Intercepting Ketone α-Arylation Intermediates in the DalPhos/Ni-Catalyzed Synthesis of Decorated Benzofurans and NH-Indoles

Employing meso-PAd2-DalPhos (meso-L1) as an ancillary ligand, a single mechanistic landscape provides access to two thermal nickel-catalyzed transformations with broad scope commencing from α-(o-chloro)aryl ketones: the synthesis of 2-substituted benzofurans via intramolecular O-arylation and the synthesis of 3-acyl-2-substituted NH-indoles when incorporating RCN reactants. Through the isolation of intermediates and kinetic analysis, the synthesis of 3-acyl-2-substituted NH-indoles is proposed to occur through a Ni(0/II) catalytic cycle involving: (1) (meso-L1)Ni(0) oxidative addition of the aryl chloride; (2) base-facilitated HCl loss forming a Ni(II) κ2-C,O enolate species; (3) net addition of the metal-coordinated enolate to the nitrile; and (4) C(sp2)–N(sp2) reductive elimination. These mechanistic studies also highlight the influence of base choice on precatalyst activation in such benzofuran syntheses and the impact of RCN electronics on overall catalytic turnover in the formation of NH-indoles, as well as enabling catalyst speciation and NMR spectroscopic resting state determination. Guided by our mechanistic results, an electron-poor variant of meso-PAd2-DalPhos (i.e., meso-L9) was synthesized to promote challenging C(sp2)–(O-enolate) reductive elimination furnishing 2-substituted benzofurans, while an electron-rich variant (i.e., meso-L10) was employed to prevent competitive C(sp2)–(O-enolate) reductive elimination en route to 3-acyl-2-substituted NH-indoles.