Rational design of iron catalysts for C-X bond activation

We have quantum chemically studied the iron-mediated CX bond activation (X = H, Cl, CH₃ ) by d⁸ -FeL₄ complexes using relativistic density functional theory at ZORA-OPBE/TZ2P. We find that by either modulating the electronic effects of a generic iron-catalyst by a set of ligands, that is, CO, BF, PH₃ , BN(CH₃ )₂ , or by manipulating structural effects through the introduction of bidentate ligands, that is, PH₂ (CH₂ )_n PH₂ with n = 6-1, one can significantly decrease the reaction barrier for the CX bond activation. The combination of both tuning handles causes a decrease of the CH activation barrier from 10.4 to 4.6 kcal mol^-1 . Our activation strain and Kohn-Sham molecular orbital analyses reveal that the electronic tuning works via optimizing the catalyst-substrate interaction by introducing a strong second backdonation interaction (i.e., "ligand-assisted" interaction), while the mechanism for structural tuning is mainly caused by the reduction of the required activation strain because of the pre-distortion of the catalyst. In all, we present design principles for iron-based catalysts that mimic the favorable behavior of their well-known palladium analogs in the bond-activation step of cross-coupling reactions.