External Photosensitizer Research Articles

Visible Light‐Mediated [4+2] Annulation of Silylimines with Olefins to 1‐Aminotetralins Enabled by Diradical Hydrogen Atom Transfer of C−H Bonds

A facile photochemical, one‐pot synthesis of highly functionalized 1‐aminotetralins derivatives (> 70 examples) from readily accessible o‐alkyl and o‐formyl aryl silylimines with olefins is described. A diradical‐mediated hydrogen atom transfer (DHAT) of primary, secondary, and tertiary C(sp3)−H bonds of o‐alkyl arylsilylimines and C(sp2)−H bonds of o‐formyl arylsilylimines enabled a [4+2] annulation with olefins in excellent diastereoselectivity. This was accomplished upon irradiation at λ = 420 nm in the presence of thioxanthen‐9‐one (10 mol%) as the sensitizer via energy transfer. Moreover, sulfur‐substituted o‐alkyl silylimines can undergo such photochemical process in the absence of an external photosensitizer. This effective protocol is compatible with a variety of functional groups and can be applied to the modification of bioactive molecules. Based on mechanistic evidences and computational studies, it is suggested that the silyl substituent enables an efficient energy transfer leading to the formation of a key C,N‐diradical and subsequent [4+2]‐cyclization was supported by a better molecular orbital matching between the HSOMO of the 1,4‐diradical intermediate and the LUMO of the olefins. Thus, upon irradiation, the excited silylimine unlocks a carbon‐to‐nitrogen DHAT and subsequent [4+2] cyclization that allows the divergent functionalization of benzylic C(sp3)−H bonds and C(sp2)−H bonds.

Visible Light-Mediated [4+2] Annulation of Silylimines with Olefins to 1-Aminotetralins Enabled by Diradical Hydrogen Atom Transfer of C-H Bonds.

A facile photochemical, one-pot synthesis of highly functionalized 1-aminotetralins derivatives (> 70 examples) from readily accessible o-alkyl and o-formyl aryl silylimines with olefins is described. A diradical-mediated hydrogen atom transfer (DHAT) of primary, secondary, and tertiary C(sp3)-H bonds of o-alkyl arylsilylimines and C(sp2)-H bonds of o-formyl arylsilylimines enabled a [4+2] annulation with olefins in excellent diastereoselectivity. This was accomplished upon irradiation at λ = 420 nm in the presence of thioxanthen-9-one (10 mol%) as the sensitizer via energy transfer. Moreover, sulfur-substituted o-alkyl silylimines can undergo such photochemical process in the absence of an external photosensitizer. This effective protocol is compatible with a variety of functional groups and can be applied to the modification of bioactive molecules. Based on mechanistic evidences and computational studies, it is suggested that the silyl substituent enables an efficient energy transfer leading to the formation of a key C,N-diradical and subsequent [4+2]-cyclization was supported by a better molecular orbital matching between the HSOMO of the 1,4-diradical intermediate and the LUMO of the olefins. Thus, upon irradiation, the excited silylimine unlocks a carbon-to-nitrogen DHAT and subsequent [4+2] cyclization that allows the divergent functionalization of benzylic C(sp3)-H bonds and C(sp2)-H bonds.

Photoinduced Transition-Metal and External Photosensitizer Free Benzylic Fluorination of Unactivated Alkylarenes.

A green and efficient protocol for the direct monofluorination of unactivated alkylarenes under visible-light irradiation has been developed, without any extraneous transition-metal catalysts or photosensitizers. This method is compatible with a broad spectrum of functional groups, including carboxylic and alcoholic scaffolds, under mild reaction conditions. Gram-scale synthesis of a fluorine-containing pharmaceutical analogue was successfully executed, underscoring the strategy's reliability and practicality. Furthermore, mechanistic studies suggest that a single-electron transfer mechanism might be responsible for the generation of the benzylic radicals in initiation step.

Liposomal rose bengal and its butyl ester derivative formulations for antimicrobial photodynamic therapy

Patients with cystic fibrosis are highly susceptible to bacterial infections, which can often lead to irreversible damage. In this context, inhalable liposomal systems have shown great promise as drug delivery mechanisms, significantly enhancing drug permeation and accumulation in the lungs. However, the development of inhalable liposomes for various therapeutic applications is still in its early stages, providing ample opportunities for extensive research by the scientific community. Within this scenario, antimicrobial photodynamic therapy may emerge as a relevant technique, promoting greater selectivity due to its light trigger. We have developed lipid–polymer hybrid liposomes (DPPC/F127) and compare the inclusion of two types of xanthenes, one more hydrophilic (Rose Bengal - RB) and one more hydrophobic (Rose Bengal butyl ester - RBBUT). The systems were characterized in terms of morphology, thermal and kinetic stability, incorporation and release efficiency, photophysical properties, and possible location of the PS in the liposome. The studies showed that incorporation into DPPC/F127 prevented self-aggregation and significantly improved the photophysical properties of RB and RBBUT. The bacterium Pseudomonas aeruginosa proved to be more resistant to the photodynamic effect, requiring long illumination times. For Staphylococcus aureus, we observed a dependence between pre-incubation time and illumination time. Our results showed that the more external photosensitizer (PS) was more effective in experiments performed without incubation. However, with pre-incubation, the efficacy of both systems became comparable. Notably, only 10 min of illumination (warm white light; fluence: 139.7 J cm⁻2) resulted in complete bacterial inactivation.

Photocatalytic Cross-Coupling of Aldehydes and Alkenes for Aryl Vinyl Ketones by a Single Catalyst.

Herein is the first example of photocatalytic cross-coupling of alkenes with aldehydes by a single catalyst without an external photosensitizer and any additives. Irradiation of the aromatic aldehyde and cobaloxime catalyst results in the formation of an acyl radical, which undergoes radical addition with alkene or indole and subsequently β-H elimination to afford alkenyl ketone. The reaction features cheap and readily available raw materials, a broad substrate scope, and mild conditions, even for late-stage derivatization of bioactive compounds.

Visible Light-Promoted Regioselective Benzannulation of Vinyl Sulfoxonium Ylides with Ynoates.

Herein, we report a highly regioselective [4 + 2]-annulation of vinyl sulfoxonium ylides with ynoates under light-mediated conditions. The reaction proceeds through the new dienyl sulfoxonium ylide, which undergoes photolysis under blue light irradiation to give highly substituted naphthalene scaffolds. The method presented here operates at room temperature and does not require the addition of an external photosensitizer. The in situ-generated dienyl sulfoxonium ylide absorbs light and acts as a photosensitizer for the formation of arenes. The synthetic potential of these benzannulations was further illustrated by various synthetic transformations and a scale-up reaction. Moreover, control experiments and quantum chemical calculations reveal the mechanistic details of the developed reaction.

Visible-Light-Driven Deoxygenative Heteroarylation of Alcohols with Heteroaryl Sulfones.

The visible-light-promoted deoxygenative radical heteroarylation of alcohols was achieved in the absence of any external photosensitizers. The processes occur through the generation of xanthate salts from alcohols, followed by SET and fragmentation, delivering alkyl radicals to react with heteroaryl sulfones. This method is amenable for a wide range of alcohols with good functional group tolerance, providing a practical strategy for the alkylation of benzo-heteroaromatics. Mechanism studies indicate that direct visible-light excitation of xanthate anions and subsequent SET initiate the reactions.

Intermolecular C-C/C-N σ-bond metathesis enabled by visible light.

Transition-metal-catalyzed double/triple bond metathesis reactions have been well-established due to the ability of transition-metal catalysts to readily interact with π bonds, facilitating the progression of the entire reaction. However, activating σ-bonds to induce σ-bond metathesis is more challenging due to the absence of π bonds and the high bond energy of σ bonds. In this study, we present a novel photo-induced approach that does not rely on transition metals or photosensitizers to drive C-C and C-N σ-bond metathesis reactions. This method enables the cross-coupling of tertiary amines with α-diketones via C-C and C-N single bonds cleavage and recombination. Notably, our protocol exhibits good compatibility with various functional groups in the absence of transition metals and external photosensitizers, resulting in the formation of aryl alkyl ketones and aromatic amides in good to high yields. To gain insights into the mechanism of this pathway, we conducted controlled experiments, intermediate trapping experiments, and DFT (Density Functional Theory) calculations. This comprehensive approach allowed us to elucidate the detailed mechanism underlying this transformative reaction.

Photoexcitation of (diarylmethylene)amino benziodoxolones for alkylamination of styrene derivatives with carboxylic acids.

The alkylamination of alkenes using pristine carboxylic acids was achieved by the photoexcitation of (diarylmethylene)amino benziodoxolones (DABXs), which serve as both an oxidant and an aminating reagent (an iminyl radical precursor). The developed method is a simple photochemical reaction without the need for external photosensitizers and shows a broad substrate scope for aliphatic carboxylic acids leading to the formation of primary, secondary, and tertiary alkyl radicals, thus enabling the facile synthesis of various structurally complex amines. Mechanistic investigations including transient absorption spectroscopy measurements using a laser flash photolysis (LFP) method disclosed the unique photochemical reactivity of DABXs, which undergoes homolysis of their I-N bonds to give an iminyl radical and ortho-iodobenzoyloxy radical, the latter of which participates in the single-electron oxidation of carboxylates.

A metal–free porous organic polymer with high CO2 adsorption for robust aqueous CO2 photoreduction via molecular regulation

Development of photocatalysts with both high CO2 adsorption capacity and robust CO2 reduction performance is promising toward carbon capture and utilization (CCU). Herein, a porous organic polymer (POP) based on molecular monomers 1,2,3,5–Tetrakis(carbazol–9–yl)–4,6–dicyanobenzene (4CzIPN) and 9–(4–([2,2′:6′,2′'–terpyridin]–4′–yl)phenyl)–9H–carbazole (CzTPY) has been prepared for metal–free photocatalytic reduction of CO2 to CO with 94.7% selectivity in 100% aqueous medium. The POP displays a yield of CO up to 265.7 mmol g–1, which is among the highest yields for POPs–based photocatalytic systems. More importantly, the POP also shows a high CO2 uptake of 109.1 cm3 g–1 (21.4 wt%) at 273 K and 1 atm. External photosensitizers or catalysts are not required in this photocatalytic system. Mechanistic studies indicate the introduction of CzTPY improved the electron transfer and charge separation. These results show a feasible way to construct POP–based photocatalysts not only capturing CO2 efficiently but also catalyzing CO2 reduction with a high yield by rational regulation of molecular monomers.

Sensitizer-Free Photochemical Regeneration of Benzimidazoline Organohydride.

Organohydrides are an important class of organic compounds that can provide hydride anions for chemical and biochemical reactions, as demonstrated by reduced nicotinamide adenine dinucleotides serving as important natural redox cofactors. The coupling of hydride transfer from the organohydride to the substrate and subsequent regeneration of the organohydride from its oxidized form can realize organohydride-catalyzed reduction reactions. Depending on the structure of the organohydride, its hydridicity and ease of regeneration vary. Benzimidazoline (BIH) is one of the strongest synthetic C-H hydride donors; however, its reductive regeneration requires highly reducing conditions. In this study, we synthesized various oxidized and reduced forms of BIH derivatives with aryl groups at the 2-position and investigated their photophysical and electrochemical properties. 4-(Dimethylamino)phenyl-substituted BIH exhibited salient red-shifted absorption compared with other synthesized BIH derivatives, and visible-light-driven regeneration without using an external photosensitizer was achieved. This knowledge has significant implications for the future development of solar-energy-based catalytic photoreduction technologies that utilize organohydride regeneration strategies.

Photoinduced Copper-Catalyzed Aminoalkylation of Amino-Pendant Olefins.

The combination of photo and copper catalysts has emerged as a novel paradigm in organic catalysis, which provides access to the acceleration of chemical synthesis. Herein, we describe an aminoalkylation of amino-dependent olefins with maleimides through a cooperative photo/copper catalytic system. In this report, the strategy allows the generation of a broad complex of functionalized nitrogenous molecules including oxazolidinones, 2-pyrrolidones, imidazolidinones, thiazolidinones, pyridines, and piperidines in the absence of an external photosensitizer and base. The approach is achieved through a photoinduced Cu(I)/Cu(II)/Cu(III) complex species of nitrogen nucleophiles, intermolecular radical addition, and hydrogen atom transfer (HAT) processes. The plausible mechanism is investigated by a series of control experiments and theoretical tests, including radical scavenging experiments, deuterium labeling experiments, ultraviolet-visible absorption, and cyclic voltammetry (CV) tests.

Light-Promoted Ni-Catalyzed Cross-Coupling of Aryl Chlorides with Hydrazides: Application to the Synthesis of Rizatriptan.

A general and highly efficient photochemical C-N coupling reaction of challenging (hetero)aryl chlorides with hydrazides is reported. Catalyzed by a Ni(II)-bipyridine complex, this reaction provides an efficient tool for the synthesis of arylhydrazines in the presence of a soluble organic amine base without an external photosensitizer. The reaction features a wide substrate range (54 examples) and excellent functional group tolerance. The method has also been successfully applied to the three-step concise synthesis of rizatriptan, an effective drug for migraine and cluster headaches.

Photoactivation of Boronic Acid Prodrugs via a Phenyl Radical Mechanism: Iridium(III) Anticancer Complex as an Example.

Boronic acid (or ester) is a well-known temporary masking group for developing anticancer prodrugs responsive to tumoral reactive oxygen species (ROS), but their clinic application is largely hampered by the low activation efficiency. Herein, we report a robust photoactivation approach that can spatiotemporally convert boronic acid-caged iridium(III) complex IrBA into bioactive IrNH2 under hypoxic tumor microenvironments. Mechanistic studies show that the phenyl boronic acid moiety in IrBA is in equilibrium with phenyl boronate anion that can be photo-oxidized to generate phenyl radical, a highly reactive species that is capable of rapidly capturing O2 at extremely low concentrations (down to 0.02%). As a result, while IrBA could hardly be activated by intrinsic ROS in cancer cells, upon light irradiation, the prodrug is efficiently converted into IrNH2 even in limited O2 supply, along with direct damage to mitochondrial DNA and potent antitumor activities in hypoxic 2D monolayer cells, 3D tumor spheroids, and mice bearing tumor xenografts. Of note, the photoactivation approach could be extended to intermolecular photocatalytic activation by external photosensitizers with red absorption and to activate prodrugs of clinic compounds, thus offering a general approach for activation of anticancer organoboron prodrugs.

Ruthenium (II) Complexes of CNC Pincers and Bipyridine in the Photocatalytic CO2 Reduction Reaction to CO Using Visible Light: Catalysis, Kinetics, and Computational Insights

A series of five ruthenium (II) complexes containing a tridentate CNC pincer ligand, a bidentate 2,2′-bipyridine (bpy) ligand, and a monodentate ligand (chloride, bromide, or acetonitrile) were synthesized. The CNC pincer ligands used imidazole or benzimidazole-derived N-heterocyclic carbenes (NHCs) as the C donors and a 4-methoxy-substituted central pyridyl ring as the N donor. All of the complexes were characterized by analytical, spectroscopic, and single-crystal X-ray diffraction methods. These complexes were used as catalysts for visible-light-driven CO2 reduction in the presence and absence of an external photosensitizer (PS). Notably, complex 4C with a benzimidazole-derived CNC pincer ligand and bromide as the monodentate ligand was the most active catalyst tested for both sensitized and self-sensitized CO2 reduction. Thus, this catalyst was the subject of further mechanistic studies using transient absorption spectroscopy (TAS), absorption spectroelectrochemistry (SEC), and computational studies. A mechanism has been proposed for self-sensitized CO2 reduction involving (1) light excitation of the catalyst, (2) reduction by sacrificial donors, (3) halide loss, and (4) CO2 binding to form [RuCO2]+ as the catalyst resting state. The timeline for these steps and the structures of key intermediates are all supported by experimental observations (including TAS and SEC) and supporting computational studies. Subsequent steps in the cycle past [RuCO2]+ were not experimentally observable, but they are supported by computations. Experiments were also used to explain the differences observed for sensitized catalysis. Catalyst 4C is an unusually active catalyst for both sensitized and self-sensitized CO2 reduction, and thus being able to understand how it functions and which steps are turnover-limiting is an important development facilitating the design of commercially viable catalysts for solar fuel formation.

Metal-free 3D donor–acceptor COF with low exciton binding for solar fuel production based on CO2reduction

A donor–acceptor based 3D TT-COF is employed as a metal-free photocatalyst for CO2reduction. TT-COF selectively produces CO from CO2using visible light, without external photosensitizers or cocatalysts by minimizing exciton binding energy.

Visible-light-induced Csp3-H functionalization of glycine derivatives by cerium catalysis.

A Ce(III)-catalyzed, visible-light-induced aerobic oxidative dehydrogenative coupling/aromatization reaction between glycine derivatives and alkenes has been developed, which provides an efficient approach for the synthesis of quinoline derivatives and post-modification of oligopeptides containing glycine residues under mild conditions without the need for external photosensitizers.

Visible-light induced C(sp3)-H arylation of glycine derivatives by cerium catalysis.

A Ce(III)-catalyzed, visible-light induced aerobic oxidative dehydrogenative coupling reaction between glycine derivatives and electron-rich arenes is disclosed. The protocol proceeds efficiently under mild conditions, providing an efficient method for the rapid synthesis of α-arylglycine derivatives without the need for an external photosensitizer and additional oxidant. Moreover, this protocol could be performed on a 5 mmol scale, without obvious reduction of the efficiency.

Photoinduced Dehydrogenative Borylation via Dihydrogen Bond Bridged Electron Donor and Acceptor Complexes.

Air-stable amine- and phosphine-boranes are discovered as donors to integrate with pyridinium acceptor for generating photoactive electron-donor-acceptor (EDA) complexes. Experimental results and DFT calculations suggest a dihydrogen bond bridging the donor and acceptor. Irradiating the EDA complex enables an intra-complex single electron transfer to give a boron-centered radical for dehydrogenative borylation with no need of external photosensitizer and radical initiator. The deprotonation of Wheland-like radical intermediate rather than its generation is believed to determine the good ortho-selectivity based on DFT calculations. A variety of α-borylated pyridine derivatives have been readily synthesized with good functional group tolerance.

Photochemical Synthesis of Anilines via Ni-Catalyzed Coupling of Aryl Halides with Ammonium Salts

Easy, efficient, and economic synthesis of anilines remains an important challenge in synthetic chemistry. In this study, a Ni(OAc)2-bipyridine complex is shown to readily catalyze the amination of aryl halides with ammonium salts under direct excitation of light, allowing a broad array of aryl chlorides and bromides to be converted into the corresponding primary (hetero)arylamines in the absence of an external photosensitizer. Late-stage modification of drug molecules and 15N-labeling of primary aryl amines are also demonstrated with a number of examples. Photoinduced generation of Ni(I)-bipyridine species is believed to be the key step in the reaction, enabling a Ni(I)/Ni(III) cycle for catalytic turnover.