Electron Donor-acceptor Complexes Research Articles

Electron donor-acceptor complex enabled photocascade strategy for the synthesis of trans-dihydrofuro[3,2-c]chromen-4-one scaffolds via radical conjugate addition of pyridinium ylide.

A visible-light-induced photocascade strategy is disclosed for the synthesis of trans-dihydrofuro[3,2-c]chromen-4-one scaffolds. The photocascade consists of electron donor-acceptor (EDA) complex enabled formation of arylidene coumarinone, followed by 1,4-radical conjugate addition (1,4-RCA) of an in situ generated pyridinium ylide radical (PyYR) towards diastereoselective formation of the trans-dihydrofuro[3,2-c]chromen-4-one scaffold in good to excellent yield. Thorough mechanistic investigations comprising photophysical, spectroscopic, electrochemical and DFT studies provide further insights into the reaction mechanism.

Unique Electron Donor–Acceptor Complex Conformation Ensures Both the Efficiency and Enantioselectivity of Photoinduced Radical Cyclization in a Non-natural Photoenzyme

Unique Electron Donor–Acceptor Complex Conformation Ensures Both the Efficiency and Enantioselectivity of Photoinduced Radical Cyclization in a Non-natural Photoenzyme

C(sp2)-Arylsulfones Directly from Arylsulfonyl Chlorides with Boronic Acids by Photoactivation of Boosted EDA Complexes.

Directly with arylsulfonyl chlorides, a green and efficient deborylativesulfonylation of aryl(alkenyl)boronic acids has been developed to access both diarylsulfones and vinylarylsulfones in moderate to excellent yields at room temperature under visible-light irradiation. This protocol features broad C(sp2)-arylsulfone applicability, simple operation, accessibility of raw materials and ease of scale-up. The key to the success of this photoredox transformation is introducing catalytic amounts of additives, naphthalen-2-ols, thus boosting the formed electron donor-acceptor (EDA) complexes, which can dramatically improve not only the reaction efficiency but also the selectivity. This strategywas inspired and derived from specific substrates, representing a rare paradigm of how to exploit a more general reaction system. Moreover, extensive control experiments provide insights into the proposed mechanism.

Traceless Nucleophile Strategy for C5-Selective C-H Sulfonylation of Pyridines.

The functionalization of pyridines is crucial for the rapid construction and derivatization of agrochemicals, pharmaceuticals, and materials. Conventional functionalization approaches have primarily focused on the ortho- and para-positions, while achieving precise meta-selective functionalization, particularly at the C5 position in substituted pyridines, remains a formidable challenge due to the intrinsic electronic properties of pyridines. Herein, we present a new strategy for meta- and C5-selective C-H sulfonylation of N-amidopyridinium salts, which employs a transient enamine-type intermediate generated through a nucleophilic addition to N-amidopyridinium salts. This process harnesses the power of electron donor-acceptor complexes, enabling high selectivity and broad applicability, including the construction of complex pyridines bearing valuable sulfonyl functionalities under mild conditions without the need for an external photocatalyst. The remarkable C5 selectivity, combined with the broad applicability to late-stage functionalization, significantly expands the toolbox for pyridine functionalization, unlocking access to previously unattainable meta-sulfonylated pyridines.

Insight into C4 Selectivity in the Light-Driven C-H Fluoroalkylation of Pyridines and Quinolines.

Given the prevalence of pyridine motifs in FDA-approved drugs, selective fluoroalkylation of pyridines and quinolines is essential for preparing diverse bioisosteres. However, challenges are often faced with conventional Minisci reactions in achieving precise regioselectivity owing to competing reaction sites of pyridine and the limited availability of fluoroalkyl radical sources. Herein, we present a light-driven, C4-selective fluoroalkylation of azines utilizing N-aminopyridinium salts and readily available sulfinates. Our approach employs electron donor-acceptor complexes, achieving highly C4-selective fluoroalkylation under mild conditions without an external photocatalyst. This practical method not only enables the installation of CF2H groups but also allows for the incorporation of CF2-alkyl groups with diverse functional entities, surpassing the limitations of previous methods. The versatility of the radical pathway is further demonstrated through straightforward three-component reactions involving alkenes and [1.1.1]propellane. Detailed experimental and computational studies have elucidated the origins of regioselectivity, providing profound insights into the mechanistic aspects.

Electron Donor-Acceptor Complex-Assisted Photochemical Conversion of O-2-Nitrobenzyl Protected Hydroxamates to Amides.

The hydroxamic acid functionality is present in various medicinal agents and has attracted special interest for synthetic transformations in both organic and medicinal chemistry. The N-O bond cleavage of hydroxamic acid derivatives provides an interesting transformation for the generation of various products. We demonstrate, herein, that O-benzyl-type protected hydroxamic acids may undergo photochemical N-O bond cleavage, in the presence orabsence of a catalyst, leading to amides. Although some O-benzyl protected aromatic hydroxamates may be photochemically converted to amides in the presence of a base and anthracene as the catalyst, employing O-2-nitrobenzyl group allowed the smooth conversion of both aliphatic and aromatic hydroxamates to primary or secondary amides in good to excellent yields in the presence of an amine, bypassing the need of a catalyst. DFT and UV-Vis studies supported the effective generation of an electron donor-acceptor (EDA) complex between O-2-nitrobenzyl hydroxamates and amines, which enabled the successful product formation under these photochemical conditions. An extensive substrate scope was demonstrated, showcasing that both aliphatic or aromatic hydroxamates are compatible with this protocol, affording a wide variety of primary and secondary amides.

Photoinduced Electron Donor Acceptor Complex-Enabled α-C(sp3)-H Alkenylation of Amines.

Allylic amines are prevalent and vital structural components present in many bioactive compounds and natural products. Additionally, they serve as valuable intermediates and building blocks, with wide-ranging applications in organic synthesis. However, direct α-C(sp3)-H alkenylation of feedstock amines, particularly for the preparation of α-alkenylated cyclic amines, has posed a longstanding challenge. Herein, we present a general, mild, operationally simple, and transition-metal-free α-alkenylation of various readily available amines with alkenylborate esters in excellent E/Z - and diastereoselectivities. This method features good compatibility with water and oxygen, broad substrate scope, and excellent functional group tolerance, thereby enabling the late-stage modification of various complex molecules. Mechanistic studies suggest that the formation of a photoactive electron donor-acceptor complex between 2-iodobenzamide and the tetraalkoxyborate anion, which subsequently undergoes photoinduced single electron transfer and intramolecular 1,5-hydrogen atom transfer to generate the crucial α-amino radicals, is the key to success of this chemistry.

Catalytic Generation of Pyridyl Radicals via Electron Donor-Acceptor Complex Photoexcitation: Synthesis of 2-Pyridylindole-Based Heterobiaryls.

We report the catalytic generation of pyridyl radicals through photoexcitation of the electron donor-acceptor (EDA) complex, which enables the C2-selective heteroarylation of indole under ambient conditions. In this manifold, catalytic triarylamine and chloropyridine aggregate into an EDA complex in the presence of an inorganic base, making readily available chloropyridines good precursors for the generation of diverse pyridyl radicals. Given the broad reaction scope, this catalytic EDA complex protocol provides robust access to heterobiaryl scaffolds that are widely present in biologically important molecules.

Arylcyanation of Styrenes by Photoactive Electron Donor-Acceptor Complexes/Copper Catalysis.

A novel electron donor-acceptor (EDA) complex/copper catalysis model has been proposed for the construction of 2,3-diarylpropionitriles under visible light conditions. The developed protocol proceeds via intermolecular charge transfer between the photoactive EDA complex of dibutamine (DBA), aryl thianthrenium salts, and trimethylsilyl cyanide (TMSCN), followed by a copper catalytic cycle. UV-vis absorption measurements confirm the participation of EDA complexes as reactive intermediates. This three-component process proceeds smoothly in the presence of pharmaceutically relevant core structures and sensitive functional groups, which offers the possibility of the precise editing of drug molecules with important scaffolds.

Photoactivated Reactions without Traditional Photocatalysts: Electron-Donor Complexation of 1,2,3-Triazoles Initiates Denitrogenative Transformations.

We present a set of visible-light-promoted denitrogenative transformations of 1,2,3-triazoles that generate high product yields without the use of a traditional, external photocatalyst, with the reaction viable for both benzotriazole and benzotriazinone. Mechanistic studies using UV-vis absorption, 1H NMR spectroscopy, and density functional theory indicate that these reactions are initiated by an electron donor-acceptor (EDA) complex which forms between N,N-diisopropylethylamine (DIPEA) and the 1,2,3-triazole. A comprehensive analysis of how irradiation wavelength impacts reactivity was obtained using an online photochemical reactor coupled mass spectrometer, indicating a lack of correlation between absorptivity and photoreactivity for the reaction between benzotriazinone and methyl acrylate. The reaction was photoinitiated by light-emitting diodes (LEDs) at wavelengths longer than 400 nm, which is unexpected on the basis of solely the absorption spectra of the starting materials.

S-Arylation of Thioic S-Acid Using Thianthrenium Salts via Photoactivation of Electron Donor-Acceptor Complex.

Thioesters make up an important class of bioactive compounds. Due to their chemoselectivity, they have been widely used in the synthesis of a wide range of complex bioactive molecules and natural products. At present, chemists have developed a variety of methods for the preparation of thioester compounds. However, these methods usually require the use of transition metal catalysis or harsh reaction conditions. The strategy of synthesizing thioester compounds via visible light-induced electron donor-acceptor (EDA) complex reactions avoids the problems associated with conventional methods through the development of photocatalysis. Here we report a sustainable method for thiocarbonylating aryl sulfonium salts via a visible light-induced EDA complex process without transition metals.

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.

Electron Donor-Acceptor Complex-Enabled Autoinductive Conversion of Acylnitromethanes to Acylnitrile Oxides in a Photochemical Machetti-De Sarlo Reaction: Synthesis of 5-Substituted 3-Acylisoxazoles.

A photochemical Machetti-De Sarlo reaction has been developed for preparing 5-substituted 3-acylisoxazoles from acylnitromethanes and terminal alkynes. This photochemical protocol utilizes an innovative electron donor-acceptor complex, generated in situ from acylnitromethanes, catalytic LiOtBu, and 1,1,1,3,3,3-hexafluoro-2-propanol, as a photosensitizer to promote rapid conversion with a broad substrate scope in up to 80% efficiency. A sigmoidal autoinductive kinetic profile is revealed, demonstrating the novel and unique dual catalysis in the first photochemical approach of this reaction.

Visible‐Light‐Driven Heterocyclic Fluoroalkylation Via Electron Donor−Acceptor Complexes

AbstractHeterocyclic fluoroalkylation is initiated through a photochemical reaction involving an electron donor–acceptor complex. The reaction proceeds smoothly without requiring a photocatalyst, transition metal catalyst or additional oxidant. Through extensive experiments, we optimised the heterocyclic fluoroalkylation method and confirmed its versatility and effectiveness on various substrates. The process synthesises fluoroalkylated quinoxalinones and indolones with high efficiency and was successfully extended to gram‐scale applications, highlighting its practical utility. Detailed mechanistic analyses, supported by density functional theory calculations elucidated the role of the electron donor–acceptor complexes and deciphered the distinct radical chain reaction mechanism inherent in the halogen‐atom transfer pathway. Given the importance of fluoroalkyl groups in pharmaceuticals, this simple and efficient method promises substantial applications in medicinal chemistry and materials science.

Visible-Light-Induced Domino Perfluoroalkylation/Cyclization to Access Perfluoroalkylated Quinazolinones by an EDA Complex.

The electron donor-acceptor (EDA) complexes have been extensively studied, which formed an electronically excited state, obviating the need for an exogenous photocatalyst. Herein, we report a mild and efficient strategy for photoinduced radical domino perfluoroalkylation/cyclization using N,N,N',N'-tetramethylethane-1,2-diamine (TMEDA) as an electron donor. This protocol could be well expanded to access various polycyclic quinazolinones containing perfluoroalkyl groups, exhibiting photocatalyst-free, good functional group tolerance, and environmentally friendly features.

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.

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

AbstractExcitation 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.

Visible-Light-Driven Iron-Catalyzed 1,2-Difluoroalkylthiolation of Alkenes.

The synthesis of medicinally interesting aryldifluoromethylated compounds has drawn significant research attention in recent years. Herein, we report an unprecedented iron-mediated process for the selective defluorination of trifluoromethylarenes to achieve the 1,2-difluoroalkylthiolation of alkenes. Preliminary mechanistic studies revealed that thiolate anion, trifluoromethylarene, and iron cation could form an electron donor-acceptor (EDA) complex, which induced selective defluorination and then difunctionalization of alkenes to obtain aryldifluoromethylated products. The generated aryldifluoromethylated compounds make it difficult to form an EDA complex again, thus avoiding excessive defluorination. This conversion has concise and ambient reaction conditions and provides an alternative solution for obtaining difluorobenzylic intermediates.

Electron Donor-Acceptor Complex Enabled Cyclization/Sulfonylation Cascade of N-Heterocycles with Thianthrenium Salts.

We report a visible-light-promoted cyclization/sulfonylation cascade of N-heterocycles with thianthrenium salts using DABSO as the SO2 surrogate. This method features excellent functional group tolerance, wide substrate scope, and late-stage elaboration of bioactive relevant molecules. Mechanistic investigations reveal that the photoactive electron donor-acceptor (EDA) complexes between thianthrenium salts and DABCO are capable of the generation of aryl radicals, which induce the following SO2 insertion by attacking DABSO, thus triggering the key radical cyclization step.

Catalytic photoactivation of a triarylamine electron donor-acceptor complex for difunctionalization of alkenes

Catalytic photoactivation of a triarylamine electron donor-acceptor complex for difunctionalization of alkenes