Development of a Deactivation-Resistant Dialkylbiarylphosphine Ligand for Pd-Catalyzed Arylation of Secondary Amines.

ABSTRACT: Despite the prevalence of N-heteroarenes in small-molecule pharmaceuticals, Pd-catalyzed C-N cross-coupling reactions of aryl halides and amines containing these rings remain challenging due to their ability to displace the supporting ligand via coordination to the metal center. To address this limitation, we report the development of a highly robust Pd catalyst supported by a new dialkylbiarylphosphine ligand, FPhos. The FPhos-supported catalyst effectively resists N-heteroarene-mediated catalyst deactivation to readily promote C-N coupling between a wide variety of Lewis-basic aryl halides and secondary amines, including densely functionalized pharmaceuticals. Mechanistic and structural investigations, as well as principal component analysis and density functional theory, elucidated two

SUBMITTER: Feng K 

PROVIDER: S-EPMC11906018 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature