Calix[3]pyrrole: A Missing Link in Porphyrin-Related Chemistry

A long-standing question in porphyrin chemistry is why pyrrole monomers selectively form tetrapyrrolic macrocycles, whereas the corresponding tripyrrolic macrocycles are never observed. Calix[3]pyrrole, a tripyrrolic porphyrinogen-like macrocycle bearing three sp3-carbon linkages, is a missing link molecule that might hold the key to this enigma; however, it has remained elusive. Here we report the synthesis and strain-induced transformations of calix[3]pyrrole and its furan analogue, calix[3]furan. These macrocycles are readily accessed from cyclic oligoketones. Crystallographic and theoretical analyses reveal that these three-subunit systems possess the largest strain energy among known calix[n]-type macrocycles. The ring-strain triggers transformation of calix[3]pyrrole into first calix[6]pyrrole and then calix[4]pyrrole under porphyrin cyclization conditions. The present results help explain the absence of naturally occurring three-pyrrole macrocycles and the fact that they are not observed as products or intermediate during classic porphyrin syntheses.