Rational Synthesis of Trans-Substituted Porphyrin Building Blocks Containing One Sulfur or Oxygen Atom in Place of Nitrogen at a Designated Site

The use of heteroatom-substituted porphyrins in bioorganic and materials chemistry requires the ability to position a variety of substituents in a controlled manner about the porphyrin periphery. We describe a rational route to trans -AB 2 C-type porphyrins bearing one oxygen atom (N 3 O) or one sulfur atom (N 3 S) in a designated location in the porphyrin core. The synthesis involved four stages: (1) Acid-catalyzed condensation of a furyl- or thienylcarbinol in excess pyrrole afforded the aryl-substituted furyl- or thienylpyrromethane in high yield. (2) Treatment of the furyl- or thienylpyrromethane with an acid chloride catalyzed by SnCl 4 or AlCl 3 afforded the corresponding diketo product. (3) Reduction with NaBH 4 in alcoholic solvents gave the furyl- or thienylpyrromethanediols. (4) Reaction of a furylpyrromethanediol, thienylpyrromethanediol, or dipyrromethanediol with a dipyrromethane in a one-flask process of condensation followed by oxidation gave the corresponding porphyrin. Reaction conditions previously identified to minimize scrambling in a dipyrromethane−aldehyde condensation were found to be effective in this application. Thus, reaction with 10 mM reactants in acetonitrile at 0 °C containing BF 3 ·Et 2 O and NH 4 Cl followed by oxidation with DDQ resulted in the desired porphyrin (10−20% yields) without acidolysis. In this manner, N 3 O-, N 3 S-, or N 4 -porphyrins bearing 5-( p -iodophenyl), 15-[4-(2-(trimethylsilyl)ethynyl)phenyl], and 10,20-di- p -tolyl groups have been made. This set of trans-substituted porphyrin building blocks is expected to be useful in the synthesis of biomimetic energy transduction systems.