Remote Hydroxylation through Radical Translocation and Polar Crossover

Hollister, Kyle A.; Conner, Elizabeth S.; Spell, Mark L.; Deveaux, Kristina; Maneval, Léa; Beal, Michael W.; Ragains, Justin R.

doi:10.1002/ange.201500880

Cited by 21 publications

(1 citation statement)

References 78 publications

(31 reference statements)

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“…An examination of various electron-donating and electron-withdrawing groups on the phenyl ring found higher yields for electron-donating functionality, potentially due to the ability to better stabilize a benzylic carbocation, and thus a more facile RPC oxidation (21)(22)(23)(24)(25)(26)(27). The formal hydride abstraction was not deterred by meta (28,29) or ortho (30) substitution. Excellent yields were obtained at the benzylic position of fused 5-and 6-membered rings (31,32).…”

Section: Reaction Designmentioning

confidence: 99%

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

Zhang

Na²,

Das³

et al. 2021

Preprint

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While a great number of C–H functionalization methods have been developed in recent years, new mechanistic paradigms to deconstruct such bonds have been comparatively rare. Amongst possible strategies for breaking a Csp3–H bond are deprotonation, oxidative addition with a metal catalyst, direct insertion via a nitrene intermediate, hydrogen atom transfer (HAT) with both organic and metal-based abstractors, and lastly, hydride abstraction. The latter is a relatively unexplored approach due to the unfavorable thermodynamics of such an event, and thus has not been developed as a general way to target both activated and unactivated Csp3–H bonds on hydrocarbon substrates. Herein, we report our successful efforts in establishing a catalytic C–H functionalization manifold for accessing an intermediate carbocation by formally abstracting hydride from unactivated Csp3–H bonds. The novel catalytic design relies on a stepwise strategy driven by visible light photoredox catalysis and is demonstrated in the context of a C–H fluorination employing nucleophilic fluorine sources. Difluorination of methylene groups is also demonstrated, and represents the first C–H difluorination with nucleophilic fluoride. Additionally, the formal hydride abstraction is shown to be amenable to several other classes of nucleophiles, allowing for the construction of C–C or C–heteroatom bonds.

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Section: Reaction Designmentioning

confidence: 99%

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

Zhang

Na²,

Das³

et al. 2021

Preprint

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Iminyl Radical‐Mediated Controlled Hydroxyalkylation of Remote C(sp³)‐H Bond via Tandem 1,5‐HAT and Difunctionalization of Aryl Alkenes

Guo

et al. 2018

Adv Synth Catal

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A visible-light mediated g-hydroxyalkylation of ketones via C(sp 3 )-H functionalization has been developed under redox neutral conditions. This protocol relies on the iminyl radical-triggered 1,5-HAT followed by oxyalkylation of alkenes, wherein CÀC and CÀO bonds were constructed in one step. This three-component reaction features mild conditions, wide substrate scope and excellent functional group tolerance, thus providing a facile and highly efficient access to complex valuable ketones.

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Metal‐Free C(sp³)‐O Bond Formation through Radical Translocation: A Mild, Efficient, and Practical Approach to α‐Alkoxybenzamides

et al. 2015

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Am ild and metal-free method to functionalize aliphatic CÀHb onds adjacent to an itrogen atom through radical translocation, oxidation to an iminium intermediate, and nucleophilic trapping with alcohols is described. The transformation proceeds efficiently with edible ascorbic acid (vitamin C) as the radical initiator andr eadily available tert-butyl nitrite as the nitrosating reagent. Notably,a ny transition-metal or additive is not required. The current methodp rovides simple, efficient, and practical access to valuable a-alkoxybenzamides in moderatet o good yields.Scheme1.Strategies for the preparation of a-substituted benzamides through radical translocation. AIBN = azobisisobutyronitrile;E WG = electronwithdrawing group.

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Remote Hydroxylation through Radical Translocation and Polar Crossover

Cited by 21 publications

References 78 publications

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

Iminyl Radical‐Mediated Controlled Hydroxyalkylation of Remote C(sp³)‐H Bond via Tandem 1,5‐HAT and Difunctionalization of Aryl Alkenes

Metal‐Free C(sp³)‐O Bond Formation through Radical Translocation: A Mild, Efficient, and Practical Approach to α‐Alkoxybenzamides

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Remote Hydroxylation through Radical Translocation and Polar Crossover

Cited by 21 publications

References 78 publications

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

A Photoredox-Catalyzed Approach for Formal Hydride Abstraction to Enable Csp3–H Functionalization with Nucleophilic Partners

Iminyl Radical‐Mediated Controlled Hydroxyalkylation of Remote C(sp3)‐H Bond via Tandem 1,5‐HAT and Difunctionalization of Aryl Alkenes

Metal‐Free C(sp3)‐O Bond Formation through Radical Translocation: A Mild, Efficient, and Practical Approach to α‐Alkoxybenzamides

Contact Info

Product

Resources

About

Iminyl Radical‐Mediated Controlled Hydroxyalkylation of Remote C(sp³)‐H Bond via Tandem 1,5‐HAT and Difunctionalization of Aryl Alkenes

Metal‐Free C(sp³)‐O Bond Formation through Radical Translocation: A Mild, Efficient, and Practical Approach to α‐Alkoxybenzamides