SYNTHETIC APPROACHES TO REGIOISOMERICALLY PURE PORPHYRINS BEARING 4 DIFFERENT MESOSUBSTITUENTS

Regioisomerically pure porphyrins bearing four different meso-substitu ents have been synthesized via a 9-step route starting from pyrrole an d carbonyl-containing compounds. This synthesis builds on a one-flask synthesis of 1,9-unsubstituted dipyrromethanes. An acyl group is intro duced selectively in the 1-position of the dipyrromethane by use of an acid chloride and the dipyrromethane Grignard reagent which resembles die pyrrole Grignard reagent. In contrast to the 2- and 5-positions o f 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. Alternati vely 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(benzo xathiolyl)dipyrromethane followed by reduction of the 1,9-diacyl-dipyr romethane affords the corresponding dipyrromethane-diol, An acid-catal yzed MacDonald-type 2 + 2 condensation of the dipyrromethane-diol and a 1,9-unsubstituted dipyrromethane at room temperature followed by oxi dation with DDQ gives the porphyrin bearing four different meso-substi tuents. The reaction sequence resulted in a single porphyrin isomer wi thout acidolytic scrambling of the four meso-substituents. The porphyr in structures were confirmed by laser desorption mass spectrometry and by high field high resolution proton NMR spectroscopy. An entire synt hesis can be performed in about two weeks. The controlled stepwise syn thesis of porphyrins bearing four different meso-substituents should e nable preparation of multi-functionalized porphyrin building blocks fo r application in the synthesis of bioorganic model systems.