Introduction of N,N'-disulfonylhydrazines as new sulfonylating reagents for highly efficient synthesis of (E)-β-iodovinyl arenesulfones under mild conditions

N,N'-Disulfonylhydrazines have been proven to be the most reactive precursors of the sulfonyl radicals among all types of sulfonyl substituted hydrazines as early as half a century ago. However, the sulfonyl radicals generated from these compounds have not been used in organic synthesis except the simple self-dimerization synthesis of disulfones controlled by the “solvent-cage-effects”. In this article, N,N′-disulfonylhydrazines were introduced as new sulfonylating reagents and their combinations with NIS were disclosed as new iodosulfonylating reagents of alkynes. Finally, a highly efficient method for the synthesis of (E)-β-iodovinyl arenesulfones was developed by mixing an alkyne, a N,N′-disulfonyl-hydrazine and NIS in aqueous THF at room temperature for 5 min.     

Monoallylstannanes,reagents for allylic radical transfer. Part I

We have previously highlighted the ability of the N,N-bistrimethylsilylaminostannylene 1 to produce monoallylstannanes 2 in quantitative yields, starting from various functionalised allylic halides via an insertion reaction. In contrast with more electrophilic trihalogenotin radicals, the tin-centred radicals generated from reagents 2 are shown to be the best candidates towards allylic radical transfer, giving allylated products in similar yields as those obtained with classical tributyltin radicals.     

Reaction of Nitrogen‐Radicals with Organometallics Under Ni‐Catalysis: N‐Arylations and Amino‐Functionalization Cascades

Herein, we report a strategy for the generation of nitrogen‐radicals by ground‐state single electron transfer with organyl–Ni^I species. Depending on the philicity of the N‐radical, two types of processes have been developed. In the case of nucleophilic aminyl radicals direct N‐arylation with aryl organozinc, organoboron, and organosilicon reagents was achieved. In the case of electrophilic amidyl radicals, cascade processes involving intramolecular cyclization, followed by reaction with both aryl and alkyl organometallics have been developed. The N‐cyclization–alkylation cascade introduces a novel retrosynthetic disconnection for the assembly of substituted lactams and pyrrolidines with its potential demonstrated in the short total synthesis of four venom alkaloids.     

EPR characterization of new phosphavinyl σ radicals

A number of radicals have been added to 1,3-bis(2,4,6-tri-tert-butylphenyl)diphospha-allene at low temperature in cyclopropane solution. Addition of thiyl and alkoxyl radicals occurs regiospecifically to one of the phosphorus atoms leading to new phosphavinyl radicals, isoelectronic with vinyl radicals, which have been characterised by means of EPR spectroscopy. The results of ab initio calculations are in agreement with the experimentally determined spectral parameters and suggest that these radicals are bent, with a PCP bond angle of ca. 150°. In contrast, silyl and germyl radicals appear to add to the carbon atom of the phosphaallene.     

The quest for chiral Grignard reagents

The involvement of single electron transfer, i.e. of free radicals in the reactions of organomagnesium reagents could be detected with the aid of a chiral secondary Grignard reagent, in which the magnesium-bearing carbon atom is the sole stereogenic centre. So far, however, such reagents have not been accessible, because the standard preparation of Grignard reagents proceeds via free radicals. We review and summarize here our efforts to generate such a Grignard reagent 36 by asymmetric synthesis starting from an enantiomerically pure alpha-chloroalkyl-sulfoxide 30b using a sulfoxide/magnesium exchange reaction to give 33 followed by a carbenoid homologation reaction. Grignard reagent 36 turned out to be an ideal probe to learn about the extent to which SET is involved in reactions of organomagnesium reagents.     

Synthesis and photochemistry of a new class of photocleavable protein cross-linking reagents

A new series of photocleavable protein cross-linking reagents based on bis(maleimide) derivatives of diaryl disulfides have been synthesised. They have been functionalised with cysteine and transient absorption spectra for the photolysis reaction have been recorded by using the pump-probe technique with a time resolution of 100 femtoseconds. Photolysis of the disulfide bond yields the corresponding thiyl radicals in less than a picosecond. There is a significant amount of geminate recombination, but some of the radicals escape the solvent cage and the quantum yield for photocleavage is 30 % in water.     

Analogues of nucleotides and oligonucleotides featuring difluorophosphonate, difluorophosphonothioate and difluorophosphinate functional groups

Efforts to stereoselectively install difluorophosphonyl, difluorophosphonothioyl and difluorophosphinyl groups in place of the phosphate linking positions 3′ and 5′ of two furanoses are reviewed. Two equally efficient approaches have been worked out based on either the ionic addition of difluorophosphonothioate reagents 17 or 33 onto a ketone, or on the addition of phosphorus-centered radicals onto gem-difluoroalkenes. These methodologies resulted in the successful preparation of 3′-phosphonodifluoromethyl analogues to nucleosides-3′-phosphates, and of key intermediate 83, featuring two ribofuranosyl nuclei linked by a difluorinated phosphonothioyl unit on positions 3′ and 5′. In addition, the groundwork for the synthesis of H-difluorophosphinates and difluorophosphinates has been laid.     

An insight into copper catalyzed allylation of alkyl zinc halides. Comparison of reactivity profiles for catalytic and stoichiometric alkylzinc-copper reagents

The γ-selective allylation of catalytic and stoichiometric alkylzinc-cuprates have been kinetically studied. The reactivity profiles generated by allylation reactions of n-butylzinc chloride catalyzed by CuX compounds (X = I, Br, Cl, CN, SCN) and also catalyzed by n-butylzinc-copper reagents and di n-butylzinc-copper reagents were evaluated. Reactivity profiles for allylation of stoichiometric n-butylzinc-copper reagents and di n-butylzinc-copper reagents were also prepared. All CuX compounds have been screened for the preparation of Grignard reagent derived n-butylzinc-copper reagents and di n-butylzinc-copper reagents.The evaluation of the profiles indicates that the active catalyst might be RCu(X)ZnCl and also to some degree, R₂CuZnCl · ZnClX, which both could favor formation of γ-product. All data supports the reductive elimination of σ-allyl Cu (III) complex formed at vinylic terminal to give γ-allylated product with a quite slow isomerization to σ-allyl Cu (III) complex formed at allylic terminal to give α-allylated product. In the allylation mechanism of zinc cuprates, the role of counter ion, ZnCl⁺ has been discussed.     

The oxidation of 2-alkoxy-3,6-di-tert-butylphenols. The reversible dimerization of 2-alkoxy-3,6-di-tert-butylphenoxy radicals

The oxidation of 2-alkoxy-3,6-di-tert-butylphenols has been studied. It was found that 2-RO-3,6-di-tert-butylphenoxy radicals (R = Et, Pr, Ph) undergo dimerization by C-O coupling. The X-ray structure of 2-ethoxy-3,6-di-tert-butylphenoxy dimer has been determined. Radical dimers dissociate reversibly in solution to give two phenoxy radicals at 200-350 K. By using EPR spectroscopy the equilibrium concentration of the phenoxy radicals, equilibrium constants and ΔH and ΔS of dissociation have been determined.     

A systematic scheme of qualitative analysis for anions. III

The completeness of precipitation of anions and basic radicals by the two group reagents, zinc acetate and cadmium nitrate, has been investigated. It has been shown that the two reagents precipitate many of the anions quantitatively and can thus be used for their gravimetric estimation.     

Strained heterocycles in radical chemistry

Over the last few decades the use of radicals in synthesis has witnessed an explosive growth through introduction of efficient chain and electron-transfer reactions. Strained heterocycles, in particular, have emerged as a highly versatile and readily available class of radical precursors. The generation of carbinyl radicals of heterocycles has resulted in many elegant applications of heteroatom-centered radicals, such as beta fragmentations, cyclizations, and intramolecular hydrogen atom abstractions. Direct electron transfer to strained heterocycles has been realized through the use of arene radical anions. The method combines the virtues of radical and organometallic chemistry to yield useful functionalized organolithium compounds. Epoxides have been opened with high regioselectivity by titanocene(III) reagents in either stoichiometric or catalytic quantities to yield beta-titanoxy radicals. This development has resulted in many new applications in natural product synthesis.     

Reactions of methyl radicals with polymers—part 1: Abstraction reactions with poly(p-methoxystyrene)

The kinetics of hydrogen abstraction by methyl radicals from poly(p-methoxystyrene) have been investigated, methyl radicals being produced by the photolysis (λ = 254 nm) of the polymer under high vacuum. A new differential equation has been derived to describe simultaneous diffusion and reaction of methyl radicals; its solution, along with experimentally determined yields of methane, have been used to obtain a value for the rate constant for H abstraction from the polymer. The value of this constant is compared with previous data for poly(styrene) and the apparent agreement is found to be fortuitous. Relative to similar gas phase abstractions, the rate constants are lower by about four orders of magnitude; some of the factors contributing to this difference are discussed.     

Metal‐Free C?H Bond Activation of Branched Aldehydes with a Hypervalent Iodine(III) Catalyst under Visible‐Light Photolysis: Successful Trapping with Electron‐Deficient Olefins

Direct acyl radical formation of linear aldehydes (RCH₂‐CHO) and subsequent hydroacylation with electron‐deficient olefins can be effected with various types of metal and nonmetal catalysts/reagents. In marked contrast, however, no successful reports on the use of branched aldehydes have been made thus far because of their strong tendency of generating alkyl radicals through the facile decarbonylation of acyl radicals. Here, use of a hypervalent iodine(III) catalyst under visible light photolysis allows a mild way of generating acyl radicals from various branched aldehydes, thereby giving the corresponding hydroacylated products almost exclusively. Another characteristic feature of this approach is the catalytic use of hypervalent iodine(III) reagent, which is a rare example on the generation of radicals in hypervalent iodine chemistry.     

Metal‐Free CH Bond Activation of Branched Aldehydes with a Hypervalent Iodine(III) Catalyst under Visible‐Light Photolysis: Successful Trapping with Electron‐Deficient Olefins

Direct acyl radical formation of linear aldehydes (RCH₂‐CHO) and subsequent hydroacylation with electron‐deficient olefins can be effected with various types of metal and nonmetal catalysts/reagents. In marked contrast, however, no successful reports on the use of branched aldehydes have been made thus far because of their strong tendency of generating alkyl radicals through the facile decarbonylation of acyl radicals. Here, use of a hypervalent iodine(III) catalyst under visible light photolysis allows a mild way of generating acyl radicals from various branched aldehydes, thereby giving the corresponding hydroacylated products almost exclusively. Another characteristic feature of this approach is the catalytic use of hypervalent iodine(III) reagent, which is a rare example on the generation of radicals in hypervalent iodine chemistry.     

Design of ionic liquids as a medium for the Grignard reaction

Design of novel phosphonium ionic liquids that are compatible with Grignard reagents have been investigated; several types of phosphonium salts that have an alkyl ether moiety have been synthesized and their capability evaluated as solvents for Grignard reagents. It has been established that even basic aliphatic Grignard reagent-mediated reactions are possible when methoxyethyl(tri-n-butyl)phosphonium bis(trifluoromethanesulfonyl)imide is used as the solvent.     

Synthesis of C2-symmetrical chiral diamines: diastereoselective addition to bis(1,3-oxazolidinyl)alkanes with Grignard reagents

Asymmetric syntheses of C₂-symmetrical chiral 1,4- and 1,5-diamines with stereogenic centers adjacent to the nitrogen atom have been accomplished. Chiral diamines were prepared by diastereoselective alkylations of bisoxazolidine, which was derived from (R)-phenylglycinol. Methyl and phenyl Grignard reagents were employed as alkylating reagents. In addition, tertiary chiral diamines were readily converted to primary diamines in high yield.     

Structure and behavior of organic analytical reagents : Chelates of 2-(o-hydroxyphenyl)-benzoxazole, 2-(o-hydroxyphenyl)-benzothiazole and 2-(o-hydroxyphenyl)-benzothiazoline.

The reactions of the chelating reagents named in the title, with a number of metal ions, have been studied in order to evaluate the behavior of reagents containing reactive groupings analogous to those of 8-hydroxyquinoline, but so arranged as to form six-membered ring chelates with metal ions. All three reagents have been found to give less stable chelates than 8-hydroxyquinoline, indicating that for this type of reagent, six-membered ring chelates are less stable than five. 2-(o-Hydroxy-phenyl)-benzoxazole and 2-(o-hydroxyphenyl)-benzothiazole have been found to be potentially useful as organic precipitating agents for metal ions, being more selective than 8-hydroxyquinoline, which they somewhat resemble in behavior. In contrast to the oxazole and thiazole, 2-(o-hydroxyphenyl)-benzothiazoline was found to react with most of the metal ions tried. Because of the solubility of its chelates in organic solvents, 2-(o-hydroxyphenyl)-benzothiazoline may be a useful solvent extraction agent for metal ions.     

Iodine Catalysis for C(sp3)–H Fluorination with a Nucleophilic Fluorine Source

Iodine catalysis was developed for aliphatic fluorination through light-promoted homolytic C−H bond cleavage. The intermediary formation of amidyl radicals enables selective C−H functionalization via carbon-centered radicals. For the subsequent C−F bond formation, previous methods have typically been limited by a requirement for electrophilic fluorine reagents. We here demonstrate that the intermediary instalment of a carbon–iodine bond sets the stage for an umpolung, thereby establishing an unprecedented nucleophilic fluorination pathway.     

A short,versatile route towards benzothiadiazinyl radicals

A family of substituted 1,2,4-benzothiadiazine 1-chlorides have been prepared by treatment of N-arylamidines in neat thionyl chloride at reflux. The S(iv) 1-chlorides are readily reduced under mild conditions to persistent 1,2,4-benzothiadiazinyl radicals which have been characterised by EPR spectroscopy and cyclic voltammetry. Crystallographic studies on isolated radicals indicate that the radicals dimerise via pancake bonding in the solid-state, resulting in spin-pairing and net diamagnetism.

A family of 1,2,4-benzothiadiazinyl radicals are accessible from 1,2,4-benzothiadiazine 1-chlorides which can be prepared in a single step by treatment of N-arylamidines in neat thionyl chloride at reflux.     

Kinetics of ethylbenzene oxy-chemiluminescence in the presence of antioxidants from tissues of the marine invertebrate Eupentacta fraudatrix: Estimating the concentration and reactivity of the natural antioxidants

Extracts from tissues of the holothuria Eupentacta fraudatrix suppress the oxy-chemiluminescence of ethylbenzene in chlorobenzene initiated by azobisisobutyronitrile thermolysis and enhanced by energy transfer to 9,10-dibromoanthracene. The decrease of the chemiexcitation rate in the reaction between peroxyl radicals is caused by radical interception by the antioxidants contained in the extracts. The concentrations of the antioxidants in the extracts and the rate constants of their reactions with peroxyl radicals have been estimated from chemiluminescence kinetics.