A Chemoenzymatic\nCascade for the Formal Enantioselective\nHydroxylation and Amination of Benzylic C–H Bonds

We report the synthesis and characterization of an artificial\nperoxygenase\n(CoN<sub>4</sub>SA-POase) with CoN<sub>4</sub> active sites by supporting\nsingle-atom cobalt on polymeric carbon nitrogen, which exhibits high\nactivity, selectivity, stability, and reusability in the oxidation\nof aromatic alkanes to ketones. Density functional theory calculations\nreveal a different catalytic mechanism for the artificial peroxygenase\nfrom that of natural peroxygenases. In addition, continuous-flow systems\nare employed to combine CoN<sub>4</sub>SA-POase with enantiocomplementary\nketoreductases as well as an amine dehydrogenase, enabling the enantioselective\nsynthesis of chiral alcohols and amines from hydrocarbons with significantly\nimproved productivity. This work, emulating nature and beyond nature,\nprovides a promising design concept for heme enzyme-based transformations.