Synthetic approaches to regioisomerically pure porphyrins bearing four different meso-substituents

Article abstract of DOI:10.1016/0040-4020(95)00704-C

Regioisomerically pure porphyrins bearing four different meso-substituents have been synthesized via a 9-step route starting from pyrrole and carbonyl-containing compounds. This synthesis builds on a one-flask synthesis of 1,9-unsubstituted dipyrromethanes. An acyl group is introduced selectively in the 1-position of the dipyrromethane by use of an acid chloride and the dipyrromethane Grignard reagent, which resembles the pyrrole Grignard reagent. In contrast to the 2- and 5-positions of a monomeric pyrrole, the 1- and 9-positions of a dipyrromethane are relatively non-interacting and can be functionalized independently. A 2-aryl-1,3-benzoxathiolium tetrafluoroborate, available from carbonyl containing compounds, serves as a latent acyl equivalent and alkylates regiospecifically the 9-position of a 1-acyldipyrromethane. Alternatively the 1- and 9-positions of a dipyrromethane can be functionalized independently by successive alkylations with two different 2-aryl-1,3-benzoxathiolium tetrafluoroborates. Hydrolysis of the mono or di(benzoxathiolyl)dipyrromethane followed by reduction of the 1,9-diacyl-dipyrromethane affords the corresponding dipyrromethane-diol. An acid-catalyzed MacDonald-type 2 + 2 condensation of the dipyrromethane-diol and a 1,9-unsubstituted dipyrromethane at room temperature followed by oxidation with DDQ gives the porphyrin bearing four different meso-substituents. The reaction sequence results in a single porphyrin isomer without acidolytic scrambling of the four meso-substituents. The porphyrin structures were confirmed by laser desorption mass spectrometry and by high field high resolution proton NMR spectroscopy. An entire synthesis can be performed in about two weeks. The controlled stepwise synthesis of porphyrins bearing four different meso-substituents should enable preparation of multi-functionalized porphyrin building blocks for application in the synthesis of bioorganic model systems.