Thermal and Photoinduced Radical Cascade Annulation using Aryl Isonitriles: An Approach to Quinoline-Derived Benzophosphole Oxides.

Herein, we present a radical cascade addition cyclization sequence to access quinoline-based benzophosphole oxides from ortho-alkynylated aromatic phosphine oxides using various aryl isonitriles as radical acceptors and inexpensive tert-butyl-hydroperoxide (TBHP) as a terminal oxidant in the presence of a catalytic amount of silver acetate. Alternatively, the same cascade can be realized through a sustainable photochemical approach utilizing 1,2,3,5-tetrakis(carbazol-9-yl)-4,6-dicyanobenzene (4CzIPN) as an organic photocatalyst at room temperature. The introduced modular approach shows broad functional group tolerance and offers straightforward access to complex P,N-containing polyheterocyclic arenes. These novel π-extended benzophosphole oxides exhibit interesting photophysical and electrochemical properties such as absorption in the visible region, emission and reversible reduction at low potentials, which makes them promising for potential materials science applications. The photophysical properties can further be tuned by the addition of external Lewis and Brønsted acids.

Access to Polyheterocyclic Compounds through Iron(II)-Mediated Radical Cascade Cyclization Utilizing 2-Ethynylbenzaldehydes and Aryl Isonitriles.

An oxidative radical cascade addition cyclization approach for the synthesis of quinoline-based π-extended polyheterocyclic compounds is reported. Eco-friendly iron catalysis and inexpensive tert-butylhydroperoxide (TBHP) as the oxidant have been utilized in the transformation of various readily available ortho-alkynylated aromatic aldehydes as radical precursors with aryl isonitriles as radical acceptors. Indole and thiophene-based carbaldehydes allow the preparation of quinolines that are π-conjugated with an additional heteroarene moiety in a single sequence by applying the introduced method.

Organic Synthesis Using Nitroxides.

Nitroxides, also known as nitroxyl radicals, are long-lived or stable radicals with the general structure R1R2N-O•. The spin distribution over the nitroxide N and O atoms contributes to the thermodynamic stability of these radicals. The presence of bulky N-substituents R1 and R2 prevents nitroxide radical dimerization, ensuring their kinetic stability. Despite their reactivity toward various transient C radicals, some nitroxides can be easily stored under air at room temperature. Furthermore, nitroxides can be oxidized to oxoammonium salts (R1R2N═O+) or reduced to anions (R1R2N-O-), enabling them to act as valuable oxidants or reductants depending on their oxidation state. Therefore, they exhibit interesting reactivity across all three oxidation states. Due to these fascinating properties, nitroxides find extensive applications in diverse fields such as biochemistry, medicinal chemistry, materials science, and organic synthesis. This review focuses on the versatile applications of nitroxides in organic synthesis. For their use in other important fields, we will refer to several review articles. The introductory part provides a brief overview of the history of nitroxide chemistry. Subsequently, the key methods for preparing nitroxides are discussed, followed by an examination of their structural diversity and physical properties. The main portion of this review is dedicated to oxidation reactions, wherein parent nitroxides or their corresponding oxoammonium salts serve as active species. It will be demonstrated that various functional groups (such as alcohols, amines, enolates, and alkanes among others) can be efficiently oxidized. These oxidations can be carried out using nitroxides as catalysts in combination with various stoichiometric terminal oxidants. By reducing nitroxides to their corresponding anions, they become effective reducing reagents with intriguing applications in organic synthesis. Nitroxides possess the ability to selectively react with transient radicals, making them useful for terminating radical cascade reactions by forming alkoxyamines. Depending on their structure, alkoxyamines exhibit weak C-O bonds, allowing for the thermal generation of C radicals through reversible C-O bond cleavage. Such thermally generated C radicals can participate in various radical transformations, as discussed toward the end of this review. Furthermore, the application of this strategy in natural product synthesis will be presented.

Enantioselective Copper-Catalyzed Fukuyama Indole Synthesis from 2-Vinylphenyl Isocyanides.

Enantioenriched chiral indoles are of high interest for the pharmaceutical and agrochemical industries. Herein, we present an asymmetric Fukuyama indole synthesis through a mild and efficient radical cascade reaction to access 2-fluoroalkylated 3-(α-cyanobenzylated) indoles by stereochemical control with a chiral copper-bisoxazoline complex using 2-vinylphenyl arylisocyanides as radical acceptors and fluoroalkyl iodides as C-radical precursors. Radical addition to the isonitrile moiety, 5-exo-trig cyclization, and Cu-catalyzed stereoselective cyanation provide the targeted indoles with excellent enantioselectivity and good yields. Due to the similar electronic and steric properties of the two aryl substituents to be differentiated, the enantioselective construction of the cyano diaryl methane stereocenter is highly challenging. Mechanistic studies reveal a negative nonlinear effect which allows proposing a model to explain the stereochemical outcome. Scalability and potential utility of the enantioenriched 3-(α-cyanobenzylated) indoles as hubs for chiral tryptamines, indole-3-acetic acid derivatives, and triarylmethanes are demonstrated, and a formal synthesis of a natural product analogue is disclosed.

2,3-Difunctionalized Indoles via Radical Acylation or Trifluoromethylation of ortho-Alkynylphenyl Isonitriles.

A radical cascade to 2,3-disubstituted indoles proceeding via acylation or trifluoromethylation of ortho-alkynylphenyl isonitriles is presented. In these cascades, two C-C bonds and one C-O bond are formed using an inexpensive oxidant and a catalytic copper or iron salt. The starting isonitriles are easily accessible, and commercially available aldehydes and fluoromethylation reagents serve as reaction partners. Functional group tolerance is high, as documented by the successful preparation of a series of 2,3-disubstituted indoles.

Organic Electrochemical Transistors Based on the Conjugated Polyelectrolyte PCPDTBT-SO3 K (CPE-K).

PCPDTBT-SO3 K (CPE-K), a conjugated polyelectrolyte, is presented as a mixed conductor material that can be used to fabricate high transconductance accumulation mode organic electrochemical transistors (OECTs). OECTs are utilized in a wide range of applications such as analyte detection, neural interfacing, impedance sensing, and neuromorphic computing. The use of interdigitated contacts to enable high transconductance in a relatively small device area in comparison to standard contacts is demonstrated. Such characteristics are highly desired in applications such as neural-activity sensing, where the device area must be minimized to reduce invasiveness. The physical and electrical properties of CPE-K are fully characterized to allow a direct comparison to other top performing OECT materials. CPE-K demonstrates an electrical performance that is among the best reported in the literature for OECT materials. In addition, CPE-K OECTs operate in the accumulation mode, which allows for much lower energy consumption in comparison to commonly used depletion mode devices.

Photoswitchable Conjugated Oligoelectrolytes for a Light-Induced Change of Membrane Morphology.

The synthesis of a new conjugated oligoelectrolyte (COE), namely DSAzB, is described, which contains a conjugated core bearing a diazene moiety in the center of its electronically delocalized structure. Similar to structurally related phenylenevinylene-based COEs, DSAzB readily intercalates into model and natural lipid bilayer membranes. Photoinduced isomerization transforms the linear trans COE into a bent or C-shape form. It is thereby possible to introduce DSAzB into the bilayer of a cell and disrupt its integrity by irradiation with light. This leads to controlled permeabilization of membranes, as demonstrated by the release of calcein from DMPG/DMPC vesicles and by propidium iodide influx experiments on S. epidermidis. Both experiments support that the permeabilization is selective for the light stimulus, highly efficient, and repeatable. Target-selective and photoinduced actions demonstrated by DSAzB may have broad applications in biocatalysis and related biotechnologies.

Living Bioelectrochemical Composites.

Composites, in which two or more material elements are combined to provide properties unattainable by single components, have a historical record dating to ancient times. Few include a living microbial community as a key design element. A logical basis for enabling bioelectronic composites stems from the phenomenon that certain microorganisms transfer electrons to external surfaces, such as an electrode. A bioelectronic composite that allows cells to be addressed beyond the confines of an electrode surface can impact bioelectrochemical technologies, including microbial fuel cells for power production and bioelectrosynthesis platforms where microbes produce desired chemicals. It is shown that the conjugated polyelectrolyte CPE-K functions as a conductive matrix to electronically connect a three-dimensional network of Shewanella oneidensis MR-1 to a gold electrode, thereby increasing biocurrent ≈150-fold over control biofilms. These biocomposites spontaneously assemble from solution into an intricate arrangement of cells within a conductive polymer matrix. While increased biocurrent is due to more cells in communication with the electrode, the current extracted per cell is also enhanced, indicating efficient long-range electron transport. Further, the biocomposites show almost an order-of-magnitude lower charge transfer resistance than CPE-K alone, supporting the idea that the electroactive bacteria and the conjugated polyelectrolyte work synergistically toward an effective bioelectronic composite.

The Persistent Radical Effect in Organic Synthesis.

Radical-radical couplings are mostly nearly diffusion-controlled processes. Therefore, the selective cross-coupling of two different radicals is challenging and not a synthetically valuable transformation. However, if the radicals have different lifetimes and if they are generated at equal rates, cross-coupling will become the dominant process. This high cross-selectivity is based on a kinetic phenomenon called the persistent radical effect (PRE). In this Review, an explanation of the PRE supported by simulations of simple model systems is provided. Radical stabilities are discussed within the context of their lifetimes, and various examples of PRE-mediated radical-radical couplings in synthesis are summarized. It is shown that the PRE is not restricted to the coupling of a persistent with a transient radical. If one coupling partner is longer-lived than the other transient radical, the PRE operates and high cross-selectivity is achieved. This important point expands the scope of PRE-mediated radical chemistry. The Review is divided into two parts, namely 1) the coupling of persistent or longer-lived organic radicals and 2) "radical-metal crossover reactions"; here, metal-centered radical species and more generally longer-lived transition-metal complexes that are able to react with radicals are discussed-a field that has flourished recently.

Towards understanding the doping mechanism of organic semiconductors by Lewis acids.

Precise doping of organic semiconductors allows control over the conductivity of these materials, an essential parameter in electronic applications. Although Lewis acids have recently shown promise as dopants for solution-processed polymers, their doping mechanism is not yet fully understood. In this study, we found that B(C6F5)3 is a superior dopant to the other Lewis acids investigated (BF3, BBr3 and AlCl3). Experiments indicate that Lewis acid-base adduct formation with polymers inhibits the doping process. Electron-nuclear double-resonance and nuclear magnetic resonance experiments, together with density functional theory, show that p-type doping occurs by generation of a water-Lewis acid complex with substantial Brønsted acidity, followed by protonation of the polymer backbone and electron transfer from a neutral chain segment to a positively charged, protonated one. This study provides insight into a potential path for protonic acid doping and shows how trace levels of water can transform Lewis acids into powerful Brønsted acids.

Initiating radical reactions with non-thermal plasmas.

Non-thermal plasmas were used as radical initiators in three radical chain reactions: dehalogenation, 5-exo-trig cyclisation and trifluoromethylation with the Togni II reagent. The use of non-volatile solvents (or solvent-free conditions) gave high yields in all reactions under optimised conditions. Short reaction times and mild conditions make this method an attractive alternative to conventional radical initiators.

Iodinated (Perfluoro)alkyl Quinoxalines by Atom Transfer Radical Addition Using ortho-Diisocyanoarenes as Radical Acceptors.

A simple method for the preparation of functionalized quinoxalines is reported. Starting from readily accessible ortho-diisocyanoarenes and (perfluoro)alkyl iodides, the quinoxaline core is constructed during (perfluoro)alkylation by atom transfer radical addition (ATRA), resulting in 2-iodo-3-(perfluoro)alkylquinoxalines. The radical cascades are readily initiated either with visible light or by using α,α'-azobisisobutyronitrile (AIBN). The heteroarene products are obtained in high yields (up to 94 %), and the method can be readily scaled up. Useful follow-up chemistry documents the value of the novel radical quinoxaline synthesis.

Radical perfluoroalkylation - easy access to 2-perfluoroalkylindol-3-imines via electron catalysis.

Arylisonitriles (2 equivalents) react with alkyl and perfluoroalkyl radicals to form 2-alkylated indole-3-imines via two sequential additions to the isonitrile moiety followed by homolytic aromatic substitution. The three component reaction comprises three C-C bond formations. The endocyclic imine functionality in the products is more reactive in follow up chemistry and hydrolysis of the exocyclic imine leads to 3-oxindoles that show fluorescence properties.

9-Silafluorenes via base-promoted homolytic aromatic substitution (BHAS)--the electron as a catalyst.

Transition-metal-free intramolecular radical silylation of 2-diphenylsilylbiaryls via base-promoted homolytic aromatic substitution (BHAS) to give 9-silafluorenes is reported. 2-Diphenylsilylbiaryls are readily prepared, and cross dehydrogenative silylation occurs with tert-butylhydroperoxide (TBHP) as a cheap stoichiometric oxidant in the presence of a small amount of tetrabutylammonium iodide (TBAI) as an initiator. These cyclizations are catalyzed by the electron.

6-Aroylated phenanthridines via base promoted homolytic aromatic substitution (BHAS).

Readily accessible 2-isocyanobiphenyls react with aromatic aldehydes via base promoted homolytic aromatic substitution (BHAS) to give 6-aroylated phenanthridines. Reactions occur via addition of acyl radicals to the isonitrile functionality and subsequent intramolecular BHAS of the intermediate imidoyl radicals. Initiation of the radical chain reaction is best achieved with small amounts of FeCl3 (0.4 mol %), and the commercially available and cheap tBuOOH is used as the oxidant.

Cross dehydrogenative coupling via base-promoted homolytic aromatic substitution (BHAS): synthesis of fluorenones and xanthones.

Cross dehydrogenative coupling reactions occurring via base-promoted homolytic aromatic substitutions (BHASs) are reported. Fluorenones and xanthones are readily prepared via CDC starting with readily available ortho-formyl biphenyls and ortho-formyl biphenylethers, respectively. The commercially available and cheap tBuOOH is used as an oxidant. Initiation of the radical chain reaction is best achieved with small amounts of FeCp(2) (0.1 or 1 mol %).