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.