Pd-Catalyzed Cross-Coupling of Hindered, Electron-Deficient Anilines with Bulky (Hetero)aryl Halides Using Biaryl Phosphorinane Ligands

Biaryl
phosphorinane ligands derived from addition of biaryl primary
phosphines to trans,trans-dibenzylideneacetone
(AlisonPhos 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 alkyl-substituted 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.