Durch sichtbares Licht vermittelte Organokatalyse mit N-heterocyclischen Carbenen
Zusammenfassung der Projektergebnisse
This project has focused on exploring the combination of light activation and organocatalysis by N-heterocyclic carbenes (NHCs). Inspired by the features of NHCs as reversible carbon-based nucleophiles with radical-stabilizing properties, we considered whether acyl azolium intermediates which result from addition/elimination of NHCs to carboxylic acid derivatives would exhibit similar reactivity to conventional aromatic ketones under light irradiation. Photochemical reactions of ketones are well established processes with numerous important applications in organic synthesis, yet analogous transformations with carbonyl substrates at the carboxylic acid oxidation level are typically not successful. By transiently converting a carboxylic acid derivative to a formal ketone in the form of an acyl azolium salt during the course of an NHC-organocatalyzed reaction, this limitation could be overcome and whole new directions for carbonyl photochemistry would be opened up. In this project, we have successfully validated this concept, which we are terming “Photo-NHC” catalysis and demonstrated the first application in a catalytic photoenolization/Diels-Alder (PEDA) reaction. Moreover, studies on stoichiometric acyl azolium salts have been conducted that reveal the potential of the concept in Norrish Type II and other classical photochemical reactions. The PEDA reaction between acid fluorides and trifluoroacetophenone substrates provided valuable isochroman-2-one products. Irradiation with UVA light was found to be crucial for reactivity with no product being observed in the dark or, indeed, without the NHC. Deuteration studies on the key acyl azolium intermediate as well as UV-Vis spectroscopic measurements supported the proposed photoreactivity. This work was published in Angewandte Chemie and has since attracted significant attention from the community, being cited over 70 times as of the end of 2022. To improve our understanding of the results, an in-depth mechanistic study was performed in collaboration with the group of Dr. Jan P. Götze (FU Berlin). (TD)-DFT studies revealed interesting insights into the key photoenolization step with hydrogen atom transfer in the singlet manifold calculated to be preferred. Alongside the development of catalytic systems, the project also studied stoichiometric acyl azolium salts with the aim of exploring their photochemical reactivity in comparison to classical aromatic ketones. Focusing on alkyl-substituted derivatives, Norrish Type II eliminations were developed while an adamantyl derivative, which cannot undergo elimination by virtue of Bredt’s rule, reacted exclusively via a Norrish-Yang cyclization process. This study, together with additional promising initial results on other carbonyl photochemical reactions, further demonstrates the potential of Photo-NHC catalysis and will serve as excellent starting points for future funding applications and research programs.
Projektbezogene Publikationen (Auswahl)
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Light‐Promoted Organocatalysis with N‐Heterocyclic Carbenes. ChemPhotoChem, 4(10), 5147-5153.
Mavroskoufis, Andreas; Jakob, Michael & Hopkinson, Matthew N.
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N‐Heterocyclic Carbene Catalyzed Photoenolization/Diels–Alder Reaction of Acid Fluorides. Angewandte Chemie International Edition, 59(8), 3190-3194.
Mavroskoufis, Andreas; Rajes, Keerthana; Golz, Paul; Agrawal, Arush; Ruß, Vincent; Götze, Jan P. & Hopkinson, Matthew N.
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Photo-NHC Catalysis: Accessing Ketone Photochemistry with Carboxylic Acid Derivatives. Synlett, 32(02), 95-101.
Hopkinson, Matthew N. & Mavroskoufis, Andreas
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Norrish type II reactions of acyl azolium salts. Tetrahedron, 100, 132497.
Mavroskoufis, Andreas; Rieck, Arielle & Hopkinson, Matthew N.
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A (TD-)DFT study on photo-NHC catalysis: photoenolization/Diels–Alder reaction of acid fluorides catalyzed by N-heterocyclic carbenes. Chemical Science, 14(15), 4027-4037.
Mavroskoufis, Andreas; Lohani, Manish; Weber, Manuela; Hopkinson, Matthew N. & Götze, Jan P.
