Radical Cross-coupling Reaction Research Articles

Ni-Catalyzed Desymmetric Radical Cross-Coupling Reaction to Access Axially Chiral Biaryls

Ni-Catalyzed Desymmetric Radical Cross-Coupling Reaction to Access Axially Chiral Biaryls

Harnessing the potential of acyl triazoles in bifunctional cobalt-catalyzed radical cross-coupling reactions

Persistent radicals facilitate numerous selective radical coupling reactions. Here, we have identified acyl triazole as a new and versatile moiety for generating persistent radical intermediates through single-electron transfer processes. The efficient generation of these persistent radicals is facilitated by the formation of substrate-coordinated cobalt complexes, which subsequently engage in radical cross-coupling reactions. Remarkably, triazole-coordinated cobalt complexes exhibit metal-hydride hydrogen atom transfer (MHAT) capabilities with alkenes, enabling the efficient synthesis of diverse ketone products without the need for external ligands. By leveraging the persistent radical effect, this catalytic approach also allows for the development of other radical cross-coupling reactions with two representative radical precursors. The discovery of acyl triazoles as effective substrates for generating persistent radicals and as ligands for cobalt catalysis, combined with the bifunctional nature of the cobalt catalytic system, opens up new avenues for the design and development of efficient and sustainable organic transformations.

Formation of a Decanuclear Organometallic Dysprosium Complex via a Radical–Radical Cross–Coupling Reaction

Formation of a Decanuclear Organometallic Dysprosium Complex via a Radical–Radical Cross–Coupling Reaction

Three-Component Radical Cross-Coupling: Asymmetric Vicinal Sulfonyl-Esterification of Alkenes Involving Sulfur Dioxide.

A novel catalytic system for radical cross-coupling reactions based on copper and chiral Pyridyl-bis(imidazole) (PyBim) ligandsis described. It overcomes the challenges of chemoselectivity and enantioselectivity, achieving a highly enantioselective vicinal sulfonyl-esterification reaction of alkenes involving sulfur dioxide. This strategy involves the use of earth-abundant metal catalyst, mild reaction conditions, a broad range of substrates (84 examples), high yields (up to 97% yield), and exceptional control over enantioselectivity. The reaction system is compatible with different types of radical precursors, including O-acylhydroxylamines, cycloketone oxime esters, aryldiazonium salts, and drug molecules. Chiral ligand PyBim is identified as particularly effective in achieving the desired high enantioselectivity. Mechanistic studies reveal that copper/PyBim system plays a vital role in C─O coupling, employing an outer-sphere model. In addition, the side arm effect of ligand is observed.

Base- and metal-free visible-light driven site-selective α-C(sp3)–H functionalization reaction of glycine derivatives with hydroxamic acid derivatives

A visible-light-mediated radical–radical cross-coupling reaction between hydroxamic acid and N-phenyl glycine derivatives under base and metal free conditions is reported. A series of unnatural amino acids and peptides were obtained in good to excellent yields with good chemo-selectivity.

Nickel-catalyzed cross-coupling between benzyl alcohols and alkenyl triflates assisted by titanium-mediated radical C–O bond cleavage

Abstract A Ni-catalyzed radical cross-coupling reaction between benzyl alcohols and alkenyl triflates was discovered. A benzyl radical was generated directly from alcohols by using low-valent Ti-mediated alcohol C–O bond homolysis and was successfully utilized in a Ni-catalyzed cross-coupling reaction. The addition of tetrabutylammonium iodide (n-Bu4NI) facilitated the reaction. n-Bu4NI was found to be instrumental in transforming alkenyl triflates into iodides, which are more reactive in the subsequent cross-coupling process.

Decarboxylation of β-boryl NHPI esters enables radical 1,2-boron shift for the assembly of versatile organoborons

In recent years, numerous 1,2-R shift (R = aliphatic or aryl) based on tetracoordinate boron species have been well investigated. In the contrary, the corresponding radical migrations, especially 1,2-boryl radical shift for the construction of organoborons is still in its infancy. Given the paucity and significance of such strategies in boron chemistry, it is urgent to develop other efficient and alternative synthetic protocols to enrich these underdeveloped radical 1,2-boron migrations, before their fundamental potential applications could be fully explored at will. Herein, we have demonstrated a visible-light-induced photoredox neutral decarboxylative radical cross-coupling reaction, which undergoes a radical 1,2-boron shift to give a translocated C-radical for further capture of versatile radical acceptors. The mild reaction conditions, good functional-group tolerance, and broad β-boryl NHPI esters scope as well as versatile radical acceptors make this protocol applicable in modification of bioactive molecules. It can be expected that this methodology will be a very useful tool and an alternative strategy for the construction of primary organoborons via a novel radical 1,2-boron shift mode.

Bismuth radical catalysis in the activation and coupling of redox-active electrophiles

Radical cross-coupling reactions represent a revolutionary tool to make C(sp3)–C and C(sp3)–heteroatom bonds by means of transition metals and photoredox or electrochemical approaches. However, the use of main-group elements to harness this type of reactivity has been little explored. Here we show how a low-valency bismuth complex is able to undergo one-electron oxidative addition with redox-active alkyl-radical precursors, mimicking the behaviour of first-row transition metals. This reactivity paradigm for bismuth gives rise to well-defined oxidative addition complexes, which could be fully characterized in solution and in the solid state. The resulting Bi(III)–C(sp3) intermediates display divergent reactivity patterns depending on the α-substituents of the alkyl fragment. Mechanistic investigations of this reactivity led to the development of a bismuth-catalysed C(sp3)–N cross-coupling reaction that operates under mild conditions and accommodates synthetically relevant NH-heterocycles as coupling partners.

A General and Practical Route to Functionalized Bicyclo[1.1.1]Pentane-Heteroaryls Enabled by Photocatalytic Multicomponent Heteroarylation of [1.1.1]Propellane.

1-Aryl-substituted bicyclo[1.1.1]pentanes (BCPs) are an important class of BCP derivatives with widespread application in drug development. Most syntheses of these materials require multiple chemical steps via BCP electrophiles or nucleophiles derived from [1.1.1]propellane. Although one-step, multicomponent radical cross-coupling reactions could provide a more sustainable and rapid route to access diverse heteroarylated BCPs, current approaches are limited to tertiary alkyl radicals, leading to a decrease in their practical value. In this study, a conceptually different approach enabled by a radical multicomponent heteroarylation of [1.1.1]propellane to access functionalized heteroarylated BCPs is described. Importantly, this protocol is compatible with primary-, secondary-, and tertiary aliphatic radicals, as well as various fluoroalkyl radical sources, thus enabling rapid library generation of sought-after BCP derivatives for drug development.

Construction of C(CO)–C(CO) Bond via NHC-Catalyzed Radical Cross-Coupling Reaction

A C(sp2)-C(sp2) bond can be constructed via a photoredox/N-heterocyclic carbene (NHC)-cocatalyzed radical cross-coupling reaction, which provides a complementary strategy to classic electron pair processes. The present protocol represents the first example of an NHC-catalyzed two-component radical cross-coupling reaction involving C(sp2)-centered radical species. The decarboxylative acylation of oxamic acid with acyl fluoride was conducted under mild conditions and allowed the preparation of a variety of useful α-keto amides, including sterically congested ones.

Combined molecular dynamics and coordinate driving method for automatically searching complicated reaction pathways.

The combined molecular dynamics and coordinate driving (MD/CD) method is updated and generalized in this work to broaden its applications in automatically searching reaction pathways for complicated reactions. In this updated version, MD simulations are performed with the GFN's family of methods to systematically sample conformers for almost any systems with atomic numbers Z ≤ 86. The improved CD procedure is greatly accelerated by applying a pre-screening stage at the semiempirical GFN2-xTB level. An automatic module based on the Marcus theory and its improved version (the Wolynes theory) is designed to include single electron transfer (SET) processes into reaction pathways. The capabilities of this method are demonstrated by exploring the most possible reaction pathways of three experimentally reported reactions: the organophosphine-catalyzed trans phosphinoboration, the Fe(II) complex-mediated C(sp2)-H borylation reaction, and the SET-triggered deaminative radical cross-coupling reaction. Comprehensive reaction networks are obtained for all three reactions with reasonable computational costs. Detailed mechanisms for these reactions can account for the reported experimental facts.

Radical Cross-Coupling Reaction Based on Hydrogen Atom Abstraction of DMF and Decarboxylation of α-Ketoacid under Electricity.

The cleavage of DMF into a dimethyl carbamoyl radical under mild electrochemical conditions was revealed for the first time. Meanwhile, an electrochemical decarboxylation of α-ketoacid occurred to produce an acyl radical. The radical cross-coupling reaction of these two electron-deficient acyl radicals was carried out with high selectivity. This discovery provides a new electrochemical way for the cracking of DMF, and a milder and safer method for its application in organic synthesis.

Radical cross-coupling access to α-chiral tertiary alkylamines by a Cu(I) catalyst

The radical cross-coupling reaction is important in recent chemistry. In the September issue of Chem Catalysis , Guan, Xiong, Zhang, and co-workers reported regio- and enantioselective synthesis of α-chiral tertiary-alkylamines through Cu(I)-catalyzed radical cross-coupling. Density functional theory (DFT) computations predicted this reaction and elucidated mechanistic details. Tetrahydrofuran (THF) solvent plays crucial roles in increasing regioselectivity and yield. The radical cross-coupling reaction is important in recent chemistry. In the September issue of Chem Catalysis , Guan, Xiong, Zhang, and co-workers reported regio- and enantioselective synthesis of α-chiral tertiary-alkylamines through Cu(I)-catalyzed radical cross-coupling. Density functional theory (DFT) computations predicted this reaction and elucidated mechanistic details. Tetrahydrofuran (THF) solvent plays crucial roles in increasing regioselectivity and yield.

General and Practical Route to Diverse 1-(Difluoro)alkyl-3-aryl Bicyclo[1.1.1]pentanes Enabled by an Fe-Catalyzed Multicomponent Radical Cross-Coupling Reaction

General and Practical Route to Diverse 1-(Difluoro)alkyl-3-aryl Bicyclo[1.1.1]pentanes Enabled by an Fe-Catalyzed Multicomponent Radical Cross-Coupling Reaction

Sensitized photoreduction of selected benzophenones. Mass spectrometry studies of radical cross-coupling reactions

The hydrogen atom transfer reaction (HAT) between selected benzophenones (benzophenone BP, 3-carboxybenzophenone 3CB, and 4-carboxybenzophenone 4CB) and 2-propanol was reinvestigated focusing on stable product analysis. As expected, the primary species of these HAT's are the respective diphenyl and dimethyl ketyl radicals that eventually undergo several radical coupling reactions leading to stable photoproducts. However, the mechanisms of these free radical reactions remain unclear and open to question. In this report, we focus on the detailed analysis of the stable photoproducts of these reactions using liquid chromatography coupled with high-resolution mass spectrometry (LC-ESI-QTOF-MS/MS). Products of photopinacolization (benzpinacol and two diastereoisomers of 4CB and 3CB dimers) and isomeric radical cross-coupling adducts of respective diphenyl and dimethyl ketyl radicals were separated chromatographically, and their structures were determined by high-resolution MS/MS, and the mechanisms of the reactions are discussed.

A visible-light activated secondary phosphine oxide ligand enabling Pd-catalyzed radical cross-couplings

Although transition metal-catalyzed reactions have evolved with ligand development, ligand design for palladium-catalyzed photoreactions remains less explored. Here, we report a secondary phosphine oxide ligand bearing a visible-light sensitization moiety and apply it to Pd-catalyzed radical cross-coupling reactions. The tautomeric phosphinous acid coordinates to palladium in situ, allowing for pseudo-intramolecular single-electron transfer between the ligand and palladium. Molecular design of the metal complexes aided by time-dependent density functional theory calculations enables the involvement of allyl radicals from π-allyl palladium(II) complexes, and alkyl and aryl radicals from the corresponding halides and palladium(0) complex. This complex enables radical cross-couplings by ligand-to-Pd(II) and Pd(0)-to-ligand single-electron transfer under visible-light irradiation.

Research Progress on N-Heterocyclic Carbene Catalyzed Reactions for Synthesizing Ketones through Radical Mechanism

AbstractNHC-catalyzed radical cross-coupling reactions have been recently developed; they provide an efficient method to access ketones from aldehydes or carboxylic acid derivatives with sp3-hybridized carbon radical precursors. This reaction has indirectly solved the limitations in the scope of coupling partners in NHC umpolung catalyzed reactions of aldehydes. In this short review, we present some recent advances in NHC-catalyzed radical reactions, with a focus on the construction of the C–C(CO) bond.1 Introduction2 Oxidative Generation of NHC-Derived Ketyl Radical2.1 NHPI Redox-Active Esters2.2 Katritzky Pyridinium Salts2.3 Alkyl Halides2.4 Aryl Halides2.5 Compounds Containing N–O Bond2.6 Diazo Esters2.7 Others3 Reductive Generation of NHC-Derived Ketyl Radical3.1 Hantzsch Esters3.2 Sulfinates3.3 Electron-Rich Arenes3.4 Amines3.5 Organoborane Reagents4 Conclusion

Visible-Light-Catalyzed Radical-Radical Cross-Coupling Reaction of Benzyl Trifluoroborates and Carbonyl Compounds to Sterically Hindered Alcohols.

We report here an organic dye catalyzed direct radical-radical cross-coupling reaction based on the persistent free-radical effect (PRE), which is powered by visible light and does not require any external oxidants or reductants. In this reaction, benzyl trifluoroborates are oxidized by excited-state 4Cz-IPN to generate benzyl radicals, and the resulting boron trifluoride acts as a Lewis acid to reduce the reduction potential of carbonyl compounds. The dual roles of benzyl trifluoroborates enable aldehydes, ketones, diketones, and ketone esters to react with benzyl trifluoroborates to generate various sterically hindered alcohols.

Silyl-mediated photoredox-catalyzed radical–radical cross-coupling reaction of alkyl bromides and ketoesters

A strategy for cross-coupling between organic bromides and carbonyl compounds is developed by combining photocatalysis and halogen atom transfer using a photocatalyst and tris(trimethylsilyl)silane.

Sensitized Photoreduction of Selected Benzophenones. Mass Spectrometry Studies of Radical Cross-Coupling Reactions

Sensitized Photoreduction of Selected Benzophenones. Mass Spectrometry Studies of Radical Cross-Coupling Reactions