Technological Innovations in Photochemistry for Organic Synthesis: Flow Chemistry, High-Throughput Experimentation, Scale-up, and Photoelectrochemistry.

Photoinduced chemical transformations have received in recent years a tremendous amount of attention, providing a plethora of opportunities to synthetic organic chemists. However, performing a photochemical transformation can be quite a challenge because of various issues related to the delivery of photons. These challenges have barred the widespread adoption of photochemical steps in the chemical industry. However, in the past decade, several technological innovations have led to more reproducible, selective, and scalable photoinduced reactions. Herein, we provide a comprehensive overview of these exciting technological advances, including flow chemistry, high-throughput experimentation, reactor design and scale-up, and the combination of photo- and electro-chemistry.

Photocatalytic C-H Azolation of Arenes Using Heterogeneous Carbon Nitride in Batch and Flow.

The functionalization of aryl C(sp2 )-H bonds is a useful strategy for the late-stage modification of biologically active molecules, especially for the regioselective introduction of azole heterocycles to prepare medicinally-relevant compounds. Herein, we describe a practical photocatalytic transformation using a mesoporous carbon nitride (mpg-CNx ) photocatalyst, which enables the efficient azolation of various arenes through direct oxidation. The method exhibits a broad substrate scope and is amenable to the late-stage functionalization of several pharmaceuticals. Due to the heterogeneous nature and high photocatalytic stability of mpg-CNx , the catalyst can be easily recovered and reused leading to greener and more sustainable routes, using either batch or flow processing, to prepare these important compounds of interest in pharmaceutical and agrochemical research.

Dehydrogenative Azolation of Arenes in a Microflow Electrochemical Reactor.

The electrochemical synthesis of aryl azoles was performed for the first time in a microflow reactor. The reaction relies on the anodic oxidation of the arene partners making these substrates susceptible for C-H functionalization with azoles, thus requiring no homogeneous transition-metal-based catalysts. The synthetic protocol benefits from the implementation of a microflow setup, leading to shorter residence times (10 min), compared to previously reported batch systems. Various azolated compounds (22 examples) are obtained in good to excellent yields.

Novel Broccoli Sulforaphane-Based Analogues Inhibit the Progression of Pancreatic Cancer without Side Effects.

The naturally occurring isothiocyanate sulforaphane, found in Brassicaceae vegetables, is promising in cancer treatment, e.g., by the normalization of enhanced levels of NF-κB-signaling in tumor stem cells. We chemically synthesized seven sulforaphane analogues by substitution of the sulfinyl group (S(O)) to either sulfimidoyl (S(NR)) or sulfonimidoyl (S (O) (NR)) groups, and characterized them in the cell lines of pancreatic cancer and several other tumor entities, including the NCI-60 cell panel. MTT and colony forming assays, flow cytometry, immunohistochemistry, microRNA arrays, bioinformatics, tumor xenotransplantation, and Kaplan Meier survival curves were performed. Compared to sulforaphane, the analogue SF102 was most efficient in inhibition of viability, colony formation, tumor growth, and the induction of apoptosis, followed by SF134. Side effects were not observed, as concluded from the body weight and liver histology of chick embryos and survival of C. elegans nematodes. Among 6659 differentially regulated microRNAs, miR29b-1-5p, and miR-27b-5p were downregulated by sulforaphane compared to controls, but upregulated by SF102 and SF134 compared to sulforaphane, suggesting differential signaling. Each substance was involved in the regulation of several NF-κB-related target genes. In conclusion, sulforaphane analogues are promising for the development of highly active new drugs in cancer treatment.

Organophotoredox Hydrodefluorination of Trifluoromethylarenes with Translational Applicability to Drug Discovery.

Molecular editing such as insertion, deletion, and single atom exchange in highly functionalized compounds is an aspirational goal for all chemists. Here, we disclose a photoredox protocol for the replacement of a single fluorine atom with hydrogen in electron-deficient trifluoromethylarenes including complex drug molecules. A robustness screening experiment shows that this reductive defluorination tolerates a range of functional groups and heterocycles commonly found in bioactive molecules. Preliminary studies allude to a catalytic cycle whereby the excited state of the organophotocatalyst is reductively quenched by the hydrogen atom donor, and returned in its original oxidation state by the trifluoromethylarene.

Anion-π Interactions in Light-Induced Reactions: Role in the Amidation of (Hetero)aromatic Systems with Activated N-Aryloxyamides.

The importance of anion-π interactions as a driving force for chemical and biological processes is increasingly being recognized. In this communication, we describe for the first time its key participation in light-induced reactions. We show, in particular, how transient complexes formed through noncovalent anion-π interactions between electron-poor N-aryloxyamides and multiply-charged anions (such as carbonate or phosphate) can undergo facile light-promoted N-O cleavage, affording amidyl radicals that can subsequently be trapped by (hetero)aromatics.

Light-induced ruthenium-catalyzed nitrene transfer reactions: a photochemical approach towards N-acyl sulfimides and sulfoximines.

1,4,2-Dioxazol-5-ones are five-membered heterocycles known to decarboxylate under thermal or photochemical conditions, thus yielding N-acyl nitrenes. Described herein is a light-induced ruthenium-catalyzed N-acyl nitrene transfer to sulfides and sulfoxides by decarboxylation of 1,4,2-dioxazol-5-ones at room temperature, thus providing direct access to N-acyl sulfimides and sulfoximines under mild reaction conditions. In addition, a one-pot sulfur imidation/oxidation sequence catalyzed by a single ruthenium complex is reported.