Formation Of Donor-acceptor Complexes Research Articles

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.

Visible-Light-Promoted Radical Cascade Sulfone Alkylation/Cyclization of 2-Isocyanoaryl Thioethers Enabled by Electron Donor-Acceptor Complex Formation.

A photo-induced cascade sulfone alkylation/cyclization of 2-isocyanoaryl thioethers is explored. This visible-light-triggered reaction not only occurs under extremely mild reaction conditions but also does not require the presence of a photosensitizer. The photocatalytic process is triggered by the photochemical activity of in situ-generated electron donor-acceptor complexes, arising from the association of 2-isocyanoaryl thioethers and α-iodosulfones. The radical pathway was confirmed by UV-vis spectroscopy, radical trapping, Job's plot, and on/off irradiation experiments.

Proton-Coupled Electron Transfer Ring Opening of Cycloalkanols Followed by a Giese Radical Addition Enabled by an Electron Donor-Acceptor Complex.

Herein, we describe the formation of an electron donor-acceptor (EDA) complex between electron-rich cycloalkanols and electron-deficient alkenes that triggers the proton-coupled electron transfer ring opening of strained and unstrained cycloalkanols without the need for an external photocatalyst. This activation generates a remote alkyl radical that undergoes a Giese reaction with the Michael acceptor in an efficient manner. Mechanistic investigations corroborate both the formation of the EDA complex and the consecutive Giese reaction.

Photodecarboxylative Radical Cascade Involving N-(Acyloxy)phthalimides for the Synthesis of Pyrazolones.

We disclose N'-arylidene-N-acryloyltosylhydrazides as novel skeletons for the synthesis of biologically relevant alkylated pyrazolones through a photoinduced radical cascade with N-(acyloxy)pthalimides as readily available alkyl surrogates. The reaction proceeds through the formation of a photoactivated electron donor-acceptor (EDA) complex between alkyl N-(acyloxy)phthalimide (NHPI) esters and LiI/PPh3 as a commercially available donor system. The reaction exhibits a broad scope and scalability, thereby enabling synthesis of a broad spectrum of functionally orchestrated alkylated pyrazolones under mild and transition-metal-free conditions.

Single-Electron Oxidation-Initiated Enantioselective Hydrosulfonylation of Olefins Enabled by Photoenzymatic Catalysis.

Controlling the enantioselectivity of hydrogen atom transfer (HAT) reactions has been a long-standing synthetic challenge. While recent advances on photoenzymatic catalysis have demonstrated the great potential of non-natural photoenzymes, all of the transformations are initiated by single-electron reduction of the substrate, with only one notable exception. Herein, we report an oxidation-initiated photoenzymatic enantioselective hydrosulfonylation of olefins using a novel mutant of gluconobacter ene-reductase (GluER-W100F-W342F). Compared to known photoenzymatic systems, our approach does not rely on the formation of an electron donor-acceptor complex between the substrates and enzyme cofactor and simplifies the reaction system by obviating the addition of a cofactor regeneration mixture. More importantly, the GluER variant exhibits high reactivity and enantioselectivity and a broad substrate scope. Mechanistic studies support the proposed oxidation-initiated mechanism and reveal that a tyrosine-mediated HAT process is involved.

Visible-light-driven catalyst-free C-S cross-coupling of thiol derivatives and aryl halides.

A mild, scalable, and high-yielding visible-light-promoted C-S cross-coupling between alkyl thiol derivatives and (hetero)aryl halides without the need for metals, ligands, or photocatalysts is reported, offering advantages over traditional C-S bond forming strategies. The formation of an electron donor-acceptor (EDA) complex is supported by experimental and computational mechanistic studies, which undergoes visible-light-induced charge transfer to initiate C-S bond formation in the absence of a photoredox catalyst.

Metal- and photocatalyst-free approach to visible-light-induced acylation of quinoxalinones.

A transition-metal- and photocatalyst-free photochemical reaction was successfully developed for the direct acylation of quinoxalin-2(1H)-ones, which was enabled by the formation of electron donor-acceptor (EDA) complexes. The use of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as the electron donor allows efficient and operationally simple access to a series of C3-aroylated and acylated quinoxalin-2(1H)-ones with moderate to good yields.

Electron Donor-Acceptor Complex Enabled Radical Cyclization of α-Diazodifluoroethyl Sulfonium Salt with Unactivated Alkynes.

An α-diazodifluoroethane sulfonium reagent was developed in this study to undergo [3 + 2] radical cyclization with unactivated alkynes to give the corresponding 3-difluoromethyl pyrazoles under blue light irradiation conditions. The key to the success of this transformation lies in the formation of an electron donor-acceptor (EDA) complex between an electron-deficient α-diazo sulfonium salt and an electron-rich triaryl amine. This study circumvents a major substrate scope limitation in polar cycloaddition reactions of existent diazodifluoroethane reagents.

Photoenzymatic Enantioselective Synthesis of Oxygen-Containing Benzo-Fused Heterocycles.

New-to-nature biocatalysis in organic synthesis has recently emerged as a green and powerful strategy for the preparation of valuable chiral products, among which chiral oxygen-containing benzo-fused heterocycles are important structural motifs in pharmaceutical industry. However, the asymmetric synthesis of these compounds through radical-mediated methods is challenging. Herein, a novel asymmetric radical-mediated photoenzymatic synthesis strategy is developed to realize the efficient enantioselective synthesis of oxygen-containing benzo-fused heterocycles through structure-guided engineering of a flavin-dependent 'ene'-reductase GluER. It shows that variant GluER-W100H could efficiently produce various benzoxepinones, chromanone and indanone with different benzo-fused rings in high yields with great stereoselectivities under visible light. Moreover, these results are well supported by mechanistic experiments, revealing that this photoenzymatic process involves electron donor-acceptor complex formation, single electron transfer and hydrogen atom transfer. Therefore, we provide an alternative green approach for efficient chemoenzymatic synthesis of important chiral skeletons of bioactive pharmaceuticals.

Photoinduced Five-Component Radical Relay Aminocarbonylation of Alkenes.

Radical single carbonylation reactions with CO constitute a direct and robust strategy toward various carbonyl compounds from readily available chemicals, and have been extensively studied over the past decades. However, realizing highly selective catalytic systems for controlled double radical carbonylation reactions has remained a substantial challenge, particularly for the more advanced multi-component variants, despite their great potential value. Herein, we report a visible light-driven radical relayed five-component radical double aminocarbonylation reaction of unactivated alkenes using CO under metal-free conditions. This protocol provides direct access to valuable γ-trifluoromethyl α-ketoamides with good yields and high selectivity. Crucial was the identification of distinct dual roles of amine coupling partners, sequentially acting as electron donors for the formation of photoactive electron donor-acceptor (EDA) complexes with radical precursors and then as a CO acceptor via nitrogen radical cations to form carbamoyl radicals. Cross-coupling of carbamoyl radicals with the acyl radicals that are formed in an alkene-based relay process affords double aminocarbonylation products.

Metal- and Photocatalyst-Free, Visible-Light-Initiated C3 α-Aminomethylation of Quinoxalin-2(1H)-ones via Electron Donor-Acceptor Complexes.

We report a metal- and photocatalyst-free C3 α-aminomethylation of quinoxalin-2(1H)-ones with N-alkyl-N-methylanilines. The reaction proceeds through the formation of a photoactivated electron donor-acceptor complex between quinoxalin-2(1H)-ones and N-alkyl-N-methylanilines. The present method provides a mild and environmentally friendly protocol that exhibits good atom economy and excellent functional group tolerance to obtain a library of biologically significant C3 α-aminomethylated quinoxalin-2(1H)-ones in good yields.

Structures and Stability of Mixed Main Group Hydrides [PBEH6]n (E = C, Si, Ge; n = 1-4) and Donor-Acceptor Stabilization of Monomeric Chain Isomers.

Structures and stability of mixed group 13-14-15 element hydrides PBEH6 (E = C, Si, Ge), their oligomers, and complexes with Lewis acids and Lewis base are computationally studied at the B3LYP-D3/def2-TZVP level of theory. Unsubstituted chain hydrides are unstable and are expected to form cyclic oligomers. Cyclization can be prevented by the donor-acceptor complex formation. For complexes of chain hydrides with Lewis acid in many cases additional reactivity beyond the donor-acceptor complex formation is observed: cyclization and migration of terminal group from the group 13 Lewis acid to the boron or group 14 terminal atoms of the hydride. The most promising compounds for the experimental studies have been identified. Joint stabilization by both W(CO)5 and trimethylamine provides a synergetic effect, allowing stabilization of 13-14-15 chain compounds.

Difluoroalkylation of Anilines via Photoinduced Methods.

The development of sustainable and mild protocols for the fluoroalkylation of organic backbones is of current interest in chemical organic synthesis. Herein, we present operationally simple and practical transition-metal-free methods for the preparation of difluoroalkyl anilines. First, a visible-light organophotocatalytic system working via oxidative quenching is described, providing access to a wide range of difluoroalkyl anilines under mild conditions. In addition, the formation of an unprecedented electron donor-acceptor (EDA) complex between anilines and ethyl difluoroiodoacetate is reported and exploited as an alternative, efficient, and straightforward strategy to prepare difluoroalkyl derivatives.

Photodecarboxylative C-H Alkylation of Azauracils with N-(Acyloxy)phthalimides.

We disclose a transition-metal-free NaI/PPh3-mediated direct C-H alkylation of azauracils using N-(acyloxy)pthalimides (NHPIs) as readily available alkyl surrogates under visible light irradiation. Detailed mechanistic studies reveal formation of a photoactivated electron donor-acceptor (EDA) complex between NaI/PPh3, TMEDA, and alkyl NHPI ester and establish the crucial role of TMEDA in increasing the activity of the photoredox system. The reaction demonstrates a broad scope, scalability, and appreciable functional group tolerance. A variety of azauracils are shown to undergo alkylation by primary, secondary, and tertiary NHPI esters under mild conditions, furnishing the desired products in good to excellent yields.

Some halogenated anticancer agents, role of halide (-X) and their interaction mechanism with AT/GC base pairs: A computational study

Recently, a new class of halogen-based active anticancer agents have widely been developed which shows effective binding with AT/GC base pairs of DNA nucleobases. Usually intercalation, groove binding and covalent binding mechanisms are the most common drug-DNA binding pathways; but, the groove binding mechanism plays a crucial role in the stability of such drug-DNA complexes. As anticancer agent-DNA nucleobase interactions are very difficult to investigate by using common experimental techniques; therefore, theoretical methods may be quite helpful to analyze the proper mode of interaction for such drug-DNA systems. Past literature reveals that, quantum mechanical (QM) density functional theory (DFT) method is one of the best known tool for analyzing the different binding modes of halogenated anticancer agents with DNA nucleobases. Moreover, the halogen-bonding interaction in any biological system is fundamentally understood by investigating the mechanism of donor-acceptor complex formation between donor halogens and acceptor atoms within a receptor; such study is very competent for exploring the favoured anticancer agent-DNA interaction. In this current work, our main objective is to explore the effect of some intercalating and groove binding halogen-based anticancer agents with DNA nucleobase using computational method.

Tuning Selectivity in the Visible-Light-Promoted Coupling of Thiols with Alkenes by EDA vs TOCO Complex Formation.

The visible-light-promoted catalyst-free condition has been demonstrated for self- and cross-coupling reactions of thiols in an ambient atmosphere. Further, synthesis of β-hydroxysulfides is accomplished under very mild conditions involving the formation of an electron donor-acceptor (EDA) complex between a disulfide and an alkene. However, the direct reaction of thiol with alkene via the formation of a thiol-oxygen co-oxidation (TOCO) complex failed to produce the desired compounds in high yields. The protocol was successful with several aryl and alkyl thiols for the formation of disulfides. However, the formation of β-hydroxysulfides required an aromatic unit on the disulfide fragment, which supports the formation of the EDA complex during the course of the reaction. The approaches presented in this paper for the coupling reaction of thiols and the synthesis of β-hydroxysulfides are unique and do not require toxic organic or metal catalysts.

Deconstructive Pyridylation of Unstrained Cyclic Amines through a One-Pot Umpolung Approach.

A one-pot umpolung method for the ring-opening pyridylation of unstrained cyclic amines was developed using N-amidopyridinium salts. This process involves the formation of electron donor-acceptor complexes between bromide and N-amidopyridinium salts, ultimately leading to the functionalization of pyridines. This protocol is compatible with a range of 5- or 6-membered cyclic amines and pyridines, thereby providing a powerful synthon for preparing C4-functionalized pyridines under visible-light conditions in the absence of an external photocatalyst.

Permittivity Threshold and Thermodynamics of Integer Charge-Transfer Complexation for an Organic Donor–Acceptor Pair

Molecular charge doping involves the formation of donor-acceptor charge-transfer complexes (CTCs) through integer or partial electron transfer; understanding how local chemical environment impacts complexation is important for controlling the properties of organic materials. We present steady-state and temperature-dependent spectroscopic investigations of the p-dopant 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane (F4TCNQ) complexed with the electron donor and hole transport material N,N'-diphenyl-N,N'-di-p-tolylbenzene-1,4-diamine (MPDA). Equilibrium formation constants (KCT) were determined for donor-acceptor pairs dissolved in a series of solvents covering a range of values of permittivity. A threshold for highly favorable complex formation was observed to occur at ϵ ∼ 8-9, with large (>104) and small (<103) values of KCT obtained in solvents of higher and lower permittivity, respectively, but with chloroform (ϵ = 4.81) exhibiting an anomalously high formation constant. Temperature-dependent formation constants were determined in order to evaluate the thermodynamics of complex formation. In 1,2-dichloroethane (ϵ = 10.36) and chlorobenzene (ϵ = 5.62), complex formation is both enthalpically and entropically favorable, with higher enthalpic and entropic stabilization in the solvent with higher permittivity. Complexation in chloroform is exothermic and entropically disfavored, indicating that specific, inner-shell solvent-solute interactions stabilize the charge-separated complex and result in a net increase in local solution structure. Our results provide insight into how modification to the chemical environment may be utilized to support stable integer charge transfer for molecular doping applications and requiring only modest changes in local permittivity.

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

AbstractThe 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.

Diquat Based Dyes: A New Class of Photoredox Catalysts and Their Use in Aerobic Thiocyanation.

A series of new organic donor-π-acceptor dyes incorporating a diquat moiety as a novel electron-acceptor unit have been synthesized and characterized. The analytical data were supported by DFT calculations. These dyes were explored in the aerobic thiocyanation of indoles and pyrroles. Here they showed a high photocatalytic activity under visible light, giving isolated yields of up to 97 %. In addition, the photocatalytic activity of standalone diquat and methyl viologen through formation of an electron donor acceptor complex is presented.