Efficient synthesis of monoacyl dipyrromethanes and their use in the preparation of sterically unhindered trans-porphyrins

The condensation of an aldehyde with a dipyrromethane bearing a sterically unhindered aryl substituent at the 5-position typically results in low yiel d and a mixture of porphyrin products derived from acidolytic scrambling. W e have developed a concise nonscrambling synthesis of such trans-porphyrins that takes advantage of the availability of multigram quantities of dipyrr omethanes. This route involves the selective monoacylation of the dipyrrome thanes with a pyridyl thioester, reduction of the monoacyl dipyrromethane t o the corresponding carbinol, and self-condensation of the carbinol to form the porphyrin. The monoacylation procedure has wide scope as demonstrated by the preparation of a set of 15 diverse monoacyl dipyrromethanes in good yield at the multigram scale. The dipyrromethanecarbinol self-condensation reaction is extremely rapid (<3 min) under mild room-temperature conditions and affords the trans-porphyrin in 16-28% yield. Analysis by laser-desorpt ion mass spectrometry (LD-MS) of samples from the elude reaction mixture re vealed no scrambling within the limit of detection (1 part in 100). The sel f-condensation is compatible with a range of electron-withdrawing or -relea sing substituents as well as substituents for building block applications ( TMS-ethyne, ethyne, iodo, ester). The absence of any detectable scrambling in the self-condensation enables a simple purification. The synthesis readi ly affords gram quantities of pure, sterically unhindered trans-porphyrins in a process involving minimal chromatography.