Iron-Catalyzed C(sp2)-C(sp3) Suzuki Cross-Coupling Using an Alkoxide Base

The synthesis and characterization of iron(II) alkyl precatalysts for C(sp2)–C(sp3) Suzuki-Miyaura cross-coupling of aryl boronic esters and alkyl bromides is described. Addition of phenoxyimines (FI) to (py)2Fe(CH2SiMe3)2 (py = pyridine) afforded the high-spin iron(II) alkyl derivatives, (FI)Fe(CH2SiMe3)(py) with varying N-imine substituents. With both neopentyl glycol-protected (BNeo) and pinacol-protected boronic ester (BPin) aryl nucleophiles, an iron-catalyzed cross-coupling method was realized that utilized synthetically preferred alkoxide bases. Optimal performance was observed in non-polar solvents with anisole and fluorobenzene identified as more benign alternatives to benzene. The scope of this transformation included high efficiency C(sp2)–C(sp3) bond formation with both primary and secondary alkyl bromides with electron-deficient aryl and heteroaryl nucleophiles. Radical clock experiments support the formation of electrophile-derived radicals during catalysis and experiments with pre-formed potassium aryl boronates demonstrate the role of boronate intermediates in transmetalation.