This highlight is the second installment of a series of highlights on nonprecious-metal-catalyzed reactions of interest to the pharmaceutical industry. Selected transformations from March to June 2020 are summarized. Our goal is to facilitate advancements in the areas of safer and greener chemical manufacturing using earth-abundant metals.

Biaryl phosphorinane ligands derived from addition of biaryl primary phosphines to trans,trans-dibenzylideneacetone (Alison-Phos and AliPhos) form highly active ligands for Pd-catalyzed coupling of hindered, electron-deficient anilines with hindered (hetero)aryl halides, a challenging class of C−N cross-coupling reaction with few precedents. Broad substrate scope and functional group tolerance were observed under the reaction conditions. Computational studies suggest that ligands containing phenyl substituents provide greater activity through more favorable aniline binding in the catalytic cycle in comparison to alkylsubstituted phosphorinanes. A general and high-yielding procedure for the synthesis of biaryl phosphorinanes by phospha-Michael addition of primary biarylphosphines to 1,4-dien-3-ones in 1,1,1,3,3,3-hexafluoroisopropanol (HFIP), under relatively mild conditions (23−110 °C), is also described. HFIP as the solvent significantly accelerates the phospha-Michael addition, allowing the preparation of previously inaccessible ligands and higher yields overall.