Structure–Activity Relationship in CuN4‐Catalyzed Reactions: The Exposition of Electronic and Steric Effects on Catalytic Reactivity

Abstract A series of tetra‐pyrrolic mononuclear‐ CuN 4 complexes, CuL NO2 , CuL COOMe , CuL H , CuL mes , and CuL por , have been structurally characterized. They contain twist angles between 0° and 66°, produced by variations in the spatial arrangements of N 4 ‐ligands around copper and give a wide range of formal oxidation potential (+0.4 to +0.9 V versus Fc/Fc + ). As molecular descriptors of CuN 4 complexes, quantitative estimation of percent buried volume (%V bur = 51%–57%) for steric and HOMO energy ( E HOMO ) for electronic contribution was done. Using CuN 4 complexes as catalysts, yields upto 85%, 99%, 99%, and 100% were found for aziridination, aziridine ring‐opening, alcohol oxidation and p ‐nitrophenol reduction reactions, respectively. Structure–activity relationship was established by developing a 3D free energy relationship using the rate constant ( k ) as the dependent variable vs. %V bur and E HOMO as the independent variables. Theoretical reactivity modelled through multiple linear regression showed good convergence with the experimental reactivity (98 ≥ R 2 ≥ 84 & 0.019 ≤ MAE ≤ 1.394). The steric‐to‐electronic contribution of 69:31, 14:86, 07:93, and 77:23 was estimated for CuN 4 ‐catalyzed alcohol oxidation, aziridination, aziridine ring‐opening, and p ‐nitrophenol reduction reactions, respectively. Furthermore, interpolation studies were extended to 14 CuN 4 complexes using the developed models that allowed the estimation of their theoretical reactivities and enabled the development of predictive catalysis.