalyst. This silver salt has a weakly coordinating carborane anion. The team chlorinated a variety of arenes at room temperature using PhICl₂ as a chlorinating agent, [Ag]₂[B₁₂Cl₁₂] as a catalyst, and CHCl₃ as the solvent. The method was also extended to the dichlorination of alkenes and alkynes. The researchers propose a “iodonium”-type mechanism (pictured below), in which Ag⁺ abstracts a chloride ion from PhICl_2, resulting in an active [PhICl]⁺ species, which might be stabilized by the weakly coordinating [B₁₂Cl₁₂]^2– anion.

 

[Ag]₂[B₁₂Cl₁₂] outperformed several commercially available Ag(I) salts. [Ag]₂[B₁₂Cl₁₂] and related carborane reagents are typically only used by the inorganic chemistry community, but the researchers hope that this work encourages others to further investigate its application in organic synthesis.

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• [Ag]₂[B₁₂Cl₁2] as a Catalyst in PhICl₂ Mediated Chlorination,
  Tiffany B. Poynder, Sevan David Houston, Jason L. Dutton,
  Eur. J. Org. Chem. 2021.
  https://doi.org/10.1002/ejoc.202100447