General Paradigm in Photoredox Nickel‐Catalyzed Cross‐Coupling Allows for Light‐Free Access to Reactivity

Self‐sustained Ni^I/III cycles are established as a potentially general paradigm in photoredox Ni‐catalyzed carbon–heteroatom cross‐coupling reactions through a strategy that allows us to recapitulate photoredox‐like reactivity in the absence of light across a wide range of substrates in the amination, etherification, and esterification of aryl bromides, the latter of which has remained, hitherto, elusive under thermal Ni catalysis. Moreover, the accessibility of esterification in the absence of light is especially notable because previous mechanistic studies on this transformation under photoredox conditions have unanimously invoked energy‐transfer‐mediated pathways.     

Visible Light Activation of Boronic Esters Enables Efficient Photoredox C(sp2)–C(sp3) Cross‐Couplings in Flow

We report herein a new method for the photoredox activation of boronic esters. Using these reagents, an efficient and high‐throughput continuous flow process was developed to perform a dual iridium‐ and nickel‐catalyzed C(sp²)–C(sp³) coupling by circumventing solubility issues associated with potassium trifluoroborate salts. Formation of an adduct with a pyridine‐derived Lewis base was found to be essential for the photoredox activation of the boronic esters. Based on these results we were able to develop a further simplified visible light mediated C(sp²)–C(sp³) coupling method using boronic esters and cyano heteroarenes under flow conditions.     

One‐Pot Tandem Photoredox and Cross‐Coupling Catalysis with a Single Palladium Carbodicarbene Complex

The combination of conventional transition‐metal‐catalyzed coupling (2 e^? process) and photoredox catalysis (1 e^? process) has emerged as a powerful approach to catalyze difficult cross‐coupling reactions under mild reaction conditions. Reported is a palladium carbodicarbene (CDC) complex that mediates both a Suzuki–Miyaura coupling and photoredox catalysis for C?N bond formation upon visible‐light irradiation. These two catalytic pathways can be combined to promote both conventional transition‐metal‐catalyzed coupling and photoredox catalysis to mediate C?H arylation under ambient conditions with a single catalyst in an efficient one‐pot process.     

Direct sp3 C?H Amination of Nitrogen‐Containing Benzoheterocycles Mediated by Visible‐Light‐Photoredox Catalysts

Visible‐light‐mediated direct sp³ C? H amination of benzocyclic amines via α‐aminoalkyl radicals by using photoredox catalysts is described here. The obtained N,N‐acetals were also successfully applied for carbon–carbon bond forming reactions with carbon nucleophiles. The procedure is suitable for a late‐stage modification of C? H bonds to C? C bonds.     

Continuous-Flow Photocatalysis for the Direct C-H Trifluoromethylation of Heterocycles with an Organic Photoredox Catalyst

Photocatalysis for direct C−H trifluoromethylation represents an ideal way to synthesize trifluoromethyl-containing chemical compounds, but the conventional batch processes are inefficient with limited light penetration and indispensably irradiated for a long while. Herein, we report a continuous-flow protocol for photocatalytic direct C−H trifluoromethylation of heterocycles in the presence of an organic photoredox catalyst: 2,4,6-tris(diphenylamino)-3,5-difluorobenzonitrile (3DPA2FBN). In this approach, benefiting from the merger of organic photoredox catalysis and continuous-flow techniques, a variety of trifluoromethylated heterocycles were rapidly synthesized up to 85 % yield with 80 min residence time under metal- and oxidant-free reaction conditions.     

Visible‐Light‐Mediated Decarboxylation/Oxidative Amidation of α‐Keto Acids with Amines under Mild Reaction Conditions Using O2

Photochemistry has ushered in a new era in the development of chemistry, and photoredox catalysis has become a hot topic, especially over the last five years, with the combination of visible‐light photoredox catalysis and radical reactions. A novel, simple, and efficient radical oxidative decarboxylative coupling with the assistant of the photocatalyst [Ru(phen)₃]Cl₂ is described. Various functional groups are well‐tolerated in this reaction and thus provides a new approach to developing advanced methods for aerobic oxidative decarboxylation. The preliminary mechanistic studies revealed that: 1) an SET process between [Ru(phen)₃]²⁺* and aniline play an important role; 2) O₂ activation might be the rate‐determining step; and 3) the decarboxylation step is an irreversible and fast process.     

Green-light-driven thioxanthylium-based organophotoredox catalysts: Organophotoredox promoted radical cation Diels-Alder reaction

Thioxanthylium-based organophotoredox catalysts that operate under irradiation with green light have been developed. These catalysts present high excited-state reduction potentials (E₀′(C¹/C^?)?=?+1.79–1.94?V vs SCE). They are able to efficiently activate dienophiles under green or blue light irradiation afforded the targeted radical cation Diels-Alder cycloadducts in good yields. The present thioxanthylium-based catalysts provide a new green-light-driven photoredox catalysis system.     

Visible-light mediated trifluoromethylation of p-quinone methides by 1,6-conjugate addition using pyrylium salt as organic photocatalyst

A transition metal free visible light mediated organo photoredox catalyzed trifluoromethylation of p-quinone methides (p-QMs) to construct fluoro-analogs of dichlorodiphenyltrichloroethane (DDT) is reported using a bench stable, inexpensive Langlois reagent as a trifluoromethyl radical source. This protocol could generate a benzylic C(sp³)-CF₃ bond with excellent yield under mild reaction conditions using 1,6-conjugate addition/aromatization of trifluoromethyl radical in the absence of any external additives. Further, we demonstrate di-trifluoromethylation and gram scale synthesis of this reaction.     

Synthesis of Prebiotic Building Blocks by Photochemistry

Ultraviolet(UV) light is a very competent energy source for the synthesis of prebiotic building blocks on early Earth. In aqueous solution, hydrated electron is produced by irradiating ferrocyanide/cuprous cyanide/hydrosulfide by 254 nm UV light. Hydrated electron is a powerful reducing reagent driving the formation of prebiotic building blocks under prebiotically plausible conditions. Here we summarize the photoredox synthesis of prebiotic related building blocks from hydrogen cyanide(HCN) and other prebiotically related molecules. These results indicate biological related building blocks can be generated on the surface of early Earth.     

Visible‐Light‐Catalyzed Direct Benzylic C(sp3)–H Amination Reaction by Cross‐Dehydrogenative Coupling

A conceptually new and synthetically valuable cross‐dehydrogenative benzylic C(sp³)–H amination reaction is reported by visible‐light photoredox catalysis. This protocol employs DCA (9,10‐dicyanoanthracene) as a visible‐light‐absorbing photoredox catalyst and an amide as the nitrogen source without the need of either a transition metal or an external oxidant.     

Characterizing chain processes in visible light photoredox catalysis

The recognition that Ru(bpy)₃²⁺ and similar visible light absorbing transition metal complexes can be photocatalysts for a variety of synthetically useful organic reactions has resulted in a recent resurgence of interest in photoredox catalysis. However, many of the critical mechanistic aspects of this class of reactions remain poorly understood. In particular, the degree to which visible light photoredox reactions involve radical chain processes has been a point of some disagreement that has not been subjected to systematic analysis. We have now performed quantum yield measurements to demonstrate that three representative, mechanistically distinct photoredox processes involve product-forming chain reactions. Moreover, we show that the combination of quantum yield and luminescence quenching experiments provides a rapid method to estimate the length of these chains. Together, these measurements constitute a robust, operationally facile strategy for characterizing chain processes in a wide range of visible light photoredox reactions.     

Visible-Light-Mediated Click Chemistry for Highly Regioselective Azide–Alkyne Cycloaddition by a Photoredox Electron-Transfer Strategy

Click chemistry focuses on the development of highly selective reactions using simple precursors for the exquisite synthesis of molecules. Undisputedly, the Cu^I-catalyzed azide–alkyne cycloaddition (CuAAC) is one of the most valuable examples of click chemistry, but it suffers from some limitations as it requires additional reducing agents and ligands as well as cytotoxic copper. Here, we demonstrate a novel strategy for the azide–alkyne cycloaddition reaction that involves a photoredox electron-transfer radical mechanism instead of the traditional metal-catalyzed coordination process. This newly developed photocatalyzed azide–alkyne cycloaddition reaction can be performed under mild conditions at room temperature in the presence of air and visible light and shows good functional group tolerance, excellent atom economy, high yields of up to 99 %, and absolute regioselectivity, affording a variety of 1,4-disubstituted 1,2,3-triazole derivatives, including bioactive molecules and pharmaceuticals. The use of a recyclable photocatalyst, solar energy, and water as solvent makes this photocatalytic system sustainable and environmentally friendly. Moreover, the azide–alkyne cycloaddition reaction could be photocatalyzed in the presence of a metal-free catalyst with excellent regioselectivity, which represents an important development for click chemistry and should find versatile applications in organic synthesis, chemical biology, and materials science.     

Immobilization and Continuous Recycling of Photoredox Catalysts in Ionic Liquids for Applications in Batch Reactions and Flow Systems: Catalytic Alkene Isomerization by Using Visible Light

A catalytic (E)‐ to (Z)‐isomerization of olefins using a photoredox catalyst under mild reaction conditions is presented. A variety of (Z)‐alkenes can be prepared in the presence of visible light. A new reaction system allows an easy and efficient scale‐up, as well as a continuous flow process in which the photocatalyst is immobilized in an ionic liquid and continuously recycled by simple phase separation.     

Photocatalytic Modification of Amino Acids,Peptides, and Proteins

In the last decade, visible-light photoredox catalysis has emerged as a powerful strategy to enable novel transformations in organic synthesis. Owing to mild reaction conditions (i.e., room temperature, use of visible light) and high functional-group tolerance, photoredox catalysis could represent an ideal strategy for chemoselective biomolecule modification. Indeed, a recent trend in photoredox catalysis is its application to the development of novel methodologies for amino acid modification. Herein, an up-to-date overview of photocatalytic methodologies for the modification of single amino acids, peptides, and proteins is provided. The advantages offered by photoredox catalysis and its suitability in the development of novel biocompatible methodologies are described. In addition, a brief consideration of the current limitations of photocatalytic approaches, as well as future challenges to be addressed, are discussed.     

Recent Advances in Visible-Light-Mediated Amide Synthesis

Visible-light photoredox catalysis has attracted tremendous interest within the synthetic community. As such, the activation mode potentially provides a more sustainable and efficient platform for the activation of organic molecules, enabling the invention of many controlled radical-involved reactions under mild conditions. In this context, amide synthesis via the strategy of photoredox catalysis has received growing interest due to the ubiquitous presence of this structural motif in numerous natural products, pharmaceuticals and functionalized materials. Employing this strategy, a wide variety of amides can be prepared effectively from halides, arenes and even alkanes under irradiation of visible light. These methods provide a robust alternative to well-established strategies for amide synthesis that involve condensation between a carboxylic acid and amine mediated by a stoichiometric activating agent. In this review, the representative progresses made on the synthesis of amides through visible light-mediated radical reactions are summarized.     

Visible-light-induced synthesis of benzothiophenes and benzoselenophenes via the annulation of thiophenols or 1,2-diphenyldiselane with alkynes

An effective metal-free photoredox-mediated tandem addition/cyclization reaction of thiophenols or 1,2-diphenyldiselane with alkynes leads to 2,3-disubstituted benzothiophenes and benzoselenophenes. Blue light irradiation of the organic dye, Mes-Acr-Me⁺, initiates the photoredox catalysis. A series of functional groups could be tolerated under ambient conditions, and good to excellent yields were generated.     

Generating Hydrated Electrons for Chemical Syntheses by Using a Green Light‐Emitting Diode (LED)

We present the first working system for accessing and utilizing laboratory‐scale concentrations of hydrated electrons by photoredox catalysis with a green light‐emitting diode (LED). Decisive are micellar compartmentalization and photon pooling in an intermediate that decays with second‐order kinetics. The only consumable is the nontoxic and bioavailable vitamin C. A turnover number of 1380 shows the LED method to be on par with electron generation by high‐power pulsed lasers, but at a fraction of the cost. The extreme reducing power of the electron and its long unquenched life as a ground‐state species are synergistic. We demonstrate the applicability to the dechlorination, defluorination, and hydrogenation of compounds that are inert towards all other visible‐light photoredox catalysts known to date. A comprehensive mechanistic investigation from microseconds to hours yields results of general validity for photoredox catalysis with photon pooling, allowing optimization and upscaling.     

Visible‐Light‐Irradiated Graphitic Carbon Nitride Photocatalyzed Diels–Alder Reactions with Dioxygen as Sustainable Mediator for Photoinduced Electrons

Photocatalytic Diels–Alder (D–A) reactions with electron rich olefins are realized by graphitic carbon nitride (g‐C₃N₄) under visible‐light irradiation and aerobic conditions. This heterogeneous photoredox reaction system is highly efficient, and the apparent quantum yield reaches a remarkable value of 47 % for the model reaction. Dioxygen plays a critical role as electron mediator, which is distinct from the previous reports in the homogeneous Ru^II complex photoredox system. Moreover, the reaction intermediate vinylcyclobutane is captured and monitored during the reaction, serving as a direct evidence for the proposed reaction mechanism. The cycloaddition process is thereby determined to be the combination of direct [4+2] cycloaddition and [2+2] cycloaddition followed by photocatalytic rearrangement of the vinylcyclobutane intermediate.     

Visible light-promoted metal-free intramolecular cross dehydrogenative coupling approach to 1,3-oxazines

Visible light promoted intramolecular cross dehydrogenative coupling of 1-aminoalkyl-2-naphthols to 1,3-oxazines is developed. Green LED lamp was used as the light source and eosin Y functions as photoredox catalyst. The reaction was carried out in the absence of transition-metal photoredox catalysts and additional additives. Aerial oxygen was used as the terminal oxidant. The method offers clean and efficient synthesis of these important classes of heterocycles.     

Functionalization of C‐H Bonds by Photoredox Catalysis

Visible‐light photoredox catalysis has been successfully used in the functionalization of inert C?H bonds including C(sp²)‐H bonds of arenes and C(sp³)‐H bonds of aliphatic compounds over the past decade. These transformations are typically promoted by the process of single‐electron‐transfer (SET) between substrates and photo‐excited photocatalyst upon visible light irradiation (household bulbs or LEDs). Compared with other synthetic strategies, such as the transition‐metal catalysis and traditional radical reactions, visible‐light photoredox approach has distinct advantages in terms of operational simplicity and practicability. Versatile direct functionalization of inert C(sp²)‐H and C(sp³)‐H bonds including alkylation, trifluoromethylation, arylation and amidation, has been achieved using this practical strategy.