Palladium-Catalyzed Direct α-Arylation of Arylacetonitriles with Aryl Tosylates and Mesylates

The first general palladium-catalyzed α-arylation of arylacetonitriles with aryl and heteroaryl sulfonates are reported. Pd(OAc)₂ associated with XPhos serves as the effective catalyst to facilitate this reaction. A broad range of electron-rich, -neutral, -deficient, and sterically hindered aryl/heteroaryl tosylates and mesylates are coupled with arylacetonitriles bearing different substituents to give the corresponding products in good to excellent yields. Catalyst loading down to 0.1 mol-% Pd was achieved, and 22 unprecedented compounds were synthesized from 43 demonstrated examples using this method. Its applicability with the modification of biological phenolic compounds was successfully demonstrated. The Pd/XPhos system catalyzed the α-arylation and followed by alkylation in one-pot sequential conditions, resulting in the direct synthesis of compounds containing quaternary center- and deuterium-containing compounds in good to excellent yields.