Directional Second Sphere Effect on CO₂ Activation and Reduction by Iron Porphyrin in Aprotic and Protic Media

The topological directionality of functional groups in the secondary coordination sphere (SCS) plays a decisive role in enzymatic small-molecule activation but remains underexplored in synthetic systems. Here, we investigate how symmetry remodeling of a urea-based SCS modulates electrocatalytic CO₂-to-CO reduction using two atropisomeric iron porphyrins, αβαβ-UrFe and α₂β₂-UrFe, which differ solely in the spatial arrangement of identical hydrogen-bond donor groups. Switching from a face-to-face to an adjacent urea-arms configuration enables unprecedented CO₂-to-CO conversion under strictly aprotic conditions, in the absence of Brønsted or Lewis acids. Combined electrochemical, spectroscopic, kinetic, and DFT studies reveal that the adjacent positioning of the urea arms weakens the stabilization of the initial [Fe─CO₂] intermediate but creates a more open and dynamically reorganizable SCS that permits insertion of a second CO₂ molecule as an oxygen-atom acceptor, to yield CO and CO₃ ²-. Under protic conditions, this improved active-site accessibility, combined with a dissymmetrization of the activated CO₂ molecule, accelerates proton transfer, with CO₂-to-CO reduction reaching turnover frequency of up to 2.72 × 10⁷ s^-1, among the highest reported for homogeneous catalysis. These results establish directional interactions within the SCS as powerful design strategy for boosting molecular catalysis.