Copper(II) Induced Oxidation of Enolates via Visible Light Induced Homolysis

Projektinformationen

CuII-VLIH

ID Finanzhilfevereinbarung: 101066526

DOI

10.3030/101066526

Projekt abgeschlossen

EK-Unterschriftsdatum 16 August 2022

Startdatum 1 September 2022

Enddatum 31 August 2024

Finanziert unter

• Marie Skłodowska-Curie Actions (MSCA)

Gesamtkosten

Keine Daten

EU-Beitrag

€ 189 687,36

Koordiniert durch

UNIVERSITAET REGENSBURG
Germany

Periodic Reporting for period 1 - CuII-VLIH (Copper(II) Induced Oxidation of Enolates via Visible Light Induced Homolysis)

Berichtszeitraum: 2022-09-01 bis 2024-08-31

Zusammenfassung vom Kontext und den Gesamtzielen des Projekts

CuII-VLIH is envisaged and designed to develop novel synthetic strategies to access a wide variety of bioactive cyclic and acyclic 1,4-dicarbonyl organic compounds via Cu(II) mediated oxidation of enolates using visible light-induced homolysis (VLIH). Considering the earth's abundance and low cost, Cu(II)-based complexes are recently being utilized as efficient photocatalysts and as low-cost alternatives to the Ru- or Ir-based complexes. A range of Cu(II)-complexes was screened in the proposed work for optimizing the efficiency of the aforementioned enolate oxidation processes via photoredox catalysis. Using this concept, we could develop the oxoalkylation of styrenes through the generation of photoinduced reactive species (enol radicals) from 1,3-dicarbonyls. The enol radicals are productively exploited for the synthesis of a range of biologically significant dicarbonyl compounds by successive reactions with an alkene acceptor followed by quenching with molecular oxygen. We believe this concept of enol radical generation using CuII-VLIH will address the long-standing problem of finding an appropriate classical activation mode for different varieties of enolizable ketones. Thus CuII-VLIH bridges the gap between the fields of medicine and energy by enabling facile and highly selective synthesis of a wide array of high-value heterocyclic moieties by utilizing copper complexes as environmentally benign photoredox catalysts and visible light as a sustainable source of energy.

Arbeit, die ab Beginn des Projekts bis zum Ende des durch den Bericht erfassten Berichtszeitraums geleistet wurde, und die wichtigsten bis dahin erzielten Ergebnisse

Using this concept, we could develop the oxoalkylation of styrenes through the generation of photoinduced reactive species (enol radicals) from 1,3-dicarbonyls. The enol radicals are productively exploited for the synthesis of a range of biologically significant dicarbonyl compounds by successive reactions with an alkene acceptor followed by quenching with molecular oxygen and this result has been published in a top-tier journal, ACS Catal. 2022, 12, 14398-14407. Using the concept of VLIH we have further developed an efficient strategy using low-cost bulk chemical acetyl halides or haloformates for the visible-light-mediated Cu(II)-catalyzed synthesis of α-haloketones from vinyl arenes under aerobic conditions (ACS Organic & Inorganic Au 2023, 3, 171-176). An extensive and instructive review article on the various aspects of photocatalytic enolate oxidation has been already written and will be published very soon.

Fortschritte, die über den aktuellen Stand der Technik hinausgehen und voraussichtliche potenzielle Auswirkungen (einschließlich der bis dato erzielten sozioökonomischen Auswirkungen und weiter gefassten gesellschaftlichen Auswirkungen des Projekts)

The researcher also worked on generation of aryl carboxyl radical intermediate via VLIH of a ArCOO-Cu(II) complex which would add to an alkyne to produce vinyl radical intermediate. If this is possible, the vinyl radical can undergo cascade cyclization divergently depending on the reaction conditions to produce spirolactone dienone compounds and isocoumarin analogs. Despite several trials taking benzoic acid and phenylacetylene as model substrate, we have failed to achieve the target molecules with varying different reaction parameters. A deep dive into the photocatalytic cycle has led to the conclusion that the reoxidation of Cu(I) to Cu(II) to close the catalytic cycle could not take place in the absence of an external oxidant. In this context, we thought electrochemical anodic oxidation of Cu(I) to Cu(II) could solve this longstanding issue. However, combining benzoic acid and phenylacetylene through electrochemical paired electrolysis, led to a completely different product 2-methyl-3,6-diphenylpyridine and this outcome incited us to explore more, and we could publish the work in a high-impact journal, Angew. Chem. Int. Ed. 2024, doi.org/10.1002/anie.202411930. However, we still aim to find an alternative to the terminal reoxidation step of the Cu(II)-photocatalytic cycle by combining anodic oxidation with the VLIH process to accomplish an overall catalytic pathway avoiding stoichiometric external oxidant.

Heteroleptic Cu(I)-complexes (synthesis of heteroleptic CuII-complexes are difficult) were not suitable for the enolate oxidation process, however, they could be efficiently utilized for olefin difucntionalization e.g. β-chloroacylation of alkenes and alkynes (10.26434/chemrxiv-2024-kzmzm-v2; submitted in Nature Catalysis).

Mechanistic rationale for Photocatalytic enolate oxidation using CuII and 4CZIPN