A Polycomponent Metal‐Catalyzed Aliphatic, Allylic, and Benzylic Fluorination

Bloom, Steven; Pitts, Cody Ross; Miller, David C.; Haselton, Nathan; Holl, Maxwell Gargiulo; Urheim, Ellen; Lectka, Thomas

doi:10.1002/ange.201203642

Cited by 69 publications

(17 citation statements)

References 43 publications

(32 reference statements)

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“…A reason may be a lack of studies of substitution reactions by radicals of high electron affinity. While the TEDA 2+• radical dication has been proposed as an intermediate in recently reported aliphatic C–H oxidation methodologies utilizing Selectfluor, 22 - 24 to our knowledge addition of this radical to unsaturated systems has not been investigated. The most commonly employed radicals in a synthetic context are uncharged carbon-, oxygen-, nitrogen-, and halogen-based radicals, which have electron affinities in the range of 0.8–3.6 eV, far below the value for TEDA 2+• (12.44 eV, Figure 3 ).…”

Section: Resultsmentioning

confidence: 99%

Charge-transfer-directed radical substitution enables para-selective C–H functionalization

et al. 2016

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Efficient C–H functionalization requires selectivity for specific C–H bonds. Progress has been made for directed aromatic substitution reactions to achieve ortho- and meta- selectivity, but a general strategy for para-selective C–H functionalization has remained elusive. Herein, we introduce a previously unappreciated concept which enables nearly complete para selectivity. We propose that radicals with high electron affinity elicit areneto-radical charge transfer in the transition state of radical addition, which is the factor primarily responsible for high positional selectivity. We demonstrate that the selectivity is predictable by a simple theoretical tool and show the utility of the concept through a direct synthesis of aryl piperazines. Our results contradict the notion, widely held by organic chemists, that radical aromatic substitution reactions are inherently unselective. The concept of charge transfer directed radical substitution could serve as the basis for the development of new, highly selective C–H functionalization reactions.

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Section: Resultsmentioning

confidence: 99%

Charge-transfer-directed radical substitution enables para-selective C–H functionalization

et al. 2016

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“…Thus, the development of regioselective halogenation by C‐H activation with wide functional‐ and protecting‐group tolerance has far‐reaching consequences. To this end, manganese‐catalyzed chlorination and fluorination by Groves,9 palladium‐catalyzed iodination by Yu,10 biphasic radical‐based halogenation by Schreiner,11 and copper‐catalyzed fluorination by Lectka12 are some noteworthy recent examples.…”

Section: Introductionmentioning

confidence: 99%

Selective Bromination of sp³ CH Bonds by Organophotoredox Catalysis

et al. 2013

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We report that bromination of aliphatic and benzylic sp3 CH bonds can be achieved with visible light photoredox catalysis by using a low loading of Eosin Y disodium salt, an inexpensive organic dye, as a photoredox catalyst. The light source is a low‐power household lamp and the reaction can be performed without the need of an inert atmosphere and anhydrous solvent. Easy‐to‐handle CBr4 is the source of bromine and morpholine is necessary for the reaction. Preliminary experimental and computational studies on the mechanism strongly suggest that an N‐morpholino radical is responsible for the CH activation step. This led us to propose that this is a radical relay reaction, in which a longer‐lived morpholine radical is generated from a CBr3 radical, which is relatively more transient, by a thermodynamically favorable reaction. Additional evidence for the existence of such an N‐radical was obtained from radical trapping experiments. The strong preference of this reaction for electron‐rich hydrogen atoms, and the high sensitivity to the steric environment around the CH bond enables bromination to occur on the relatively stronger CH bond (as quantified by bond dissociation enthalpy) on the same molecule. The potential for utilizing this reaction to achieve mild and regioselective bromination of sp3 CH bonds in complex molecules is exemplified by the bromination of (+)‐sclareolide and acetate‐protected estrone.

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“…Since Subramanian and Manzer reported the CuF 2mediated fluorination of aromatics, [6] copper-catalyzed C À F bond formation has been developed by the groups of Hartwig, Lectka, and others. [7] In contrast, for catalytic CÀF bond activation, copper has been rarely studied. Ribas and coworkers recently showed that a Cu I /Cu III redox cycle activated C À X bonds (X = halogens) using triazamacrocyclic ligand, thus indicating an oxidative addition mechanism.…”

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confidence: 99%

Copper‐Catalyzed Hydrodefluorination of Fluoroarenes by Copper Hydride Intermediates

Cai

Zhang

2013

Angew Chem Int Ed

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A Polycomponent Metal‐Catalyzed Aliphatic, Allylic, and Benzylic Fluorination

Cited by 69 publications

References 43 publications

Charge-transfer-directed radical substitution enables para-selective C–H functionalization

Charge-transfer-directed radical substitution enables para-selective C–H functionalization

Selective Bromination of sp³ CH Bonds by Organophotoredox Catalysis

Copper‐Catalyzed Hydrodefluorination of Fluoroarenes by Copper Hydride Intermediates

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A Polycomponent Metal‐Catalyzed Aliphatic, Allylic, and Benzylic Fluorination

Cited by 69 publications

References 43 publications

Charge-transfer-directed radical substitution enables para-selective C–H functionalization

Charge-transfer-directed radical substitution enables para-selective C–H functionalization

Selective Bromination of sp3 CH Bonds by Organophotoredox Catalysis

Copper‐Catalyzed Hydrodefluorination of Fluoroarenes by Copper Hydride Intermediates

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Selective Bromination of sp³ CH Bonds by Organophotoredox Catalysis