α,β-Unsaturated diesters: radical acceptors in dialkylzinc-mediated tandem radical addition/aldol condensation. A straightforward synthesis of rac-nephrosteranic acid

The sequence involving conjugate radical addition/aldol condensation/lactonization is a high yielding route to di- and tri-substituted γ-lactones starting from fumaric or maleic diesters. The reactions are mediated with dialkylzincs. The domino process relies on the ability of dialkylzinc to transform α-alkoxycarbonylalkyl radicals into zinc enolates. Compared to diethylzinc, dimethylzinc enables the use of a wider range of alkyl radical precursors. In addition, dimethylzinc is a convenient source of methyl radical, which leads to a straightforward synthesis of methylated derivatives related to α-methyl-paraconic acids.     

Copper-catalyzed synthesis of oxime ethers from iminoxy radical (CN–O) and maleimides via radical addition

An efficient Cu(II)-catalyzed radical addition of maleimides has been achieved. The identified copper catalyst enables the formation of oxime radicals (N–O) by cleaving the O–H bond in ketoximes, followed by the radical addition to N-substituted maleimides. The oxime radicals (N–O) were detected and confirmed by EPR spectroscopy and variable-temperature ¹H NMR. The simple one-pot reaction realizes the facile preparation of a variety of oxime ether adduct products in moderate to good yields.     

Synthesis and polymerization of novel fluorinated acrylates and methacrylates bearing alkoxyl groups derived from radical addition reaction of perfluoroisopropenyl ester

Radical addition of 2-benzoxypentafluoropropene [CF₂C(CF₃)OCOC₆H₅] (BPFP) with alcohols such as ethanol and 2-propanol was investigated to afford fluorinated alcohols. Radical addition of BPFP with cyclic ethers such as tetrahydrofuran, 1,3-dioxolane and tetrahydropyran was also achieved to afford addition products followed by hydrolysis to yield fluorinated alcohols possessing cyclic structures. Novel fluoroalkyl acrylates and methacrylates were synthesized from the fluorinated alcohols with (meth)acryloyl chlorides. Radical polymerization of the fluoroalkyl (meth)acrylates yielded polymers of 1.2 × 10⁵ as the highest molecular weight.     

Block copolymers prepared by polymeric radical addition cross‐coupling reaction to different double bonds

We present an efficient method for synthesis of block copolymer by radical addition cross‐coupling reaction between two different polymeric radicals and different double bonds. Two different monobromo polymers (P₁‐Br and P₂‐Br) were reacted with Cu(0)/N,N,N′,N″,N″‐pentamethyldiethylenetriamine in the presence of ethyl dithiobenzoate or 1,1‐diphenylethylene (X) and the block copolymer (P₁‐X‐P₂) can be obtained with high efficiency, which cannot be prepared by normal atom transfer radical coupling of mixture of P₁‐Br and P₂‐Br. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 2817–2823.     

Highly diastereoselective radical addition to glyoxylate imines of chiral amines without additional heteroatoms

The diastereoselective addition of alkyl radicals to glyoxylate imines of α-alkylbenzylamines has been investigated and it was found that diastereoselectivity improved as the size of the alkyl group increased.     

Enantioselective addition of diethylzinc to aryl aldehydes catalyzed by 1,2,3,4-tetrahydroisoquinoline β-amino alcohol

<正>A highly effective,new chiral 1,2,3,4-tetrahydroisoquinoline catalyst 1 for the diethylzinc addition to aryl aldehydes has been investigated.Using 10 mol%of this chiral catalyst,secondary alcohols can be obtained in up to 87%yield and 99.5%ee under mild conditions.     

Physical factors determining the activation energy of alkyl radical addition to unsaturated compounds

A parabolic model of the transition state is used for the analysis of experimental data (rate constants and activation energies) for reactions of addition of alkyl and phenyl radicals to multiple bonds of unsaturated compounds. The parameters describing the activation energy as a function of the enthalpy of the reactions were calculated from the experimental data. The activation energy depends also on the strength of the forming C−C bond, the presence of π-bonds in the α-position near the attacked C=C bond and the presence of polar groups in the monomer and radical. The empirical dependence of the activation energy of a thermoneutral addition reactionE _e0 on the dissociation energyD _e of the forming C−C bond was obtained:E _e0=(5.95±0.06)·10⁻⁴ D _e ² kJ mol⁻¹, indicating the important role of triplet repulsion in the formation of the transition state of radical addition. The contribution of the polar interaction to the activation energy of addition of polar radicals to polar monomers was calculated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 445–450, March, 1999.     

Synthesis of new chiral 1,2,3,4-tertrahydroisoquinoline β-amino alcohol for asymmetric diethylzinc addition to aryl aldehydes (I)

Four new chiral 1,2,3,4-tetrahydroisoquinoline-derived β-amino alcohols were synthesized from commercially available L-DOPA.These ligands were evaluated in the asymmetric addition of diethylzinc to benzaldehydes and showed different catalytic activities (up to 86% ee).The solvent played an important role in the enantioselective process.The transition state models were proposed to explain the reversion of the product configuration.     

Asymmetric addition of diethylzinc to aromatic aldehydes by chiral ferrocene-based catalysts

A series of chiral C₁- and C₂-symmetric ferrocenyl Schiff bases (1a-c), ferrocenyl aminoalcohols (2a), ferrocenylphosphinamides (2b-c), 1,1′-ferrocenyl-diol (3), and 1,1′-ferrocenyl-disulfonamide (4) were prepared and employed as base catalysts or as ligand for titanium(IV) complexes in the asymmetric addition of diethylzinc to aromatic aldehydes. High enantioselectivity up to almost 100% ee was achieved for the alkylation of benzaldehyde and p-methoxybenzaldehyde with 1 or 3. In contrast, however, the β-aminoalcohol (2a) and phosphinamides (2b and c) that are ubiquitous classes of base catalysts for this reaction proved inefficient in our hands, regardless of the types of substrates or reaction conditions. Comparative studies show that there exist various reaction parameters governing not only chemical yields but also optical yields. These include steric and electronic environment of the substrate, the solvent, the reaction temperature, and the nature of the ferrocene moieties.     

Indium-mediated radical addition of perfluoroalkyl iodide in water

Reaction of perfluoroalkyl groups with carbon-carbon unsaturated compounds using indium in water proceeded smoothly to provide the addition products in high yields.     

The addition of fluorine to perhalogenated compounds containing carbon-nitrogen double bonds

The reaction of elementary fluorine with ten perhalogenated compounds containing carbon-nitrogen double bonds is reported. The reactions were carried out without added catalysts in a static system. With CF₃N=CF₂, (CF₃)₂NCF=NCF₃, SF₅N=CF₂, CF₂=NCl, CF₃CF=NCl and CF₂=NF a simple addition of fluorine to the carbon-nitrogen double bond was observed forming the respective N-fluoroamines in high yield. Two imines, CF₃CF=NF and (CF=NF)₂, were unreactive under the same conditions and reactions of CF₃CF₂CF=NF and (CF₃)₂C=NF were explosive.     

Enantioselective addition of diethylzinc to aldehydes in the presence of chiral hydrazone and imine ligands

Optically active hydrazone and imine were found to act as effective ligands for enantioselective addition of diethylzinc to aldehydes. This reaction provided optically active secondary alcohols with ee up to 71%.     

A convenient AIBN-initiated radical addition of ethyl iododifluoroacetate to alkenes

The AIBN-initiated addition of ethyl 4-iodo-2,2-difluoroacetate to a variety of alkene substrates is described. The addition generally led to the corresponding addition products in good to excellent yields and various functional groups could be tolerated under the reaction conditions.     

Transition states in the reaction of radical addition to the vinyl double bond

The transition states for the addition of^.CH₃, CH₃O^.,^.CCl₃,^.CF₃, and HOO^. radicals to the C and C atoms of ethylene, propylene, styrerie, acrylonitrile, methyl acrylate, vinyl acetate, and vinyl- and vinylidene chlorides were calculated using the MNDO method. A satisfactory correlation between the heats of reaction and activation energies was found. The calculated coefficients of proportionality, 0.4–0.5, are twice as high as those in the Polyani—Semenov equation. The calculated heat of reaction of radical addition was shown to be as «strong» an index of reactivity as the calculated activation barrier.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 4, pp. 680–684, April, 1993.     

Microwave-assisted atom transfer radical addition of polychlorinated compounds to olefins without addition of metal catalysts

A new operationally simple and robust protocol for the metal-free atom transfer radical reaction (ATRA) has been developed. Polychlorinated compounds were effectively reacted with unactivated terminal olefins to generate 1,3-dichlorinated adducts under microwave irradiation in the presence of silicon carbide (SiC) as a heating element. The present microwave-assisted ATRA proceeds under essentially neutral conditions; thus, polar functionalities are well tolerated. In addition, an oxygen or a nitrogen unit was introduced to the internal side of the carbon chain via nucleophilic cyclization of the 1,3-dichlorinated adducts, and single-step formation of the six-membered carbocycle was realized through cyclization of the intermediate radical. The present methodology provides an expeditious way to prepare synthetically useful molecules from simple and unactivated terminal olefins.     

Formamide as an efficient nitrogen nucleophile for the Michael addition to nitroalkenes

Secondary acyclic formamide serves as an efficient nucleophile to nitroalkenes to give corresponding Michael adducts in good yields. The nitro group in the adducts was useful for further heterocyclic synthesis.     

Homo- and heterogeneous organocatalysis: enantioselective Mannich addition of ketones to endocyclic carbon-nitrogen double bonds

The proline-catalyzed Mannich addition of ketones to chalkogenazines is reported. Yields and enantioselectivities of the corresponding products were good to excellent, using different types of organocatalysts. Furthermore the immobilization of hydroxyproline into a readily synthesized polystyrene-copolymer was accomplished. The catalytic performance of this heterogeneous catalyst was successfully demonstrated in the discussed Mannich reaction.     

Theoretical study of azide anion addition to nonpolar and polar double and triple bonds

Transition structures for the 1,3-polar addition of azide anion to hydrogen cyanide, formaldimine, nitrogen, cis- andtrans -diazene, ethylene and acetylene were obtained at the MP2/6-31+G^* theoretical model. The additions can be divided into two groups: addition to a triple bond, giving rise to an aromatic heterocyclic product, and addition to a double bond, forming a non-aromatic product. All transition structures correspond to a concerted mechanism for the polar cycloaddition. Symmetrical dienophiles, apart from cis-diazene, give rise to synchronous transition structures. The anomaly is explained in terms of strong n-n repulsion of the reactants in the transition structure. The reactivity of the compounds can be rationalized in terms of the bond orders of the newly forming bonds, from the frontier orbital energy differences and from the charge transfer from the azide anion to the dienophile. The quantitative correlation of the reactivity has been judged on the basis of the activation energies of the reactions calculated at MP2/6-31+G^* and MP3/6-31+G^*. It is predicted that the addition of azide to nitrogen is the slowest and that the additions to hydrogen cyanide and acetylene have the lowest barriers, in agreement with literature data.     

Manganese(III)-mediated oxidative radical addition of malonates to 2-cyanoindoles

2-Cyanoindole and N-methyl-2-cyanoindole undergo manganese(III)-mediated radical addition with activated methylene and methine compounds. Products of the methylene addition underwent additional oxidation during the course of the reaction to furnish the corresponding acetoxy compounds. Several structures were confirmed by X-ray crystallography.     

C2-symmetrical bis(camphorsulfonamides) as chiral ligands for enantioselective addition of diethylzinc to benzaldehyde

Purpose of the research was to determine the activity of chiral bis(sulfonamide) ligands derived from camphor in the addition of diethylzinc to benzaldehyde. Chiral bis(ketosulfonamides) and bis(hydroxysulfonamides), have been synthesized in a reaction of diamines with camphorsulfonic acid chloride. Their activity in a reaction of asymmetric addition of dialkylzinc to benzaldehyde in a presence of titanium(IV) tetraisopropoxide was determined. The bis(ketosulfonamide) ligands reveal low enantioselectivity, with the ee% not exceeding 12%. The bis(hydroxysulfonamides) reveal much higher asymmetric induction in the investigated ZnEt₂ addition. The best enantiomeric excess (62%) has been observed for bis(hydroxysulfonamide) obtained from 1,3-diaminepropane. The yields of the reaction obtained after 18 h are 92–96%. Crystal structures have been solved for bis(ketosulfonamide) ligands obtained from diamines based on C₂ to C₄ chain. The (2R) configuration in the rings systems of bis(hydroxysulfonamide) containing the C₃ bridge was also determined by the crystal structure analysis. The sulfonamides have been characterized by IR, ¹H and ¹³C NMR.