Heterogeneous Semiconductors as Versatile Photocatalysts for Organic Synthesis

Visible-light is a powerful “reagent” for sustainable synthetic organic chemistry. In particular, the combination of photo- and nickel catalysis (metallaphotocatalysis) has emerged as a valuable strategy for carbon–carbon and carbon–heteroatom cross-couplings. This research field is dominated by expensive homogeneous noble metal complexes that can only convert a small portion of visible light (<500 nm) into chemical energy. The highenergy photons that excite the photocatalyst can result in unwanted side reactions and the homogenous nature of these does not allow for straightforward catalyst recycling. Heterogeneous semiconductors that absorb visible light are a promising sustainable alternative to noble metal photocatalysts (Chapter 2). Their potential for metallaphotocatalytic C–N cross-couplings was demonstrated (Chapter 3). This transformation suffers from deactivation of the nickel catalyst using homogeneous photocatalysts. The broad absorption range (up to 700 nm) of an organic, heterogeneous carbon nitride photocatalyst (CN‐OA‐m) allows controlling the rate of the bond-forming step by carefully selecting the wavelength thereby preventing catalyst deactivation. This is not only crucial for the reproducibility of such reactions, but also expands the scope to substrates that were previously unsuitable. The redox potential of a carbon nitride photocatalyst can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials (Chapter 4). This was the key to design photo‐chemo‐enzymatic cascades that enable the synthesis of (S)‐ or (R)‐ 1-phenylethan-1-ol from ethylbenzene by choosing the irradiation wavelength and the enzyme co-catalyst. In contrast to common photocatalysts that can be only excited using short wavelengths, abundant organic dyes absorb broadly across the entire visible-light spectrum. Inspired by dye-sensitized solar cells, the short-lived excited singlet states of such dyes were harnessed for light-mediated cross-coupling reactions (Chapter 5). Immobilization of a nickel catalyst on dye-sensitized titanium dioxide results in a material that catalyzes carbon–heteroatom and carbon–carbon bond formations. The modular approach of dye-sensitized metallaphotocatalysts (DSMPs) accesses the entire visible light spectrum and allows tackling selectivity issues resulting from low-wavelengths strategically. The concept overcomes current limitations of metallaphotocatalysis by unlocking the potential of dyes that were previously unsuitable. However, recycling studies suffered from a gradual decrease of the yield due to leaching of the nickel catalyst and the dye from the surface of TiO2. This was rationalized by the weak interaction between carboxylic acid anchoring groups and titanium dioxide. Therefore, recyclable, bifunctional materials for metallaphotocatalytic C–S cross-couplings were developed (Chapter 6). Key to the success was the permanent immobilization through phosphonic acid anchor groups. The optimized catalyst harvests a broad range of the visible light spectrum and requires a nickel loading of only ~0.1 mol%. Another robust alternative to organic dyes that does not suffer from photobleaching was realized, by immobilizing carbon dots on titanium dioxid (Chapter 7). The potential of these sustainable materials was demonstrated for various carbon–heteroatom cross-couplings

Emerging concepts in photocatalytic organic synthesis

Visible light photocatalysis has become a powerful tool in organic synthesis that uses photons as traceless, sustainable reagents. Most of the activities in the field focus on the development of new reactions via common photoredox cycles, but recently a number of exciting new concepts and strategies entered less charted territories. We survey approaches that enable the use of longer wavelengths and show that the wavelength and intensity of photons are import parameters that enable tuning of the reactivity of a photocatalyst to control or change the selectivity of chemical reactions. In addition, we discuss recent efforts to substitute strong reductants, such as elemental lithium and sodium, by light and technological advances in the field

Heterogeneous metallaphotoredox catalysis in a continuous-flow packed-bed reactor

Metallaphotoredox catalysis is a powerful and versatile synthetic platform that enables cross-couplings under mild conditions without the need for noble metals. Its growing adoption in drug discovery has translated into an increased interest in sustainable and scalable reaction conditions. Here, we report a continuous-flow approach to metallaphotoredox catalysis using a heterogeneous catalyst that combines the function of a photo- and a nickel catalyst in a single material. The catalyst is embedded in a packed-bed reactor to combine reaction and (catalyst) separation in one step. The use of a packed bed simplifies the translation of optimized batch reaction conditions to continuous flow, as the only components present in the reaction mixture are the substrate and a base. The metallaphotoredox cross-coupling of sulfinates with aryl halides was used as a model system. The catalyst was shown to be stable, with a very low decrease of the yield (≈1% per day) during a continuous experiment over seven days, and to be effective for C–O arylations when carboxylic acids are used as nucleophile instead of sulfinates

Programmable Photocatalytic Activity of Multicomponent Covalent Organic Frameworks Used as Metallaphotocatalysts

The multicomponent approach allows to incorporate several functionalities into a single covalent organic framework (COF) and consequently allows the construction of bifunctional materials for cooperative catalysis. The well-defined structure of such multicomponent COFs is furthermore ideally suited for structure-activity relationship studies. We report a series of multicomponent COFs that contain acridine- and 2,2’-bipyridine linkers connected through 1,3,5-benzenetrialdehyde derivatives. The acridine motif is responsible for broad light absorption, while the bipyridine unit enables complexation of nickel catalysts. These features enable the usage of the framework materials as catalysts for light-mediated carbon−heteroatom cross-couplings. Variation of the node units shows that the catalytic activity correlates to the keto-enamine tautomer isomerism. This allows switching between high charge-carrier mobility and persistent, localized charge-separated species depending on the nodes, a tool to tailor the materials for specific reactions. Moreover, nickel-loaded COFs are recyclable and catalyze cross-couplings even using red light irradiation

Chromoselective Photocatalysis Enables Stereocomplementary Biocatalytic Pathways

Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photochemo-enzymatic cascades that give either the (S)- or the (R)- enantiomer of phenylethanol. In combination with an unspecific peroxygenase from Agrocybe aegerita, green light irradiation of CNOA-m led to the enantioselective hydroxylation of ethylbenzene to (R)-1-phenylethanol (99% e.e.). In contrast, blue light irradiation triggered the photocatalytic oxidation of ethylbenzene to acetophenone, which in turn was enantioselectively reduced with an alcohol dehydrogenase from Rhodococcus ruber to form (S)-1-phenylethanol (93% e.e.)

Intraligand Charge Transfer Enables Visible‐Light‐Mediated Nickel‐Catalyzed Cross‐Coupling Reactions

We demonstrate that several visible‐light‐mediated carbon−heteroatom cross‐coupling reactions can be carried out using a photoactive NiII precatalyst that forms in situ from a nickel salt and a bipyridine ligand decorated with two carbazole groups (Ni(Czbpy)Cl2). The activation of this precatalyst towards cross‐coupling reactions follows a hitherto undisclosed mechanism that is different from previously reported light‐responsive nickel complexes that undergo metal‐to‐ligand charge transfer. Theoretical and spectroscopic investigations revealed that irradiation of Ni(Czbpy)Cl2 with visible light causes an initial intraligand charge transfer event that triggers productive catalysis. Ligand polymerization affords a porous, recyclable organic polymer for heterogeneous nickel catalysis of cross‐coupling reactions. The heterogeneous catalyst shows stable performance in a packed‐bed flow reactor during a week of continuous operation

Overcoming Limitations in Dual Photoredox/Nickel catalyzed C–N Cross-Couplings due to Catalyst Deactivation

Dual photoreodox/nickel catalyzed C–N cross-couplings are an attractive alternative to the palladium catalyzed Buchwald-Hartwig reaction, but are limited to aryl halides containing electron-withdrawing groups. We show that the formation of catalytically inactive nickel-black is responsible for this limitation. Deposition of nickel-black further deactivates heterogeneous photocatalysts restricting their recyclability. We demonstrate that catalyst deactivation can be avoided by the combination of nickel catalysis and a carbon nitride semiconductor. The broad absorption range of the organic, heterogeneous photocatalyst enables a wavelength dependent reactivity control to prevent nickel-black formation. A second approach is to run the reactions at high concentrations to increase the formation of nickel-amine complexes that reduce nickel-black formation. This allows reproducible, selective C–N cross-couplings of electron-rich aryl bromides.<br /

Carbon dot/TiO2 nanocomposites as photocatalysts for metallaphotocatalytic carbon–heteroatom cross-couplings

Carbon dots have been previosly immobilized on titanium dioxide to generate photocatalysts for pollutant degradation and water splitting. Here we demonstrate that these nanocomposites are valuable photocatalysts for metallaphotocatalytic carbon–heteroatom cross-couplings. These sustainable materials show a large applicability, high photostability, excellent reusability, and broadly absorb across the visible-light spectrum

Switching Between Enantiomers by Combining Chromoselective Photocatalysis and Biocatalysis

Controlling the selectivity of a chemical reaction with external stimuli is common in thermal processes, but rare in visible-light photocatalysis. Here we show that the redox potential of a carbon nitride photocatalyst (CN-OA-m) can be tuned by changing the irradiation wavelength to generate electron holes with different oxidation potentials. This tuning was the key to realizing photo-chemo-enzymatic cascades that give either the (S)- or the (R)-enantiomer of phenylethanol. In combination with an unspecific peroxygenase from Agrocybe aegerita, green light irradiation of CN-OA-m led to the enantioselective hydroxylation of ethylbenzene to (R)-1-phenylethanol (99% ee). In contrast, blue light irradiation triggered the photocatalytic oxidation of ethylbenzene to acetophenone, which in turn was enantioselectively reduced with an alcohol dehydrogenase from Rhodococcus ruber to form (S)-1-phenylethanol (93% ee).</a