Efficient Synthesis of Monoacyl Dipyrromethanes and Their Use in the Preparation of Sterically Unhindered trans-Porphyrins

Abstract

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.

De NovoSynthesis of Gem-Dialkyl Chlorophyll Analogues for Probing and Emulating Our Green World

“…240,301 The dipyrromethane undergoes 1-acylation 313 upon conversion to the bis(pyrrole Grignard reagent) and treatment with an S -(2-pyridyl) thioate (Mukaiyama reagent, 121 ; Scheme 43) or phenyl formate (Scheme 44). 302,303,305 The acyl substituent ( B or H) and the aldehyde substituent ( A ) of the acyldipyrromethane ( 119, 120 ) are destined to become the chlorin 5- and 10-substituents, respectively.…”

Strategic Synthetic Approaches to Porphyrin-Based Artificial Light-Harvesting Systems for Solar Energy Utilization

“…The procedures for forming the dipyrromethane and elaborating the dipyrromethane to give the dipyrromethane-1,9-dicarbinol are reasonably well-developed and meet all six objectives. [29][30][31][32][33][34] However, the final porphyrin-forming step still presents a number of limitations despite extensive investigation. 27 The route to ABCD-porphyrins (depicted in Scheme 2) retains the desirable features of the existing "2 + 2" (dipyrromethane + dipyrromethane-1,9-dicarbinol) method, such as absence of scrambling, yet has significant advantages.…”

Recent Advances in the Synthesis of Corroles and Core-Modified Corroles

“…The ultimate solution (rooted in Lindsey's recent methodology [45] ) to this problem would lie in the reaction of diol 14 with bipyrrole (15). Unfortunately, this approach, similar to earlier attempts of Vogel et al, [46] failed (Scheme 9).…”