Origin of the regioselective reduction of chlorins

The reduction of a free-base chlorin generally forms a bacteriochlorin (BC), while the reduction of the corresponding metallochlorin forms a metalloisobacteriochlorin (M-iBC). This regioselectivity has been long known but was never fully rationalized. In the free-base case, this regioselectivity can be explained using resonance arguments, but the explanations for the regioselectivity in the metallochlorin reactions requires a more sophisticated approach. A combination of DFT-calculated average local ionization energies (ALIEs), thermodynamics of the products, and the transition-state trajectories of reduction reactions of meso-tetraaryl- and β-octaethylchlorins, as their free bases and zinc complexes, now fully delineate the theoretical basis of the reduction regioselectivity. The reactions are kinetically controlled. Steric effects originating in the conformational flexibility of the chlorin macrocycle direct the reactions toward the formation of iBCs. Only when electronic effects are strong enough to override the steric effects are BCs formed. Depending on the substituents present on the chlorin, this regioselectivity may change, but ALIE calculations provide reliable guidelines to predict this. The practical value of this work lies in the presentation of a simple predictive method toward synthetic tetrahydroporphyrins by reduction of chlorins.