Indole Nucleophile Triggers Mechanistic Divergence in Ni-Photoredox N-Arylation.

This study presents a Ni-photoredox method for indole N-arylation, broadening the range of substrates to include indoles with unprotected C3-positions and base-sensitive groups. Through detailed mechanistic inquiries, a Ni(I/III) mechanism was uncovered, distinct from those commonly proposed for Ni-catalyzed amine, thiol, and alcohol arylation, as well as from the Ni(0/II/III) cycle identified for amide arylation under almost identical conditions. The key finding is the formation of a Ni(I) intermediate bearing the indole nucleophile as a ligand prior to oxidative addition, which is rare for Ni-photoredox carbon-heteroatom coupling and has a profound impact on the reaction kinetics and scope. The pre-coordination of indole renders a more electron-rich Ni(I) intermediate, which broadens the scope by enabling fast reactivity even with challenging electron-rich aryl bromide substrates. Thus, this work highlights the often-overlooked influence of X-type ligands on Ni oxidative addition rates and illustrates yet another mechanistic divergence in Ni-photoredox C-heteroatom couplings.

Benzoic Acid Serves as Precursor of Catalytic HAT Reagent in a Two-Molecule Photoredox System.

The photoinduced regioselective HAT reactions of acetals, ethers, and alcohols using benzoic acids in a two-molecule photoredox system led to the formation of new C-C bonds with alkenes under mild conditions. Aryl carboxy radicals generated from benzoic acids in a two-molecule photoredox system can function as catalytic HAT reagents, even though an excess amount of a hydrogen donor substrate is required. Various acetals, ethers, alcohols, and alkenes can be employed in the photoreaction to provide both high yields of adducts and high recoveries of benzoic acids.

Benzylic C(sp3)-H fluorination.

The selective fluorination of C(sp3)-H bonds is an attractive target, particularly for pharmaceutical and agrochemical applications. Consequently, over recent years much attention has been focused on C(sp3)-H fluorination, and several methods that are selective for benzylic C-H bonds have been reported. These protocols operate via several distinct mechanistic pathways and involve a variety of fluorine sources with distinct reactivity profiles. This review aims to give context to these transformations and strategies, highlighting the different tactics to achieve fluorination of benzylic C-H bonds.

Benzothiadiazole-Based Ordered Mesoporous Polymer as a Versatile, Metal-Free Heterogeneous Photocatalyst.

Visible-light active heterogeneous organophotocatalysts have recently gained considerable interest in organic synthetic community. Ordered mesoporous polymers (OMPs) are highly promising as heterogeneous alternative to traditional precious metal/organic dyes-based photocatalysts. Herein, we report the preparation of a benzothiadiazole functionalized OMPs (BT-MPs) through a "bottom-up" strategy. High ordered periodic porosity, large surface area, excellent stability and rational energy-band structures guarantee the high catalytic activity of BT-MPs. As a result, at least six conversions, e.g., the [3+2] cycloaddition of phenols with olefins, the selective oxidation of sulfides, the C-3 thiocyanation of indole and the aminothiocyanation of ß-keto ester, could be promoted smoothly by BT-MPs. In addition, BT-MPs was readily recovered with well maintaining its photocatalytic activity and could be reused for at least eight times. This study highlights the potential of exploiting photoactive OMPs as recyclable, robust and metal-free heterogeneous photocatalysts.

Biomimetic Activation of N-Nitrosamides with Red Light-Triggered Nitric Oxide Release via Mediated Electron Transfer.

Mediated electron transfer (MET) is fundamental to many biological functions, including cellular respiration, photosynthesis, and enzymatic catalysis. However, leveraging the MET process to enable the release of therapeutic gases has been largely unexplored. Herein, we report the bio-inspired activation of a series of UV-absorbing N-nitrosamide derivatives (NOA) under red light exposure, enabling the quantitative release of nitric oxide (NO) gasotransmitter via an MET process. The cornerstone of our design is the covalent linkage of a 2,4-dinitroaniline moiety, which acts as an electron mediator to the N-nitrosamide groups. This facilitates efficient electron transfer from the excited palladium(II) meso-tetraphenyltetrabenzoporphyrin (PdTPTBP) photocatalyst and the selective activation of NOA. Our approach has been validated with distinct photocatalysts and various N-nitrosamides, including those derived from carbamates, amides, and ureas. Notably, the modulation of the linker length between the electron mediator and N-nitrosamide groups serves as a regulatory mechanism for controlling NO release kinetics. Moreover, this biomimetic NO release platform demonstrates effective operation under both normoxic and hypoxic conditions, and it enables localized delivery of NO under physiological conditions, exhibiting significant anticancer efficacy within the phototherapeutic window and enhanced selectivity towards tumor cells.

Synthesis of 1-azabicyclo[2.1.1]hexanes via formal single electron reduction of azabicyclo[1.1.0]butanes under photochemical conditions.

C(sp3)-rich heterocycles are privileged building blocks for pharmaceuticals and agrochemicals. Therefore, synthetic methods that provide access to novel saturated nitrogen-containing heterocycles are in high demand. Herein, we report a general synthesis of 1-azabicyclo[2.1.1]hexanes (1-aza-BCH) via a formal cycloaddition of azabicyclo[1.1.0]butanes (ABB) with styrenes under photochemical conditions. To overcome the challenging direct single electron reduction of ABBs, we designed a polar-radical-polar relay strategy that leverages a fast acid-mediated ring-opening of ABBs to form bromoazetidines, which undergo efficient debrominative radical formation to initiate the cycloaddition reaction. The reaction is applicable to a broad range of ABB-ketones and we demonstrate the 1-aza-BCH products can be further functionalised to access larger saturated, conformationally rigid heterocycles.

Photoinduced Ligand-to-Metal Charge Transfer in Base-Metal Catalysis.

The absorption of light by photosensitizers has been shown to offer novel reactive pathways through electronic excited state intermediates, complementing ground state mechanisms. Such strategies have been applied in both photocatalysis and photoredox catalysis, driven by generating reactive intermediates from their long-lived excited states. One developing area is photoinduced ligand-to-metal charge transfer (LMCT) catalysis, in which coordination of a ligand to a metal center and subsequent excitation with light results in the formation of a reactive radical and a reduced metal center. This mini review concerns the foundations and recent developments in ligand-to-metal charge transfer in transition metal catalysis focusing on the organic transformations made possible through this mechanism.

Dual-Catalytic Structural Isomerisation as a Route to α-Arylated Ketones.

Isomerisation reactions provide streamlined routes to organic compounds which are otherwise hard to directly synthesise. The most common forms are positional, geometrical or stereochemical isomerisations which involve the relocation of a double bond or a change in relative location of groups in space. In contrast, far fewer examples of structural (or constitutional) isomerisation exist where the connectivity between atoms is altered. The development of platforms capable of such rearrangement poses a unique set of challenges because chemical bonds must be selectively cleaved, and new ones formed without overall addition or removal of atoms. Here, we show that a dual catalytic system can enable the structural isomerisation of readily available allylic alcohols into more challenging-to-synthesise α-arylated ketones via a H-atom transfer initiated semi-pinacol rearrangement. Key to our strategy is the combination of a cobalt catalyst and photocatalyst under reductive, protic conditions which allows intermediates to propagate catalytic turnover. By providing an unusual disconnection to structural motifs which are difficult to access through direct arylation, we anticipate inspiring other advanced catalytic isomerisation strategies that will further retrosynthetic logic for complex molecule synthesis.

All-in-One: Plasmonic Janus Heterostructures for Efficient Cooperative Photoredox Catalysis.

Janus heterostructures consisting of multiple jointed components with distinct properties have gained growing interest in the photoredox catalytic field. Herein, we have developed a facile low-temperature method to gain anisotropic one-dimensional Au-tipped CdS (Au-CdS) nanorods (NRs), followed by assembling Ru molecular co-catalyst (RuN5) onto the surface of the NRs. The CdS NRs decorated with plasmonic Au nanoparticles (NPs) and RuN5 complex harness the virtues of metal-semiconductor and inorganic-organic interface, giving directional charge transfer channels, spatially separated reaction sites, and enhanced local electric field distribution. As a result, the Au-CdS-RuN5 can act as an efficient dual-function photocatalyst for simultaneous H2 evolution and valorization of biomass-derived alcohols. Benefiting from the interfacial charge decoupling and selective chemical bond activation, the optimal all-in-one Au-CdS-RuN5 heterostructure shows greatly enhanced photoactivity and selectivity as compared to bare CdS NRs, along with a remarkable apparent quantum yield of 40.2% at 400 nm. The structural evolution and working mechanism of the heterostructures are systematically analyzed based on experimental and computational results.

Nanometric-Mapping and In Situ Quantification of Site-specific Photoredox Activities on 2D Nanoplates.

Defective layered bismuth oxychloride (BiOCl) exhibits excellent photocatalytic activities in water purification and environmental remediation. Herein, in situ single-molecule fluorescence microscopy is used to spatially resolve the photocatalytic heterogeneity and quantify the photoredox activities on individual structural features of BiOCl. The BiOCl nanoplates with respective dominant {001} and {010} facets (BOC-001 and BOC-010) are fabricated through tuning the pH of the solution. The corner position of BOC-001 exhibits the highest photo-oxidation turnover rate of 262.7 ± 30.8 s-1 µm-2, which is 2.1 and 65.7 times of those of edges and basal planes, respectively. A similar trend is also observed on BOC-010, which can be explained by the heterogeneous distribution of defects at each structure. Besides, BOC-001 shows a higher photoredox activity than BOC-010 at corners and edges. This can be attributed to the superior charge separation ability, active high-index facets of BOC-001, and its co-exposure of anisotropic facets steering the charge flow. Therefore, this work provides an effective strategy to understand the facet-dependent properties of single-crystalline materials at nanometer resolution. The quantification of site-specific photoredox activities on BiOCl nanoplates sheds more light on the design and optimization of 2D materials at the single-molecule level.

Photoredox Catalytic Deracemization Enabled Enantioselective and Modular Access to Axially Chiral N-Arylquinazolinones.

Visible light-driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of deracemization of allenes have been established, where the activated energy of photosensitizer should surpass that of the substrates, representing an intrinsic requirement. Accordingly, this method is not applicable for axially chiral molecules with significantly high triplet energies. In this study, we present a photoredox catalytic deracemization approach that enables the efficient synthesis of valuable yet challenging-to-access axially chiral 2-azaarene-functionalized quinazolinones. The substrate scope is extensive, allowing for both 3-axis and unmet 1-axis assembly through facile oxidation of diverse central chiral 2,3-dihydroquinazolin-4(1H)-ones that can be easily prepared and achieve enantiomer enrichment via deracemization. Mechanistic studies reveal the importance of photosensitizer selection in attaining excellent chemoselectivity and highlight the indispensability of a chiral Brønsted acid in enabling highly enantioselective protonation to accomplish efficient deracemization.

A General Copper-Box System for the Asymmetric Arylative Functionalization of Benzylic, Propargylic or Allenylic Radicals.

Radical-involved arylative cross-coupling reactions have recently emerged as an attractive strategy to access valuable aryl-substituted motifs. However, there still exist several challenges such as limited scope of radical precursors/acceptors, and lack of general asymmetric catalytic systems, especially regarding the multicomponent variants. Herein, we reported a general copper-Box system for asymmetric three-component arylative radical cross-coupling of vinylarenes and 1,3-enynes, with oxime carbonates and aryl boronic acids. The reactions proceed under practical conditions in the absence or presence of visible-light irradiation, affording chiral 1,1-diarylalkanes, benzylic alkynes and allenes with good enantioselectivities. Mechanistic studies imply that the copper/Box complexes play a dual role in both radical generation and ensuing asymmetric cross-coupling. In the cases of 1,3-enynes, visible-light irradiation could improve the activity of copper/Box complex toward the initial radical generation, enabling better efficiency match between radical formation and cross-coupling.

Photo-induced imine reduction by a photoredox biocatalyst consisting of a pentapeptide and a Ru bipyridine terpyridine complex.

Imine reduction is a useful reaction in the preparation of amine derivatives. Various catalysts have been reported to promote this reaction and photoredox catalysts are promising candidates for sustainable amine synthesis. Improvement of this reaction using biomolecule-based reaction scaffolds is expected to increase the utility of the reaction. In this context, we have recently investigated photoredox Ru complexes with pentapeptide scaffolds via coordination bonds as catalysts for photoreduction of dihydroisoquinoline derivatives. First, Ru bipyridine terpyridine complexes coordinated with five different pentapeptides (XVHVV: X = V, F, W, Y, C) were prepared and characterized by mass spectrometry. Catalytic activities of the Ru complexes with XVHVV were evaluated for photoreduction of dihydroisoquinoline derivatives in the presence of ascorbate and thiol compounds as sacrificial reagents and hydrogen sources. Interestingly, the turnover number of the Ru complex with VVHVV is 531, which is two-fold higher than that of a simple Ru complex with an imidazole ligand. The detailed emission lifetime measurements indicate that the enhanced catalytic activity provided by the peptide scaffold is caused by an efficient reaction with the thiol derivative to accelerate reductive quenching of Ru complex. The quenching behavior suggests formation of an active species such as a Ru(I) complex. These findings reveal that the simple pentapeptide serves as an effective scaffold to enhance the photocatalytic activity of a photoactive Ru complex.

A Dual Cobalt-Photoredox Catalytic Approach for Asymmetric Dearomatization of Indoles with Aryl Amides via C-H Activation.

In this study, we unveil a novel method for the asymmetric dearomatization of indoles under cobalt/photoredox catalysis. By strategically activating C-H bonds of amides and subsequent migratory insertion of  p-bonds present in indole as reactive partner, we achieve syn-selective tetrahydro-5H-indolo[2,3-c]isoquinolin-5-one derivatives with excellent yields and enantiomeric excesses of up to >99%. The developed method operates without a metal oxidant, relying solely on oxygen as the oxidant and employing an organic dye as a photocatalyst under irradiation. Control experiments and stoichiometric studies elucidate the reversible nature of the enantiodetermining C-H activation step, albeit not being rate-determining. This study not only expands the horizon of cobalt-catalyzed asymmetric C-H bond functionalization, but also showcases the potential synergy between cobalt and photoredox catalysis in enabling asymmetric synthesis of complex molecules.

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis.

Organic photocatalysts frequently possess dual singlet and triplet photoreactivity and a thorough photochemical characterization is essential for efficient light-driven applications. In this article, the mode of action of a polyazahelicene catalyst (Aza-H) was investigated using laser flash photolysis (LFP). The study revealed that the chromophore can function as a singlet-state photoredox catalyst in the sulfonylation/arylation of styrenes and as a triplet sensitizer in energy transfer catalysis. The singlet lifetime is sufficiently long to exploit the exceptional excited state reduction potential for the activation of 4-cyanopyridine. Photoinduced electron transfer generating the radical cation was directly observed confirming the previously proposed mechanism of a three-component reaction. Several steps of the photoredox cycle were investigated separately, providing deep insights into the complex mechanism. The triplet-excited Aza-H, which was studied with quantitative LFP, is formed with a quantum yield of 0.34. The pronounced triplet formation was exploited for the isomerization reaction of (E)-stilbene to the Z-isomer and the cyclization of cinnamyl chloride. Catalyst degradation mainly occurs through the long-lived Aza-H triplet (28 µs), but the photostability is greatly increased when the triplet efficiently reacts in a catalytic cycle such that turnover numbers exceeding 4400 are achievable with this organocatalyst.

A Photoredox Thiol-yne Reaction for the Synthesis of Vinyl Sulfide-Based Coumarins and its Effect on Fluorescence Properties.

Coumarins still remain one of the most widely explored fluorescent dyes, with a broad spectrum of applications spanning various fields, such as molecular imaging, bioorganic chemistry, materials chemistry, or medical sciences. Their fluorescence is strongly based on a push-pull mechanism involving an electron-donating group (EDG), mainly located at the C7 or C8 positions of the dye core. Unfortunately, up to now, these positions have been very limited to hydroxyl or amino groups. In this study, we present in detail the synthesis of the first series of coumarins bearing a vinyl sulfide as the EDG at the C7 position. These derivatives were prepared by thiol-yne reaction, promoted by ruthenium- or porphyrin-based photoredox catalysis, enabling rapid late-stage diversification. We also functionalized coumarins with short peptides, and BSA protein as a proof-of-concept study, in a single-step process. This strategy, capable of proceeding under aqueous conditions, overcomes the protection/deprotection steps usually required by traditional methods, which also use strong bases and organic solvents. Moreover, the photophysical properties such as absorption and emission of obtained coumarins (for 3-CF3, 3-benzothiazole, 6-8-difluoro derivatives), predominantly exhibited large Stokes shifts (up to 204 nm) and maintained intramolecular charge transfer (ICT) characteristics.

Asymmetric Dearomatization of Indoles through Cobalt-Catalyzed Enantioselective C-H Functionalization Enabled by Photocatalysis.

Photocatalysis holds a pivotal position in modern organic synthesis, capable of inducing novel reactivities under mild and environmentally friendly reaction conditions. However, the merger of photocatalysis and transition-metal-catalyzed asymmetric C-H activation as an efficient and sustainable method for the construction of chiral molecules remains elusive and challenging. Herein, we develop a cobalt-catalyzed enantioselective C-H activation reaction enabled by visible-light photoredox catalysis, providing a synergistic catalytic strategy for the asymmetric dearomatization of indoles with high levels of enantioselectivity (96% to >99% ee). Mechanistic studies indicate that the excited photocatalyst was quenched by divalent cobalt species in the presence of Salox ligand, leading to the formation of catalytically active chiral Co(III) complex. Moreover, stoichiometric reactions of cobaltacycle intermediate with indole suggest that the irradiation of visible light also play a critical role in the dearomatization step.

Photoredox Catalysis by 21-Thiaporphyrins: A Green and Efficient Approach for C-N Borylation and C-H Arylation.

Photoredox catalysis provides a green and sustainable alternative for C-H activation of organic molecules that eludes harsh conditions and use of transition metals. The photocatalytic C-N borylation and C-H arylation mostly depend on the ruthenium and iridium complexes or eosin Y and the use of porphyrin catalysts is still in infancy. A series of novel 21-thiaporphyrins (A2B2 and A3B type) were synthesized having carbazole/phenothiazine moieties at their meso-positions and screened as catalysts for C-N borylation and C-H arylation. This paper demonstrates the 21-thiaporphyrin catalyzed C-N borylation and het-arylation of anilines under visible light. The method utilizes only 0.1 mol % of 21-thiaporphyrin catalyst under blue light for the direct C-N borylation and het-arylation reactions. A variety of substituted anilines were used as source for expensive and unstable aryl diazonium salts in the reactions. The heterobiaryls and aryl boronic esters were obtained in decent yields (up to 88 %). Versatility of the 21-thiaporphyrin catalyst was tested by thiolation and selenylation of anilines under similar conditions. Mechanistic insight was obtained from DFT studies, suggesting that 21-thiaporphyrin undergo an oxidative quenching pathway. The photoredox process catalyzed by 21-thiaporphyrins offers a mild, efficient and metal-free alternative for the formation of C-C, C-S, and C-Se bonds in aryl compounds; it can also be extended to borylation reaction.

Chromium Catalyzed Asymmetric Reformatsky Reaction.

This study describes an unprecedented chromium-catalyzed asymmetric Reformatsky reaction, enabling the synthesis of chiral ß-hydroxy carbonyl compounds from α-chlorinated or α-brominated esters and amides. By employing a chiral chromium/diarylamine bis(oxazoline) catalyst, we achieved relatively broad functional group tolerance. Distinct from known reports, the protocol operates under both classical and photoredox conditions, facilitated by the in situ formation of a nucleophilic chiral chromium intermediate through a radical-polar crossover mechanism. Preliminary mechanistic insights, supported by DFT calculations, identify the nucleophilic aldehyde addition as the key stereo-determining step. This approach not only overcomes the limitations of existing Reformatsky reactions but also provides a versatile strategy for accessing complex chiral molecules.

Size-Dependent Photocatalytic Reactivity of Conjugated Microporous Polymer Nanoparticles.

Particle size is a critical factor for improving photocatalytic reactivity of conjugated microporous polymers (CMPs) as mass transfer in the porous materials is often the rate-limiting step. However, due to the synthetic challenge of controlling the size of CMPs, the impact of particle size is yet to be investigated. To address this problem, a simple and versatile dispersion polymerization route that can synthesize dispersible CMP nanoparticles with controlled size from 15 to 180 nm is proposed. Leveraging the precise control of the size, it is demonstrated that smaller CMP nanoparticles have dramatically higher photocatalytic reactivity in various organic transformations, achieving more than 1000% enhancement in the reaction rates by decreasing the size from 180 to 15 nm. The size-dependent photocatalytic reactivity is further scrutinized using a kinetic model and transient absorption spectroscopy, revealing that only the initial 5 nm-thick surface layer of CMP nanoparticles is involved in the photocatalytic reactions because of internal mass transfer limitations. This finding substantiates the potential of small CMP nanoparticles to efficiently use photo-generated excitons and improve energy-efficiency of numerous photocatalytic reactions.