Regioselective Synthesis of Conformationally Designed Porphyrins with Mixedmeso-Substituent Types and Distortion Modes

Abstract

Porphyrins can be substituted easily and in high yield at the meso positions by using organolithium reagents. When S4-symmetric porphyrins such as 2,3,7,8,12,13,17,18-octaethylporphyrins are used as starting materials, it is possible to perform four such substitution reactions in sequence, resulting in the formation of nona-, deca-, undeca-, and dodecasubstituted porphyrins. Introduction of the first and second meso substituents can be achieved in almost quantitative yields, while the third and fourth meso substitutions proceed in about 50−70% yield with the remainder of the starting material being converted into stable porphomethenes. When one meso substituent is already present, introduction of the second residue proceeds with regiochemical preference for the 5,10-orientation over the 5,15-orientation, permitting a directed synthesis of 5,10-disubstituted porphyrins. Direct oxidation of the Meisenheimer-type intermediate formed after addition of RLi permits the introduction of two meso substituents in a one-pot reaction, again with preferential formation of the 5,10-disubstituted product. Using BuLi and PhLi as representative alkyl and aryllithium reagents, general reaction sequences were developed. These allow the preparation of meso-substituted octaethylporphyrins with almost any desired regiochemical combination of alkyl and aryl substituents. The synthesis of asymmetric, chiral, dodecasubstituted porphyrins can now be achieved in 4 to 6 steps, with overall yields in the range of 20−30%. X-ray crystallographic studies of the reaction products provided the means for the first analysis of the conformational effects of different types and arrangements of meso substituents present in one molecule. The results indicate that, depending on substituent type and localization, a mixing of distortion modes occurs. This offers significant opportunities for modulating the conformation, and thus the physicochemical properties, of these macrocycles and provides for the targeted design of biomimetic and potentially catalytically active porphyrins with specific conformations and binding cavities.