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 yield and a mixture of porphyrin products derived from acidolytic scrambling. We have developed a concise nonscrambling synthesis of such trans-porphyrins that takes advantage of the availability of multigram quantities of dipyrromethanes. This route involves the selective monoacylation of the dipyrromethanes with a pyridyl thioester, reduction of the monoacyl dipyrromethane to 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-desorption mass spectrometry (LD-MS) of samples from the crude reaction mixture revealed no scrambling within the limit of detection (1 part in 100). The self-condensation is compatible with a range of electron-withdrawing or -releasing 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 readily affords gram quantities of pure, sterically unhindered trans-porphyrins in a process involving minimal chromatography.
Rao
P D
PD
Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.
Littler
B J
BJ
Geier III
G R
GR
Lindsey
J S
JS
D000215:Acylation; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D011166:Porphyrins; D011758:Pyrroles; D008697:Methane