Challenges and Future Perspectives in Photocatalysis: Conclusions from an Interdisciplinary Workshop.

Photocatalysis is a versatile and rapidly developing field with applications spanning artificial photosynthesis, photo-biocatalysis, photoredox catalysis in solution or supramolecular structures, utilization of abundant metals and organocatalysts, sustainable synthesis, and plastic degradation. In this Perspective, we summarize conclusions from an interdisciplinary workshop of young principal investigators held at the Lorentz Center in Leiden in March 2023. We explore how diverse fields within photocatalysis can benefit from one another.

Simultaneous Inside and Outside Functionalization of Single-Walled Carbon Nanotubes.

Functionalizing single-walled carbon nanotubes (SWCNTs) in a robust way that does not affect the sp carbon framework is a considerable research challenge. Here we describe how triiodide salts of positively charged macrocycles can be used not only to functionalize SWCNTs from the outside, but simultaneously from the inside. We employed disulfide exchange in aqueous solvent to maximize the solvophobic effect and therefore achieve a high degree of macrocycle immobilization.

Triplet Energy Transfer Mechanism in Copper Photocatalytic N- and O-Methylation.

Methylation reactions are chemically simple but challenging to perform under mild and non-toxic conditions. A photochemical energy transfer strategy was merged with copper catalysis to enable fast reaction times of minutes and broad applicability to N-heterocycles, (hetero-)aromatic carboxylic acids, and drug-like molecules in high yields and good functional group tolerance. Detailed mechanistic investigations, using kinetic analysis, aprotic MS, UV/Vis, and luminescence quenching experiments revealed a triplet-triplet energy transfer mechanism between hypervalent iodine(III) reagents and readily available photosensitizers.

Site-Selective Electrochemical Oxidation of Glycosides.

Quinuclidine-mediated electrochemical oxidation of glycopyranosides provides C3-ketosaccharides with high selectivity and good yields. The method is a versatile alternative to Pd-catalyzed or photochemical oxidation and is complementary to the 2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPO)-mediated C6-selective oxidation. Contrary to the electrochemical oxidation of methylene and methine groups, the reaction proceeds without oxygen.

Carboxylic Acids as Adaptive Functional Groups in Metallaphotoredox Catalysis.

The development of palladium-catalyzed cross-coupling methods for the activation of C(sp)-Br bonds facilitated access to arene-rich molecules, enabling a concomitant increase in the prevalence of this structural motif in drug molecules in recent decades. Today, there is a growing appreciation of the value of incorporating saturated C(sp)-rich scaffolds into pharmaceutically active molecules as a means to achieve improved solubility and physiological stability, providing the impetus to develop new coupling strategies to access these challenging motifs in the most straightforward way possible. As an alternative to classical two-electron chemistry, redox chemistry can enable access to elusive transformations, most recently, by interfacing abundant first-row transition-metal catalysis with photoredox catalysis.

Allocolchicines─Synthesis with Electro-organic Key Transformations.

The naturally occurring colchicine and allocolchicines in the meadow saffron are potentially active ingredients for cancer therapy. A concise protocol for the sustainable synthesis of allocolchicines using up to two electro-organic key transformations is demonstrated. This straightforward synthesis of -acetylcolchinol methyl ether in a five-step protocol was adopted using protecting groups to enable access to -acetylcolchinol and the phosphate derivative ZD6126.

Facile access to foldable redox-active flavin-peptide conjugates.

A convenient approach for the synthesis of foldable redox-active flavin peptide conjugates was established. A model β-hairpin oligopeptide motif was utilized to demonstrate that azidolysine side-chains are readily functionalised with an alkyne-bearing flavine derivative. The folding equilibrium of the peptide backbone as well as the redox behaviour of the flavin moieties remains intact after the conjugation.

Reproducibility in Electroorganic Synthesis-Myths and Misunderstandings.

The use of electric current as a traceless activator and reagent is experiencing a renaissance. This sustainable synthetic method is evolving into a hot topic in contemporary organic chemistry. Since researchers with various scientific backgrounds are entering this interdisciplinary field, different parameters and methods are reported to describe the experiments.

Dynamic Covalent Formation of Concave Disulfide Macrocycles Mechanically Interlocked with Single-Walled Carbon Nanotubes.

The formation of discrete macrocycles wrapped around single-walled carbon nanotubes (SWCNTs) has recently emerged as an appealing strategy to functionalize these carbon nanomaterials and modify their properties. Here, we demonstrate that the reversible disulfide exchange reaction, which proceeds under mild conditions, can install relatively large amounts of mechanically interlocked disulfide macrocycles on the one-dimensional nanotubes. Size-selective functionalization of a mixture of SWCNTs of different diameters were observed, presumably arising from error correction and the presence of relatively rigid, curved π-systems in the key building blocks.

About the selectivity and reactivity of active nickel electrodes in C-C coupling reactions.

Active anodes which are operating in highly stable protic media such as 1,1,1,3,3,3-hexafluoroisopropanol are rare. Nickel forms, within this unique solvent, a non-sacrificial active anode at constant current conditions, which is superior to the reported powerful molybdenum system. The reactivity for dehydrogenative coupling reactions of this novel active anode increases when the electrolyte is not stirred during electrolysis.

Scalable and safe synthetic organic electroreduction inspired by Li-ion battery chemistry.

Reductive electrosynthesis has faced long-standing challenges in applications to complex organic substrates at scale. Here, we show how decades of research in lithium-ion battery materials, electrolytes, and additives can serve as an inspiration for achieving practically scalable reductive electrosynthetic conditions for the Birch reduction. Specifically, we demonstrate that using a sacrificial anode material (magnesium or aluminum), combined with a cheap, nontoxic, and water-soluble proton source (dimethylurea), and an overcharge protectant inspired by battery technology [tris(pyrrolidino)phosphoramide] can allow for multigram-scale synthesis of pharmaceutically relevant building blocks.

Mo-Based Oxidizers as Powerful Tools for the Synthesis of Thia- and Selenaheterocycles.

A highly efficient synthetic protocol for the synthesis of thia- and selenaheterocycles has been developed. By employing a MoCl -mediated intramolecular dehydrogenative coupling reaction, a broad variety of structural motifs was isolated in yields up to 94 %. The electrophilic key transformation is tolerated by several labile moieties like halides and tertiary alkyl groups.

Mild, Fast, and Easy To Conduct MoCl-Mediated Dehydrogenative Coupling Reactions in Flow.

A convenient and straightforward approach to performing oxidative coupling reactions in flow is presented. A collection of electron-rich benzene derivatives was subjected to this protocol, and the distinct utility of molybdenum pentachloride (MoCl) is established. Using this unexplored protocol, biphenyls could be obtained in 21-91% isolated yield.

Electrochemical instability of highly fluorinated tetraphenyl borates and syntheses of their respective biphenyls.

Highly fluorinated tetraphenyl borate anions are of importance as weakly coordinating anions in metalorganic reactions. However, at high positive potentials their electrochemical stability in organic solvents is not sufficient. This was investigated by a comprehensive cyclic voltammetry study and can be used synthetically to generate highly fluorinated biphenyls.

Active Molybdenum-Based Anode for Dehydrogenative Coupling Reactions.

A new and powerful active anode system that can be operated in 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) has been discovered. In HFIP the molybdenum anode forms a compact, conductive, and electroactive layer of higher-valent molybdenum species. This system can replace powerful but stoichiometrically required Mo reagents for the dehydrogenative coupling of aryls.