Radical Cation Diels-Alder Reaction Research Articles

Radical Cation Diels–Alder Reaction by Photocatalysis at a Dye Sensitized Photoanode

Radical Cation Diels–Alder Reaction by Photocatalysis at a Dye Sensitized Photoanode

Redox-Tag-Guided Radical Cation Diels–Alder Reactions: Use of Enol Ethers as Dienophiles

AbstractAlthough radical cation Diels–Alder reactions enable the formation of cyclohexene ring systems between electronically mismatched (both electron-rich) dienes and dienophiles, which is otherwise difficult or impossible to achieve under thermal conditions, the substrate scope has been limited. Herein, we disclose that a radical cation Diels–Alder reaction using an enol ether as an electron-rich (and therefore oxidizable) dienophile is possible through a rationally designed redox tag strategy. Electrochemical and TiO2 photochemical approaches are effective in driving the reaction, where both intermolecular and intramolecular electron transfers are the key.

Radical cation Diels-Alder reactions of arylidene cycloalkanes.

TiO2 photoelectrochemical and electrochemical radical cation Diels–Alder reactions of arylidene cycloalkanes are described, leading to the construction of spiro ring systems. Although the mechanism remains an open question, arylidene cyclobutanes are found to be much more effective in the reaction than other cycloalkanes. Since the reaction is completed with a substoichiometric amount of electricity, a radical cation chain pathway is likely to be involved.

EC-Backward-E Electrochemistry in Radical Cation Diels-Alder Reactions

Cascade processes, including electron transfer (E), chemical reaction (C), and backward electron transfer (E), are known as EC-backward-E mechanisms; however, they are rarely observed directly. Herein, we demonstrate that direct observation of EC-backward-E processes in radical cation Diels-Alder reactions is possible using cyclic voltammetry measurements. Formal expressions for the plausible reaction mechanisms provide a reasonable understanding of the processes, which are also supported by the highest occupied molecular orbitals and spin density distributions plotted from density functional theory calculations.

Radical Cation Diels-Alder Reactions by TiO2 Photocatalysis.

Radical cation Diels-Alder reactions by titanium dioxide (TiO2) photocatalysis in lithium perchlorate/nitromethane solution are described. TiO2 photocatalysis promotes reactions between electron-rich dienes and dienophiles, which would otherwise be difficult to accomplish due to electronic mismatching. The reactions are triggered by hole oxidation of the dienophile and are completed by the excited electron reduction of the radical cation intermediate at the dispersed surface in the absence of any sacrificial substrate.

Discovery and Elucidation of Counteranion Dependence in Photoredox Catalysis.

Over the past decade, there has been a renewed interest in the use of transition metal polypyridyl complexes as photoredox catalysts for a variety of innovative synthetic applications. Many derivatives of these complexes are known, and the effect of ligand modifications on their efficacy as photoredox catalysts has been the subject of extensive, systematic investigation. However, the influence of the photocatalyst counteranion has received little attention, despite the fact that these complexes are generally cationic in nature. Herein, we demonstrate that counteranion effects exert a surprising, dramatic impact on the rate of a representative photocatalytic radical cation Diels-Alder reaction. A detailed analysis reveals that counteranion identity impacts multiple aspects of the reaction mechanism. Most notably, photocatalysts with more noncoordinating counteranions yield a more powerful triplet excited state oxidant and longer radical cation chain length. It is proposed that this counteranion effect arises from Coulombic ion-pairing interactions between the counteranion and both the cationic photoredox catalyst and the radical cation intermediate, respectively. The comparatively slower rate of reaction with coordinating counteranions can be rescued by using hydrogen-bonding anion binders that attenuate deleterious ion-pairing interactions. These results demonstrate the importance of counteranion identity as a variable in the design and optimization of photoredox transformations and suggest a novel strategy for the optimization of organic reactions using this class of transition metal photocatalysts.

Interplay of arene radical cations with anions and fluorinated alcohols in hole catalysis

Chemical reactions via radical cation intermediates are of great interest in photoredox catalysis and electrosynthesis, while their reactivities are not clearly understood. For example, how the counter anions correlate with the reactivity of radical cations is still ambiguous. Here we report the effect of anions and fluorinated alcohols on the reactivity of organic radical cations in hole catalysis. The addition of salts in a radical cation Diels–Alder reaction under photoredox catalysis demonstrates that common anions significantly decease the efficiency of hole catalysis. The use of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) restores the reaction efficiency in the presence of salts, presumably due to solvation of the anions by HFIP to reduce their nucleophilicity. These findings enable hole catalysis under electrolytic conditions with greatly improved efficiency. The effect of anions and fluorinated alcohol described in this paper gives important insights on the fundamental understanding for the reactivity of arene radical cations.

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′(C∗/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.

Stepwise radical cation Diels-Alder reaction via multiple pathways.

Herein we disclose the radical cation Diels–Alder reaction of aryl vinyl ethers by electrocatalysis, which is triggered by an oxidative SET process. The reaction clearly proceeds in a stepwise fashion, which is a rare mechanism in this class. We also found that two distinctive pathways, including “direct” and “indirect”, are possible to construct the Diels–Alder adduct.

Radical Cation Diels-Alder By Electrocatalyst

In recent years, redox reactions with single electron transfer have received significant attention from many chemists. Organo-catalysts and photo-catalysts have been growing as a promising approach to electron path-ways. The electrochemical method is also playing roles as one of the most straightforward processes. With this method, we designed intermolecular carbon-carbon bond forming reactions, in which electron is the key reagent and the catalytic amount of electricity is enough for the full conversion. For example, radical cation Diels-Alder reaction with aromatic "redox tag" is in accordance with it. In this reaction, the chain cycle is the key factor to realize the significant decrease of consumed electricity. Our success leads to the development of the environmentally friendly and extreme high productivity synthetic method to produce the compound which has useful chemical structure for natural compounds and pharmaceuticals. Our investigation commenced with the reaction between trans-anethole (1) and isoprene (2), using electrocatalytic approach. In the reaction, it is understood well that the radical cation (3 ・ +) is generated, accompanying by chain process (Fig. 1). From cyclic voltammetry investigation, it is indicated that 1 (Ep ox = 1.07 V vs. Ag/AgCl) is anodically oxidized selectively in the presence of 2 (Ep ox = 1.83 V vs Ag/AgCl). Based on this, we demonstrate that the aromatic radical cation, which is given by the intermolecular [4 + 2] cycloaddition between radical cation 1 ・ + and 2, gives rise to a radical cation chain cycles and completion of the reaction with the catalytic amount of electricity. Here, we envisioned that the aromatic ring of 1might work as a redox tag to accomplish an electrocatalytic Diels-Alder reaction. Hence, we carried out anodic oxidation of 1in the presence of 2 equiv. of 2 at 1.00 V vs. Ag/AgCl. Beyond our expectation, only 0.1 F/mol of electricity was sufficient to make the reaction completed in excellent yield. This result suggests that the aromatic radical cation 3 ・ + was reduced predominantly by 1, comparing the reduction at the electrodes. Furthermore, the investigation of Cyclic Voltammetry shows that the oxidation peak of Diels-Alder adduct (3) is 1.40 V vs Ag/AgCl, which is sufficiently higher than that of 1. It can explain that radical cation 3 ・ + would oxidize 1 preferably, leading to the chain propagation. Based upon the mechanistic comprehension, we confirmed the applicable range of substrates, which are dienophile and diene, in the electrocatalytic Diels-Alder reaction. It showed that the moderate range of dienes was available, but the scope of styrene structures was limited. To obtain deeper insight into the mechanism, we conducted density functional theory (DFT) calculations. The calculation results demonstrate that the Dies-Alder reaction is proceed in stepwise mechanism. Besides, we speculated that the combination of electrolyte and solvent had an important role in this reaction. Although we have tried to use a variety of electrolytes and solvents, we have not found better media than LiClO4 / Nitromethane which leads this reaction to the excellent yield and faraday efficiency. Considering that using tetrabutylammonium perchlorate did not work in this reaction, we assume that Li+ has the important role. With the investigation of 7Li NMR and the heat of solution, it is implied that the solvation of ions is the key factor to achieve the electrocatalytic C-C bond forming reaction. Then, we turned out interest to how much we could improve the electro-energy efficiency. As we demonstrated above, only 0.1 F/mol, was enough to complete the reaction. However, we postulated that it still has room to be encouraged. We screened several factors; type of cell, type of electrodes, electrode’s surface area, reaction temperature, concentration of starting materials, concentration of electrolyte, etc… Surprisingly, it turned out that the concentration of substrates had the significant impact on the efficient production. Based upon the optimized condition, we have succeeded in that only 0.015 F/mol realized the full conversion. It is demonstrated by GC-MS monitoring that from 0.005 F/mol to 0.01 F/mol, the average number of chain cycle is 106. This optimized condition has the potential of having a big impact on chemical and pharmaceutical production. Our electrochemical approach realizes the environmentally friendly and extreme high productive synthetic method; requiring only a small amount of solvent and electrolyte, high electro-energy efficiency and recyclable. Taking advantage of these points, we demonstrate that we can scale up the production of the compounds that have useful chemical structure for natural compounds and pharmaceuticals. It is noted that electro chemical approach is promising for not only green but also economical chemistry. Figure 1

Electrochemically-Induced Radical Cation Diels-Alder Reactions Assisted By "Redox Tag Strategy"

Diels-Alder (DA) reaction is among the most important reaction for constructing carbon-carbon bond in organic chemistry. The mechanisms into it are well understood; diene and dienophile should have complementary electronic characters for smooth reaction. In the situation where both substrates are electron-rich, significantly higher temperature or longer time are required. One of the most effective solution for such electronically-mismatched DA is umpolung process, which can give highly electrophilic radical cation from otherwise nucleophilic electron-rich starting substrates by one electron oxidation. Namely, the radical cations generated from electron-rich olefins can readily afford the DA adduct with nucleophilic electron rich dienes.1 Since electrochemical method has proven to be the simplest approach for the umpolung reaction, anodic method has been developed for the radical cation-mediated DA (rDA).2 Our group have been focused on the anodically-induced C-C bond forming reactions using lithium perchlorate nitromethane electrolyte solution system.3 In particular, [2 + 2] cycloaddition reaction4 between enol ether and unactivated terminal olefin is initiated by one electron oxidation of enol ether to give corresponding radical cation. The reaction allow for the mechanistic study of radical cation species, providing information, for example, intramolecular electron transfer properties5 and functionality of aromatic radical cation intermediates.6 In the talk to be presented, anodically-induced rDA (Scheme 1) will be reported especially to electrochemical condition, scope and limitations, and new design of the rDA based on the previous study of radical cation properties.

ChemInform Abstract: Formal Synthesis of Kingianin A (IV) Based upon a Novel Electrochemically‐Induced Radical Cation Diels—Alder Reaction.

ChemInform Abstract: Formal Synthesis of Kingianin A (IV) Based upon a Novel Electrochemically‐Induced Radical Cation Diels—Alder Reaction.

Formal synthesis of kingianin A based upon a novel electrochemically-induced radical cation Diels-Alder reaction.

The application of electrochemical reactions in natural product synthesis has burgeoned in recent years. We herein report a formal synthesis of the complex and dimeric natural product kingianin A, which employs an electrochemically-mediated radical cation Diels-Alder cycloaddition as the key step.

Total synthesis of kingianin A.

A 12-step synthesis of kingianin A, an inhibitor of the antiapoptotic protein Bcl-xL, is based on a radical cation Diels-Alder reaction (RCDA). This approach is thought to be biomimetic. The use of a tether in the key RCDA step controls the regiochemistry of the cycloaddition, leading to the desired core structure and a separable diastereomer.

Visible light photocatalysis of intramolecular radical cation Diels–Alder cycloadditions

Intramolecular radical cation Diels–Alder reactions can be conducted under photocatalytic conditions using visible light irradiation. The photocatalyst system involves the use of a Ru(bpy)32+ chromophore and methyl viologen as a co-oxidant. These reactions enable the cycloaddition of substrates whose thermal Diels–Alder cycloadditions are electronically mismatched and thus require forcing conditions. Nevertheless, the radical cation cycloadditions can be conducted on gram scale using ambient sunlight as the only source of irradiation.

ChemInform Abstract: Radical Cation Diels-Alder Reaction of Indoles and Exocyclic Dienes.

Abstract A convergent synthesis of [b]-annelated tetrahydrocarbazoles through a radical cation Diels-Alder reaction is described. The reaction is induced by photo electron transfer (PET). The previously predicted stepwise mechanism of this reaction is proved by stereochemical analysis of the products.

Diels-Alder Reaction of phosphaethene with 1,3-dienes: an ab initio study.

Computations on Diels-Alder (DA) reactions of phosphaethene with 1,3-butadiene and with isoprene reveal asynchronous transition structures. The DFT (B3LYP/6-311+G) activation energies of these reactions, 12-14 kcal/mol, are much lower than that of the parent ethene-butadiene reaction, 28 kcal/mol, even though the exothermicities of all lie in the same range, from -29 to -33 kcal/mol. The transition states (TSs) for the phosphethene-butadiene or isoprene DA reactions are earlier than the TSs of the butadiene-ethene cycloaddition. Due to the weakness of the C=P pi bond compared to the C=C pi bonds, the energies required to reach the phosphaethene TSs are much less than the carbocyclic cases. The computed (1)H NMR chemical shifts and nucleus independent chemical shifts (NICS) quantify the aromatic character of the transition states. Regioselectivities of the neutral phosphaethene-isoprene DA reactions are modest, at best. However, computations on radical cation DA reactions of phosphaethene with isoprene, which proceed stepwise with open chain intermediates, can account for the high regioselectivities that have been observed in some cases.

Diels–Alder cycloadditions of the N-vinylcarbazole radical cation

The first radical cation Diels–Alder reactions of N-vinylcarbazole, the substrate for which radical cation cycloaddition (cyclodimerization) was first observed more than 30 years ago, have now been observed. The additions of N-vinylcarbazole to both cyclopenta-1,3-diene and cyclohexa-1,3-diene, catalyzed by tris(4-bromophenyl)aminium hexachloroantimonate, have been observed. Further, a two step mechanism for these cycloadditions has been established through the use of stereospecifically labelled substrate ((Z)-N-(2-deuteriovinyl)carbazole).

ChemInform Abstract: Radical Cation Diels—Alder Reaction Between Indoles and Exocyclic 1,3‐Dienes with Incorporated Intentional Cleaving Points.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Radical cation Diels–Alder reaction between indoles and exocyclic 1,3-dienes with incorporated intentional cleaving points

A photoinduced electron transfer catalyzed radical cation Diels–Alder reaction between exocyclic dienes, containing an N–O or N–N bond as an intentional cleaving point in the ring moiety, and indoles yields, after cleavage of the N–O or N–N bond, highly functionalized tetrahydrocarbazole derivatives, products of a formal Diels–Alder reaction between indole and open chain 1,3-dienes.