Benzylic C(sp³ )-H Bond Oxidation with Ketone Selectivity by a Cobalt(IV)-Oxo Embedded in a β-Barrel Protein

Artificial metalloenzymes have emerged as biohybrid catalysts that allow to combine the reactivity of a metal catalyst with the flexibility of protein scaffolds. This work reports the artificial metalloenzymes based on the β-barrel protein nitrobindin NB4, in which a cofactor [Co^II X(Me₃ TACD-Mal)]⁺ X^- (X=Cl, Br; Me₃ TACD=N,N^' ,N''-trimethyl-1,4,7,10-tetraazacyclododecane, Mal=CH₂ CH₂ CH₂ NC₄ H₂ O₂ ) was covalently anchored via a Michael addition reaction. These biohybrid catalysts showed higher efficiency than the free cobalt complexes for the oxidation of benzylic C(sp³ )-H bonds in aqueous media. Using commercially available oxone (2KHSO₅  ⋅ KHSO₄  ⋅ K₂ SO₄ ) as oxidant, a total turnover number of up to 220 and 97 % ketone selectivity were achieved for tetralin. As catalytically active intermediate, a mononuclear terminal cobalt(IV)-oxo species [Co(IV)=O]²⁺ was generated by reacting the cobalt(II) cofactor with oxone in aqueous solution and characterized by ESI-TOF MS.