DalPhos on Demand: Facile Ligand Generation Enables New Ligand Discovery and Expedient Catalyst Screening

DalPhos/Ni-based catalysts have emerged as top performers in C–N and C–O cross-couplings. Expedient means of generating such ligands would facilitate the discovery of effective DalPhos ligand variants as well as accelerate reaction development processes for end users. A protocol for generating structurally varied phosphine- and phosphonite-type DalPhos ligands from a single ligand precursor upon treatment with commercial reagents and without the need for chromatographic purification is disclosed. The formation of DalPhos ligands via this divergent synthetic strategy was exploited in the expedited screening of representative Ni-catalyzed C–N and C–O cross-couplings, leading to the identification of the DalPhos ligand variants (i.e., BnPAd-DalPhos, L4, and OAdPAd-DalPhos, L9) that, in turn, were carried forward for reaction scope analysis in challenging cross-couplings of fluoroalkylamines, by use of prepared (DalPhos)Ni(aryl)Cl precatalyst complexes. The reported methodology offers a user-friendly means of generating DalPhos variants in reaction development.