Generation Of Alkoxyl Radicals Research Articles

Photocatalytic α‐Difluoroalkoxyketones Synthesis via Radical Intermolecular Alkoxylation of Difluoroenol Silyl Ethers

AbstractWe present a metal‐free photocatalytic approach for the synthesis of difluoroalkoxylatedketones. This strategy involves the generation of alkoxyl radicals from pyridinium salts upon the activity of a catalytic electron‐donor‐acceptor (EDA) complex. This mild process tolerates several functional groups and can be scaled up to gram scale. Diverse products manipulations accounts for the versatility of the obtained fluorinated products, highlighting the synthetic usefulness of this method.

Zn-Mediated Fragmentation of N-Alkoxyphthalimides Enabling the Synthesis of gem-Difluoroalkenes.

Zn-mediated generation of alkoxyl radicals from N-alkoxyphthalimides emerged as an efficient approach for forming diverse and valuable alkyl radicals through β-scission or a hydrogen atom transfer process. The alkyl radical species can be further trapped by α-trifluoromethyl alkenes to construct a series of gem-difluoroalkenes.

Density Functional Theory Calculations Decipher Complex Reaction Pathways of 6:2 Fluorotelomer Sulfonate to Perfluoroalkyl Carboxylates Initiated by Hydroxyl Radical.

6:2 Fluorotelomer sulfonate (6:2 FTSA) is a ubiquitous environmental contaminant belonging to the family of per- and polyfluoroalkyl substances. Previous studies showed that hydroxyl radical (•OH) efficiently transforms 6:2 FTSA into perfluoroalkyl carboxylates (PFCAs) of different chain lengths (C2-C7), yet the reaction mechanisms were not elucidated. This study used density functional theory (DFT) calculations to map the entire reaction path of 6:2 FTSA initiated by •OH and experimentally verified the theoretical results. Optimal reaction pathways were obtained by comparing the rate constants calculated from the transition-state theory. We found that 6:2 FTSA was first transformed to C7 PFCA and C6F13•; C6F13• was then further reacted to C2-C6 PFCAs. The parallel addition of •OH and O2 to CnF2n+1• was essential to producing C2-C6 PFCAs. The critical step is the generation of alkoxyl radicals, which withdraw electrons from the adjacent C-C groups to result in chain cleavage. The validity of the calculated optimal reaction pathways was further confirmed by the consistency with our experimental data in the aspects of O2 involvement, identified intermediates, and the final PFCA profile. This study provides valuable insight into the transformation of polyfluoroalkyl substances containing aliphatic carbons in •OH-based oxidation processes.

Tuning the reactivity of alkoxyl radicals from 1,5-hydrogen atom transfer to 1,2-silyl transfer

Controlling the reactivity of reactive intermediates is essential to achieve selective transformations. Due to the facile 1,5-hydrogen atom transfer (HAT), alkoxyl radicals have been proven to be important synthetic intermediates for the δ-functionalization of alcohols. Herein, we disclose a strategy to inhibit 1,5-HAT by introducing a silyl group into the α-position of alkoxyl radicals. The efficient radical 1,2-silyl transfer (SiT) allows us to make various α-functionalized products from alcohol substrates. Compared with the direct generation of α-carbon radicals from oxidation of α-C-H bond of alcohols, the 1,2-SiT strategy distinguishes itself by the generation of alkoxyl radicals, the tolerance of many functional groups, such as intramolecular hydroxyl groups and C-H bonds next to oxygen atoms, and the use of silyl alcohols as limiting reagents.

Selective C-C Bond Scission of Ketones via Visible-Light-Mediated Cerium Catalysis

Summary Here, we report a general catalytic manifold for the selective C–C bond scission of ketones via the exploitation of the ligand-to-metal charge transfer (LMCT) excitation mode. Through a cooperative utilization of Lewis acid catalysis and LMCT catalysis, the C–C bond of ketones could be selectively and effectively cleaved, enabling the installation of different functionalities at each carbon of the cleaved C–C bond through a sequential and orthogonal manner. This reaction manifold serves as a photocatalytic alternative to the Norrish type I reaction with the combination of visible light and inexpensive cerium salts. Under operationally simple conditions, a wide range of acyclic and cyclic ketones, from simple strained cyclobutanones to complex androsterone with less strained cyclopentanone moiety, could be successfully transformed into versatile chemical building blocks.

Remote C(sp3 )-H Arylation and Vinylation of N-Alkoxypyridinium Salts to δ-Aryl and δ-Vinyl Alcohols.

The reaction of readily available and bench-stable N-alkoxypyridinium salts with arylboronic and vinylboronic acids afforded δ-aryl and δ-vinyl alcohols, respectively, in the presence of fac-Ir(ppy)3 and Cu(OTf)2 dual catalysts. The reaction takes place through a domino process involving the reductive generation of alkoxyl radicals, 1,5-hydrogen atom transfer (1,5-HAT) and the copper-catalyzed cross-coupling reaction of the resulting translocated carbon radicals with boronic acids. Complementary to the Minisci reaction, this method allows for the arylation of nucleophilic alkyl radicals with both electron-rich and electron-poor arenes under mild reaction conditions.

Synergistic CO2 Mediation and Photocatalysis for α-Alkylation of Primary Aliphatic Amines

Recent work published by Rovis, Schoenebeck, and co-workers in Nature Chemistry describes a synergistic CO2 mediation and photocatalysis strategy for challenging α-alkylation of primary aliphatic amines by using quinuclidine as a hydrogen atom transfer (HAT) catalyst for γ-lactam synthesis. Electrostatic attraction between the in-situ-generated carbamate and quinuclidinium radical cation is critical for the selectivity.

Tertiary-Alcohol-Directed Functionalization of Remote C(sp3 )-H Bonds by Sequential Hydrogen Atom and Heteroaryl Migrations.

Reported for the first time is a tertiary-alcohol-guided heteroarylation of remote C(sp3 )-H bonds. The mild and direct generation of alkoxyl radicals from alcohols is enabled by visible-light photocatalysis. A remote hydrogen atom and heteroaryl migration sequence are involved in the reaction. Many sensitive groups remain intact in the reaction, thus illustrating wide functional-group compatibility. This protocol provides a practical strategy for the late-stage modification of alkyl ketones.

Visible-light-induced alkoxyl radical generation for inert chemical bond cleavage/functionalization.

Inert chemical bond cleavage and functionalization reactions provide expedient synthetic routes and are fundamental in organic synthesis. Alkoxyl radicals enable inert chemical bond cleavages by hydrogen atom transfer and β-fragmentation reactivity; however their further synthetic transformations and functional group compatibility are limited by traditional alkoxyl radical generation methods. Recently, visible-light-induced alkoxyl radical generation methods have emerged and led to new advancements in inert chemical bond cleavage reactions and subsequent functionalization, with excellent chemoselectivity and functional group compatibility. In this Feature Article, the generation of alkoxyl radicals by different visible-light-induced methods and their common or distinct reactivity are discussed, which are categorized by C(sp3)-H, C(sp3)-C(sp3), and C(sp3)-X bond cleavages and subsequent transformations.

Donor–Acceptor Complex Enables Alkoxyl Radical Generation for Metal‐Free C(sp3)–C(sp3) Cleavage and Allylation/Alkenylation

AbstractThe alkoxyl radical is an essential and prevalent reactive intermediate for chemical and biological studies. Here we report the first donor–acceptor complex‐enabled alkoxyl radical generation under metal‐free reaction conditions induced by visible light. Hantzsch ester forms the key donor–acceptor complex with N‐alkoxyl derivatives, which is elucidated by a series of spectrometry and mechanistic experiments. Selective C(sp3)‐C(sp3) bond cleavage and allylation/alkenylation is demonstrated for the first time using this photocatalyst‐free approach with linear primary, secondary, and tertiary alkoxyl radicals.

Donor-Acceptor Complex Enables Alkoxyl Radical Generation for Metal-Free C(sp3 )-C(sp3 ) Cleavage and Allylation/Alkenylation.

The alkoxyl radical is an essential and prevalent reactive intermediate for chemical and biological studies. Here we report the first donor-acceptor complex-enabled alkoxyl radical generation under metal-free reaction conditions induced by visible light. Hantzsch ester forms the key donor-acceptor complex with N-alkoxyl derivatives, which is elucidated by a series of spectrometry and mechanistic experiments. Selective C(sp3 )-C(sp3 ) bond cleavage and allylation/alkenylation is demonstrated for the first time using this photocatalyst-free approach with linear primary, secondary, and tertiary alkoxyl radicals.

Selective Carbonyl−C(sp3) Bond Cleavage To Construct Ynamides, Ynoates, and Ynones by Photoredox Catalysis

AbstractCarbon–carbon bond cleavage/functionalization is synthetically valuable, and selective carbonyl−C(sp3) bond cleavage/alkynylation presents a new perspective in constructing ynamides, ynoates, and ynones. Reported here is the first alkoxyl‐radical‐enabled carbonyl−C(sp3) bond cleavage/alkynylation reaction by photoredox catalysis. The use of novel cyclic iodine(III) reagents are essential for β‐carbonyl alkoxyl radical generation from β‐carbonyl alcohols, including alcohols with high redox potential ( >2.2 V vs. SCE in MeCN). β‐Amide, β‐ester, and β‐ketone alcohols yield ynamides, ynoates, and ynones, respectively, for the first time, with excellent regio‐ and chemoselectivity under mild reaction conditions.

Selective Carbonyl-C(sp3 ) Bond Cleavage To Construct Ynamides, Ynoates, and Ynones by Photoredox Catalysis.

Carbon-carbon bond cleavage/functionalization is synthetically valuable, and selective carbonyl-C(sp3 ) bond cleavage/alkynylation presents a new perspective in constructing ynamides, ynoates, and ynones. Reported here is the first alkoxyl-radical-enabled carbonyl-C(sp3 ) bond cleavage/alkynylation reaction by photoredox catalysis. The use of novel cyclic iodine(III) reagents are essential for β-carbonyl alkoxyl radical generation from β-carbonyl alcohols, including alcohols with high redox potential (Epox >2.2 V vs. SCE in MeCN). β-Amide, β-ester, and β-ketone alcohols yield ynamides, ynoates, and ynones, respectively, for the first time, with excellent regio- and chemoselectivity under mild reaction conditions.

ChemInform Abstract: Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp3)‐H Functionalization under Mild Reaction Conditions.

ChemInformVolume 47, Issue 23 Preparative Organic Chemistry ChemInform Abstract: Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp3)-H Functionalization under Mild Reaction Conditions. Jing Zhang, Jing Zhang State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorYang Li, Yang Li State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorFuyuan Zhang, Fuyuan Zhang State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorChenchen Hu, Chenchen Hu State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorYiyun Chen, Yiyun Chen State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this author Jing Zhang, Jing Zhang State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorYang Li, Yang Li State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorFuyuan Zhang, Fuyuan Zhang State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorChenchen Hu, Chenchen Hu State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this authorYiyun Chen, Yiyun Chen State Key Lab. Bioorg. Nat. Prod. Chem., Shanghai Inst. Org. Chem., Acad. Sci., Shanghai 200032, Peop. Rep. ChinaSearch for more papers by this author First published: 19 May 2016 https://doi.org/10.1002/chin.201623058Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume47, Issue23May, 2016 RelatedInformation

Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp3)−H Functionalization under Mild Reaction Conditions

AbstractReported herein is the first visible‐light‐induced formation of alkoxyl radicals from N‐alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction. The selective hydrogen atom abstraction by the alkoxyl radical enables C(sp3)−H allylation and alkenylation reactions under mild reaction conditions at room temperature. Broad substrate variations, including a structurally complexed steroid, undergo the C(sp3)−H functionalization reaction effectively with high regio‐ and chemoselectivity.

Generation of Alkoxyl Radicals by Photoredox Catalysis Enables Selective C(sp(3))-H Functionalization under Mild Reaction Conditions.

Reported herein is the first visible-light-induced formation of alkoxyl radicals from N-alkoxyphthalimides, and the Hantzsch ester as the reductant is crucial for the reaction. The selective hydrogen atom abstraction by the alkoxyl radical enables C(sp(3))-H allylation and alkenylation reactions under mild reaction conditions at room temperature. Broad substrate variations, including a structurally complexed steroid, undergo the C(sp(3))-H functionalization reaction effectively with high regio- and chemoselectivity.

Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions

Oxidised low density lipoprotein (LDL) may be involved in the pathogenesis of atherosclerosis. We have therefore investigated the mechanisms underlying the antioxidant/pro-oxidant behavior of dehydroascorbate, the oxidation product of ascorbic acid, toward LDL incubated with Cu 2+ ions. By monitoring lipid peroxidation through the formation of conjugated dienes and lipid hydroperoxides, we show that the pro-oxidant activity of dehydroascorbate is critically dependent on the presence of lipid hydroperoxides, which accumulate during the early stages of oxidation. Using electron paramagnetic resonance spectroscopy, we show that dehydroascorbate amplifies the generation of alkoxyl radicals during the interaction of copper ions with the model alkyl hydroperoxide, tert-butylhydroperoxide. Under continuous-flow conditions, a prominent doublet signal was detected, which we attribute to both the erythroascorbate and ascorbate free radicals. On this basis, we propose that the pro-oxidant activity of dehydroascorbate toward LDL is due to its known spontaneous interconversion to erythroascorbate and ascorbate, which reduce Cu 2+ to Cu + and thereby promote the decomposition of lipid hydroperoxides. Various mechanisms, including copper chelation and Cu + oxidation, are suggested to underlie the antioxidant behavior of dehydroascorbate in LDL that is essentially free of lipid hydroperoxides.

Numerical revelation of the kinetic significance of individual steps in the reaction mechanism of methyl linoleate peroxidation inhibited by α-tocopherol

A kinetic model was constructed to describe the reactions involved in the oxidation of methyl linoleate (ML) inhibited by α-tocopherol (TH). The initial model of the reaction mechanism included 53 individual steps, which were numerically analyzed by the value method based on Hamiltonian systematization of kinetic equations. Good accord was obtained with experimental data at 40 and 50 °C. The dominant steps responsible for the antioxidant and pro-oxidant properties of TH in the process of ML peroxidation were revealed. Tocopherol-mediated peroxidation (TMP) and generation of alkoxyl radicals as a result of the reduction of hydroperoxides by TH or the decomposition tocopherol alkyl peroxides are the dominant reactions responsible for the pro-oxidant activities of α-tocopherol. The extreme behavior of reaction induction period in relation to TH initial concentration is related to the increase in the ratios of [tocopheroxyl radical]/[peroxyl radical] and the TMP rate/rate of termination by combination of tocopheroxyl and peroxyl radicals.

Generation of Alkoxyl Radicals from N‐Alkoxy‐2‐pyridones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Involvement of alkoxyl radical intermediates in the photolysis of 1-alkylcycloalkanols in the presence of bis(pyridine)iodonium tetrafluoroborate: Comparison with the (diacetoxyiodo)benzene/I 2 system

The product distributions observed after visible light irradiation of a series of 1-alkylcycloalkanols ( 1– 3) and bis(pyridine)iodonium tetrafluoroborate (IPy 2BF 4), have been compared with those observed after irradiation of the same substrates in the presence of (diacetoxy)iodobenzene (DIB) and I 2, i.e. under bona fide conditions for alkoxyl radical generation. The observation of very similar product distributions with the two systems strongly supports the previous hypothesis that alkoxyl radical intermediates are formed after photolysis of substrates 1– 3 in the presence of IPy 2BF 4.