Visible-Light-Driven Germyl Radical Generation via EDA-Catalyzed ET-HAT Process.

We have established a facile and efficient protocol for the generation of germyl radicals by employing photo-excited electron transfer (ET) in an electron donor-acceptor (EDA) complex to drive hydrogen-atom transfer (HAT) from germyl hydride (R3GeH). Using a catalytic amount of EDA complex of commercially available thiol and benzophenone derivatives, the ET-HAT cycle smoothly proceeds simply upon blue-light irradiation without any transition metal or photocatalyst. This protocol also affords silyl radical from silyl hydride.

Perfluoroalkylation of Triarylamines by EDA Complexes and Ulterior Sensitized [6π]-Electrocyclization to Perfluoroalkylated Endo-Carbazoles. Mechanistic and Photophysical Studies.

Blue LEDs-irradiation of a mixture of N,N,N',N'-tetramethylethylenediamine (TMEDA) and perfluoroalkyl iodides (RF-I) - Electron Donor Acceptor (EDA)-complex - in the presence of triphenylamines (TPAs) in an aqueous solvent mixture afforded mono-perfluoroalkylated triphenylamines (RF-TPA) in good yields. These RF-TPA were further subjected to acetone-sensitized [6π]-electrocyclization at 315 nm-irradiation affording exclusively perfluoroalkylated endo-carbazole derivatives (RF-CBz) in quantitative yields. Mechanistic studies and photophysical properties of products are studied.

Photoreduction of Trifluoromethyl Group: Lithium Ion Assisted Fluoride-Coupled Electron Transfer from EDA Complex.

Photoinduced single-electron reduction is an efficient method for the mono-selective activation of the C-F bond on a trifluoromethyl group to construct a difluoroalkyl group. We have developed an electron-donor-acceptor (EDA) complex mediated single-electron transfer (EDA-SET) of α,α,α-trifluoromethyl arenes in the presence of lithium salt to give α,α-difluoroalkylarenes. The C-F bond reduction was realized by lithium iodide and triethylamine, two common feedstock reagents. Mechanistic studies revealed the generation of a α,α-difluoromethyl radical by single-electron reduction and defluorination, followed by the radical addition to alkenes. Lithium salt interacted with the fluorine atom to promote the photoinduced reduction mediated by the EDA complex. Computational studies indicated that the lithium-assisted defluorination and the single-electron reduction occurred concertedly. We call this phenomenon fluoride-coupled electron transfer (FCET). FCET is a novel approach to C-F bond activation for the synthesis of organofluorine compounds.

A General Photoactive H-Bonding EDA Complex Model Drives the Selective Hydrothiolation and Hydroxysulfenylation of Carbonyl Activated Alkenes.

Excitation of photoactive electron donor-acceptor (EDA) complexes to generate radical is a promising approach in radical chemistry. In this study, we introduce a new model of H-bonding EDA complexes for the selective hydrothiolation and hydroxysulfenylation of carbonyl-activated alkenes with diverse thiols under visible light conditions. The reliability of this H-bonding EDA complex model has been confirmed by meticulous experimental and theoretical calculations. Mechanistic investigations have revealed the significant influence of the solvent in determining whether the excitation of photoactive H-bonding EDA complex leads to charge transfer (CT) or energy-charge transfer (En-CT), thereby controlling Markovnikov and anti-Markovnikov selectivity. Notably, the Quantum Theory of Atoms in Molecules (QTAIM) analysis clearly shows that the excited state of the C=O-H-S EDA complex involves closed-shell partially covalent interactions.

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.

Effective Formation of New C(sp2 )-S Bonds via Photoactivation of Alkylamine-based Electron Donor-Acceptor Complexes.

A novel visible light promoted formation of CAryl- S bonds through electron donor-acceptor (EDA) complexes of alkylamines with 5- and 6-membered (hetero)arene halides is presented. This represents the first EDA-based thiolation method not relying on π-π or a thiolate-anion-π interactions and provides a facile access to heteroarene radicals, which can be suitably trapped by disulfide derivatives to form the corresponding versatile arylsulfides. Mechanistic investigations on the aspects of the whole process were conducted by spectroscopic measurements, demonstrating the hypothesized EDA complex formation. Moreover, the strength of this method has been proven by a gram-scale synthesis of thiolated products and the late-stage derivatization of an anticoagulant drug.

Enforced Electronic-Donor-Acceptor Complex Formation in Water for Photochemical Cross-Coupling.

The amino alcohol meglumine solubilizes organic compounds in water and enforces the formation of electron donor acceptor (EDA) complexes of haloarenes with indoles, anilines, anisoles or thiols, which are not observed in organic solvents. UV-A photoinduced electron transfer within the EDA complexes induces the mesolytic cleavage of the halide ion and radical recombination of the arenes leading, after rearomatization and proton loss to C-C or C-S coupling products. Depending on the substitution pattern selective and unique cross-couplings are observed. UV and NMR measurements reveal the importance of the assembly for the photoinduced reaction. Enforced EDA aggregate formation in water allows new activation modes for organic photochemical synthesis.

Sulfonium Salts as Acceptors in Electron Donor-Acceptor Complexes.

The photoactivation of electron donor-acceptor complexes has emerged as a sustainable, selective and versatile strategy for the generation of radical species. Electron donor-acceptor (EDA) complexation, however, imposes electronic constraints on the donor and acceptor components and this can limit the range of radicals that can be generated using the approach. New EDA complexation strategies exploiting sulfonium salts allow radicals to be generated from native functionality. For example, aryl sulfonium salts, formed by the activation of arenes, can serve as the acceptor components in EDA complexes due to their electron-deficient nature. This "sulfonium tag" approach relaxes the electronic constraints on the parent substrate and dramatically expands the range of radicals that can be generated using EDA complexation. In this review, these new applications of sulfonium salts will be introduced and the areas of chemical space rendered accessible through this innovation will be highlighted.

Direct C2-H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes.

A light-driven metal-free protocol for the synthesis of sulfone-containing indoles under mild conditions is reported. Specifically, the process is driven by the photochemical activity of halogen-bonded complexes formed upon complexation of a sacrificial donor, namely 1,4-diazabicyclo[2.2.2]octane (DABCO), with α-iodosulfones. The reaction provides a variety of densely functionalized products in good yields (up to 96% yield). Mechanistic investigations are reported. These studies provide convincing evidences for the photochemical formation of reactive open-shell species.

Visible-light-induced nickel-catalyzed α-hydroxytrifluoroethylation of alkyl carboxylic acids: Access to trifluoromethyl alkyl acyloins.

A visible-light-induced nickel-catalyzed cross coupling of alkyl carboxylic acids with N-trifluoroethoxyphthalimide is described. Under purple light irradiation, an α-hydroxytrifluoroethyl radical generated from a photoactive electron donor-acceptor complex between Hantzsch ester and N-trifluoroethoxyphthalimide was subsequently engaged in a nickel-catalyzed coupling reaction with in situ-activated alkyl carboxylic acids. This convenient protocol does not require photocatalysts and metal reductants, providing a straightforward and efficient access to trifluoromethyl alkyl acyloins in good yields with broad substrate compatibility. The complex bioactive molecules were also compatible with this catalytic system to afford the corresponding products.

Dimsyl Anion Enables Visible-Light-Promoted Charge Transfer in Cross-Coupling Reactions of Aryl Halides.

A methodology is reported for visible-light-promoted synthesis of unsymmetrical chalcogenides enabled by dimsyl anion in the absence of transition-metals or photoredox catalysts. The cross-coupling reaction between aryl halides and diaryl dichalcogenides proceeds with electron-rich, electron-poor, and heteroaromatic moieties. Mechanistic investigations using UV-Vis spectroscopy, time-dependent density functional theory (TD-DFT) calculations, and control reactions suggest that dimsyl anion forms an electron-donor-acceptor (EDA) complex capable of absorbing blue light, leading to a charge transfer responsible for generation of aryl radicals from aryl halides. This previously unreported mechanistic pathway may be applied to other light-induced transformations performed in DMSO in the presence of bases and aryl halides.

Azolium/Hydroquinone Organo-Radical Co-Catalysis: Aerobic C-C-Bond Cleavage in Ketones.

Organo-radical catalysts have recently attracted great interest, and the development of this field can be expected to broaden the applications of organocatalysis. Herein, the first example of a radical-generating system is reported that does not require any photoirradiation, radical initiators, or preactivated substrates. The oxidative C-C-bond cleavage of 2-substituted cyclohexanones was achieved using an azolium salt and a hydroquinone as co-catalysts. A catalytic mechanism was proposed based on the results of diffusion-ordered spectroscopy and cyclic voltammetry measurements, as well as computational studies.

Recent Advances on Photoinduced Cascade Strategies for the Synthesis of N-Heterocycles.

Over the last decade, visible-light photocatalysis has proved to be a powerful tool for the construction of N-heterocyclic frameworks, important constituents of natural products, insecticides, pharmacologically relevant therapeutic agents and catalysts. This account highlights recent developments and established methods towards the photocatalytic cascades for preparation of different classes of N-heterocycles, giving emphasis on our contribution to the field.

Synthetic reactions driven by electron-donor-acceptor (EDA) complexes.

The reversible, weak ground-state aggregate formed by dipole-dipole interactions between an electron donor and an electron acceptor is referred to as an electron-donor-acceptor (EDA) complex. Generally, upon light irradiation, the EDA complex turns into the excited state, causing an electron transfer to give radicals and to initiate subsequent reactions. Besides light as an external energy source, reactions involving the participation of EDA complexes are mild, obviating transition metal catalysts or photosensitizers in the majority of cases and are in line with the theme of green chemistry. This review discusses the synthetic reactions concerned with EDA complexes as well as the mechanisms that have been shown over the past five years.

Ultrasound-assisted reaction of 1,4-naphthoquinone with anilines through an EDA complex.

Naphthoquinone amino derivatives exhibit interesting physicochemical properties and a wide range of biological activities with potential medicinal applications. A clean, fast and simple method for the preparation of phenylamino-1,4-naphthoquinones is presented by the reaction of naphthoquinone (NQ) and anilines under ultrasound irradiation (US). Anilino derivatives were synthesized in good yields and shorter reaction times in comparison with the conventional method. This ultrasound procedure can be applied to the preparation of naphthoquinone derivatives with anilines containing electron-donor substituents (2-OMe, 4-OMe, 4-Me and 4-OEt) or halogen or electron-withdrawing substituents (4-F, 4-Cl, 4-Br, 3-F, 3-Cl, 3-Br, 4-Ac). This procedure was also applied to the reaction of anilines with 2,3-dichloro-1,4-naphthoquinone (DCNQ). A reaction mechanism involving an EDA complex is proposed based on NMR experiments and previous studies about solid/solid reactions.

A Computational Study of Photoinduced Borylation for Selected Boron Sources.

This research article uses density functional theory (DFT) to study photoinduced borylation. This work examined the electron donor-acceptor complex (EDA) of bis(catecholato)diboron with different redox-active leaving groups and bis(pinacol)diboron with aryl N-hydroxyphthalimide. The results of these DFT studies show the complex ratio of B2cat2 and N, N-dimethylacetamide (DMA) should be 1 : 2 which is consistent with the experimental results in the literature. We further proposed a reaction mechanism and calculated the energies associated with each step.

C-H Functionalization of Heteroarenes via Electron Donor-Acceptor Complex Photoactivation.

C-H Functionalization of heteroarenes stands as a potent instrument in organic synthesis, and with the incorporation of visible light, it emerged as a transformative game-changer. In this domain, electron donor-acceptor (EDA) complex, formed through the pairing of an electron-rich substrate with an electron-accepting molecule, has garnered substantial consideration in recent years due to the related avoidance of the requirement of photocatalyst as well as oxidant. EDA complexes can undergo photoactivation under mild conditions and exhibit high functional group tolerance, making them potentially suitable for the functionalization of biologically relevant heteroarenes. This review article provides an overview of recent advancements in the field of C-H functionalization of heteroarenes via EDA complex photoactivation with literature coverage up to April, 2024.

Visible-light promoted catalyst-free (VLCF) multi-component synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids: evaluation of in vitro anticancer activity, molecular docking, MD simulation and DFT studies.

A new and highly efficient visible-light-promoted catalyst free (VLCF) strategy for neat and clean synthesis of spiro indolo-quinazolinone-pyrrolo[3,4-a]pyrrolizine hybrids (6a-d) has been introduced. We have performed visible-light triggered 1,3-Dipolar cycloaddition reaction of maleimide (5a-d) with azomethine ylide generated in situ derived from tryptanthrin (3) and L-proline (4) to obtain desired products (6a-d) in good to excellent yield. Authentication and characterization of product was done using various spectroscopic techniques such as IR, 1H NMR, 13C NMR, Mass spectrometry and single crystal XRD analysis. To explain the reaction spontaneity, product stability, reactivity as well as possible mode of the interaction a quantum chemical investigation was performed and depicted through DFT studies. The synthesized compound 6a was also evaluated for anti-proliferative activity against a panel of five cancer cell lines (MCF-7, MDA-MB-231, HeLa, PC-3 and Ishikawa) and normal human embryonic kidney (HEK-293) cell line by using MTT assay. Compound 6a showed very good in vitro anti-proliferative activity (IC50  = 6.58-17.98 µM) against four cancer cell lines and no cytotoxicity against normal HEK-293. In order to evaluate the anticancer potential of compounds 6a-d, molecular docking was performed against wild type and mutant EGFR. The results suggest that all the compounds occupied the active site of both enzymes, with a strong binding energy (-10.2 to -11.5 kcal/mol). These results have been confirmed by molecular dynamics simulation by evaluating root mean square deviation (RMSD) and root mean square fluctuation (RMSF), along with principal component analysis (PCA).Communicated by Ramaswamy H. Sarma.

EDA Photochemistry: Mechanistic Investigations and Future Opportunities.

Recently, organic synthesis has seen a renaissance in radical chemistry due to the accessibility of mild methods for radical generation using visible light. While renewed interest in synthetic radical chemistry has been driven by the advent of photoredox catalysis, a resurgence of electron donor-acceptor (EDA) photochemistry has also led to many new radical transformations. Similar to photoredox catalysis, EDA photochemistry involves light-promoted single-electron transfer pathways. However, the mechanism of electron transfer in EDA systems is unique wherein the lifetimes of radical intermediates are often shorter due to competitive back-electron transfer. Distinguishing between EDA and photoredox mechanisms can be challenging since they can form identical products. In this perspective, we seek to provide insight on the mechanistic studies which can distinguish between EDA and photoredox manifolds. Additionally, we highlight some key challenges in EDA photochemistry and suggest future goals which could advance the synthetic potential of this field of research.

Asymmetric Photocatalysis Enabled by Chiral Organocatalysts.

Visible-light photocatalysis has advanced as a versatile tool in organic synthesis. However, attaining precise stereocontrol in photocatalytic reactions has been a longstanding challenge due to undesired photochemical background reactions and the involvement of highly reactive radicals or radical ion intermediates generated under photocatalytic conditions. To address this problem and expand the synthetic utility of photocatalytic reactions, a number of innovative strategies, including mono- and dual-catalytic approaches, have recently emerged. Of these, exploiting chiral organocatalysis, such as enamine catalysis, iminium-ion catalysis, Brønsted acid/base catalysis, and N-heterocyclic carbene catalysis, to induce chirality transfer of photocatalytic reactions has been widely explored. This Review aims to provide a current, comprehensive overview of asymmetric photocatalytic reactions enabled by chiral organocatalysts published through June 2021. The substrate scope, advantages, limitations, and proposed reaction mechanisms of each reaction are discussed. This review should serve as a reference for the development of visible-light-induced asymmetric photocatalysis and promote the improvement of the chemical reactivity and stereoselectivity of these reactions.