Iron(III) Ejection from a "Beheaded" TAML Activator: Catalytically Relevant Mechanistic Insight into the Deceleration...

Kinetic studies of the acid-induced ejection of iron(III) show that the more electron-rich tetra-amido-N macrocyclic ligand (TAML) activator [Fe^III{(Me₂CNCOCMe₂NCO)₂CMe₂}OH₂]^- (4), which does not have a benzene ring in its head component ("beheaded" TAML), is up to 1 × 10⁴ times more resistant than much less electron-rich [Fe^III{1,2-C₆H₄(NCOCMe₂NCO)₂CMe₂}OH₂]^- (1a) to the electrophilic attack. This counterintuitive increased resistance is seen in both the specific acid (k_obs = k₁[H⁺]/(K + [H⁺])) and phosphate general acid (k_II = (k_diK_a1 + k_tri[H⁺])/(K_a1+[H⁺])) demetalation pathways. Insight into this reactivity puzzle was obtained from coupling kinetic data with theoretical density functional theory modeling. First, although 1a and related complexes are six-coordinate in water, 4 has a strong tendency to repel the second aqua ligand favoring [LFe(OH₂)]^- and making appropriate the comparison of monoaqua-4 with diaqua-1a in the demetalation process. Second, dearomatization exerts a strong effect on the highest occupied molecular orbital (HOMO) energy of five-coordinate monoaqua-4, the presumed target in proton-induced demetalation, stabilizing it by ca. 51 kJ mol^-1 compared with monoaqua-1a. Third, the monoaqua-4 HOMO is localized over the N-p_π system of all four N donors in contrast with monoaqua-1a, where N-p_π contributions from the head amides only mix with the aromatic ring π system. Fourth, addition of a second water ligand to monoaqua-1a giving [LFe(OH₂)₂]^- reshapes the monoaqua-1a HOMO by shifting its entire locus from the head to the tail diamido-N section-this HOMO is by 54 kJ mol^-1 less stable than the monoaqua-4 HOMO. These features provide the foundations for mechanistic conclusions concerning demetalation that (i) axial water ligands enable a favored path in the six-coordinate case of 1a, where a proton "slides" toward the Fe-N bond and (ii) early and late transition states are realized for 4 and 1a, respectively, with a larger free energy of activation for the beheaded TAML activator 4.