Radical–anion coupling through reagent design: hydroxylation of aryl halides

Greener, Andrew J.; Ubysz, Patrycja; Owens-Ward, Will; Smith, George W.; Ocaña, Ivan; Whitwood, Adrian C.; Chechik, Victor; James, Michael J.

doi:10.1039/d1sc04748e

Cited by 13 publications

(17 citation statements)

References 63 publications

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“…[12b,c] Because the intermediate containing the (2c,3e) half-bond has a much higher reduction potential than other species present in the reaction, it can be selectively oxidized by a relatively mild oxidant, for example, molecular oxygen. Additional examples of redox chains mediated by highly reducing upconverted radical anion intermediates continue to appear, for example, a photochemical thiol-yne click reaction reported by Ananikov et al, [15] hydroxylation reaction of aryl halides with oximes by James et al [16] and a number of other transformations. [17] Recently, Jui and co-workers have demonstrated a facile transformation of formate into upconverted CO 2 *À species (a traditionally challenging reductant to make, E 1/2 = À 2.2 V vs. SCE) capable of reducing a broad range of substrates.…”

Section: Introductionmentioning

confidence: 99%

Two Paths to Oxidative C−H Amination Under Basic Conditions: A Theoretical Case Study Reveals Hidden Opportunities Provided by Electron Upconversion**

Eckhardt

Elliott

Alabugin

et al. 2022

Chemistry A European J

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Traditionally, cross-dehydrogenative coupling (CDC) leads to CÀ N bond formation under basic and oxidative conditions and is proposed to proceed via a two-electron bond formation mediated by carbenium ions. However, the formation of such high-energy intermediates is only possible in the presence of strong oxidants, which may lead to undesired side reactions and poor functional group tolerance. In this work we explore if oxidation under basic conditions allows the formation of three-electron bonds (resulting in "upconverted" highly-reducing radical-anions). The benefit of this "upconversion" process is in the ability to use milder oxidants (e. g., O 2 ) and to avoid high-energy intermediates. Comparison of the two-and three-electron pathways using quantum mechanical calculations reveals that not only does the absence of a strong oxidant shut down two-electron pathways in favor of a three-electron path but, paradoxically, weaker oxidants react faster with the upconverted reductants by avoiding the inverted Marcus region for electron transfer.

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Section: Introductionmentioning

confidence: 99%

Two Paths to Oxidative C−H Amination Under Basic Conditions: A Theoretical Case Study Reveals Hidden Opportunities Provided by Electron Upconversion**

Eckhardt

Elliott

Alabugin

et al. 2022

Chemistry A European J

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“…been debated, with several radical-based alternatives proposed. [9] Inspired by this work, and our recent study, [10,11] in which we postulated that oxime anion 4 can substitute aryl halides 5 through an electron-catalysed radical-nucleophilic substitution (S RN 1) chain mechanism (Scheme 1c), [12,13] we sought to determine if a general denitrative hydroxylation protocol using our designed reagent could be realised. We rationalised that a broad range nitroarenes may also be substituted by an S RN 1 mechanism if aryl radicals can be formed via the fragmentation of nitroarene radical-anions.…”

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confidence: 99%

Denitrative Hydroxylation of Unactivated Nitroarenes**

Duff

Meakin

Richardson

et al. 2023

Chemistry A European J

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A one-step method for the conversion of nitroarenes into phenols under operationally simple, transitionmetal-free conditions is described. This denitrative functionalization protocol provides a concise and economical alterna-tive to conventional three-step synthetic sequences. Experimental and computational studies suggest that nitroarenes may be substituted by an electron-catalysed radical-nucleophilic substitution (S RN 1) chain mechanism.Nitroarenes are easily prepared, abundant chemical feedstocks, and privileged synthetic intermediates in organic chemistry. [1,2] The nitro group can be converted into a large variety of functional groups through a well-established three-step sequence consisting of (1) reduction, (2) diazotization and (3) substitution through Sandmeyer-type reactions (Scheme 1a). [3] Whilst generally reliable, this approach requires multiple synthetic steps, typically involving harsh reaction conditions and the handling of hazardous intermediates. The development of more efficient, single-step denitrative functionalization reactions is therefore an area of significant synthetic value and interest. [4,5] In this regard, direct nucleophilic substitution is an attractive synthetic approach due to its low cost and operational simplicity. [6] However, these methods are typically limited to electron-deficient (activated) nitroarenes bearing strong electron-withdrawing groups in the ortho or para positions. [7] Methods which can overcome this limitation are known, but are rare and of limited scope. For example, Snyder and co-workers reported that unactivated nitroarene 1 could be substituted with oxime anion 2 to form phenol 3 in 20 % yield (Scheme 1b). [8] This denitrative hydroxylation reaction was proposed to proceed via a stepwise addition-elimination nucleophilic aromatic substitution (S N Ar) mechanism (followed by the elimination of an O-aryl oxime intermediate to form phenol 3). However, the mechanism of this reaction -along with many such denitrative substitution reactions -has long [a

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“…[74b] Both secondary and tertiary amides (134) bearing diverse functional groups were obtained in moderate to good yields. Additionally, the authors demonstrated a one-pot procedure to obtain amides directly from aldehydes (133), amines and TMSCN via in situ generation of α-aminonitriles (132). Radical scavenging experiments indicated that an anionic pathway was involved in the CÀ CN bond cleavage process.…”

Section: Amidation Applying New Alternative Strategiesmentioning

confidence: 99%

Recent Advances in Carbon‐Nitrogen/Carbon‐Oxygen Bond Formation Under Transition‐Metal‐Free Conditions

Zhang

Song

Shi

et al. 2023

The Chemical Record

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Carbon‐heteroatom bond formation under transition‐metal free conditions provides a powerful synthetic alternative for the efficient synthesis of valuable molecules. In particular, C−N and C−O bonds are two important types of carbon‐heteroatom bonds. Thus, continuous efforts have been deployed to develop novel C−N/C−O bond formation methodologies involving various catalysts or promoters under TM‐free conditions, which enables the synthesis of various functional molecules comprising C−N/C−O bonds in a facile and sustainable manner. Considering the significance of C−N/C−O bond construction in organic synthesis and materials science, this review aims to comprehensively present selected examples on the construction of C−N (including amination and amidation) and C−O (including etherification and hydroxylation) bonds without transition metals. Besides, the involved promoters/catalysts, substrate scope, potential application and possible reaction mechanisms are also systematically discussed.

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Radical–anion coupling through reagent design: hydroxylation of aryl halides

Abstract: The design and development of an oxime-based hydroxylation reagent, which can chemoselectively convert aryl halides (X = F, Cl, Br, I) into phenols under operationally simple, transition-metal-free conditions is described....

Cited by 13 publications

References 63 publications

Two Paths to Oxidative C−H Amination Under Basic Conditions: A Theoretical Case Study Reveals Hidden Opportunities Provided by Electron Upconversion**

Two Paths to Oxidative C−H Amination Under Basic Conditions: A Theoretical Case Study Reveals Hidden Opportunities Provided by Electron Upconversion**

Denitrative Hydroxylation of Unactivated Nitroarenes**

Recent Advances in Carbon‐Nitrogen/Carbon‐Oxygen Bond Formation Under Transition‐Metal‐Free Conditions

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