- NEW GENERAL AND CONVENIENT SOURCES OF ALKYL RADICALS, USEFUL FOR SELECTIVE SYNTHESES
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Alkyl radicals are obtained from alkyl iodides under very simple conditions and with cheap reagents: i) H2O2 and DMSO; ii) H2O2 and acetone; iii) t-BuOOH.The alkyl radicals can be utilized for selective syntheses, mainly selective formation of carbon-carb
- Fontana, Francesca,Minisci, Francesco,Vismara, Elena
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- Radical chain monoalkylation of pyridines
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The monoalkylation of N-methoxypyridinium salts with alkyl radicals generated from alkenes (via hydroboration with catecholborane), alkyl iodides (via iodine atom transfer) and xanthates is reported. The reaction proceeds under neutral conditions since no acid is needed to activate the heterocycle and no external oxidant is required. A rate constant for the addition of a primary radical to N-methoxylepidinium >107 M-1 s-1 was experimentally determined. This rate constant is more than one order of magnitude larger than the one measured for the addition of primary alkyl radicals to protonated lepidine demonstrating the remarkable reactivity of methoxypyridinium salts towards radicals. The reaction has been used for the preparation of unique pyridinylated terpenoids and was extended to a three-component carbopyridinylation of electron-rich alkenes including enol esters, enol ethers and enamides.
- Dénès, Fabrice,Jangra, Harish,Meléndez, Camilo,Mulliri, Kleni,Renaud, Philippe,Rieder, Samuel,Zipse, Hendrik
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p. 15362 - 15373
(2021/12/14)
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- C-H alkylation of heteroarenes with alkyl oxalates by molecular photoelectrocatalysis
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An oxidant- and metal-free photoelectrocatalytic C-H alkylation reaction of heteroarenes with alkyl oxalates has been developed. Several classes of heteroaromatics, such as quinolines, isoquinolines, pyridines, and phenanthridines, can be alkylated with t
- Xu, Fan,Lai, Xiao-Li,Xu, Hai-Chao
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p. 369 - 372
(2020/12/07)
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- A General Organocatalytic System for Electron Donor-Acceptor Complex Photoactivation and Its Use in Radical Processes
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We report herein a modular class of organic catalysts that, acting as donors, can readily form photoactive electron donor-acceptor (EDA) complexes with a variety of radical precursors. Excitation with visible light generates open-shell intermediates under mild conditions, including nonstabilized carbon radicals and nitrogen-centered radicals. The modular nature of the commercially available xanthogenate and dithiocarbamate anion organocatalysts offers a versatile EDA complex catalytic platform for developing mechanistically distinct radical reactions, encompassing redox-neutral and net-reductive processes. Mechanistic investigations, by means of quantum yield determination, established that a closed catalytic cycle is operational for all of the developed radical processes, highlighting the ability of the organic catalysts to turn over and iteratively drive every catalytic cycle. We also demonstrate how the catalysts' stability and the method's high functional group tolerance could be advantageous for the direct radical functionalization of abundant functional groups, including aliphatic carboxylic acids and amines, and for applications in the late-stage elaboration of biorelevant compounds and enantioselective radical catalysis.
- De Pedro Beato, Eduardo,Melchiorre, Paolo,Spinnato, Davide,Zhou, Wei
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supporting information
p. 12304 - 12314
(2021/08/20)
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- Terminal-oxidant-free photocatalytic C-H alkylations of heteroarenes with alkylsilicates as alkyl radical precursors
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We report the photocatalytic C-H alkylations of heteroarenes with alkylsilicates bearing C,O-bidentate ligands under acidic conditions. Irradiation of heteroaromatics in the presence of the silicates and trifluoroacetic acid produced the corresponding alkylated compounds. The present reaction system does not require any terminal oxidant although the reaction seems to be a formal oxidation reaction. This study demonstrates that alkylsilicates can be used in photocatalytic radical chemistry under acidic conditions.
- Ikarashi, Gun,Morofuji, Tatsuya,Kano, Naokazu
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p. 10006 - 10009
(2020/09/23)
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- A Heck reaction/photochemical alkene isomerization sequence to prepare functionalized quinolines
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A route to prepare functionalized quinolines based on a Heck reaction/UV-induced alkene isomerization sequence is described. The method allows for the preparation of quinolines under mild and neutral conditions and has broad functional group tolerance. Acid-sensitive functional groups that would not be tolerated under previous approaches can be included and a one-pot quinoline forming procedure is also reported.
- Donohoe, Timothy J.,Hoff, Oskar,Hoffman, Jack B.,Kelly, Alex,Walker, Johannes C. L.,Werrel, Simon
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- Cross-Dehydrogenative Coupling of Strong C(sp3)-H with N-Heteroarenes through Visible-Light-Induced Energy Transfer
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The sustainable cross-dehydrogenative coupling of strong C(sp3)-H with N-heteroarenes has been developed using an efficient organic photocatalyst. It features atomic- and step-economy, and acid-free conditions. Mechanism studies suggest a previous elusive
- An, Guanghui,Li, Guangming,Tian, Chao,Tian, Haitao,Yang, Hui
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supporting information
p. 7709 - 7715
(2020/10/09)
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- Scalable Photoelectrochemical Dehydrogenative Cross-Coupling of Heteroarenes with Aliphatic C?H Bonds
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Heteroarenes are structural motifs found in many bioactive compounds and functional materials. Dehydrogenative cross-coupling of heteroarenes with aliphatic C?H bonds provides straightforward access to functionalized heteroarenes from readily available materials. Established methods employ stoichiometric chemical oxidants under conditions of heating or light irradiation. By merging electrochemistry and photochemistry, we have achieved efficient photoelectrochemical dehydrogenative cross-coupling of heteroarenes and C(sp3)?H donors through H2 evolution, without the addition of metal catalysts or chemical oxidants. Mechanistically, the C(sp3)?H donor is converted to a nucleophilic carbon radical through H-atom transfer with chlorine atom, which is produced by light irradiation of anodically generated Cl2 from Cl?. The carbon radical then undergoes radical substitution to the heteroarene to afford alkylated heteroarene products.
- Chen, Peng-Yu,Xu, Hai-Chao,Xu, Pin
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supporting information
p. 14275 - 14280
(2020/07/13)
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- Method for catalyzing decarboxylation of active carboxylic ester to introduce nitrogen heterocycle through photo-induced non-metal
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The invention provides a method for catalyzing decarboxylation of active carboxylic ester to introduce a nitrogen heterocycle through a photo-induced non-metal. According to the method, the decarboxylation of the active carboxylic ester is realized throug
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Paragraph 0055; 0056; 0057; 0058; 0059; 0188; 0190; 0191
(2019/01/23)
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- Cobalt-Catalyzed Electrophilic Aminations with Anthranils: An Expedient Route to Condensed Quinolines
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The reaction of various organozinc pivalates with anthranils provides anilines derivatives, which cyclize under acidic conditions providing condensed quinolines. Using alkenylzinc pivalates, electron-rich arylzinc pivalates or heterocyclic zinc pivalates produces directly the condensed quinolines of which several structures belong to new heterocyclic scaffolds. These N-heterocycles are of particular interest for organic light emitting diodes with their high photoluminescence quantum yields and long exciton lifetimes as well as for hole-transporting materials in methylammonium lead iodide perovskites solar cells due to an optimal band alignment for holes and a large bandgap.
- Li, Jie,Tan, Eric,Keller, Niklas,Chen, Yi-Hung,Zehetmaier, Peter M.,Jakowetz, Andreas C.,Bein, Thomas,Knochel, Paul
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supporting information
p. 98 - 103
(2019/01/08)
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- Photocatalytic decarboxylative alkylations mediated by triphenylphosphine and sodium iodide
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Most photoredox catalysts in current use are precious metal complexes or synthetically elaborate organic dyes, the cost of which can impede their application for large-scale industrial processes. We found that a combination of triphenylphosphine and sodium iodide under 456-nanometer irradiation by blue light–emitting diodes can catalyze the alkylation of silyl enol ethers by decarboxylative coupling with redox-active esters in the absence of transition metals. Deaminative alkylation using Katritzky’s N-alkylpyridinium salts and trifluoromethylation using Togni’s reagent are also demonstrated. Moreover, the phosphine/iodide-based photoredox system catalyzes Minisci-type alkylation of N-heterocycles and can operate in tandem with chiral phosphoric acids to achieve high enantioselectivity in this reaction.
- Fu, Ming-Chen,Shang, Rui,Zhao, Bin,Wang, Bing,Fu, Yao
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p. 1429 - 1434
(2019/04/30)
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- Catalyst-free electrochemical decarboxylative cross-coupling of: N -hydroxyphthalimide esters and N-heteroarenes towards C(sp3)-C(sp2) bond formation
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Cheap and widely available carboxylic acids are a class of ideal substrates to construct valuable compounds. As a candidate of decarboxylative reactions, the acid-based neutral N-hydroxyphthalimide ester undergoes a reductive decarboxylative process rather than a common oxidative decarboxylative process, which is a potential transformation mode for new reactions. In this work, we developed an electrochemical C(sp3)-C(sp2) coupling of N-hydroxyphthalimide esters and N-heteroarenes without any catalysts. Remarkably, this electrochemical protocol can not only be directly realised by carboxylic acids in a one-pot fashion, but also be scaled up using a continuous-flow reactor.
- Liu, Yichang,Xue, Liwei,Shi, Biyin,Bu, Faxiang,Wang, Dan,Lu, Lijun,Shi, Renyi,Lei, Aiwen
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supporting information
p. 14922 - 14925
(2019/12/24)
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- Rapid Assessment of the Reaction-Condition-Based Sensitivity of Chemical Transformations
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A systematic, user-friendly assessment tool that delivers a clear overview of the sensitivity of reactions to key parameters is highly desirable. Herein, the development of such a method is described. The intuitive, standardized presentation of the result
- Pitzer, Lena,Sch?fers, Felix,Glorius, Frank
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supporting information
p. 8572 - 8576
(2019/05/28)
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- Visible-light-induced C(sp3)-H oxidative arylation with heteroarenes
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Considering the ubiquitous C(sp3)-H and the important value of alkylated heteroarenes, developing a universal method for C(sp3)-H arylation with heteroarenes is significant. Herein, we proposed a method where Selectfluor can promote
- Liang, Xing-An,Niu, Linbin,Wang, Shengchun,Liu, Jiamei,Lei, Aiwen
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supporting information
p. 2441 - 2444
(2019/03/26)
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- Visible Light-Promoted Aliphatic C-H Arylation Using Selectfluor as a Hydrogen Atom Transfer Reagent
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A mild, practical method for direct arylation of unactivated C(sp3)-H bonds with heteroarenes has been achieved via photochemistry. Selectfluor is used as a hydrogen atom transfer reagent under visible light irradiation. A diverse range of chem
- Zhao, Hong,Jin, Jian
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supporting information
p. 6179 - 6184
(2019/09/06)
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- Introduction of Heteroaromatic Bases onto Cycloalkanes with BPO
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Heteroaromatic bases, such as lepidine, phenanthridine, isoquinoline, etc., were treated with cycloalkanes, such as cyclopentane, cyclohexane, cycloheptane, cyclooctane, etc., under warming conditions with benzoyl peroxide (BPO) to form heteroaromatic bases bearing cycloalkyl groups in good yields. Here, the inert C(sp3)-H bond of cycloalkanes could be functionalized to C(sp3)-heteroaromatic bases via an oxidative radical reaction pathway under transition-metal-free conditions.
- Zhou, Luan,Togo, Hideo
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p. 1627 - 1634
(2019/02/19)
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- Visible-light-mediated Minisci C-H alkylation of heteroarenes with unactivated alkyl halides using O2 as an oxidant
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Herein, we report a protocol for direct visible-light-mediated Minisci C-H alkylation of heteroarenes with unactivated alkyl halides using molecular oxygen as an oxidant at room temperature. This mild protocol is compatible with a wide array of sensitive
- Dong, Jianyang,Lyu, Xueli,Wang, Zhen,Wang, Xiaochen,Song, Hongjian,Liu, Yuxiu,Wang, Qingmin
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p. 976 - 982
(2019/02/03)
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- Organocatalyzed, Visible-Light Photoredox-Mediated, One-Pot Minisci Reaction Using Carboxylic Acids via N-(Acyloxy)phthalimides
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An improved, one-pot Minisci reaction has been developed using visible light, an organic photocatalyst, and carboxylic acids as radical precursors via the intermediacy of in situ-generated N-(acyloxy)phthalimides. The conditions employed are mild, demonstrate a high degree of functional group tolerance, and do not require a large excess of the carboxylic acid reactant. As a result, this reaction can be applied to drug-like scaffolds and molecules with sensitive functional groups, enabling late-stage functionalization, which is of high interest to medicinal chemistry.
- Sherwood, Trevor C.,Li, Ning,Yazdani, Aliza N.,Dhar, T. G. Murali
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p. 3000 - 3012
(2018/03/09)
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- A Metal-Free Approach for Bronsted Acid Promoted C-H Alkylation of Heteroarenes with Alkyl Peroxides
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A metal-free protocol for Minisci C-H alkylation of heteroarenes using alkyl peroxides as the alkylating reagents and internal oxidants simultaneously under promotion of Bronsted acid has been demonstrated. A series of alkyl substituted heteroarenes were readily prepared by the C-H alkylation in moderate to good yields. A possible pathway involving the addition of alkyl radical to heterocycle followed by rearomatization is described.
- Zeng, Yuehua,Qian, Bo,Li, Yajun,Bao, Hongli
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p. 3250 - 3256
(2018/06/08)
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- Synthesis of Functionalized Quinolines through a Reaction of Amides and Alkynes Promoted by Triflic Anhydride/Pyridine
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A concise, novel and flexible metal-free single step to synthesize functionalized quinolines is reported. Triflic anhydride-mediated (Tf2O) activation of amides is discussed in the presence of pyridine to offer strong electrophiles, thereby showcasing excellent productivity, high regio- and chemoselectivity, and widely tolerable substrates. This approach provides a straightforward and efficient way to construct azaheterocycle structures.
- Li, Lian-Hua,Niu, Zhi-Jie,Liang, Yong-Min
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supporting information
p. 15300 - 15304
(2017/10/20)
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- Deaminative Strategy for the Visible-Light-Mediated Generation of Alkyl Radicals
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A deaminative strategy for the visible-light-mediated generation of alkyl radicals from redox-activated primary amine precursors is described. Abundant and inexpensive primary amine feedstocks, including amino acids, were converted in a single step into redox-active pyridinium salts and subsequently into alkyl radicals by reaction with an excited-state photocatalyst. The broad synthetic potential of this protocol was demonstrated by the alkylation of a number of heteroarenes under mild conditions.
- Klauck, Felix J. R.,James, Michael J.,Glorius, Frank
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p. 12336 - 12339
(2017/09/06)
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- Versatile cross-dehydrogenative coupling of heteroaromatics and hydrogen donors via decatungstate photocatalysis
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A facile sunlight-induced derivatization of heteroaromatics via photocatalyzed C-H functionalization in amides, ethers, alkanes and aldehydes is described. Tetrabutylammonium decatungstate (TBADT) was used as the photocatalyst and allowed to carry out the
- Quattrini, Matteo C.,Fujii, Saki,Yamada, Keiichi,Fukuyama, Takahide,Ravelli, Davide,Fagnoni, Maurizio,Ryu, Ilhyong
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supporting information
p. 2335 - 2338
(2017/02/23)
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- Photoredox-mediated Minisci C-H alkylation of N-heteroarenes using boronic acids and hypervalent iodine
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A photoredox-mediated Minisci C-H alkylation reaction of N-heteroarenes with alkyl boronic acids is reported. A broad range of primary and secondary alkyl groups can be efficiently incorporated into various N-heteroarenes using [Ru(bpy)3]Cl2 as photocatalyst and acetoxybenziodoxole as oxidant under mild conditions. The reaction exhibits excellent substrate scope and functional group tolerance, and offers a broadly applicable method for late-stage functionalization of complex substrates. Mechanistic experiments and computational studies suggest that an intramolecularly stabilized ortho-iodobenzoyloxy radical intermediate might play a key role in this reaction system.
- Li, Guo-Xing,Morales-Rivera, Christian A.,Wang, Yaxin,Gao, Fang,He, Gang,Liu, Peng,Chen, Gong
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p. 6407 - 6412
(2016/09/28)
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- Direct alkylation of heteroarenes with unactivated bromoalkanes using photoredox gold catalysis
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Although visible light photoredox catalysis has emerged as a powerful tool for the construction of C-C bonds, common catalysts and/or their photoexcited states suffer from low redox potentials, limiting their applicability to alkyl radical generation from substrates with activated carbon-halogen bonds. Radicals derived from these activated compounds, being highly electrophilic or stabilized, do not undergo efficient addition to heteroarenes. Herein we describe the photocatalytic generation of nucleophilic alkyl radicals from unactivated bromoalkanes as part of a universal and efficient cross-coupling strategy for the direct alkylation of heteroarenes using a dimeric gold(i) photoredox catalyst, [Au2(bis(diphenylphosphino)methane)2]Cl2. The method proves to be efficient for alkylation of arenes under mild conditions in the absence of directing groups.
- McCallum,Barriault
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p. 4754 - 4758
(2016/07/06)
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- Direct selective oxidative cross-coupling of simple alkanes with heteroarenes
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A dream reaction: An efficient and practical method for the oxidative cross-coupling of heteroaromatic compounds and simple alkanes has been developed. The desired products are smoothly and regioselectively formed under mild reaction conditions at ambient temperature in a hypervalent-iodine-mediated transformation. The method allows for preferential transformation of stronger C sp 3-H bonds in the presence of weaker C sp 3-H bonds under metal-free conditions.
- Antonchick, Andrey P.,Burgmann, Lars
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supporting information
p. 3267 - 3271
(2013/04/10)
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- Trapping of free-radicals in the oxidation of ethers, aldehydes and alkanes by dimethyldioxirane
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Alkyl, α-oxyalkyl and acyl radical intermediates in the oxidation of alkanes, ethers and aldehydes by dimethyldioxirane are trapped by protonated quinolines and a free-radical chain is suggested for the α-acetoxylation of ketones.
- Minisci, Francesco,Zhao, Lihua,Fontana, Francesca,Bravo, Anna
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p. 1895 - 1898
(2007/10/02)
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- Polar Effects in Free-Radical Reactions. Homolytic Heteroaromatic Substitutions by Alkyl Bromides
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Alkyl bromides have been utilized for the first time as radical sources for heteroaromatic substitution.A variety of procedures was revealed to be successful for bromine abstraction: Bu3SnH with AIBN, (Me3Si)3SiH with AIBN, Ph2SiH2, or Et3SiH associated with peroxides (H2O2, t-BuOOH, (t-BuO)2, (t-BuOOCO)2, (PhCOO)2).The importance of the polar effects is discussed.
- Minisci, Francesco,Fontana, Francesca,Pianese, Guiseppe,Yan, Yong Ming
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p. 4207 - 4211
(2007/10/02)
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- A NEW PHOTOCHEMICAL METHOD OF HOMOLYTIC ALKYLATION OF HETEROAROMATIC BASES BY ALKYL IODIDES AND IODOSOBENZENE DIACETATE
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Photolysis of iodobenzene diacetate in the presence of alkyl iodides, protonated heteroaromatic bases and benzoic acid resulted in the selective alkylation of the α and γ positions on lepidine and quinoline.
- Fontana, Francesca,Minisci, Francesco,Barbosa, Maria Claudia Nogueira,Vismara, Elena
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p. 167 - 168
(2007/10/02)
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- New General Processes of Homolytic Alkylation of Heteroaromatic Bases by t-BuOOH or (t-BuO)2 and Alkyl Iodides
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New general, selective processes of homolytic alkylation of protonated heteroaromatic bases have been developed using alkyl iodides and t-BuOOH or (t-BuO)2 as sources of alkyl radicals.Both processes are based on the generation of methyl radical from the peroxides, and on iodine abstraction from the alkyl iodide by the methyl radical.The selective processes are the result of combined enthalpic and polar effects.The enthalpic factor governs the equilibrium of iodine abstraction, whereas the polar effect governs the reactivity of the alkyl radicals with the protonated heteroaromatic ring.A redox chain is operative with t-BuOOH and an unusual free-radical chain process is involved with (t-BuO)2.Both chains are particularly effective because of the electron-transfer oxidation of the pyridyl radical intermediate, the ionization potential of which (5.4-6.0 eV) is close to that of lithium (5.39 eV) or sodium (5.14 eV).
- Fontana, Francesca,Minisci, Francesco,Barbosa, Maria Claudia Nogueira,Vismara, Elena
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p. 995 - 999
(2007/10/02)
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- Polar Effects in Free-Radical Reactions. Rate Constants in Phenylation and New Methods of Selective Alkylation of Heteroaromatic Bases
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The rate constants for the addition of the phenyl radical to protonated and unprotonated 4-substituted pyridines have been determined by competition with chlorine abstraction from CCl4.The constants range from 2 * 105 to 6 * 106 M-1 s-1 depending on the substituent and on the degree of protonation.The phenyl radical shows a clear-cut nucleophilic character.On the basis of these rate constants, the use of phenyl radical from diazonium salt or benzoyl peroxide to generate alkyl radicals by iodine or hydrogen abstraction has been developed as a general procedure for the alkylation of heteroaromatic bases.This reaction is characterized by high yields and selectivities.
- Minisci, Francesco,Vismara, Elena,Fontana, Francesca,Morini, Giampiero,Serravalle, Marco,Giordano, Claudio
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p. 4411 - 4416
(2007/10/02)
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- A NEW GENERAL METHOD OF HOMOLYTIC ALKYLATION OF PROTONATED HETEROAROMATIC BASES
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Alkyl iodides and benzoyl peroxides provide a new general method of homolytic alkylation of protonated heteroaromatic bases.Yields are good and the substitution is selective in the positions ortho and para to the heteroatom.
- Castaldi, Graziano,Minisci, Francesko,Tortelli, Vito,Vismara, Elena
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p. 3897 - 3900
(2007/10/02)
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