Two-Step, One-Flask Synthesis of a Meso-Substituted Phlorin

A two-step, one-flask reaction of pyrrole with pentafluorobenzaldehyde and acetone was investigated to determine the potential for a streamlined synthesis of a phlorin and/or 5-isocorrole as an alternative to stepwise, dipyrromethanecarbinol routes. Analytical-scale reactions were performed examining the effect of reactant concentration, reactant ratio, acid catalyst (TFA or BF3·OEt2), concentration of acid catalyst, oxidant quantity, and reaction time on the distribution of phlorin and 5-isocorrole as well as three additional porphyrinoids (porphodimethene, porphyrin, and corrole). Phlorin was observed ubiquitously in yields up to 20-26%, whereas 5-isocorrole was not detected. Promising reaction conditions for the one-flask synthesis of the phlorin were performed on a preparative scale. The best reaction condition afforded the phlorin in an isolated yield of 20-21% (249-268 mg). Preliminary attempts to extend the methodology to the preparation of phlorins derived from other ketones resulted in a low yield of phlorin from acetophenone (5%) and no detectable phlorin from benzophenone. The discovery of reaction conditions for the two-step, one-flask synthesis of a phlorin provides easier access to this interesting compound, and provides encouragement for the further study of reactions of pyrrole with an aldehyde and a ketone.