Copper-catalysed photoinduced decarboxylative alkynylation: a combined experimental and computational study

Redox-active esters (RAEs) as alkyl radical precursors have demonstrated great advantages for C–C bond formation. A decarboxylative cross-coupling method is described to afford substituted alkynes from various carboxylic acids using copper catalysts CuCl and Cu(acac)₂. The photoexcitation of copper acetylides with electron-rich NEt₃ as a ligand provides a general strategy to generate a range of alkyl radicals from RAEs of carboxylic acids, which can be readily coupled with a variety of aromatic alkynes. The scope of this cross-coupling reaction can be further expanded to aliphatic alkynes and alkynyl silanes using a catalytic amount of preformed copper-phenylacetylide. In addition, DFT calculations revealed the favorable reaction pathway and that the bidentate acetylacetonate ligand of the copper intermediate plays an important role in inhibiting the homo-coupling of the alkyne.

Redox-active esters (RAEs) as alkyl radical precursors have demonstrated great advantages for Cu-catalysed C–C bond formation.     

β-Carbonyl radicals as three-carbon building blocks for carbon-carbon bond forming reactions

From aldehydes, ketones and esters β-carbonyl radicals $\text{47}$ can be generated via enolization, cyclopropanation, solvomercuration and reduction with NaBH₄. Radicals $\text{47}$ react with electron-poor alkenes $\text{27}$ to give products of CC-bond forming reactions (Tables 1–3). Carbonyl compounds are therefore precursors of three-carbon building blocks. The products result from reactions with “Umpolung”.     

Laser flash photolysis studies of alkoxyl radical kinetics using 4-nitrobenzenesulfenate esters as radical precursors

4-Nitrobenzenesulfenate esters were used as precursors for the generation of alkoxyl radicals under laser flash photolysis conditions. The esters were efficiently cleaved using the Nd:YAG third harmonic (355 nm) to produce alkoxyl radicals and the 4-nitrobenzenethiyl radical. Rate constants for beta-scission and 1, 5-hydrogen abstraction reactions of alkoxyl radicals were measured.     

Leaving Group Assisted Strategy for Photoinduced Fluoroalkylations Using N‐Hydroxybenzimidoyl Chloride Esters

Redox‐active esters (RAEs) as alkyl radical precursors have been extensively developed for C?C bond formations. However, the analogous transformations of fluoroalkyl radicals from the corresponding acid or ester precursors remain challenging because of the high oxidation potential of the fluoroalkyl carboxylate anions. The newly developed N‐hydroxybenzimidoylchloride (NHBC) ester provides a general leaving group assisted strategy to generate a portfolio of fluoroalkyl radicals, and can be successfully applied in photoinduced decarboxylative hydrofluoroalkylation and heteroarylation of unactivated olefins. In addition, DFT calculations revealed that the NHBC ester proceeds by the fluorocarbon radical pathway, whereas other well‐known RAEs proceed by the nitrogen radical pathway.     

Role of molecular oxygen and its active forms in generation of electrochemiluminescence

A short review is dedicated to the role of molecular oxygen and its active forms in generation of electrochemiluminescence (ECL). It is shown at the example of such widely used luminogens as luminol, lucigenin, acridine esters, acridane, and indoles that the role of O₂ and its active forms, such as hydrogen peroxide, superoxide and hydroperoxide radicals in generation of ECL by organic compounds is largely reduced to oxidation of the initial luminogen or intermediates of its partial electrochemical preoxidation/prereduction. Such intermediates are most often particles in the doublet state (radical-cation, radical-anion, or free radicals) that form unstable emitter precursors of peroxide (dioxetanone) type under interaction with O₂, hydrogen peroxide, or other active oxygen forms. It is also shown that the product of secondary transformations of active oxygen forms is singlet oxygen that may also be a radiation source as a result of cooperative transitions.     

Cyclisation of α-chiral aminyl radicals

α-Chiral aminyl radicals have been generated from sulfenamides of α-amino acid esters and α-phenylethylamine using Bu₃SnH. The aminyl radicals of α-amino acid esters undergo 5-exo-trig cyclisation reactions onto side chain alkenes to yield proline analogues with reasonable diastereoselectivity. Preliminary studies show urethanyl radicals generated from sulfenamides of alkenyl urethane derivatives of α-amino acid esters and α-phenylethylamine undergo 5-exo-rig cyclisations to providing a protocol for the radical amination of unactivated alkenes. The α-ester of the amino acid or the urethane groups impart electrophilic behaviour to the aminyl radicals and facilitates cyclisation onto alkenes.     

BF2-Chelates of N-Acylhydrazones as Versatile Coupling Partners in Photoredox Promoted Reactions

Five-membered difluoroboryl chelate complexes are competent substrates for radical reactions with various radical precursors including potassium trifluoroborates, bis(catecholato)siliconates, 4-alkyl-substituted Hantzsch esters, dihydroquinazolinones, esters of N-hydroxyphthalimide, Katritzky salts, alkyl iodides and thiols. Using these reagents, primary, secondary, and tertiary radicals can be generated under oxidative or reductive conditions and add at the C=N bond of the difluoroboryl chelates leading to hydrazide products.     

Relative rate constants of reactions of alkyl radicals of methacrylates and acrylates with oxygen and stable nitroxyl radicals

Conclusions In methacrylates and acrylates undergoing oxidation, stable nitroxyl radicals react with the alkyl radicals of the monomers. The relative rate constants of the reactions of and O₂ with alkyl radicals for the different esters range from 0.36 to 5.20.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 4, pp. 753–756, April, 1977.We thank V. A. Golubev for providing the stable nitroxyl radicals.     

Intramolecular Homolytic Substitution of Sulfinates and Sulfinamides

A general and efficient method for the synthesis of cyclic sulfinates and sulfinamides based on intramolecular homolytic substitution (S_Hi) at the sulfur atom by aryl or alkyl radicals is described. Both alkyl and benzofused compounds can be accessed directly from easily prepared acyclic precursors. Enantiomerically enriched sulfur‐based heterocycles were formed through an S_Hi process with inversion of configuration at the sulfur atom. Cyclization of prochiral radicals proceeded with varying stereochemical outcomes, depending on the size of the incoming radical. 2‐Pyridyl and 2‐quinolyl radicals led to biaryl compounds, which result from attack onto the ortho position of the arylsulfinate rather than a thiophilic substitution.     

Cu‐Catalyzed Selective Oxy‐Cyanoalkylation of Allylamines with Cycloketone Oxime Esters and CO2

The radical‐initiated carboxylative cyclization of allylamines with CO₂ represents an efficient and highly promising strategy to afford valuable 2‐oxazolidinones. However, the radical precursors and pathways to generate radicals in such processes are still limited. Herein, we report the first Cu‐catalyzed selective oxy‐cyanoalkylation of allylamines with cycloketone oxime esters and CO₂ via C—C bond cleavage. Many cyanoalkyl‐substituted 2‐oxazolidinones are obtained in moderate to good yields with high regio‐ and chemo‐selectivities. The utility of this redox‐neutral and cyanide‐free method is demonstrated with mild conditions, broad substrate scope, good functional group tolerance and easy scalability.     

Positive-ion fragmentation mechanisms of some organophosphorus esters

The mass spectra of the dimethyl and diethyl esters of phosphonic, phosphorochloridic and phosphorochloridothioic acid have been obtained, and the main paths of decomposition of their positiveions have been compared. Losses of formaldehyde occur from positive ions of all the methyl esters. Losses of C₂H₃˙ radicals occur consistently from the positive ions of the ethyl esters, but diethyl phosphorochloridothioate differs in showing a principal decomposition path involving initial loss of acetaldehyde. Other details are discussed.     

ESR studies of vinyl polymerization. II. Initial reactions of vinyl esters with redox systems in aqueous media

ESR measurements of transient radicals during redox polymerization of various vinyl esters in aqueous solutions have been made by using the rapid-mixing flow method. The initiation was by means of hydroxyl and amino radicals from the systems titanous chloride-hydrogen peroxide and titanous chloride-hydroxylamine, respectively. The well resolved hyperfine structures obtained at monomer concentrations of about 0.05 mole/1. are unambiguously assigned to the monomer radicals formed by addition of initiator radicals to monomers. At higher monomer concentrations, additional weak signals attributed to the growing polymer radicals were observed. The effect of reaction conditions on the signal intensity has been studied in particular for vinyl acetate. The coupling constants of monomer radicals from various vinyl esters (acetate, propionate, butyrate, crotonate, and isopropenyl acetate) were obtained and the spin densities calculated. From the ESR spectra, the monomer radicals have a conformation with the substituent R (R = HO or NH₂) of R? CH₂? CH(OCOR′) locked in a position above or below the radical plane. This is tentatively interpreted as due to formation of intramolecular hydrogen bonds to ring structures or complexes with titanium ions. In addition, hydrogen abstraction reactions of some model compounds for poly(vinyl acetate) have been briefly studied in relation to chain transfer and grafting reactions.     

Generation of Glycosyl Radicals from Glycosyl Sulfoxides and Its Use in the Synthesis of C‐linked Glycoconjugates

We here report glycosyl sulfoxides appended with an aryl iodide moiety as readily available, air and moisture stable precursors to glycosyl radicals. These glycosyl sulfoxides could be converted to glycosyl radicals by way of a rapid and efficient intramolecular radical substitution event. The use of this type of precursors enabled the synthesis of various complex C‐linked glycoconjugates under mild conditions. This reaction could be performed in aqueous media and is amenable to the synthesis of glycopeptidomimetics and carbohydrate‐DNA conjugates.     

Synthesis of C-acyl furanosides via the cross-coupling of glycosyl esters with carboxylic acids

C-Acyl furanosides are versatile synthetic precursors to a variety of natural products, nucleoside analogues, and pharmaceutical molecules. This report addresses the unmet challenge in preparing C-acyl furanosides by developing a cross-coupling reaction between glycosyl esters and carboxylic acids. A key step is the photoredox activation of the glycosyl ester, which promotes the homolysis of the strong anomeric C–O bond through CO₂ evolution to afford glycosyl radicals. This method embraces a large scope of furanoses, pyranoses, and carboxylic acids, and is readily applicable to the synthesis of a thymidine analogue and diplobifuranylone B, as well as the late-stage modification of (+)-sclareolide. The convenient preparation of the redox active glycosyl ester from native sugars and the compatibility with common furanoses exemplifies the potential of this method in medicinal chemistry.

A cross-coupling of glycosyl esters with carboxylic acids to prepare C-acyl furanosides and pyranosides. The reaction proceeds through photoredox activation of the glycosyl ester to afford glycosyl radicals.     

Palladium-catalyzed selective alkoxycarbonylation of α,β-unsaturated amides: a novel approach toward new ω-amido esters and N-substituted cyclic succinimides

The alkoxycarbonylation of α,β-unsaturated amides proceeded efficiently and regioselectivity to give ω-amido esters with complete conversion in the presence of the catalyst system: Pd(PPh₃)₂Cl₂/MeOH/CO/H₂O. The reaction was successfully applied to the alkoxycarbonylation of bis-acrylamides yielding, selectively, the corresponding di-ω-amido esters. These mono and di-ω-amido esters have been used as precursors for the synthesis of N-substituted cyclic succinimides in moderate to high yields.     

Direct oxidative esterification of toluene with 1,3‐dicarbonyl compounds catalysed by copper complex supported on magnetic nanoparticles

Toluene oxidation is one of the substantial industrial technologies since oxidized products are industrially very important intermediates. A Fe₃O₄@cysteine@Cu‐catalysed reaction that uses tert ‐butyl hydroperoxide as oxidant to produce esters from toluene and β‐diketones or β‐keto esters, enolate precursors, has been developed. Oxidative esterification of toluene with 1,3‐dicarbonyl derivatives led to C─O bond formation and direct C─H functionalization.     

Synthesis and radical fragmentation of carbohydrate anomeric nitrates. Formation of convenient chiral synthetic intermediates

A new procedure for the C1–C2 fragmentation of cyclic carbohydrates, through the formation of anomeric alkoxy radicals from the corresponding nitrate esters, with ⁿBu₃SnH/azobisisobutyronitrile (AIBN), affords acyclic alditols in good yields.     

On the use of (TMS)3CH as novel tin-free radical reducing agent

(TMS)₃CH is an efficient free radical reducing agent. Debromination, deiodation, dechlorination as well as decarboxylation of Barton and Kim esters can proceed smoothly using this tin-free reducing agent. Rate constants for hydrogen atom abstraction from TMS₃CH by primary radicals were also determined.     

Isomer-Selective Generation and Spectroscopic Characterization of Picolyl Radicals

Nitrogen-containing resonance-stabilized radicals such as the picolyl radical are important in combustion chemistry and astrochemistry. They have only been scarcely studied because an isomer-selective generation is often difficult. Herein, we present threshold photoelectron spectra of the three picolyl radical isomers, C₆H₆N, that were obtained with synchrotron radiation. The radicals were selectively generated by flash pyrolysis from aminomethylpyridine precursors through deamination. Ionization energies of 7.70, 7.59, and 8.01 eV were determined for 2-, 3-, and 4-picolyl, respectively. The observed vibrational structure was assigned to an in-plane deformation mode of the aromatic ring. The spectroscopic insight gained in this study can be used to distinguish different picolyl isomers in on-line combustion analysis, for example.     

Interaction of the cholinesterases of warm-blooded animals with esters of N-(β-hydroxypropyl)piperidines and the methiodides

The influence of esters of N-(β-hydroxypropyl)pyridines (alkyl radicals from CH₃ to C₄H₉) on the enzymatic activity of acetylcholinesterase (ACE) from human blood erythrocytes and on that of butyrylcholinesterase (BCE) from horse blood serum has been studied. At pH 7.5 and 25°C the majority of the piperidine derivatives inhibit reversibly (by the competitive type of inhibition) both ACE and BCE, their inhibiting properties depending only slightly on the presence of the corresponding alkyl radicals in the acid part of the molecule.