Iron-catalyzed aliphatic C-H functionalization to construct carbon-carbon bonds.

Although cytochrome P450 enzymes are powerful catalysts for hydrogen-atom abstraction from alkanes by iron-oxo species, the process typically leads to oxygenated products due to ultrafast oxygen rebound. Developing synthetic catalysts that mimic this activity while avoiding oxygenation remains challenging, especially for intermolecular carbon-carbon bond formation. Here, we report an iron/bioinspired ligand catalyst that uses hydrogen peroxide to enable undirected methylene C-H functionalization with 1,4-quinones and azines, allowing direct formation of medicinally relevant C-C bonds while suppressing oxygen rebound. The reactions proceed efficiently with two equivalents of diverse alkanes, and the site selectivities, which differ from those observed in traditional methods, can be predicted based on steric, electronic, and stereoelectronic effects, even in complex molecules. This catalyst overcomes the intrinsic limitation of P450s, which favor oxygen incorporation over free radical formation, offering a promising strategy for selective alkylation of quinones and heterocycles using feedstock alkanes.