3-Aryl-2,5-Dihydropyrroles via Catalytic Carbonyl-Olefin Metathesis

Abstract

Herein, we describe the development of a synthetic strategy towards chiral 3-pyrrolines based on the design principle of iron(III)-catalyzed carbonyl-olefin metathesis. This approach takes advantage of commercially available amino acids as chiral pool reagents and FeCl3 as a Lewis acid catalyst. Our strategy is characterized by its operational simplicity, mild reaction conditions and functional group tolerance. Investigations show that an electron-deficient nitrogen protecting group overcomes limitations arising from competitive binding of the Lewis acid catalyst to unfavorable Lewis basic sites, which ultimately enables catalytic turnover.

Mechanistic Investigations of the Iron(III)-Catalyzed Carbonyl-Olefin Metathesis Reaction

“…4 Recently, in an effort to enhance the synthetic utility of carbonyl-olefin metathesis, our group has reported a catalytic variant of this reaction which relies on FeCl 3 as an environmentally benign and economically sustainable catalyst, which was followed by a report from Li and coworkers. 5 While our previously reported catalytic carbonyl-olefin metathesis strategy has proven useful toward the synthesis of many cyclic scaffolds including cycloalkenes, 5,6 polycyclic aromatic hydrocarbons, 7 and azacycles, 8 we anticipate that a theoretical and experimental investigation of the reaction mechanism can provide insight which will lead to further improvements in the reaction design.…”

Catalytic Isofunctional Reactions—Expanding the Repertoire of Shuttle and Metathesis Reactions

“…Ther eaction exhibited broad functional group tolerance and proved applicable to the synthesis of tetra-substituted alkenes.A lthough geminal dimethyl-substituted alkenes afforded the highest reaction yields,o ther alkenes bearing cis or trans aryl groups also proved to be suitable substrates.D etailed mechanistic studies were performed to elucidate the mechanism of this process (Scheme 29 B). [99] Shortly after the initial publication from the group of Schindler,t he group of Li also reported an FeCl 3 -catalyzed ring-closing,c arbonyl/alkene metathesis. As ac onsequence,t he authors propose that the formation and fragmentation of the intermediate oxetane 66 is concerted and this was ratified by DFT studies.T he Schindler group have also applied this methodology towards the synthesis of polycyclic aromatic hydrocarbons [98] and dihydropyrroles.…”

Katalytische, isofunktionelle Reaktionen – Erweiterung des Repertoires an Shuttle‐ und Metathesereaktionen

“…[20] Urprünglich wurde dies durch die Wittig-Reaktion und andere verwandte Methoden, darunter Horner-Wadsworth-Emmons-, Peterson-und Julia-artige Reaktionen, erreicht. [94] Es wurde entdeckt, dass das bizyklische Hydrazin 55 die Carbonyl/Alken-Metathese von Cyclopropenen und Aldehyden zu b,g-ungesättigten Aldehyden [98] und Dihydropyrrolen [99] an. In Falle der Wittig-Reaktion liefert die Entstehung einer P=O-Bindung die Tr iebkraft.…”

“…Der erste stammt von der Gruppe um Lambert und nutzt einen organokatalytischen Ansatz (Schema 27 A). [ [98] und Dihydropyrrolen [99] an.…”