Iron Intermediates in Aminoquinoline-Directed C(sp2)-H Activation/C-C Coupling

Over the past two decades, iron-catalyzed aminoquinoline-directed C-H functionalization has attracted significant attention due to the low cost and sustainability of iron, the mild conditions required for catalysis, and the novel mechanistic manifolds compared to those with other first row metals. This report describes organometallic studies that provide insights into FeII, FeIII, and FeIV intermediates involved in an aminoquinoline-directed C(sp2)-H activation/C(sp2)-C(sp2) coupling reaction to yield a dimeric product. These investigations reveal that 2,3,4,5-tetrafluoro-N-(quinolin-8-yl)benzamide reacts with Fe(OAc)2 and Cs2CO3 to afford a high spin octahedral FeII coordination complex featuring two bidentate aminoquinoline ligands along with a k2-acetate. This intermediate does not react with acetate or carbonate salts (bases that promote C(sp2)-H activation at analogous first row transition metal complexes); furthermore, an intractable mixture is formed with PhMgBr (a common base in iron C-H functionalization catalysis). However, treatment with sodium hexamethyldisilazide (NaHMDS) results in rapid cyclometalation of both coordinated aminoquinoline ligands to yield a low spin octahedral FeII product. Two sequential single electron oxidations then enable C-C bond-forming reductive elimination from this complex via a putative FeIV intermediate. The isolated FeII and FeIII complexes from these organometallic studies serve as viable catalysts for this oxidative dimerization reaction with NaHMDS as base and AgOAc as oxidant, validating the feasibility of this pathway in catalytic C-H functionalization.