One-Flask Synthesis of Meso-Substituted Dipyrromethanes and Their Application in the Synthesis of Trans-Substituted Porphyrin Building Blocks

The reaction at room temperature of an aldehyde with excess pyrrole in the absence of solvent affords the meso-substituted dipyrromethane. The reaction is catalyzed with trifluoroacetic acid or with BF9,0(Et)2. The dipyrromethaue is purified by crystallixation or by flash chromatography on silica with eluants containing 1% triethylamine. The reaction is compatible with aliphatic or aromatic aldehydes, including 2,6disubstituted benraklehydes. Nine dipyrromethanes have been prepared in this manner in yields of 47-865, indicating the broad scope of tbe reaction. The dipyrromethanes are stable in the purified form in the absence of light and air. Similar reaction with terephthalaldehyde and pyrrole affords the correspondmg bis-dipyrromethane. The reaction of a mesosubstituted dipyrrometbane with an aldehyde muter the conditions of the two-step one-flask porphyrin synthesis affords a direct route to trans-substituted meso-porphyrins. Acidolysis of the dipyrromethane is negligible under the conditions of the porphyrin-forming reaction. Four porphyrins bearing peripheral functional groups and faciallyencumbering groups have been prepared which serve as key building blocks in the synthesis of linear porphyrin aoays. As part of a building block approach toward porphyrin model systems?-4 we had need of a direct synthesis of truns-substituted porphyrins. Trans-substituted porphyrins can be prepared by mixed aldehyde condensations, but tlte cis and rruns-substituted porphyrins usually am difficult to separate. Direct approaches to trans-substituted porphyrins are provided by condensation of dipyrromethanes with aldehydes. Four such routes, each distinguished by the type of dipyrromethane employed, ate shown in Scheme 1. In Route 1, reaction of a g-substituted, meso-substituted dipyrromethane with an aldehyde affords a porphyrin bearing substituents at the eight g and four meso-positions. 56 In Route 2. reaction of a ~-substituted dipyrromethane (lacking a meso-substituent) with an aldehyde affords a porphyrin bearing substituents at the eight p and two meso-positions.7 Steric interactions of the p and meso-substituents cause such porphyrins to be ruffled, and syntheses of h-substituted dipyrromethanes have often required laborious syntheses, yet these routes have been widely utilized due to lack of better alternatives. In Route 3, reaction of dipyrromethane (lacking p and meso-substituents) with an aldehyde affords the truns-substituted porphyrin bearing only two meso-substituents.* However, the synthesis of dipyrrometbane involves a three-step procedure starting from pyrrole and thiophosgene. For our purposes rrans-substituted meso-porphyrins without g-pyrrole substituents were the most desirable for model systems applications. As shown in Route 4, these porphyrins require access to meso-substituted dipyrrometbanes.