Determination of rate constants for trifluoromethyl radical addition to various alkenes via a practical method

Hartmann, Marcel; Li, Y.; Studer, Armido

doi:10.1039/c5ob02210j

Cited by 47 publications

(46 citation statements)

References 28 publications

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“…( k trap =8.1×10 8 m −1 s −1 ) to TEMPO‐CF 3 is the dominant reaction pathway. Kinetic studies revealed rate constants from 0.13 to 11×10 7 m −1 s −1 for k add in such systems. This bifunctionalization strategy was later successfully expanded to radical alkene amidooxygenation with NFSI, to alkene azidooxygenation with the Zhdankin reagent, and to alkene aryloxygenation using either aryldiazonium salts or hypervalent iodine compounds as aryl radical precursors.…”

Section: Metal‐free Processesmentioning

confidence: 95%

The Persistent Radical Effect in Organic Synthesis

2019

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Radical–radical couplings are mostly nearly diffusion‐controlled processes. Therefore, the selective cross‐coupling of two different radicals is challenging and not a synthetically valuable transformation. However, if the radicals have different lifetimes and if they are generated at equal rates, cross‐coupling will become the dominant process. This high cross‐selectivity is based on a kinetic phenomenon called the persistent radical effect (PRE). In this Review, an explanation of the PRE supported by simulations of simple model systems is provided. Radical stabilities are discussed within the context of their lifetimes, and various examples of PRE‐mediated radical–radical couplings in synthesis are summarized. It is shown that the PRE is not restricted to the coupling of a persistent with a transient radical. If one coupling partner is longer‐lived than the other transient radical, the PRE operates and high cross‐selectivity is achieved. This important point expands the scope of PRE‐mediated radical chemistry. The Review is divided into two parts, namely 1) the coupling of persistent or longer‐lived organic radicals and 2) “radical–metal crossover reactions”; here, metal‐centered radical species and more generally longer‐lived transition‐metal complexes that are able to react with radicals are discussed—a field that has flourished recently.

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Section: Metal‐free Processesmentioning

confidence: 95%

The Persistent Radical Effect in Organic Synthesis

2019

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“…14 The TEMPONa mediated CF 3 -radical addition was identified as a tool to estimate such rate constants. 15 If the addition of the CF 3 -radical to the alkene is slow, trapping of the CF 3 -radical by TEMPO that is concomitantly formed in the initial SET step (see Scheme 6) to form TEMPO–CF 3 occurs as a side reaction. The rate constant for trapping of TEMPO by the CF 3 -radical ( k trap = (8.1 ± 0.3) × 10 8 M –1 s –1 ) was determined and used as a radical clock for estimation of all other rate constants (Scheme 7).…”

Section: Trifluoromethylation Via Set Reduction Of the Togni Reagentmentioning

confidence: 99%

“…Product ratio of TEMPO trapping versus trifluoromethylaminoxylation was used to calculate the rate constant k add for CF 3 -radical addition according to eq 1. 15 CF 3 -radical addition to styrene and its derivatives is fast and lies in the order of 10 7 to 10 8 M –1 s –1 . Additions proceed faster for electron-rich styrene derivatives and steric effects play a role.…”

Section: Trifluoromethylation Via Set Reduction Of the Togni Reagentmentioning

confidence: 99%

Iodine(III) Reagents in Radical Chemistry

2017

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ConspectusThe chemistry of hypervalent iodine(III) compounds has gained great interest over the past 30 years. Hypervalent iodine(III) compounds show valuable ionic reactivity due to their high electrophilicity but also express radical reactivity as single electron oxidants for carbon and heteroatom radical generation. Looking at ionic chemistry, these iodine(III) reagents can act as electrophiles to efficiently construct C–CF3, X–CF3 (X = heteroatom), C–Rf (Rf = perfluoroalkyl), X–Rf, C–N3, C–CN, S–CN, and C–X bonds. In some cases, a Lewis or a Bronsted acid is necessary to increase their electrophilicity. In these transformations, the iodine(III) compounds react as formal “CF3+”, “Rf+”, “N3+”, “Ar+”, “CN+”, and “X+” equivalents. On the other hand, one electron reduction of the I(III) reagents opens the door to the radical world, which is the topic of this Account that focuses on radical reactivity of hypervalent iodine(III) compounds such as the Togni reagent, Zhdankin reagent, diaryliodonium salts, aryliodonium ylides, aryl(cyano)iodonium triflates, and aryl(perfluoroalkyl)iodonium triflates. Radical generation starting with I(III) reagents can also occur via thermal or light mediated homolysis of the weak hypervalent bond in such reagents. This reactivity can be used for alkane C–H functionalization. We will address important pioneering work in the area but will mainly focus on studies that have been conducted by our group over the last 5 years.We entered the field by investigating transition metal free single electron reduction of Togni type reagents using the readily available sodium 2,2,6,6-tetramethylpiperidine-1-oxyl salt (TEMPONa) as an organic one electron reductant for clean generation of the trifluoromethyl radical and perfluoroalkyl radicals. That valuable approach was later successfully also applied to the generation of azidyl and aryl radicals starting with the corresponding benziodoxole (Zhdankin reagent) and iodonium salts. In the presence of alkenes as radical acceptors, vicinal trifluoromethyl-, azido-, and arylaminoxylation products result via a sequence comprising radical addition to the alkene and subsequent TEMPO trapping. Electron-rich arenes also react with I(III) reagents via single electron transfer (SET) to give arene radical cations, which can then engage in arylation reactions. We also recognized that the isonitrile functionality in aryl isonitriles is a highly efficient perfluoroalkyl radical acceptor, and reaction of Rf-benziodoxoles (Togni type reagents) in the presence of a radical initiator provides various perfluoroalkylated N-heterocycles (indoles, phenanthridines, quinolines, etc.). We further found that aryliodonium ylides, previously used as carbene precursors in metal-mediated cyclopropanation reactions, react via SET reduction with TEMPONa to the corresponding aryl radicals. As a drawback of all these transformations, we realized that only one ligand of the iodine(III) reagent gets transferred to the substrate. To further increase atom-economy of such conversions, we ide...

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“…[28] Agood result was obtained for the reaction of ethyl iododifluoroacetate with 3a to give quinoxaline 5am (74 %). [28] Agood result was obtained for the reaction of ethyl iododifluoroacetate with 3a to give quinoxaline 5am (74 %).…”

mentioning

confidence: 99%

Iodinated (Perfluoro)alkyl Quinoxalines by Atom Transfer Radical Addition Using ortho‐Diisocyanoarenes as Radical Acceptors

Leifert

Studer

2016

Angew Chem Int Ed

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A simple method for the preparation of functionalized quinoxalines is reported. Starting from readily accessible ortho-diisocyanoarenes and (perfluoro)alkyl iodides, the quinoxaline core is constructed during (perfluoro)alkylation by atom transfer radical addition (ATRA), resulting in 2-iodo-3-(perfluoro)alkylquinoxalines. The radical cascades are readily initiated either with visible light or by using α,α'-azobisisobutyronitrile (AIBN). The heteroarene products are obtained in high yields (up to 94 %), and the method can be readily scaled up. Useful follow-up chemistry documents the value of the novel radical quinoxaline synthesis.

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Determination of rate constants for trifluoromethyl radical addition to various alkenes via a practical method

Cited by 47 publications

References 28 publications

The Persistent Radical Effect in Organic Synthesis

The Persistent Radical Effect in Organic Synthesis

Iodine(III) Reagents in Radical Chemistry

Iodinated (Perfluoro)alkyl Quinoxalines by Atom Transfer Radical Addition Using ortho‐Diisocyanoarenes as Radical Acceptors

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