Atom Transfer Radical Cyclization Reactions Research Articles

Photochemically Induced Hydrogen Atom Transfer and Intramolecular Radical Cyclization Reactions with Oxazolones.

Photochemically induced intramolecular hydrogen atom transfer in oxazolones is reported. An acetal or thioacetal function at the side chain acts as a hydrogen donor while the photochemical exited oxazolone is the acceptor. A one-step process─the electron and the proton are simultaneously transferred─is productive, while electron transfer followed by proton transfer is inefficient. Radical combination then takes place, leading to the formation of a C-C or C-N bond. The regioselectivity of the reaction is explained by the diradical/zwitterion dichotomy of radical intermediates at the singlet state. In the present case, the zwitterion structure plays a central role, and intramolecular electron transfer favors spin-orbit coupling and thus the intersystem crossing to the singlet state. The reaction of corresponding thioacetal derivatives is less efficient. In this case, photochemical electron transfer is competitive. The photoproducts resulting from C-C bond formation easily undergo stepwise thermal decarboxylation in which zwitterionic and polar transition states are involved. A computational study of this step has also been performed.

Atom-transfer radical cyclization of α-bromocarboxamides under organophotocatalytic conditions

The atom-transfer radical cyclization (ATRC) reaction gives halogenated heterocycles from the corresponding halocarbonyls that possess a C–C double bond. In contrast, the reductive ATRC reaction gives non-halogenated heterocycles in the presence of a reductant. In this research, we successfully control the ATRC and reductive ATRC reactions of N-allyl-α-haloamides under visible-light irradiation in the presence/absence of the Hantzsch ester as a reductant.

Visible-Light-Promoted Manganese-Catalyzed Atom Transfer Radical Cyclization of Unactivated Alkyl Iodides

An expedient visible-light-promoted atom transfer radical cyclization (ATRC) reaction of unactivated alkyl iodides facilitated by earth-abundant and inexpensive manganese catalysis is described. The practical protocol shows a broad substrate scope and good functional-group tolerance, allowing for the preparation of synthetically valuable alkenyl iodides and diquinanes under simple and mild reaction conditions. Notably, the method provides a net redox-neutral strategy for ATRC reactions that avoids classic hydrogen atom transfer mechanism.

DPPF-Catalyzed Atom-Transfer Radical Cyclization via Allylic Radical.

A general iron-catalyzed strategy for the atom-transfer radical cyclization (ATRC) of allylic halide is reported. Critical to this strategy is the use of DPPF [1,1'-bis(diphenylphosphino)ferrocene] as catalyst, which allows for efficient generation of the allylic radical species via a single-electron transfer (SET) process. The feasibility of achieving ATRC reactions of propargyl chlorides is also demonstrated, which affords products with an exocyclic allene moiety.

Copper Catalyzed Atom Transfer Radical Cyclization Reactions

AbstractAtom transfer radical cyclization (ATRC) is a powerful technique to prepare functionalized 4–10 membered ring systems using transition metal catalysts. In this review recent advances in the use of copper complexes are described. In particular the effect of different ligands on reactivity, selectivity and product outcome are illustrated with application to heterocycle and natural product synthesis. New approaches that increase catalyst efficiency with supplemental reducing agents are reviewed and examples using green solvents, benign reducing agents (e.g. ascorbic acid) and with catalyst loadings as low as 0.05 mol‐% are highlighted. Radical addition to aromatic rings and rearrangement reactions under ATRC conditions as well as application to radical‐polar crossover reactions are also described.

Intermolecular Visible‐Light Photoredox Atom‐Transfer Radical [3+2]‐Cyclization of 2‐(Iodomethyl)cyclopropane‐1,1‐dicarboxylate with Alkenes and Alkynes

Radical chemistry! A visible-light-promoted, tin/boron-free intermolecular [3+2] atom-transfer radical cyclization reaction was developed by using iridium polyphenylpridinyl complex as the sensitizer. 2-(Iodomethyl)cyclopropane-1,1-dicarboxylate reacted with various alkenes and alkynes to form cyclopentane and cyclopentene derivatives.

ChemInform Abstract: Ruthenium‐Catalyzed Atom Transfer Radical Addition Reactions

AbstractReview: 53 refs.

ChemInform Abstract: Halogen and Chalcogen Transfer Chemistry

AbstractReview: 185 refs.

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.

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

AbstractReview: 209 refs.

Photoinitiated ambient temperature copper-catalyzed atom transfer radical addition (ATRA) and cyclization (ATRC) reactions in the presence of free-radical diazo initiator (AIBN)

The use of UV light in copper-catalyzed atom transfer radical addition (ATRA) and cyclization (ATRC) reactions of various (poly)halogenated compounds to highly active alkenes in the presence of AIBN is reported. Radicals generated from photodecomposition of AIBN efficiently regenerated the copper(I) complex at ambient temperature enabling ATRA of CCl(4) and CBr(4) with catalyst loadings as low as 0.05 mol-%. The desired monoadduct was obtained in lower yields in the ATRA of less active halogenated compounds, which was mostly due to incomplete alkene conversions. Ambient temperature ATRA of CCl(4) to various 1,6-dienes followed by sequential ATRC was also performed in the presence of UV light using [Cu(II)(TPMA)Cl][Cl] complex and AIBN. High yields of the 5-exo-trig cyclic product were obtained for all dienes with preferential formation of the cis isomer.

Ruthenium vs. Osmium Complexes as Catalysts for Atom Transfer Radical Addition Reactions

AbstractThe catalytic activity of [Cp*OsBr2(PPh3)] in conjunction with Mg has been evaluated for atom transfer radical addition (ATRA) and cyclization (ATRC) reactions. The Os complex enabled these reactions to be performed with similar efficiency as that of the analogous Ru complex [Cp*RuCl2(PPh3)]. The olefin complex [Cp*OsBr(H2C=CHPh)(PPh3)] was obtained by reduction of [Cp*OsBr2(PPh3)] with Mg in the presence of an excess of styrene, whereas an analogous Ru complex was not observed. Kinetic investigations suggest that olefin complexes of Os can form under catalytic conditions.

ChemInform Abstract: Nucleosides and Nucleotides. Part 188. A One-Pot Method for the Stereoselective Introduction of a Vinyl Group via an Atom-Transfer Radical-Cyclization Reaction with a Diphenylvinylsilyl Group as a Temporary Connecting Tether. Synthesi

ChemInform Abstract: Nucleosides and Nucleotides. Part 188. A One-Pot Method for the Stereoselective Introduction of a Vinyl Group via an Atom-Transfer Radical-Cyclization Reaction with a Diphenylvinylsilyl Group as a Temporary Connecting Tether. Synthesi

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

This article reports on recent advances in the area of catalyst regeneration in copper mediated atom transfer radical addition (ATRA) and cyclization (ATRC) reactions using free‐radical diazo initiators as reducing agents. The role of reducing agent in both processes is to continuously regenerate the activator (copper(I) complex) from the deactivator (copper(II) complex). As a result, single addition adducts in ATRA and ATRC reactions can be synthesized using very low concentrations of copper catalysts (5–100 pm). Previously, efficient catalysis for both processes required as much as several thousands ppm of copper. It is envisioned that the recent developments in this area could have important industrial implications on the synthesis of small organic molecules, natural products and pharmaceutical drugs.

Copper-catalyzed atom transfer radical addition (ATRA) and cyclization (ATRC) reactions in the presence of environmentally benign ascorbic acid as a reducing agent

In recent years, copper-catalyzed atom transfer radical addition (ATRA) has emerged as a viable organic procedure for the formation of carbon-carbon bonds starting from alkyl halides and alkenes. Studies have primarily focused on the use of free-radical initiators to regenerate the copper(I) complex or activator in situ. Although these initiators led to a significant decrease in the amount of metal catalyst, they were much less effective for highly active alkenes that readily undergo free-radical polymerization. In this study, the non-radical reducing agent ascorbic acid (commonly known as Vitamin C) was effectively employed resulting in TONs as high as 15,200 in the homogenous ATRA of polyhalogenated compounds to α-olefins, and enabling selective monoadduct formation for highly active alkenes such as acrylonitrile (TONs as high as 11,800). As low as 7-20 mol% of ascorbic acid relative to substrate was sufficient for all ATRA and ATRC reactions examined. Further, product isolations for all selected syntheses were quite facile and nearly quantitative, requiring only simple liquid-liquid extraction techniques. Reactions in the presence of ascorbic acid were also examined kinetically via (1)H NMR and UV/Vis spectroscopy. A half order rate dependence on reducing agent concentration was observed, but the first order kinetic plots became nonlinear as the concentration of ascorbic acid was increased. Finally, the use of ascorbic acid circumvented otherwise necessary purging techniques, successfully furthering the utility of these reactions in organic synthesis.

Stereoselective Quaternary Center Construction via Atom-Transfer Radical Cyclization Using Silicon Tethers on Acyclic Precursors

A novel strategy for the stereoselective construction of all-carbon quaternary centers on acyclic molecules using a two-step tandem process is reported. The first step involves an intramolecular and stereoselective atom transfer radical cyclization reaction from an allyl or vinyl subunit attached on a silyloxy, serving as a tether, to a tertiary radical alpha to an ester. A subsequent mild acidic elimination leads stereoselectively to a quaternary center bearing an allyl or a vinyl in high yield.

Synthesis, Structure, and Reactivity of the Methoxy-Bridged Dimer [Cp∧Ru(μ-OMe)]2 (Cp∧ = η5-1-Methoxy-2,4-di-tert-butyl-3-neopentylcyclopentadienyl)

The methoxy-bridged RuII complex [Cp∧Ru(μ-OMe)]2 (Cp∧ = η5-1-methoxy-2,4-di-tert-butyl-3-neopentylcyclopentadienyl) was obtained from the RuIII complex [Cp∧RuCl(μ-Cl)]2 by reaction with K2CO3 in methanol. In the presence of EtOH, the complex was converted into the ethoxy-bridged dimer [Cp∧Ru(μ-OEt)]2. Due to the steric demand of the Cp∧ π-ligand, complex [Cp∧Ru(μ-OMe)]2 behaves differently than the parent complex [Cp*Ru(μ-OMe)]2. Reaction with Me3SiCl in the presence of LiCl gave the electronically unsaturated complex [Cp∧Ru(μ-Cl)]2, whereas a tetrameric structure had been reported for the analogous Cp* complex. In contrast to the expected addition reaction, a monomeric complex [Cp∧Ru(CO)2(CO2Me)] was obtained by ligand insertion of CO in the Ru−OMe bond. Moreover, an unprecedented transformation of cyclooctadiene into ethylbenzene in the coordination sphere of Ru was observed. Complex [Cp∧Ru(μ-OMe)]2 was found to act as a highly active catalyst for atom transfer radical cyclization (ATRC) reactions on a diverse range of substrates such as N-substituted dichloro- and trichloroacetamides, enamides, ethers, and esters.

A copper-catalyzed domino radical cyclization route to benzospiro-indolizidinepyrrolidinones

In this Letter the synthesis of benzospiro-indolizidinepyrrolidinones is described by a domino atom transfer radical cyclization reaction using a copper catalyst. The structure of one of the products was established by single crystal X-ray diffraction. The investigated precursors, bearing a homo allyl substituent on the N-indole, result in a 5- exo- trig, followed by a 6- endo- trig cyclization. When the N-indole is substituted with an allyl group, only the spiro-cyclization occurs.

Copper(I)‐Catalyzed Chlorine Atom Transfer Radical Cyclization Reactions of Unsaturated α‐Chloro β‐Keto Esters.

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