9-Acylation of 1-Acyldipyrromethanes Containing a Dialkylboron Mask for the α-Acylpyrrole Motif

Abstract

1,9-Diacyldipyrromethanes are important precursors to porphyrins, yet synthetic access remains limited owing to (1) poor conversion in the 9-acylation of 1-acyldipyrromethanes and (2) handling difficulties because acyldipyrromethanes typically streak upon chromatography and give amorphous powders upon attempted crystallization. A reliable means for converting a dipyrromethane to a 1-acyldipyrromethane-dialkylboron complex was recently developed, where the dialkylboron (BR(2)) unit renders the complex hydrophobic and thereby facilitates isolation. Herein a refined preparation of 1,9-diacyldipyrromethanes is presented that employs the 1-acyldipyrromethane-BR(2) complex as a substrate for 9-acylation. The dialkylboron unit provides protection for the alpha-acylpyrrole unit. 9-Acylation requires formation of the pyrrolyl-MgBr reagent and the presence of 1 equiv of a nonnucleophilic base to quench the proton liberated upon alpha-acylation. Reaction of the 1-acyldipyrromethane-BR(2) complex (1 equiv) with mesitylmagnesium bromide (2 equiv) followed by the addition of an acylating agent (S-2-pyridyl thioate or acid chloride, 1.1 equiv) gives the corresponding 1,9-diacyldipyrromethane-BR(2) complex. The acylation method afforded 1,9-diacyldipyrromethane-BR(2) complexes with limited or no chromatography in yields of 64-92%. The 1,9-diacyldipyrromethane-BR(2) complexes are stable to routine handling, are readily soluble in common organic solvents, crystallize readily, and can now be prepared in multigram quantities through use of stoichiometric quantities of reagents.

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

“…Regioselective Bromination of a Western Half–Dialkylboron Complex (Left) 296 and Examples of Related Complexes (Right) 303,304,433 …”

Progress towards synthetic chlorins with graded polarity, conjugatable substituents, and wavelength tunability

“…The synthesis of the Eastern half begins with dipyrromethane 1 [45–47], which contains the protected phenol. Treatment of 1 with EtMgBr at room temperature for 10 min followed by Mukaiyama reagent 2 [48] at −78 °C for 20 min gave the 1-acyldipyrromethane 3 in crude form. The latter was complexed with 9-BBN-OTf in the presence of triethylamine (TEA) to afford the complex 4 in 73% yield (two steps from 1 ).…”

“…The latter was complexed with 9-BBN-OTf in the presence of triethylamine (TEA) to afford the complex 4 in 73% yield (two steps from 1 ). Such 1-acyldipyrromethane–boron complexes are more readily handled and derivatized given the masking of the α-acylpyrrole motif [48,49]. Bromination of 4 using NBS following a standard procedure [48] afforded the compound 5 in 77% yield.…”

“…Such 1-acyldipyrromethane–boron complexes are more readily handled and derivatized given the masking of the α-acylpyrrole motif [48,49]. Bromination of 4 using NBS following a standard procedure [48] afforded the compound 5 in 77% yield. Compound 5 was used directly for the chlorin-forming reaction without decomplexation of the boron moiety.…”

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.…”