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

Abstract

AbstractArtificial 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 [CoIIX(Me3TACD‐Mal)]+X− (X=Cl, Br; Me3TACD=N,N',N''‐trimethyl‐1,4,7,10‐tetraazacyclododecane, Mal=CH2CH2CH2NC4H2O2) 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 ⋅ K2SO4) 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.