Atom Transfer Radical Addition Research Articles

(R)-2-Methyl-5-[(R)-2,4,4,4-tetrachlorobutan-2-yl]cyclohex-2-enone

The title compound, C11H14Cl4O, was efficiently synthesized by atom-transfer radical addition between (R)-carvone and tetra­chloro­methane. In the mol­ecule, both chiral centres are of the absolute configuration R. The cyclo­hex-2-enone ring has an envelope conformation with the chiral C atom displaced by 0.633 (2) Å from the mean plane through the other five C atoms [maximum deviation = 0.036 (2) Å]. In the crystal, mol­ecules are linked via C—H⋯O inter­actions, leading to the formation of helical chains propagating along [100].

Ruthenium-catalyzed Atom Transfer Radical Addition Reactions

Certain ruthenium complexes are potent catalysts for atom transfer radical addition (ATRA) and cyclization (ATRC) reactions, in particular if they are used in conjunction with reducing agents such as magnesium. This short overview summarizes recent developments in this area with special focus on contributions from our laboratory.

Radical Carbon–Carbon Bond Formations Enabled by Visible Light Active Photocatalysts

This mini-review highlights the Stephenson group's contribution to the field of photoredox catalysis with emphasis on carbon-carbon bond formation. The realization of photoredox mediated reductive dehalogenation initiated investigations toward both intra- and intermolecular coupling reactions. These reactions commenced via visible light-mediated reduction of activated halogens to give carbon-centered radicals that were subsequently involved in carbon-carbon bond forming transformations. The developed protocols using Ru and Ir based polypyridyl complexes as photoredox catalysts were further tuned to efficiently catalyze overall redox neutral atom transfer radical addition reactions. Most recently, a simplistic flow reactor technique has been utilized to affect a broad scope of photocatalytic transformations with significant enhancement in reaction efficiency.

Carbocyanation of trisubstituted olefins via Cu-catalyzed atom transfer radical addition

A regioselective Cu(I)-catalyzed carbocyanation of non-polarized trisubstituted olefins 1 has been achieved by employing chlorinated cyanides 2 as starting materials. The present reaction gives the carbocyanated product 3 through radical-based 1,3-transfer of CN. Consequently, two different carbon units, cyano and chlorocyanomethyl groups, are introduced into the highly substituted olefins, generating consecutive quaternary and tertiary carbons. Since both of the attached carbon units can be used as handles for further synthetic elaborations, the present transformation offers a new synthetic methodology for rapid construction of architecturally complex carboskeletons.

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.

Periodic Vinyl Copolymers Containing γ-Butyrolactone via ADMET Polymerization of Designed Diene Monomers with Built-in Sequence

The synthesis of a new family of periodic copolymers containing γ-butyrolactones by acyclic diene metathesis polymerization (ADMET) and their thermal properties are presented. Two symmetric diene monomers, M6 and M8, were designed. Both monomers contain two γ-butyrolactone units, but they are different in the length of methylene spacers between cyclic structures and terminal alkenes. The monomers have been prepared by a two-step approach; first, the atom transfer radical addition (ATRA) of diethyl meso-2,5-diiodohexanedioate with either 1,5-hexadiene or 1,7-octadiene was conducted to yield intermediates containing two γ-iodo ester sequences; subsequently, the specific sequence was transformed into γ-butyrolactone unit via intramolecular cyclization upon heating. The two monomers were polymerized using two Grubbs catalysts (Grubbs I and Grubbs II) to produce four polymers with moderate to high molecular weights (P6-1, P6-2, P8-1, and P8-2) and hydrogenation of which gave the final saturated polymers. The expected periodic copolymers have been obtained and were characterized with a variety of methods, indicating that the γ-butyrolactone units could endure the polymerization and hydrogenation. Polymers catalyzed by Grubbs II catalyst suffer from chain heterogeneity due to severe olefin isomerization. Thermal properties of the polymers were investigated via thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). TGA measurements show that these polymers are stable up to 350 °C. DSC results demonstrate that the glass transition and melting behaviors of the polymers are not only affected by the rigidity of γ-butyrolactone units in polyethylene chains but also dependent on the methylene spacer length and chain homogeneity. Copolymerization of M6 or M8 with 1,9-decadiene resulted in random copolymers with lower γ-butyrolactone content and less regular chain structure. These copolymers exhibit lower Tg or Tm compared with the periodic copolymers.

Visible Light-Mediated Atom Transfer Radical Addition via Oxidative and Reductive Quenching of Photocatalysts

Herein, the development of visible light-mediated atom transfer radical addition (ATRA) of haloalkanes onto alkenes and alkynes using the reductive and oxidative quenching of [Ir{dF(CF(3))ppy}(2)(dtbbpy)]PF(6) and [Ru(bpy)(3)]Cl(2) is presented. Initial investigations indicated that the oxidative quenching of photocatalysts could effectively be utilized for ATRA, and since that report, the protocol has been expanded by broadening the scope of the reaction in terms of the photocatalysts, substrates, and solvents. In addition, further modifications of the reaction conditions allowed for the efficient ATRA of perfluoroalkyl iodides onto alkenes and alkynes utilizing the reductive quenching cycle of [Ru(bpy)(3)]Cl(2) with sodium ascorbate as the sacrificial electron donor. These results signify the complementary nature of the oxidative and reductive quenching pathways of photocatalysts and the ability to predictably direct reaction outcome through modification of the reaction conditions.

Cu(dap)2Cl] As an Efficient Visible‐Light‐Driven Photoredox Catalyst in Carbon–Carbon Bond‐Forming Reactions

Copper sees the light of day: [Cu(dap)(2)Cl] proved to be an excellent photoredox catalyst for atom-transfer radical addition reactions, as well as for allylation reactions (see scheme), providing an attractive alternative to commonly used iridium- and ruthenium-based catalysts.

Synthesis of Functionalized Polytriazoles via One‐Pot Sequential Copper‐Catalyzed Azide–Alkyne [3+2] Cycloaddition and Atom Transfer Radical Addition (ATRA)

AbstractAs a continuing effort of expanding the scope of catalyst regeneration in the presence of environmentally benign reducing agents, one‐pot sequential azide–alkyne [3+2] cycloaddition and atom transfer radical addition (ATRA) reactions were performed via in situ reduction of copper(II) by ascorbic acid. The formation of functionalized triazoles was achieved utilizing a ligand‐free catalytic system for the cycloaddition between tripropargylamine and vinylbenzyl azide and subsequent addition of tris(2‐pyridyl)methylamine (TPMA) ligand in the ATRA step. With this strategy, reactions with carbon tetrachloride and carbon tetrabromide proceeded efficiently providing the desired triazoles in nearly quantitative yields (>90 %) using 10 mol % of copper. Sequential azide–alkyne [3+2] cycloaddition and ATRA reactions were also extended to less active alkyl halides such as methyl trichloroacetate, methyl dichloroacetate and dichloroacetonitrile. The corresponding products were obtained in modest yields (50–80 %). The presented methodology enables efficient synthesis of functionalized polytriazoles, which could have a potential use as chelating agents for a variety of transition metals.

Atom transfer radical addition (ATRA) of carbon tetrachloride and chlorinated esters to various olefins catalyzed by Cp′Ru(PPh3)(PR3)Cl complexes

Cp∗Ru(PPh3)(PR3)Cl complexes, where PR3=PMe3, PPh3, or PTA (PTA=1,3,5-triaza-7-phosphaadamantane), were used to catalyze the atom transfer radical addition of chlorinated esters (CCl3CO2Et, CH2ClCO2Et) to styrene, and that of CCl4 to a variety of olefins. The monoadducts were obtained in moderate to excellent yields. Moreover, high selectivities were obtained for the addition of CCl4 to internal olefins. The activity of Cp∗Ru(PTA)(PPh3)Cl and Cp∗Ru(PTA)(PMe3)Cl were comparable to that of the highly efficient ATRA catalyst, Cp∗Ru(PPh3)2Cl. The addition of CCl3CO2Et to styrene catalyzed by Cp′Ru(PPh3)(PR3)Cl (Cp′=Dp, Ind, Cp, Tp) are also reported here. Two new compounds, 3-chloro-3-phenyl-2-(trichloromethyl)-1-phenylpropan-1-one and 1,3,3,3-tetrachloro-1,2-diphenylpropane, resulting from the addition of CCl4 to chalcone and cis-stilbene have been isolated and characterized by NMR spectroscopy and X-ray crystallography.

Ruthenium‐Catalyzed Sequential Enyne Cross‐Metathesis/ATRA Reactions

AbstractSequential enyne cross‐metathesis reactions of arylalkynes with ethylene followed by atom transfer radical addition (ATRA) with ethyl dichloroacetate or dichloroacetonitrile provide 1,5‐dichloropent‐2‐ene derivatives. The second‐generation Grubbs alkylidene complex [RuCl2(=CHPh)(PCy3)(NHC)] [NHC = 1,3‐bis(2,4,6‐trimethylphenyl)‐2‐imidazolidinylidene] is used as the catalyst precursor for both reactions. Preliminary results show that the reaction products can be converted into vinylcyclopropanes by dechlorination with magnesium or manganese.

Modulating the Steric, Electronic, and Catalytic Properties of Cp* Ruthenium Half-Sandwich Complexes with β-Diketiminato Ligands

Five different types of β-diketiminate ligands, bearing electron-donating to strongly electron-withdrawing substituents, were synthesized and used in the synthesis of Cp* ruthenium complexes (Cp* = η5-C5Me5). One series consists of complexes with a covalent RuIII–Cl bond, and the other series features a reduced RuII center, where the chloride is abstracted by treatment of the corresponding RuIII compounds with Zn or Mg. All compounds were characterized by single-crystal X-ray diffraction, UV–visible spectroscopy, and cyclic voltammetry. In the case of RuII complexes, solution NMR techniques provided key information regarding the electronic and structural differences induced by the different β-diketiminate ligands employed. Capitalizing on the facile reduction–oxidation cycle of the Cp* ruthenium β-diketiminato complexes, catalytic atom transfer radical addition (ATRA) and cyclization (ATRC) reactions were performed on relevant substrates. The turnover rates are strongly dependent on the type of β-diketimi...

ChemInform Abstract: Atom Transfer Radical Reactions as a Tool for Olefin Functionalization — On the Way to Practical Applications

AbstractReview: ca. 100 refs.

Structural characterization and investigation of iron(III) complexes with nitrogen and phosphorus based ligands in atom transfer radical addition (ATRA)

The solid state molecular structures of FeIIICl3 complexes with 2,2′-bipyridine, 1,10-phenanthroline, 5-methyl-1,10-phenanthroline, bis(2-pyridylmethyl)amine, tris(2-pyridylmethyl)amine and 1,2-bis(diphenylphosphino)ethane were reported. Most complexes adopted a distorted octahedral geometry, often incorporating coordinated solvent molecules (acetonitrile, methanol or water). Rearrangement involving ligand and/or halide exchange was also observed resulting in the formation of complexes in which the anion commonly contained [FeIIICl4]−. The isolated iron(III) complexes showed moderate activity in the ATRA of carbon tetrachloride to α-olefins in the presence of free-radical diazo initiator (AIBN) and were largely inactive for styrene and methyl acrylate. Furthermore, the activity was relatively independent on the nature and denticity of complexing ligand, and similar to FeIIICl3 in the presence of stoichiometric amounts of tetrabutylammonium chloride. Kinetic results coupled with cyclic voltammetry suggested that [FeIIICl4]− anions could be responsible for catalytic activity in these systems.

ChemInform Abstract: Intermolecular Atom Transfer Radical Addition to Olefins Mediated by Oxidative Quenching of Photoredox Catalysts.

AbstractThe title protocol is characterized by excellent yields, mild conditions, low catalyst loading, and broad scope.

Self-assembly of thermo-responsive poly(oligo(ethylene glycol) methyl ether methacrylate)-C 60 in water-methanol mixtures

Well-defined statistical copolymer of poly (di(ethylene glycol) methyl ether methacrylate–stat-oligo(ethylene glycol) methyl ether methacrylate-C 60 ((PMEO 2MA-stat-POEGMA 300)-C 60) was synthesized via atom transfer radical polymerization (ATRP) reaction and atom transfer radical addition (ATRA) processes. The lower critical solution temperature (LCST) of PMEO 2MA-stat-POEGMA 300 increased from 42 to 95 °C when the amounts of methanol was increased from 0 to 30 vol%, beyond which the LCST could not be quantified. Similarly, the LCST of (PMEO 2MA-stat-POEGMA 300)-C 60 also increased with methanol content, however it was lower than PMEO 2MA- stat-POEGMA 300 for all methanol/water compositions. The CMC of (PMEO 2MA-stat-POEGMA 300)-C 60 increased with increasing methanol content, suggesting that methanol is a better solvent for PMEO 2MA-stat-POEGMA 300 segment. The amphiphilic (PMEO 2MA-stat-POEGMA 300)-C 60 structure formed spherical micelles in water/methanol mixture, and larger micelles were formed at higher methanol content. The hydrodynamic radius (R h) remained constant at temperature below the LCST. It increased dramatically at temperature greater than the LCST, and the (R g/R h) increased from ∼0.75 to ∼1.0. We believe that the (PMEO 2MA- stat-POEGMA 300) coronas dehydrate at higher temperature, and the micelles associate to form larger aggregates. In water/methanol mixtures, core-shell micelles and large compound micelles are produced below and above the LCST respectively.

Atom Transfer Radical Reactions as a Tool for Olefin Functionalization – On the Way to Practical Applications

AbstractTransition‐metal‐catalyzed atom transfer radical reactions of halogenated compounds with olefins constitute a versatile tool in organic synthesis within the area of C–C bond forming transformations. The inter‐ or intramolecular versions, atom transfer radical addition (ATRA) or cyclization (ATRC), respectively, lead to the atom‐economic, useful synthesis of compounds that can be further functionalized. This contribution summarizes the recent developments in this area in terms of catalyst design as well as the applicability of this methodology in sequential, domino, or tandem reactions.

ChemInform Abstract: Copper‐Catalyzed Atom Transfer Radical Addition (ATRA) and Cyclization (ATRC) Reactions in the Presence of Reducing Agents

AbstractReview: 209 refs.

Intermolecular atom transfer radical addition to olefins mediated by oxidative quenching of photoredox catalysts.

Atom transfer radical addition of haloalkanes and α-halocarbonyls to olefins is efficiently performed with the photocatalyst Ir[(dF(CF(3))ppy)(2)(dtbbpy)]PF(6). This protocol is characterized by excellent yields, mild conditions, low catalyst loading, and broad scope. In addition, the atom transfer protocol can be used to quickly and efficiently introduce vinyl trifluoromethyl groups to olefins and access 1,1-cyclopropane diesters.

Mechanistic and Computational Studies of the Atom Transfer Radical Addition of CCl4 to Styrene Catalyzed by Copper Homoscorpionate Complexes

Experimental as well as theoretical studies have been carried out with the aim of elucidating the mechanism of the atom transfer radical addition (ATRA) of styrene and carbon tetrachloride with a Tp(x)Cu(NCMe) complex as the catalyst precursor (Tp(x) = hydrotrispyrazolyl-borate ligand). The studies shown herein demonstrate the effect of different variables in the kinetic behavior. A mechanistic proposal consistent with theoretical and experimental data is presented.