Radical Coupling Process Research Articles

Applications of Organosilanes in Visible Light‐induced Catalytic Asymmetric Reactions

AbstractOver the past decades, visible light‐mediated photocatalysis has found a mainstream of applications in synthetic chemistry. Organosilanes have been proven to be a useful class of electron donors to generate the highly active radical species via photoinduced single electron transfer oxidation/fragmentation sequence, which may undergo follow‐up radical coupling or addition process. This minireview highlights the comprehensive advances of organosilanes in photoredox catalyzed asymmetric organic synthesis, with particular emphasis placed on reaction mechanisms. We hope that this review will inspire further design and development of new reactions with such class of readily accessible reagents.

Visible-Light-Promoted α-C(sp3)-H Amination of Ethers with Azoles and Amides.

A visible-light-induced highly efficient C(sp3)-H amination of ethers with amides and azoles has been presented under mild conditions via a nitrogen- and carbon-centered radical coupling process. This protocol successfully utilizes 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) and tert-butyl nitrite (TBN) as cocatalysts to deliver the aminated products of ethers under aerobic conditions. Notably, the developed reaction features the corresponding products in good yields (up to 93%) with a wide substrate scope. The mechanistic study indicates that C-N bond formation proceeds via a direct radical cross-coupling process. Preliminary biological activity analysis indicates that the resulting products have good and selective inhibitory activity on osteosarcoma (OS) cell lines and are promising for use as hits for drug discovery.

Radical Cross Coupling and Enantioselective Protonation through Asymmetric Photoredox Catalysis.

An unprecedented enantioselective protonation reaction enabled by photoredox catalytic radical coupling is developed. Under cooperative dicynopyrazine-derived chromophore (DPZ) as a photosensitizer and a chiral phosphoric acid catalyst, and Hantzsch ester as a sacrificial reductant, the transformations between α-substituted enones and cyanoazaarenes or 2-(chloromethyl)azaaren-1-iums can proceed a tandem reduction, radical coupling, and enantioselective protonation process efficiently. Two classes of pharmaceutically important enantioenriched azaarene variants, which contain a synthetically versatile ketone-substituted tertiary carbon stereocenter at the β- or γ-position of the azaarenes, are synthesized with high yields and ees.

Photoelectrocatalytic peroxymonosulfate activation over CoFe2O4-BiVO4 photoanode for environmental purification: Unveiling of multi-active sites, interfacial engineering and degradation pathways

This work reported on the development of CoFe2O4-BiVO4 photoanode based photoelectrocatalytic system collaborating with peroxymonosulfate activation for organic contaminants removal. CoFe2O4 layer not only provided active sites for direct peroxymonosulfate activation but also accelerated charge separation process for the enhancement of photocurrent density and photoelectrocatalytic performance. Junction of CoFe2O4 layer on BiVO4 photoanode led to the improvement of photocurrent density to 4.43 mA/cm2 at 1.23 VRHE, which was approximately 4.06 times higher than that of pure BiVO4. Subsequently, the corresponding optimal degradation efficiency toward the tetracycline model contaminant achieved to be 89.1% with total organic carbon removal value of about 43.7% within 60 min. Moreover, the degradation rate constant of CoFe2O4-BiVO4 photoanode in photoelectrocatalytic system was 0.037 min−1, which was about 1.23, 2.64 and 3.70 times higher than the values in photocatalysis, electrocatalysis and PMS only based systems, respectively. In addition, radical scavenging experiments and electron spin resonance spectra indicated a synergy of radical and nonradical coupling process where •OH and 1O2 played vital roles during tetracycline degradation. Plausible photoelectrocatalytic mechanism and degradation pathway were proposed. This work provided an effective strategy to construct peroxymonosulfate assisted photoelectrocatalytic system toward green environmental applications.

Photo-induced Benzylation of Quinolines with Tetra-coordinate Benzylboron Reagents

Direct photo-activation of quinolinium ion generated in situ enabled its benzylation reaction with tetra-coordinate benzylboron reagents under mild reaction conditions, where the 1,2-addition was preferred to give 2-benzyl-1,2-dihydroquinoline derivatives. Radical trapping experiments with TEMPO showed that a radical coupling process was included, which indicated the probable photo-induced single electron transfer mechanism.

Copper-Catalyzed Annulation of O-Acyl Oximes with Cyclic 1,3-Diones for the Synthesis of 7,8-Dihydroindolizin-5(6H)-ones and Cyclohexanone-Fused Furans.

A copper-catalyzed annulation of O-acyl oximes with cyclic 1,3-diones has been developed for the concise synthesis of 7,8-dihydroindolizin-5(6H)-ones and cyclohexanone-fused furans through the substituent-controlled selective radical coupling process. 2-Alkyl cyclic 1,3-diones undergo C-C radical coupling, while 2-unsubstituted cyclic 1,3-diones undergo C-O radical coupling.

Sc(OTf)3 catalyzed intramolecular single-electron transfer of 2-alkyl-1,4-benzoquinones: synthesis of 6-chromanols from donor-acceptor cyclopropanes.

A Sc(OTf)3 catalyzed intramolecular cyclization reaction of 2-alkyl-1,4-benzoquinone derived from D-A cyclopropane was discovered. This reaction involves single-electron transfer, proton-transfer, an aromatization driven spin center shift, and radical coupling processes, and offers an efficient method for the synthesis of 6-chromanols from D-A cyclopropanes.

Cathodic Carbonyl Alkylation of Aryl Ketones or Aldehydes with Unactivated Alkyl Halides.

An efficient cathodic carbonyl alkylation of aryl ketones or aldehydes with unactivated alkyl halides has been realized through the electrochemical activation of iron. The protocol is believed to include a radical-radical coupling or nucleophilic addition process, and the formation of ketyl radicals and alkyl radicals has been demonstrated. The protocol provides various tertiary or secondary alcohols by the formation of intermolecular C-C bonds under safe and mild conditions, is scalable, consumes little energy, and exhibits a broad substrate scope.

Chromophore‐Inspired Design of Pyridinium‐Based Metal–Organic Polymers for Dual Photoredox Catalysis

Abstract2,4,6‐Triphenylpyrylium (TPT+) functions as a classic organic photocatalyst and exhibits a noteworthy absorption in the visible range, strongly oxidizing excited states, and a somewhat unstable structure. Inspired by the nuclear chromophore and dual catalysis strategy, herein, we report a universal photoredox platform constructed byTPT+‐mimic bridging ligands and reductive metal ions on the basis of metal–organic supramolecular systems for various organic couplings and molecular oxygen activation under visible‐light irradiation. Significant photoinduced electron transfer and ligand‐to‐metal charge‐transfer events are both integrated and regulated by the spatial and kinetic confinement effects of the structurally confined microenvironments, effectively improving the efficiency of electron transfer and radical–radical coupling processes in photocatalysis. This package deal provides a promising way for the design of novel photocatalysts and the development of versatile and sustainable synthetic chemistry.

Switching the O–O bond-formation mechanism by controlling water activity

Switching the O–O bond-formation mechanism by controlling water activity

Direct Evidence of Visible Light-Induced Homolysis in Chlorobis(2,9-dimethyl-1,10-phenanthroline)copper(II).

Developments in the field of photoredox catalysis that leveraged the long-lived excited states of Ir(III) and Ru(II) photosensitizers to enable radical coupling processes paved the way for explorations of synthetic transformations that would otherwise remain unrealized. While first row transition metal photocatalysts have not been as extensively investigated, valuable synthetic transformations covering broad scopes of olefin functionalization have been recently reported featuring photoactivated chlorobis(phenanthroline) Cu(II) complexes. In this study, the photochemical processes underpinning the catalytic activity of [Cu(dmp)2Cl]Cl (dmp = 2,9-dimethyl-1,10-phenanthroline) were studied. The combined results from static spectroscopic measurements and conventional photochemistry, ultrafast transient absorption, and electron paramagnetic resonance spin trapping experiments strongly support blue light (λex = 427 or 470 nm)-induced Cu-Cl homolytic bond cleavage in [Cu(dmp)2Cl]+ occurring in <100 fs. On the basis of electronic structure calculations, this bond-breaking photochemistry corresponds to the Cl → Cu(II) ligand-to-metal charge transfer transition, unmasking a Cu(I) species [Cu(dmp)2]+ and a Cl atom, thereby serving as a departure point for both Cu(I)- or Cu(II)-based photoredox transformations. No net photochemistry was observed through direct excitation of the ligand-field transitions in the red (λex = 785 or 800 nm), and all combined experiments indicated no evidence of Cu-Cl bond cleavage under these conditions. The underlying visible light-induced homolysis of a metal-ligand bond yielding a one-electron-reduced photosensitizer and a radical species may form the basis for novel transformations initiated by photoinduced homolysis featuring in situ-formed metal-substrate adducts utilizing first row transition metal complexes.

Transition Metal‐Free Synthesis of α‐Aminophosphine Oxides through C(sp3)−P Coupling of 2‐Azaallyls

AbstractRadical reactions have been widely applied in C−P bond‐forming strategies. Most of these strategies require initiators, transition metal catalysts, or organometallic reagents. Herein, a transition metal‐free C(sp3)−P bond formation to prepare α‐aminophosphine oxides via deprotonative radical coupling processes of 2‐azaallyls with chlorodiphenylphosphine oxides was presented. Deprotonation of N‐benzyl imines may generate super‐electron‐donor (SED) 2‐azaallyl anions that reduced chlorodiphenylphosphine oxides to phosphine oxide radicals. Single‐electron transfer (SET) process transformed the 2‐azaallyl anions into 2‐azaallyl radicals, which may couple with phosphine oxide radicals to construct C−P bonds. The deprotonative radical coupling approach enables the synthesis of α‐aminophosphine oxides bearing various functional groups under mild conditions and without precious transition metal catalysts or oxidants.magnified image

Chiral Phosphoric Acid Creates Promising Opportunities for Enantioselective Photoredox Catalysis

In recent years, visible light driven enantioselective chemical transformations have emerged as new additions to the toolkit of synthetic chemists to accomplish more efficient assembly of chiral molecules. Nonetheless, implementing precise stereocontrol on photoinduced intermolecular radical coupling process remains arduous. Recent studies unveil the underexplored competence of chiral phosphoric acid for this class of asymmetric photoredox reactions, endowed by its capability as a bifunctional H‐bonding catalyst for synchronous interaction with radical intermediate and substrate while channeling the cross‐coupling in a highly enantioselective manner. This paper highlights the recent advances, future outlook as well as the prospective challenges in this research area.

A Pyridine-Pyridine Cross-Coupling Reaction via Dearomatized Radical Intermediates.

A pyridine-pyridine coupling reaction has been developed between pyridyl phosphonium salts and cyanopyridines using B2 pin2 as an electron-transfer reagent. Complete regio- and cross-selectivity are observed when forming a range of valuable 2,4'-bipyridines. Phosphonium salts were found to be the only viable radical precursors in this process, and mechanistic studies indicate that the process does not proceed through a Minisci-type coupling involving a pyridyl radical. Instead, a radical-radical coupling process between a boryl phosphonium pyridyl radical and a boryl-stabilized cyanopyridine radical explains the C-C bond-forming step.

A Pyridine–Pyridine Cross‐Coupling Reaction via Dearomatized Radical Intermediates

AbstractA pyridine–pyridine coupling reaction has been developed between pyridyl phosphonium salts and cyanopyridines using B2pin2 as an electron‐transfer reagent. Complete regio‐ and cross‐selectivity are observed when forming a range of valuable 2,4′‐bipyridines. Phosphonium salts were found to be the only viable radical precursors in this process, and mechanistic studies indicate that the process does not proceed through a Minisci‐type coupling involving a pyridyl radical. Instead, a radical–radical coupling process between a boryl phosphonium pyridyl radical and a boryl‐stabilized cyanopyridine radical explains the C−C bond‐forming step.

Preparation of Single Chain Nanoparticles via Photoinduced Double Collapse Process

AbstractA straightforward method is described to achieve polymeric nanoparticles by double folding of single linear chains. The side chain functional polystyrene with controlled molecular weight is converted to pendant azide and benzophenone motifs via postmodification reactions. Resulting functionalized chains undergo intramolecular crosslinking upon ultraviolet (UV) illumination using simultaneous and subsequent pathways at a dilute concentration. Particle size of nanoparticles can be tuned by changing the degree of crosslinking using a second folding process. Obtained single and double collapsed chains indicate higher glass transition temperatures and lower hydrodynamic radii compared to their intermediates. To our knowledge, the combination of photoinduced azide crosslinking and radical coupling processes is the first attempt to prepare double folding single polymer chains.

Preparation of single chain nanoparticles via photoinduced radical coupling process

This contribution introduces a straightforward method for preparing well-defined polymeric nanoparticles using radical coupling process of ketyl moieties resulted from triplet excitation of pendant benzophenone groups. In the first step, poly(styrene-co-chloromethylstyrene) is synthesized by thermally initiated controlled radical copolymerization technique and subsequently, pendant chloride groups undergo post-modification with 4–hydroxybenzophenone. Achieved well-defined side–chain benzophenone containing copolymers generate ketyl radicals in the presence of excess hydrogen donor molecule upon UV-light irradiation and intramolecularly crosslinked nanoparticles are formed by radical coupling process in dilute regime. Resulting single chain nanoparticles and intermediates are characterized by 1H NMR, gel permeation chromatography, differential scanning calorimetry, UV–Vis spectrometry and electron microscopy techniques.

Ligand-free nickel-catalyzed Kumada couplings of aryl bromides with tert-butyl Grignard reagents

A ligand-free nickel-catalyzed Kumada cross-coupling of aryl bromides and tert-butyl Grignard reagents led to the formation of a series of tert-butyl aryls in moderate to good yields, excellent tBu/iBu ratios, and good functional group compatibility. A radical coupling process is indicated and a mechanism with a Ni(I)-Ni(III) catalytic cycle is proposed.

Mechanisms of Covalent Coupling Reaction of Dibromofluoranthene on Au(111)

The reaction mechanism of on-surface coupling of 7,10-dibromofluoranthene (Br2FL) on Au(111) was studied on the basis of density functional theory calculations, as a possible route for fabricating graphene nanoribbons (GNRs) including pentagonal rings. The reaction pathways and energy barriers of debromination, radical coupling, and diffusion processes were investigated. The results indicate that the reaction mechanism is substantially different for Br2FL compared to that for the phenyl radical, which has been extensively studied as a model system. The rate-limiting step was radical coupling associated with the formation of a gold-metallic intermediate, which is rarely observed on Au(111), because of steric repulsion between the two radicals and that between the radicals and the substrate. The energy barriers were comparable with those for cyclohexa-m-phenylene on Ag(111), and the reaction rate estimated using transition state theory was consistent with the experimental results. These results suggest that Br2FL is preferred as a precursor of the coupling reaction to fabricate fluoranthene polymers. Well-defined GNRs including pentagonal rings would be formed by further cyclodehydrogenation.

Metal-free deoxygenative sulfonylation of quinoline N-oxides with sodium sulfinates via a dual radical coupling process

The first example of a metal- and reductant-free deoxygenative sulfonylation of quinoline N-oxides with sodium sulfinates via a dual radical coupling process is reported.