Radical Acceptors Research Articles

Photogeneration of β-Borylsilyl Radical via Decarboxylation of N-Hydroxyphthalimide Esters.

Gem-borylsilylalkanes are versatile intermediates in organic synthesis, and the traditional synthesis methods have mainly focused on metal reagents, the insertion reactions of diazo compounds, and hydrosilylation/hydroborylation reactions of unsaturated bonds. Herein, a novel, efficient gem-borylsilylalkanes synthesis via a radical approach is reported. This method introduced a β-gem-borylsilyl NHPI ester as the precursor of the β-borylsilyl radical that, coupling with radical acceptors under photo conditions, and the corresponding gem-borylsilylalkanes bearing unsaturated bonds, facilitate subsequent transformations.

Iron-Catalyzed Deboronation/Cyanoalkylation of Vinyl Boronic Acids with Cyclobutanone Ketoximes

AbstractIn this paper, an iron-catalyzed deboronation/cyanoalkylation of vinyl boronic acids for the preparation of distal cyanoalkyl alkenes with vinyl boronic acids as radical acceptor and activator is reported. In this reaction, various cyclobutanone oximes and substituted vinyl boronic acids can be transformed into the corresponding cyanoalkylated alkenes in moderate to good yields under these conditions. Mechanistic studies indicated that a single-electron transfer process may be involved in this transformation.

Direct Excitation Strategy for Deacylative Couplings of Ketones.

The homolysis of chemical bonds represents one of the most fundamental reactivities of excited molecules. Historically, it has been exploited to generate radicals under ultraviolet (UV) light irradiation. However, unlike most contemporary radical-generating mechanisms, the direct excitation to homolyze chemical bonds and produce aliphatic carbon-centered radicals under visible light remains rare, especially in metallaphotoredox cross couplings. Herein, we present our design of the dihydropyrimidoquinolinone (DHPQ) reagents derived from ketones, which can undergo formal deacylation and homolytic C-C bond cleavage to release alkyl radicals without external photocatalysts. Spectroscopic and computational analysis reveal unique optical and structural features of DHPQs, rationalizing their faster kinetics in alkyl radical generation than a structurally similar but visible-light transparent radical precursor. Such a capability allows DHPQ to facilitate a wide range of Ni-metallaphotoredox cross couplings with aryl, alkynyl and acyl halides. Other catalytic and non-catalyzed alkylative transformations of DHPQs are also feasible with various radical acceptors. We believe this work would be of broad interest, aiding the synthetic planning with simplified operation and expanding the synthetic reach of photocatalyst-free approaches in cutting-edge research.

Direct excitation strategy for deacylative couplings of ketones

The homolysis of chemical bonds represents one of the most fundamental reactivities of excited molecules. Historically, it has been exploited to generate radicals under ultraviolet (UV) light irradiation. However, unlike most contemporary radical‐generating mechanisms, the direct excitation to homolyze chemical bonds and produce aliphatic carbon‐centered radicals under visible light remains rare, especially in metallaphotoredox cross couplings. Herein, we present our design of the dihydropyrimidoquinolinone (DHPQ) reagents derived from ketones, which can undergo formal deacylation and homolytic C–C bond cleavage to release alkyl radicals without external photocatalysts. Spectroscopic and computational analysis reveal unique optical and structural features of DHPQs, rationalizing their faster kinetics in alkyl radical generation than a structurally similar but visible‐light transparent radical precursor. Such a capability allows DHPQ to facilitate a wide range of Ni‐metallaphotoredox cross couplings with aryl, alkynyl and acyl halides. Other catalytic and non‐catalyzed alkylative transformations of DHPQs are also feasible with various radical acceptors. We believe this work would be of broad interest, aiding the synthetic planning with simplified operation and expanding the synthetic reach of photocatalyst‐free approaches in cutting‐edge research.

Synthesis of Enamides through Hydro‐Functionalization of Ynamides

Most of the methods for the synthesis of functionalized enamides from ynamides were developed in the last two decades showing the contemporary interest in the exploration of ynamide chemistry. The utilization of the intrinsic reactivity of the ynamide triple bond through keteniminium intermediacy, coordination with metals, and as a radical acceptor toward the development of strategies for the synthesis of functionalized enamides reflect the constant strive and creativity in the design and execution of synthetic methods. The present review summarizes the synthetic strategies developed during the last two decades and is divided into the sections depending on the type of hydrofunctionalization reaction. It may be predicted that this field of chemistry will continue to grow exponentially in the coming years and the ready availability of a wide range of ynamides now provides an excellent opportunity to further enrich mainstream synthetic methodologies.

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.

Thermische und photoinduzierte Anellierungen über radikalische Kaskaden mit Arylisonitrilen: Ein Zugang zu Chinolin‐abgeleiteten Benzophospholoxiden

AbstractIn diesem Artikel stellen wir eine Kaskade bestehend aus einer radikalischen Addition und Zyklisierung vor, um Chinolin‐basierte Benzophospholoxide aus ortho‐alkinylierten aromatischen Phosphanoxiden zu erhalten. Dabei werden verschiedene Arylisonitrile als Radikalakzeptoren und kostengünstiges tert‐Butylhydroperoxid (TBHP) als terminales Oxidationsmittel in Gegenwart einer katalytischen Menge Silberacetat verwendet. Alternativ kann die Kaskade auch über einen nachhaltigen photochemischen Ansatz unter Verwendung von 1,2,3,5‐Tetrakis(carbazol‐9‐yl)‐4,6‐dicyanobenzol (4CzIPN) als organischem Photokatalysator bei Raumtemperatur realisiert werden. Der vorgestellte modulare Ansatz zeigt eine breite Toleranz gegenüber funktionellen Gruppen und bietet einen einfachen Zugang zu komplexen P,N‐haltigen polyheterozyklischen Arenen. Diese neuartigen π‐erweiterten Benzophospholoxide besitzen interessante photophysikalische und elektrochemische Eigenschaften wie Absorption im sichtbaren Bereich, Emission und eine reversible Reduktion bei niedrigen Potentialen, weswegen sie vielversprechend für potenzielle materialwissenschaftliche Anwendungen sind. Die photophysikalischen Eigenschaften können weiterhin durch Zugabe externer Lewis‐ und Brønsted‐Säuren beeinflusst werden.

Electrochemical Synthesis of C(sp3)‐Rich Amines by Aminative Carbofunctionalization of Carbonyl Compounds

AbstractAlkylamines form the backbone of countless nitrogen‐containing small molecules possessing desirable biological properties. Despite advances in amine synthesis through transition metal catalysis and photoredox chemistry, multicomponent reactions that leverage inexpensive materials to transform abundant chemical feedstocks into three‐dimensional α‐substituted alkylamines bearing complex substitution patterns remain scarce. Here, we report the design of a catalyst‐free electroreductive manifold that merges amines, carbonyl compounds and carbon‐based radical acceptors under ambient conditions without rigorous exclusion of air and moisture. Key to this aminative carbofunctionalization process is the chemoselective generation of nucleophilic α‐amino radical intermediates that readily couple with electrophilic partners, providing straightforward access to architecturally intricate alkylamines and drug‐like scaffolds which are inaccessible by conventional means.

Electrochemical Synthesis of C(sp3)-Rich Amines by Aminative Carbofunctionalization of Carbonyl Compounds.

Alkylamines form the backbone of countless nitrogen-containing small molecules possessing desirable biological properties. Despite advances in amine synthesis through transition metal catalysis and photoredox chemistry, multicomponent reactions that leverage inexpensive materials to transform abundant chemical feedstocks into three-dimensional α-substituted alkylamines bearing complex substitution patterns remain scarce. Here, we report the design of a catalyst-free electroreductive manifold that merges amines, carbonyl compounds and carbon-based radical acceptors under ambient conditions without rigorous exclusion of air and moisture. Key to this aminative carbofunctionalization process is the chemoselective generation of nucleophilic α-amino radical intermediates that readily couple with electrophilic partners, providing straightforward access to architecturally intricate alkylamines and drug-like scaffolds which are inaccessible by conventional means.

Visible Light-Induced Reactions of Diazo Compounds and Their Precursors.

In recent years, visible light-induced reactions of diazo compounds have attracted increasing attention in organic synthesis, leading to improvement of existing reactions, as well as to the discovery of unprecedented transformations. Thus, photochemical or photocatalytic generation of both carbenes and radicals provide milder tools toward these key intermediates for many valuable transformations. However, the vast majority of the transformations represent new reactivity modes of diazo compounds, which are achieved by the photochemical decomposition of diazo compounds and photoredox catalysis. In particular, the use of a redox-active photocatalysts opens the avenue to a plethora of radical reactions. The application of these methods to diazo compounds led to discovery of transformations inaccessible by the classical reactivity associated with carbenes and metal carbenes. In most cases, diazo compounds act as radical sources but can also serve as radical acceptors. Importantly, the described processes operate under mild, practical conditions. This Review describes this subfield of diazo compound chemistry, particularly focusing on recent advancements.

Sequential Ring Opening/In Situ SO2-Capture/Alkynylation of Cyclopropanols with Alkynyl Triflones Initiated by Energy Transfer.

A visible-light-triggered ring opening/in situ SO2-capture/alkynylation sequence of cyclopropyl alcohols with alkynyl triflones using 4CzIPN as a triplet energy transfer photocatalyst is herein described. This metal-free protocol provides a straightforward and atom-economical approach to alkynyl-substituted γ-keto sulfones with a broad scope of substituents. In this transformation, alkynyl triflones could be used as both radical acceptors and SO2 donors. Preliminary experimental mechanistic studies and synthetic utility are also demonstrated.

Photoinduced Perfluoroalkyloximation of Alkenes with Simple Perfluoroalkyl Halides

Comprehensive SummaryIn this paper, the difunctionalizative perfluoroalkyloximation of alkenes has been developed for the first time. This photochemical method allows for the synthesis of various perfluoroalkyl ethanone oximes with excellent regioselectivity and good functional group tolerance. Our method employs the most common perfluoroalkyl source, perfluoroalkyl iodides, as Rf reagents. Besides long‐chain perfluoroalkyl groups, this approach could be extended to incorporating additional groups, including trifluoromethyl, difluoromethyl, sulfonyl, and malonate, selectively into olefins, resulting in a range of β‐substituted ethanone oximes. Notably, the potential of this method in the Fukuyama indole synthesis, generating novel 2‐perfluoroalkylated 3‐(α‐oximidobenzyl)indoles via a radical cascade mechanism with 2‐vinylphenylacryloyl isocyanate as the radical acceptor, presents a compelling avenue for drug synthesis. The protocol is efficient, scalable, and useful for late‐stage modification of bioactive molecules.

Dual Acridine/Decatungstate Photocatalysis for the Decarboxylative Radical Addition of Carboxylic Acids to Azomethines.

A concept for the dual use of acridine and tetrabutylammonium decatungstate photocatalysts in the reactions of carboxylic acids is proposed. Imines generated in situ from aldehydes and p-methoxyaniline, as well as other azomethines, were used as radical acceptors. The role of the decatungstate is believed to facilitate the turnover of the acridine photocatalyst by means of hydrogen atom transfer.

Photocatalytic Site‐Selective Cascade Radical Addition of Biaryl Ynones for the Construction of Spiro‐ and Fused Carbon Rings

Comprehensive SummaryFunctionalized free radical addition/cyclization reactions represent an efficient way for introducing new functionality or coupling fragments to molecules. Ynones are good regional selectivity radical acceptors in organic synthesis, and many of bio‐relevant cyclic compounds could be easily obtained by direct radical cyclization reaction. Here, we report a photocatalytic cascade radical addition of biaryl ynones, for the divergent synthesis of privileged carbon cycles. Additionally, further transformation of the multi‐functional group product into a variety of other derivatives demonstrates the synthetic value of this developed method.

Synthesis of Diverse Oxetane Amino Acids via Visible‐Light‐Induced Photocatalytic Decarboxylative Giese‐Type Reaction

Comprehensive SummaryThe divergent synthesis of versatile 3,3′‐disubstituted oxetane amino acids by utilizing visible‐light‐induced photocatalytic decarboxylative Giese‐type reaction has been demonstrated. 3‐Methyleneoxetane‐derived substrates are readily available in a single‐step and highly reactive as radical acceptors, allowing the production of versatile oxetane γ‐ and α‐amino acids in high yields. A distinct ring strain release‐driven radical addition mechanism was preliminarily revealed. The preparative power was further highlighted by the application in the synthesis of oxetane‐containing dipeptides and azetidine amino acids, as well as the transformation of the product into novel oxetane‐containing spiro‐heterocycle pharmacophore.

Radical-Mediated Decarboxylative C-C and C-S Couplings of Carboxylic Acids via Iron Photocatalysis.

Despite the significant success of decarboxylative radical reactions, the catalytic systems vary considerably upon different radical acceptors, requiring renewed case-by-case reaction optimization. Herein, we developed an iron catalytic condition that enables the highly efficient decarboxylation of various carboxylic acids for a range of radical transformations. This operationally simple protocol was amenable to a wide array of radical acceptors, delivering structurally diverse oxime ethers, alkenylation, alkynylation, thiolation, and amidation products in useful to excellent yields (>40 examples, up to 95% yield).

Direct Construction of C-Alkyl Glycosides from Non-Activated Olefins via Nickel-Catalyzed C(sp3)─C(sp3) Coupling Reaction.

Among C-glycosides, C-alkyl glycosides are significant building blocks for natural products and glycopeptides. However, research on efficient construction methods for C-alkyl glycosides remains relatively limited. Compared with Michael acceptors, non-activated olefins are more challenging substrates and have rarely been employed in the construction of C-glycosides. Here, a highly efficient and convenient approach for the synthesis of C-alkyl glycosides through a nickel-catalyzed C(sp3)-C(sp3) coupling reaction is presented. A distinctive feature of this method is its utilization of non-activated olefins as the anomeric radical acceptors for hydroalkylation, allowing for the direct formation of C-glycoside bonds in a single step. Furthermore, this method demonstrates excellent compatibility with a broad scope of highly reactive functional groups. Mechanistic investigations suggest that the reaction proceeds via a free radical pathway, leading predominantly to the formation of products with α-configuration. Overall, this innovative methodology offers a versatile and practical approach for the synthesis of C-alkyl glycosides, offering new avenues for the production of intricate glycosides with potential applications in drug discovery and chemical biology.

Recent Advances in the Construction of Coumarin or Quinolin-2-ones Compounds via Radical Cascade Reactions

Abstract: Free radical reactions occupy an important position in synthetic organic chemistry as well as medicinal chemistry, significantly complementing and extending the synthesis of coumarin or quinolin-2-one compounds. Moreover, the use of constructing coumarin or quinolin-2-one compounds functionalized at the C3 position has certain advantages over traditional noble metalcatalyzed or high-temperature cyclization, which is more in line with the advocates of green chemistry. The design of alkenes or alkynes as radical acceptors for cascade reactions presents a novel and robust approach to obtaining coumarin or quinolin-2-one molecules. These radical cascade cyclization reactions have been well explored and studied over the past decade. As a result, we have compiled a review of the rapidly developing cutting-edge research in this field, featuring typical examples and in-depth exploration of the underlying mechanisms.

Recent advances in the radical cascade reaction for constructing nitrogen heterocycles using azides as radical acceptors.

Due to the high conversion properties, azide compounds are widely utilized in organic synthesis. For instance, azide compounds readily release nitrogen to form a new N-C bond when they function as radical acceptors for the active intermediates in the reaction. Over the past decade, strategies employing azides as radical acceptors to construct nitrogen heterocycles have been extensively developed. This approach has emerged as a crucial method for synthesizing nitrogen heterocycles. Therefore, this paper provides a review of the research advancements in tandem cyclization reactions using azides as radical acceptors, summarizing the process of reaction design, exploration, reasoning of the mechanism, and prospects for further research of these reactions.

Visible light-induced sulfonylation with sulfinates as closed-shell radical acceptors

Sulfinates as close-shell radical acceptors instead of radical precursors for redox-neutral photochemical sulfonylation.