Oxime radicals: generation, properties and application in organic synthesis

Krylov, Igor B.; Paveliev, Stanislav A.; Budnikov, Alexander S.; Terent’ev, Alexander O.

doi:10.3762/bjoc.16.107

Cited by 43 publications

(39 citation statements)

References 155 publications

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“…However, none of them catalyzed the HAT of bibenzyl. We surmise the lack of reactivity is partly due to a mismatch of BDEs between the C−H bonds of bibenzyl and the NO−H bond of the radical precursors, [45] and kinetic effects such as the electrophilicity of the N ‐oxyl radical and the transition state configuration of HAT may also play a role.…”

Section: Resultsmentioning

confidence: 94%

Electrochemical Activation of C−C Bonds through Mediated Hydrogen Atom Transfer Reactions

et al. 2022

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Activating inert sp 3 -sp 3 carbon-carbon (CÀ C) bonds remains a major bottleneck in the chemical upcycling of recalcitrant polyolefin waste. In this study, redox mediators are used to activate the inert CÀ C bonds. Specifically, N-hydroxyphthalimide (NHPI) is used as the redox mediator, which is oxidized to phthalimide-N-oxyl (PINO) radical to initiate hydrogen atom transfer (HAT) reactions with benzylic CÀ H bonds. The resulting carbon radical is readily captured by molecular oxygen to form a peroxide that decomposes into oxygenated CÀ C bond-scission fragments. This indirect approach reduces the oxidation potential by > 1.2 V compared to the direct oxidation of the substrate. Studies with model compounds reveal that the selectivity of CÀ C bond cleavage increases with decreasing CÀ C bond dissociation energy. With NHPI-mediated oxidation, oligomeric styrene (OS 510 ; M n = 510 Da) and polystyrene (PS; M n � 10 000 Da) are converted into oxygenated monomers, dimers, and oligomers.

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Section: Resultsmentioning

confidence: 94%

Electrochemical Activation of C−C Bonds through Mediated Hydrogen Atom Transfer Reactions

et al. 2022

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“…However, none of them catalyzed the HAT of bibenzyl. We surmise the lack of reactivity is partly due to a mismatch of BDEs between the C-H bonds of bibenzyl and the NO-H bond of the radical precursors, 41 although steric effects may also play a role.…”

Section: Resultsmentioning

confidence: 91%

Breaking C–C Bonds via Electrochemically Mediated Hydrogen Atom Transfer Reactions

Yan¹,

Shi²,

Beckham³

et al. 2021

Preprint

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Cleaving inert sp3-sp3 carbon-carbon (C-C) bonds selectively remains a major challenge in organic chemistry and a main bottleneck in the chemical upcycling of recalcitrant polyolefin waste. Here, we present an electrochemical strategy using redox mediators to activate and break C-C bonds at room temperature and ambient pressure. Specifically, we use N-hydroxyphthalimide (NHPI) as a redox mediator that undergoes electrochemical oxidation to form the <a>phthalimide-N-oxyl (PINO) radical </a>to initiate hydrogen atom transfer (HAT) reactions with benzylic C-H bonds. The resulting benzylic carbon radical is readily captured by molecular oxygen to form a peroxy radical that decomposes into oxygenated C-C bond-scission fragments. This indirect, mediated approach for Csp3-Csp3 bond cleavage reduces the oxidation potential by > 1.2 V compared to the direct oxidation of the substrate, thereby eliminating deleterious side reactions, such as solvent oxidation, that may occur at high potentials. Studies with a bibenzyl model compound revealed a bifurcated reaction pathway following the initial HAT step. At a bibenzyl conversion of 61.0%, the C-C bond cleavage pathway generates benzaldehyde and benzoic acid products at 38.4% selectivity, and the C-H bond oxygenation pathway leads to 1,2-diphenylethanone and benzil products at 39.2% selectivity. Changes in reaction selectivity were investigated with various model compounds, including bibenzyl, 1,3-diphenylpropane, 1,4-diphenylbutane, and their derivatives. Product selectivity is correlated with the C-C bond strength of the reactant, with weaker C-C bonds favoring the C-C bond cleavage pathway. We also evaluated the mediated oxidation of oligomeric styrene (Mn = 510 Da, OS510) which were converted into oxygenated products. Lastly, proof-of-concept depolymerization of polystyrene (PS, ~10,000 Da) into oxygenated monomers, dimers, and oligomers was demonstrated using NHPI-mediated oxidation.

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“…78 We are also interested in properties and reactivity of iminoxyl radicals, an alternative group of persistent N-oxyl radicals unexplored in SPM. 79 Mendenhall and coworkers reported a conjugation reaction between p-cresol and di-tert-butyl iminoxyl radical, which was generated in situ via one-electron oxidation of oxime 1e with ceric ammonium nitrate (CAN; Figure 2a). 80 Based on this report and our research experiences, we began to develop a novel SPM platform using iminoxyl radicals at the Tyr phenol.…”

Section: Optimization Of Tyr-selective Modification Withmentioning

confidence: 99%

Protein Modification at Tyrosine with Iminoxyl Radicals

et al. 2021

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Post-translational modifications (PTMs) of proteins are a biological mechanism for reversibly controlling protein function. Synthetic protein modifications (SPMs) at specific canonical amino acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes; isopropyl methyl piperidinium oxime 1f formed stable adducts, whereas the reaction of tert-butyl methyl piperidinium oxime 1o was reversible. The difference in reversibility between 1f and 1o, differentiated only by one methyl group, is due to the stability of iminoxyl radicals, which is partly dictated by the bond dissociation energy of oxime O-H groups. The Tyr-selective modifications with 1f and 1o proceeded under physiologicallyrelevant, mild conditions. Specifically, the stable Tyr-modification with 1f introduced functional small molecules, including an azobenzene photoswitch, to proteins, whereas the reversible modification of Tyr with 1o switched protein function on and off in an enzyme and in a monoclonal antibody by modification and deconjugation processes. ASSOCIATED CONTENTSupporting Information. Experimental procedures, characterization data, computational procedure, and data. The Supporting Information is available free of charge at https://pubs.acs.org.

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Oxime radicals: generation, properties and application in organic synthesis

Cited by 43 publications

References 155 publications

Electrochemical Activation of C−C Bonds through Mediated Hydrogen Atom Transfer Reactions

Electrochemical Activation of C−C Bonds through Mediated Hydrogen Atom Transfer Reactions

Breaking C–C Bonds via Electrochemically Mediated Hydrogen Atom Transfer Reactions

Protein Modification at Tyrosine with Iminoxyl Radicals

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