Triple adamantane expands the boundary of phosphine ligands

Phosphine ligands have played a supporting role in the success of many a transition-metal catalyst, helping to tune their activity, selectivity, and stability. Among the examples, tri(tert-butyl)phosphine has long been characterized as the most electron-releasing alkylphosphine ligand for metals. Liye Chen, Peng Ren, and Brad P. Carrow of Princeton University have succeeded in raising the bar with tri(1-adamantyl)phosphine, PAd₃, a ligand that now provides a bridge between trialkylphosphines and the stronger electron-releasing N-heterocyclic carbene ligands (J. Am. Chem. Soc. 2016, DOI: 10.1021/jacs.6b03215). Adamantane is an unusual rigid C₁₀ tricyclic alkane. Researchers have made phosphine ligands containing two adamantyl groups before, and adamantane is occasionally used as a bulky substituent for N-heterocyclic carbenes. But installing a third bulky adamantyl group on phosphorus has been a challenge, one that researchers took on with complex approaches. Carrow’s group pulled it off with a simple substitution reaction between commercially available HPAd₂ and AdCO₂CH₃. The researchers demonstrated the utility of the surprisingly stable PAd₃ by forming the palladium catalyst shown above and using it for Suzuki-Miyaura couplings, including using chlorinated heteroarenes to make drug intermediates and derivatives, with good results.