Regioselective Synthesis of Conformationally Designed Porphyrins with Mixed meso-Substitutent Types and Distortion Modes

摘要

Porphyrins can be substituted easily and in high yield at the nieso positions by using organolithium reagents. When S4-symmetric porphyrins such as 2,3,7,8,12,13,17, 18-octaethyl-porphyrins are used as starting materials, it is possible to per-form four such substitution reactions in sequence, resulting in the formation of nona- deca- undeca- and dodecasubsti-tuted porphyfins. Irdrodvwtiou ot 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 mat-erial being converted into stable porphomethenes. When one meso substituent is already present, introduction of the se-cond residue proceeds with regiochemical preference for the 5,10-orientation over the 5,15-orientation, permitting a dir-ected synthesis of 5,10-disubstituted porphyrins. Direct ox-idation of the Meisenheimer-type intermediate formed after addition of RLi permits the introduction of two meso substitu-ents in a one-pot reaction, again with preferential formationof the 5,10-disubstituted product. Using BuLi and PhLi as representative alkyl and aryllithium reagents, general reac-tion sequences were developed. These allow the preparation of meso-substituted octaethylporphyrins with almost any de-sired regiochemical combination of alkyl and aryl substitu-ents. 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 crysta ~apbic studies of the reaction products provided the means for the first ana-lysis of the conformational effects of different types and ar-rangements 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 macro-cycles and provides for the targeted design of biomimetic and potentially catalytically active porphyrins with specific conformations and binding cavities.