- Photoredox Imino Functionalizations of Olefins
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Shown herein is that polyfunctionalized nitrogen heterocycles can be easily prepared by a visible-light-mediated radical cascade process. This divergent strategy features the oxidative generation of iminyl radicals and subsequent cyclization/radical trapping, which allows the effective construction of highly functionalized heterocycles. The reactions proceed efficiently at room temperature, utilize an organic photocatalyst, use simple and readily available materials, and generate, in a single step, valuable building blocks that would be difficult to prepare by other methods.
- Davies, Jacob,Sheikh, Nadeem S.,Leonori, Daniele
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- Regio- and Stereoselective Iron-Catalyzed Oxyazidation of Enamides Using a Hypervalent Iodine Reagent
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A novel regio- and diastereoselective iron-catalyzed intermolecular oxyazidation of enamides using various azidobenziodoxolone (ABX) derivatives is presented. A variety of α-N3 amino derivatives and of α-N3 piperidines were synthesized in good yields and under mild reaction conditions. The reaction involves a radical process using cheap FeCl2 as the initiator.
- Bertho, Sylvain,Rey-Rodriguez, Romain,Colas, Cyril,Retailleau, Pascal,Gillaizeau, Isabelle
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- Enantioselective Synthesis of Homoallylic Azides and Nitriles via Palladium-Catalyzed Decarboxylative Allylation
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Azides and nitriles are important building blocks for the synthesis of nitrogen-containing bioactive compounds. The first example of enantioselective palladium-catalyzed decarboxylative allylation of α-azido and cyano β-ketoesters is reported. Indanone derivatives were obtained in 50-88% yield/77-97% ee and 46-98% yield/78-93% ee for azide and nitrile substituents, respectively. The required starting materials were synthesized in one step from ketoesters via electrophilic azidation and cyanation using benziodoxole hypervalent iodine reagents. The products could be easily converted into useful nitrogen-containing building blocks, such as triazoles, amides, or α- and β- amino ketones.
- Vita, Maria Victoria,Caramenti, Paola,Waser, Jerome
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- Practical synthesis of 2-iodosobenzoic acid (IBA) without contamination by hazardous 2-iodoxybenzoic acid (IBX) under mild conditions
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We report a convenient and practical method for the preparation of nonexplosive cyclic hypervalent iodine(III) oxidants as efficient organocatalysts and reagents for various reactions using Oxone in aqueous solution under mild conditions at room temperature. The thus obtained 2-iodosobenzoic acids (IBAs) could be used as precursors of other cyclic organoiodine(III) derivatives by the solvolytic derivatization of the hydroxy group under mild conditions of 80 °C or lower temperature. These sequential procedures are highly reliable to selectively afford cyclic hypervalent iodine compounds in excellent yields without contamination by hazardous pentavalent iodine(III) compound.
- China, Hideyasu,Dohi, Toshifumi,Kageyama, Nami,Takenaga, Naoko,Yatabe, Hotaka
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- Ethynylation of Cysteine Residues: From Peptides to Proteins in Vitro and in Living Cells
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Current approaches to introduce terminal alkynes for bioorthogonal reactions into biomolecules still present limitations in terms of either reactivity, selectivity, or adduct stability. We present a method for the ethynylation of cysteine residues based on the use of ethynylbenziodoxolone (EBX) reagents. The acetylene group is directly introduced onto the thiol group of cysteine and can be used for copper-catalyzed alkyne-azide cycloaddition (CuAAC) without further processing. Labeling proceeded with reaction rates comparable to or higher than the most often used iodoacetamide on peptides or maleimide on the antibody trastuzumab, and high cysteine selectivity was observed. The reagents were also used in living cells for cysteine proteomic profiling and displayed improved coverage of the cysteinome compared to previously reported iodoacetamide or hypervalent iodine reagents. Fine-tuning of the EBX reagents allows optimization of their reactivity and physical properties.
- Tessier, Romain,Nandi, Raj Kumar,Dwyer, Brendan G.,Abegg, Daniel,Sornay, Charlotte,Ceballos, Javier,Erb, Stéphane,Cianférani, Sarah,Wagner, Alain,Chaubet, Guilhem,Adibekian, Alexander,Waser, Jerome
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- Oxidative Cycloaddition of Aldoximes with Maleimides using Catalytic Hydroxy(aryl)iodonium Species
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A mild catalytic procedure for the efficient oxidative cyclization of aldoximes with maleimides mediated by hypervalent iodine(III) active species has been developed. This catalytic cyclization affords the corresponding pyrrolo-isoxazole products in generally good yields. The catalytic cycle involves active hydroxy(aryl)iodonium species generated in situ from 2-iodobenzoic acid as precatalyst and m-chloroperoxybenzoic acid (m-CPBA) as terminal oxidant in the presence of trifluoromethanesulfonic acid. The presence of active hydroxy(aryl)iodonium species in this reaction has been confirmed by ESI-mass spectrometry and1H NMR spectroscopy. (Figure presented.) .
- Yoshimura, Akira,Nguyen, Khiem C.,Rohde, Gregory T.,Saito, Akio,Yusubov, Mekhman S.,Zhdankin, Viktor V.
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- The direct electrophilic cyanation of β-keto esters and amides with cyano benziodoxole
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The direct electrophilic α-cyanation of β-keto esters and amides has been developed using a hypervalent iodine benziodoxole-derived cyano reagent. The procedure is accomplished within 10 min and without the use of any catalyst in DMF, at room temperature. Thus, the highly functionalized quaternary carbon-centered nitriles were produced in high to excellent yields.
- Wang, Yao-Feng,Qiu, Jiashen,Kong, Dejie,Gao, Yongtao,Lu, Feipeng,Karmaker, Pran Gopal,Chen, Fu-Xue
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- Enantioenriched Quaternary α-Pentafluoroethyl Derivatives of Alkyl 1-Indanone-2-Carboxylates
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An electrophilic enantioselective catalytic method for the α-pentafluoroethylation of 3-oxoesters is described. Under the use of La(OTf)3 in combination with a (S,R)-indanyl-pybox ligand, good results in terms of yield and enantioselectivities were achieved (up to 89% ee). The reaction proceeds under mild conditions, leading to the formation of enantioenriched quaternary centers. This methodology uses an hypervalent iodine(III)-CF2CF3 reagent, and mechanistic investigations are consistent with the involvement of a radical pathway.
- Ballesteros, Anna,Granados, Albert,Vallribera, Adelina
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- Thermal stability of N-heterocycle-stabilized iodanes-A systematic investigation
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The thermal stability of pseudocyclic and cyclic N-heterocycle-stabilized (hydroxy)aryl-and mesityl(aryl)-λ3-iodanes (NHIs) through thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) is investigated. Peak decomposition temperatures (Tpeak) were observed within a wide range between 120 and 270 °C. Decomposition enthalpies (ΔHdec) varied from-29.81 to 141.13 kJ/mol. A direct comparison between pseudocyclic and cyclic NHIs revealed high Tpeak but also higher ΔHdec values for the latter ones. NHIs bearing N-heterocycles with a high N/C-ratio such as triazoles show among the lowest Tpeak and the highest ΔHdec values. A comparison of NHIs with known (pseudo)cyclic benziodoxolones is made and we further correlated their thermal stability with reactivity in a model oxygenation.
- Boelke, Andreas,Vlasenko, Yulia A.,Yusubov, Mekhman S.,Nachtsheim, Boris J.,Postnikov, Pavel S.
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- Preparation, structure, and unexpected chemistry of phosphoranyl-derived benziodoxoles
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Novel phosphoranyl-derived benziodoxoles were prepared by the reaction of 1-acetoxybenziodoxole with stabilized phosphonium ylides [1-triphenylphosphoranylidene-2-propanone and (carbomethoxymethyl)triphenylphosphoranylidene acetate]. X-ray crystallographic analysis of these compounds demonstrates the significance of secondary bonding interactions, which link individual molecules into infinite chains. An unusual ligand exchange on an iodine(III) center resulting in the substitution of a carbon ligand with an oxygen ligand was observed in the reaction of these compounds with strong acids. Copyright
- Zhdankin, Viktor V.,Maydanovych, Olena,Herschbach, Jon,McDonald, Robert,Tykwinski, Rik R.
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- Hypervalent Iodine(III) Reagents with Transferable Primary Amines: Structure and Reactivity on the Electrophilic α-Amination of Stabilized Enolates
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A new family of hypervalent iodine reagents containing transferable primary amine groups is described. Benziodoxolone-based reagents were synthesized on the gram-scale through operationally simple reactions in up to quantitative yields. These bench-stable solids were characterized by X-ray analysis and successfully employed in the α-amination of indanone-based β-ketoesters in up to 83% yield. Mechanistic studies indicate a substitution mechanism involving an electrophilic amine.
- Poeira, Diogo L.,Negr?o, Ana Cláudia R.,Faustino, Hélio,Coelho, Jaime A. S.,Gomes, Clara S. B.,Gois, Pedro M. P.,Marques, M. Manuel B.
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supporting information
p. 776 - 781
(2022/01/20)
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- Tosyloxybenziodoxolone: A Platform for Performing the Umpolung of Alkynes in One-Pot Transformations
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Ethynylbenziodoxolones (EBXs) are commonly encountered reagents for the electrophilic alkynylation of nucleophiles. Herein, we report a one-pot, two-step process for EBX generation and their direct application in substrate functionalization. Our approach enables us to bypass the originally mandatory isolation and purification of the reagents, resulting in a more efficient synthesis. We could apply this process to seven different transformations involving both two- and one-electron nucleophiles to obtain a large variety of alkynylated products.
- Borrel, Julien,Waser, Jerome
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supporting information
p. 142 - 146
(2021/12/27)
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- N-Terminal Selective C?H Azidation of Proline-Containing Peptides: a Platform for Late-Stage Diversification
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A methodology for the C?H azidation of N-terminal proline-containing peptides was developed employing only commercially available reagents. Peptides bearing a broad range of functionalities and containing up to 6 amino acids were selectively azidated at the carbamate-protected N-terminal residue in presence of the numerous other functional groups present on the molecules. Post-functionalizations of the obtained aminal compounds were achieved: cycloaddition reactions or C?C bond formations via a sequence of imine formation/nucleophilic addition were performed, offering an easy access to diversified peptides.
- Allouche, Emmanuelle M. D.,Simonet-Davin, Rapha?l,Waser, Jerome
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supporting information
(2022/02/25)
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- Synthesis of polycyclic aminal heterocycles via decarboxylative cyclisation of dipeptide derivatives
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An oxidative-decarboxylative intramolecular cyclisation of dipeptide derivatives is reported. This transformation is promoted by phenyl iodine(iii) diacetate (PIDA) in combination with BF3·OEt2. The reaction gives access to a variety of valuable polycyclic N-heterocyclic scaffolds containing 5-, 6-, or 7-membered rings.
- Le Du, Eliott,Robert, Emma G. L.,Waser, Jerome
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supporting information
p. 3473 - 3476
(2022/03/31)
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- 1,3-Oxyalkynylation of Aryl Cyclopropanes with Ethylnylbenziodoxolones Using Photoredox Catalysis
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Alkynes and cyclopropanes are vital motifs in chemistry. Herein, a photoredox catalyzed 1,3-oxyalkynylation of aryl cyclopropanes with ethylnylbenziodoxolones (EBXs) in an atom-economic fashion is described. This cascade comprises single-electron oxidatio
- Studer, Armido,Zuo, Zhijun
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supporting information
p. 949 - 954
(2022/02/07)
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- Synthesis of Diverse Aryliodine(III) Reagents by Anodic Oxidation?
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An anodic oxidation enabled synthesis of hypervalent iodine(III) reagents from aryl iodides is demonstrated. Under mild electrochemical conditions, a range of aryliodine(III) reagents including iodosylarenes, (difunctionaliodo)arenes, benziodoxoles and diaryliodonium salts can be efficiently synthesized and derivatized in good to excellent yields with high selectivity. As only electrons serve as the oxidation reagents, this method offers a more straightforward and sustainable manner avoiding the use of expensive or hazardous chemical oxidants.
- Zu, Bing,Ke, Jie,Guo, Yonghong,He, Chuan
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supporting information
p. 627 - 632
(2021/02/12)
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- Cys–Cys and Cys–Lys Stapling of Unprotected Peptides Enabled by Hypervalent Iodine Reagents
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Easy access to a wide range of structurally diverse stapled peptides is crucial for the development of inhibitors of protein-protein interactions. Herein, we report bis-functional hypervalent iodine reagents for two-component cysteine-cysteine and cysteine-lysine stapling yielding structurally diverse thioalkyne linkers. This stapling method works with unprotected natural amino acid residues and does not require pre-functionalization or metal catalysis. The products are stable to purification and isolation. Post-stapling modification can be accessed via amidation of an activated ester, or via cycloaddition onto the formed thioalkyne group. Increased helicity and binding affinity to MDM2 was obtained for a i,i+7 stapled peptide.
- Ceballos, Javier,Grinhagena, Elija,Sangouard, Gontran,Heinis, Christian,Waser, Jerome
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supporting information
p. 9022 - 9031
(2021/03/16)
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- N-Cyanation of Primary and Secondary Amines with Cyanobenzio-doxolone (CBX) Reagent
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An efficient electrophilic N-cyanation of amines with a stable and less-toxic cyanobenziodoxole reagent towards the synthesis of cyanamides is disclosed. This synthetically practicable strategy allows the construction of a wide variety of cyanamides under very mild and simple conditions with a broad functional group compatibility, and showcases a huge potential in late-stage modification of complex molecules.
- Chen, Zimin,Yuan, Weiming
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supporting information
p. 14836 - 14840
(2021/09/30)
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- Low-Temperature Intramolecular [4+2] Cycloaddition of Allenes with Arenes for the Synthesis of Diene Ligands
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The intramolecular [4+2] cycloaddition between arenes and allenes first reported by Himbert gives rapid access to rigid polycyclic scaffolds. Herein, we report a one-pot oxyalkynylation/cycloaddition reaction proceeding under mild conditions (23–90 °C) an
- Hari, Durga Prasad,Pisella, Guillaume,Wodrich, Matthew D.,Tsymbal, Artem V.,Tirani, Farzaneh Fadaei,Scopelliti, Rosario,Waser, Jerome
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supporting information
p. 5475 - 5481
(2021/01/21)
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- Decatungstate as Direct Hydrogen Atom Transfer Photocatalyst for SOMOphilic Alkynylation
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A versatile approach for the alkynylation of a variety of aliphatic hydrogen donors, including alkanes, is reported. We used tetrabutylammonium decatungstate as photocatalyst to generate organoradicals from C-H/Si-H bonds via hydrogen atom transfer. The l
- Capaldo, Luca,Ravelli, Davide
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p. 2243 - 2247
(2021/04/05)
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- Ynonylation of Acyl Radicals by Electroinduced Homolysis of 4-Acyl-1,4-dihydropyridines
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Herein we report the conversion of 4-Acyl-1,4-dihydropyridines (DHPs) into ynones under electrochemical conditions. The reaction proceeds via the homolysis of acyl-DHP under electron activation. The resulting acyl radicals react with hypervalent iodine(III) reagents to form the target ynones or ynamides in acceptable yields. This mild reaction condition allows wider functionality tolerance that includes halides, carboxylates, or alkenes. The synthetic utility of this methodology is further demonstrated by the late-stage modification of complex molecules.
- Luo, Xiaosheng,Wang, Ping
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supporting information
p. 4960 - 4965
(2021/07/20)
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- Direct Photoexcitation of Ethynylbenziodoxolones: An Alternative to Photocatalysis for Alkynylation Reactions**
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Ethynylbenziodoxolones (EBXs) are commonly used as radical traps in photocatalytic alkynylations. Herein, we report that aryl-substituted EBX reagents can be directly activated by visible light irradiation. They act as both oxidants and radical traps, alleviating the need for a photocatalyst in several reported EBX-mediated processes, including decarboxylative and deboronative alkynylations, the oxyalkynylation of enamides and the C?H alkynylation of THF. Furthermore, the method could be applied to the synthesis of alkynylated quaternary centers from tertiary alcohols via stable oxalate salts and from tertiary amines via aryl imines. A photocatalytic process using 4CzIPN as an organic dye was also developed for the deoxyalkynylation of oxalates.
- Amos, Stephanie G. E.,Cavalli, Diana,Le Vaillant, Franck,Waser, Jerome
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supporting information
p. 23827 - 23834
(2021/09/25)
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- Site Selective Chlorination of C(sp3)?H Bonds Suitable for Late-Stage Functionalization
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C(sp3)?Cl bonds are present in numerous biologically active small molecules, and an ideal route for their preparation is by the chlorination of a C(sp3)?H bond. However, most current methods for the chlorination of C(sp3)?H bonds are insufficiently site selective and tolerant of functional groups to be applicable to the late-stage functionalization of complex molecules. We report a method for the highly selective chlorination of tertiary and benzylic C(sp3)?H bonds to produce the corresponding chlorides, generally in high yields. The reaction occurs with a mixture of an azidoiodinane, which generates a selective H-atom abstractor under mild conditions, and a readily-accessible and inexpensive copper(II) chloride complex, which efficiently transfers a chlorine atom. The reaction's exceptional functional group tolerance is demonstrated by the chlorination of >30 diversely functionalized substrates and the late-stage chlorination of a dozen derivatives of natural products and active pharmaceutical ingredients.
- Fawcett, Alexander,Keller, M. Josephine,Herrera, Zachary,Hartwig, John F.
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supporting information
p. 8276 - 8283
(2021/03/15)
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- Construction of 2-alkynyl aza-spiro[4,5]indole scaffolds: Via sequential C-H activations for modular click chemistry libraries
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Herein, we have developed a strategy of sequential C-H activations of indole to construct novel 2-alkynyl aza-spiro[4,5]indole scaffolds, which incorporated both alkyne and spiro-units into indole. Gram-scale synthesis and a one-pot, three-step synthesis demonstrated the utility of this protocol. Hybrid conjugates with an oseltamivir derivative further offered a powerful tool for the construction of a versatile spiroindole-containing library via click chemistry. This journal is
- Zhang, Jun,Wang, Mengmeng,Wang, Huiying,Xu, Hui,Chen, Junjie,Guo, Ziqiong,Ma, Biao,Ban, Shu-Rong,Dai, Hui-Xiong
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supporting information
p. 8656 - 8659
(2021/09/04)
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- Hypervalent Iodine(III)-Promoted Radical Oxidative C-H Annulation of Arylamines with α-Keto Acids
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A novel catalyst-free radical oxidative C-H annulation reaction of arylamines with α-keto acids toward benzoxazin-2-ones synthesis under mild conditions was developed. This hypervalent iodine(III)-promoted process eliminated the use of a metal catalyst or additive with high levels of functional group tolerance. Hypervalent iodine(III) was both an oxidant and a radical initiator for this reaction. The synthetic utility of this method was confirmed by the synthesis of the natural product cephalandole A.
- Long, Lipeng,Wang, Jieyan,Gu, Liuqing,Yang, Shiguang,Qiao, Liang,Luo, Guotian,Chen, Zhengwang
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p. 12084 - 12092
(2021/08/24)
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- Copper-Catalyzed Oxyalkynylation of C-S Bonds in Thiiranes and Thiethanes with Hypervalent Iodine Reagents
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We report the oxyalkynylation of thiiranes and thietanes using ethynylbenziodoxolone reagents (EBXs) to readily access functionalized building blocks bearing an alkynyl, a benzoate, and an iodide group. The reaction proceeds with high atom efficiency most
- Borrel, Julien,Pisella, Guillaume,Waser, Jerome
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supporting information
p. 422 - 427
(2020/01/31)
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- Copper-catalyzed oxyvinylation of diazo compounds
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A copper(I)-catalyzed vinylation of diazo compounds with vinylbenziodoxolone reagents (VBX) as partners is reported. The transformation tolerates diverse functionalities on both reagents delivering polyfunctionalized vinylated products. The strategy was successfully extended to a three-component/intermolecular version with alcohols. The obtained products contain synthetically versatile functional groups, such as an aryl iodide, an ester, and an allylic leaving group, enabling further modification.
- Pisella, Guillaume,Gagnebin, Alec,Waser, Jerome
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supporting information
p. 3884 - 3889
(2020/05/14)
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- Oxidative cyanation of 2-oxindoles: formal total synthesis of (±)-gliocladin C
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Efficient oxidative direct cyanations of 3-alkyl/aryl 2-oxindoles using Cyano-1,2-BenziodoXol-3(1H)-one (CBX) (2a) have been reported under 'transition metal-free' conditions to synthesize a wide variety of 3-cyano 3-alkyl/aryl 2-oxindoles sharing an all-carbon quaternary center under additive-free conditions. The application of this process is shown by the formal total synthesis of (±)-gliocladin C (11c) in a few steps.
- Bisai, Alakesh,Das, Mrinal Kanti,De, Subhadip,Maity, Arindam,Naskar, Malay,Roy, Avishek
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supporting information
p. 1679 - 1684
(2020/03/05)
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- Unconventional Reactivity of Ethynylbenziodoxolone Reagents and Thiols: Scope and Mechanism
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1,2-Dithio-1-alkenes are biologically active compounds widely implemented throughout organic synthesis, functional materials, coordination chemistry, and pharmaceuticals. Traditional methods for accessing 1,2-dithio-1-alkenes often demand transition metal
- Liu, Bin,Alegre-Requena, Juan V.,Paton, Robert S.,Miyake, Garret M.
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supporting information
p. 2386 - 2394
(2020/02/05)
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- Site-Selective Copper-Catalyzed Azidation of Benzylic C-H Bonds
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Site selectivity represents a key challenge for non-directed C-H functionalization, even when the C-H bond is intrinsically reactive. Here, we report a copper-catalyzed method for benzylic C-H azidation of diverse molecules. Experimental and density functional theory studies suggest the benzyl radical reacts with a CuII-azide species via a radical-polar crossover pathway. Comparison of this method with other C-H azidation methods highlights its unique site selectivity, and conversions of the benzyl azide products into amine, triazole, tetrazole, and pyrrole functional groups highlight the broad utility of this method for target molecule synthesis and medicinal chemistry.
- Suh, Sung-Eun,Chen, Si-Jie,Mandal, Mukunda,Guzei, Ilia A.,Cramer, Christopher J.,Stahl, Shannon S.
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supporting information
p. 11388 - 11393
(2020/07/21)
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- Photochemical Functionalization of Heterocycles with EBX Reagents: C?H Alkynylation versus Deconstructive Ring Cleavage**
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The development of novel methodologies for the functionalization of saturated heterocycles is highly desirable. Herein, we report a cheap and efficient photochemical method for the C?H functionalization of saturated O-heterocycles, as well as the deconstructive ring-cleavage of S-heterocycles, employing hypervalent iodine alkynylation reagents (ethynylbenziodoxolones, EBX). This photochemical alkynylation is performed utilizing phenylglyoxylic acid as the photoinitiator, leading to the corresponding products in good to high yields, under household fluorescent light bulb irradiation. When O-heterocycles were employed, the expected α-C?H alkynylation took place. In contrast, oxidative ring-opening to form a thioalkyne and an aldehyde was observed with S-heterocycles. Preliminary mechanistic experiments are presented to give first insights into this puzzling divergent reactivity.
- Voutyritsa, Errika,Garreau, Marion,Kokotou, Maroula G.,Triandafillidi, Ierasia,Waser, Jér?me,Kokotos, Christoforos G.
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supporting information
p. 14453 - 14460
(2020/10/12)
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- Gold-Catalyzed Alkynylative Meyer-Schuster Rearrangement
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By applying the "interplay"mode, which consolidates two key reactivity modes of gold catalysis, namely π-activation mode and cross-coupling mode, the first alkynylative Meyer-Schuster rearrangement is designed and successfully implemented. The current protocol gives straightforward access to enynones, a highly valuable building block, from easily available propargyl alcohol feedstocks. Control experiments suggest an Au(III) catalyst triggers the Meyer-Schuster rearrangement, whereas monitoring the reaction with ESI-HRMS provided strong evidence in favor of a key alkynylgold(III) intermediate which supports the proposed "interplay"scenario.
- Banerjee, Somsuvra,Banerjee, Somsuvra,Ambegave, Shivhar B.,Mule, Ravindra D.,Mule, Ravindra D.,Senthilkumar, Beeran,Senthilkumar, Beeran,Patil, Nitin T.
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supporting information
p. 4792 - 4796
(2020/06/25)
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- Revisiting the Urech Synthesis of Hydantoins: Direct Access to Enantiopure 1,5-Substituted Hydantoins Using Cyanobenziodoxolone
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A method for the synthesis of enantiopure 1,5-substituted hydantoins was developed using a hypervalent iodine cyanation reagent (cyanobenziodoxolone, CBX) as a source of electrophilic carbon. Starting from inexpensive commercially available enantiopure protected amino acids, the method allowed the synthesis of various hydantoins without epimerization. Formation of hydantoins from dipeptides was also possible, but partial epimerization was observed in this case. This synthetic strategy is user friendly as CBX is a bench-stable easy-to-handle crystalline reagent and avoids conventional multistep protocols, thus allowing the facile synthesis of a library of chiral hydantoins.
- Declas, Nina,Le Vaillant, Franck,Waser, Jerome
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supporting information
p. 524 - 528
(2019/01/14)
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- SYNTHESIS OF HYPERVALENT IODINE REAGENTS WITH DIOXYGEN
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Methods of synthesis of hypervalent iodine reagents and methods for oxidation of organic compounds are disclosed.
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Paragraph 0095-0096
(2019/01/15)
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- C-Terminal Bioconjugation of Peptides through Photoredox Catalyzed Decarboxylative Alkynylation
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We report the first decarboxylative alkynylation of the C-terminus of peptides starting from free carboxylic acids. The reaction is fast, metal-free, and proceeds cleanly to afford alkynylated peptides with a broad tolerance for the C-terminal amino acid. By the use of hypervalent iodine reagents, the introduction of a broad range of functional groups was successful. C-terminal selectivity was achieved by differentiation of the oxidation potentials of the carboxylic acids based on the use of fine-tuned organic dyes.
- Garreau, Marion,Le Vaillant, Franck,Waser, Jerome
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supporting information
p. 8182 - 8186
(2019/05/21)
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- Gold-Catalyzed Stereoselective Domino Cyclization/Alkynylation of N-Propargylcarboxamides with Benziodoxole Reagents for the Synthesis of Alkynyloxazolines
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A concise and highly stereoselective synthesis of alkynyloxazolines via a gold-catalyzed domino cyclization-alkynylation cascade of N-propargylcarboxamides with benziodoxole reagents is reported. This new protocol, which represents an attractive alternati
- Zhao, Ximei,Tian, Bing,Yang, Yangyang,Si, Xiaojia,Mulks, Florian F.,Rudolph, Matthias,Rominger, Frank,Hashmi, A. Stephen K.
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supporting information
p. 3155 - 3162
(2019/05/10)
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- Gold-Catalyzed 1,2-Oxyalkynylation of N-Allenamides with Ethylnylbenziodoxolones
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A gold-catalyzed 1,2-oxyalkynylation of N-allenamides with ethylnylbenziodoxolones (EBXs) has been achieved for the first time. The reaction, which follows a redox-neutral Au(I)/Au(III) catalytic pathway, was enabled in an attempt to exhaust the EBX reagents atom-economically by putting the nucleophilic carboxylate part of EBXs to appropriate use. This constitutes the first example for gold-catalyzed β-alkynylation of N-allenamides to construct highly valuable 1,3-enynes. The potential of the sequence is further documented by some follow-up transformations.
- Banerjee, Somsuvra,Senthilkumar, Beeran,Patil, Nitin T.
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supporting information
p. 180 - 184
(2019/01/11)
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- Visible-light mediated carbamoyl radical addition to heteroarenes
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The generation of carbamoyl radicals, followed by their addition to heteroarenes, was performed under mild conditions through a metal-free photocatalyzed decarboxylation of oxamic acids. The process has been applied to the carbamoylation of heteroaromatic bases using α-aminoacid-derived oxamic acids, leading to the corresponding amides without racemization.
- Jatoi, Ashique Hussain,Pawar, Govind Goroba,Robert, Frédéric,Landais, Yannick
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supporting information
p. 466 - 469
(2019/01/10)
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- Method for preparing 2-iodoxybenzoic acid
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The invention relates to a method for preparing 2-iodoxybenzoic acid, and belongs to the technical field of synthesis of rings containing a halogen atom as a heterocyclic atom. The method comprises the following steps: adding an oxidant to 2-iodobenzoic acid used as a raw material, carrying out a reaction in an acidic solution at 50-120 DEG C for 1-6 h, and purifying the obtained reaction productto obtain the 2-iodoxybenzoic acid. The method has the advantages of small toxicity, mild technologic conditions, economical and cheap property and suitableness for industrialization when applied to the synthesis of a catalyst.
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Paragraph 0025-0030
(2019/02/13)
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- “Doubly Orthogonal” Labeling of Peptides and Proteins
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Herein, we report a cysteine bioconjugation methodology for the introduction of hypervalent iodine compounds onto biomolecules. Ethynylbenziodoxolones (EBXs) engage thiols in small organic molecules and cysteine-containing peptides and proteins in a fast and selective addition onto the alkynyl triple bond, resulting in stable vinylbenziodoxolone hypervalent iodine conjugates. The conjugation occurs at room temperature in an open flask under physiological conditions. The use of an azide-bearing EBX reagent enables a “doubly orthogonal” functionalization of the bioconjugate via strain-release-driven cycloaddition and Suzuki-Miyaura cross-coupling of the vinyl hypervalent iodine bond. We successfully applied the methodology on relevant and complex biomolecules, such as histone proteins. Through single-molecule experiments, we illustrated the potential of this doubly reactive bioconjugate by introducing a triplet-state quencher close to a fluorophore, which extended its lifetime by suppressing photobleaching. This work is therefore expected to find broad applications for peptide and protein functionalization. Understanding the molecular basis of life is essential in the search for new medicines. Chemical biology develops molecular tools for studying biological processes, setting the basis for new diagnostics and therapeutics, and relies heavily on the ability to selectively modify biomolecules. Two approaches have been especially fruitful: (1) selective modification of natural biomolecules and (2) selective reaction between non-natural functionalities in the presence of biomolecules (the so-called orthogonal bioconjugation). In our work, we contribute to both by transferring highly reactive hypervalent iodine reagents to cysteine residues in proteins and peptides. The obtained bioconjugates retain the reactive hypervalent bonds, which can be selectively functionalized via a metal-mediated reaction. Combined with a traditional azide tag, our approach allows a doubly orthogonal functionalization of biomolecules and is hence expected to be highly useful in chemical biology. Chemical biology develops molecular tools for studying biological processes, setting the basis for new diagnostics and therapeutics, and relies heavily on the ability to modify selectively biomolecules. In our work, we introduce hypervalent iodine bonds into peptides and proteins, via functionalization of cysteine, by using unique cyclic reagents developed in our group. The hypervalent bond can then be selectively modified in the presence of both natural and synthetic functional groups, opening new opportunities for applications in chemical biology.
- Tessier, Romain,Ceballos, Javier,Guidotti, Nora,Simonet-Davin, Raphael,Fierz, Beat,Waser, Jerome
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supporting information
p. 2243 - 2263
(2019/08/08)
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- 2-Iodo-N-isopropyl-5-methoxybenzamide as a highly reactive and environmentally benign catalyst for alcohol oxidation
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Several N-isopropyliodobenzamides were evaluated as catalysts for the oxidation of benzhydrol to benzophenone in the presence of Oxone (2KHSO5·KHSO4·K2SO4) as a co-oxidant at room temperature. A study on the substituent effect of the benzene ring of N-isopropyl-2-iodobenzamide on the oxidation revealed that its reactivity increased in the following order of substitution: 5-NO2 2Me, 3-OMe 5-OAc 5-Cl H, 4-OMe 5-Me 5-OMe. The oxidation of various benzylic and aliphatic alcohols using a catalytic amount of the most reactive 5-methoxy derivative successfully resulted in moderate to excellent yields of the corresponding carbonyl compounds. The high reactivity of the 5-methoxy derivative at room temperature is a result of the rapid generation of the pentavalent species from the trivalent species during the reaction. 5-Methoxy-2-iodobenzamide would be an efficient and environmentally benign catalyst for the oxidation of alcohols, especially benzylic alcohols.
- Yakura, Takayuki,Fujiwara, Tomoya,Yamada, Akihiro,Nambu, Hisanori
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supporting information
p. 971 - 978
(2019/11/11)
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- Iridium- and Rhodium-Catalyzed Directed C-H Heteroarylation of Benzaldehydes with Benziodoxolone Hypervalent Iodine Reagents
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The C-H heteroarylation of benzaldehydes with indoles and pyrroles was realized using the benziodoxolone hypervalent iodine reagents indole- and pyrroleBX. Functionalization of the aldehyde C-H bond using either an o-hydroxy or amino directing group and catalyzed by an iridium or a rhodium complex allowed the synthesis of salicyloylindoles and (2-sulfonamino)benzoylindoles, respectively, with good to excellent yields (74-98%). This new transformation could be carried out under mild conditions (rt to 40 °C) and tolerated a broad range of functionalities, such as ethers, halogens, carbonyls, or nitro groups.
- Grenet, Erwann,Waser, Jér?me
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supporting information
p. 1473 - 1476
(2018/03/09)
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- Rhodium-catalyzed C–H functionalization of heteroarenes using indoleBX hypervalent iodine reagents
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The C–H indolation of heteroarenes was realized using the benziodoxolone hypervalent iodine reagents indoleBXs. Functionalization of the C–H bond in bipyridinones and quinoline N-oxides catalyzed by a rhodium complex allowed to incorporate indole rings into aza-heteroaromatic compounds. These new transformations displayed complete regioselectivity for the C-6 position of bipyridinones and the C-8 position of quinoline N-oxides and tolerated a broad range of functionalities, such as halogens, ethers, or trifluoromethyl groups.
- Grenet, Erwann,Das, Ashis,Caramenti, Paola,Waser, Jér?me
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supporting information
p. 1208 - 1214
(2018/06/04)
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- Regioselective: Ortho -functionalization of bromofluorenecarbaldehydes using TMPMgCl·LiCl
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A highly regioselective functionalization of 7-bromofluorene-2-carbaldehydes, potent organic chromophores, in position C3 using a mild ortho-metallation strategy (DoM) with TMPMgCl·LiCl has been developed. This approach allows the preparation of highly functionalized fluorene derivatives by conversion of the in situ generated metalated species with various electrophiles giving a fast access to novel organic phosphorescent dyes.
- G?bel, Dominik,Clamor, Nils,Nachtsheim, Boris J.
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supporting information
p. 4071 - 4075
(2018/06/12)
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- Oxidase catalysis via aerobically generated hypervalent iodine intermediates
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The development of sustainable oxidation chemistry demands strategies to harness O'2 as a terminal oxidant. Oxidase catalysis, in which O'2 serves as a chemical oxidant without necessitating incorporation of oxygen into reaction products, would allow diverse substrate functionalization chemistry to be coupled to O'2 reduction. Direct O'2 utilization suffers from intrinsic challenges imposed by the triplet ground state of O'2 and the disparate electron inventories of four-electron O'2 reduction and two-electron substrate oxidation. Here, we generate hypervalent iodine reagents - a broadly useful class of selective two-electron oxidants - from O'2. This is achieved by intercepting reactive intermediates of aldehyde autoxidation to aerobically generate hypervalent iodine reagents for a broad array of substrate oxidation reactions. The use of aryl iodides as mediators of aerobic oxidation underpins an oxidase catalysis platform that couples substrate oxidation directly to O'2 reduction. We anticipate that aerobically generated hypervalent iodine reagents will expand the scope of aerobic oxidation chemistry in chemical synthesis.
- Maity, Asim,Hyun, Sung-Min,Powers, David C.
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p. 200 - 204
(2018/02/06)
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- Oxidation Catalysis by an Aerobically Generated Dess–Martin Periodinane Analogue
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Hypervalent iodine(V) reagents, such as Dess–Martin periodinane (DMP) and 2-iodoxybenzoic acid (IBX), are broadly useful oxidants in chemical synthesis. Development of strategies to generate these reagents from dioxygen (O2) would immediately enable use of O2 as a terminal oxidant in a broad array of substrate oxidation reactions. Recently we disclosed the aerobic synthesis of I(III) reagents by intercepting reactive oxidants generated during aldehyde autoxidation. In this work, aerobic oxidation of iodobenzenes is coupled with disproportionation of the initially generated I(III) compounds to generate I(V) reagents. The aerobically generated I(V) reagents exhibit substrate oxidation chemistry analogous to that of DMP. The developed aerobic generation of I(V) has enabled the first application of I(V) intermediates in aerobic oxidation catalysis.
- Maity, Asim,Hyun, Sung-Min,Wortman, Alan K.,Powers, David C.
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supporting information
p. 7205 - 7209
(2018/05/29)
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- Preparation method of 1-hydroxyl-1,2-benziodoxol-3(1H)-one
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The invention relates to a preparation method of 1-hydroxyl-1,2-benziodoxol-3(1H)-one. O-iodobenzoic acid, sodium periodate and glacial acetic acid are sequentially added to a 250 mL round-bottom flask and stirred until o-iodobenzoic acid is completely dissolved, and then reflux is performed; after condensed water (at the temperature of 25 DEG C) is introduced into a condensation pipe from bottomto top, the round-bottom flask is put in an oil bath pan at the temperature of 120 DEG C, magnetic stirring is performed, and the mixture reacts in a dark place for 4 h; after the reaction ends, the mixture is left to stand to be cooled to the room temperature, distilled water is added, the mixture is filtered, a rough product is collected and washed with icy water and acetone three times, a product is air-dried in the dark place and a white product of 1-hydroxyl-1,2-benziodoxol-3(1H)-one is obtained. The preparation method has mild reaction conditions, is simple in the technological process and high in selectivity, has higher yield reaching 93% and is environmentally friendly. The prepared product can be applied to the field of organic synthesis and the like.
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Paragraph 0013; 0014; 0015
(2018/05/16)
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- Selective Reductive Elimination at Alkyl Palladium(IV) by Dissociative Ligand Ionization: Catalytic C(sp3)?H Amination to Azetidines
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A palladium(II)-catalyzed γ-C?H amination of cyclic alkyl amines to deliver highly substituted azetidines is reported. The use of a benziodoxole tosylate oxidant in combination with AgOAc was found to be crucial for controlling a selective reductive elimination pathway to the azetidines. The process is tolerant of a range of functional groups, including structural features derived from chiral α-amino alcohols, and leads to the diastereoselective formation of enantiopure azetidines.
- Nappi, Manuel,He, Chuan,Whitehurst, William G.,Chappell, Ben G. N.,Gaunt, Matthew J.
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supporting information
p. 3178 - 3182
(2018/02/28)
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- Cyclic Hypervalent Iodine Reagents for Azidation: Safer Reagents and Photoredox-Catalyzed Ring Expansion
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Azides are building blocks of increasing importance in synthetic chemistry, chemical biology, and materials science. Azidobenziodoxolone (ABX, Zhdankin reagent) is a valuable azide source, but its safety profile has not been thoroughly established. Herein, we report a safety study of ABX, which shows its hazardous nature. We introduce two derivatives, tBu-ABX and ABZ (azidobenziodazolone), with a better safety profile, and use them in established photoredox- and metal-mediated azidations, and in a new ring-expansion of silylated cyclobutanols to give azidated cyclopentanones.
- Alazet, Sebastien,Preindl, Johannes,Simonet-Davin, Raphael,Nicolai, Stefano,Nanchen, Annik,Meyer, Thierry,Waser, Jerome
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supporting information
p. 12334 - 12356
(2018/09/27)
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- Investigations of alkynylbenziodoxole derivatives for radical alkynylations in photoredox catalysis
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The alkynylbenziodoxole derivatives are recently developed alkynylation reagents in organic synthesis, which demonstrate excellent radical alkynylation reactivity in photoredox catalysis reactions. Herein we report the synthesis of alkynylbenziodoxole derivatives with difluoro, monofluoro, monomethoxy, and dimethoxy substitution on the benziodoxole moiety, and investigated their radical alkynylation reactivity for the first time. A series of mechanistic experiments were conducted to study the radical acceptor and oxidative quencher reactivity of alkynylbenziodoxoles, in which unsubstituted alkynylbenziodoxoles played balancing roles in both processes, while electron-rich benziodoxole derivatives demonstrate synthetic advantages in some cases.
- Pan, Yue,Jia, Kunfang,Chen, Yali,Chen, Yiyun
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supporting information
p. 1215 - 1221
(2018/06/13)
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- Light-Driven Intermolecular Charge Transfer Induced Reactivity of Ethynylbenziodoxol(on)e and Phenols
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Ethynylbenziodoxol(on)es (EBXs) have been widely used in organic synthesis as electrophilic alkyne-transfer reagents involving carbon- and heteroatom-based nucleophiles. However, potential reactions of EBXs with phenols remain uninvestigated. Here, we present the formation of (Z)-2-iodovinyl phenyl ethers with excellent regio- and stereoselectivity through the reactivity between EBXs and phenols driven by visible light. We propose that this light-activated transformation proceeds through electron donor-acceptor complexes to enable new reactivity beyond existing mechanisms for alkynylation of carbon- and heteroatom-based nucleophiles. This operationally robust process was employed for the synthesis of diverse (Z)-2-iodovinyl phenyl ethers through irradiating a solution containing a phenyl-EBX, a phenol, and the base Cs2CO3 with a commercially available blue LED at room temperature. The (Z)-2-iodovinyl phenyl ether products can be further stereospecifically functionalized to form trisubstituted alkenes, demonstrating the potential of these products en route to chemical complexity.
- Liu, Bin,Lim, Chern-Hooi,Miyake, Garret M.
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supporting information
p. 12829 - 12835
(2018/10/15)
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- Visible-light photocatalyzed oxidative decarboxylation of oxamic acids: a green route to urethanes and ureas
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A sustainable metal-free route to urethanes and ureas based on a photocatalyzed oxidative decarboxylation of oxamic acids is described. The reaction includes in situ generation of an isocyanate from the oxamic acid, using an organic dye as a photocatalyst, a hypervalent iodine reagent as an oxidant and a light source, which trigger the free-radical decarboxylation. This protocol successfully avoids the isolation, purification and storage of carcinogenic isocyanates and allows elaboration of urethanes and ureas in a one-pot process from commercially available sources.
- Pawar, Govind Goroba,Robert, Frédéric,Grau, Etienne,Cramail, Henri,Landais, Yannick
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supporting information
p. 9337 - 9340
(2018/08/31)
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- Epimerization of Tertiary Carbon Centers via Reversible Radical Cleavage of Unactivated C(sp3)-H Bonds
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Reversible cleavage of C(sp3)-H bonds can enable racemization or epimerization, offering a valuable tool to edit the stereochemistry of organic compounds. While epimerization reactions operating via cleavage of acidic C(sp3)-H bonds, such as the Cα-H of carbonyl compounds, have been widely used in organic synthesis and enzyme-catalyzed biosynthesis, epimerization of tertiary carbons bearing a nonacidic C(sp3)-H bond is much more challenging with few practical methods available. Herein, we report the first synthetically useful protocol for the epimerization of tertiary carbons via reversible radical cleavage of unactivated C(sp3)-H bonds with hypervalent iodine reagent benziodoxole azide and H2O under mild conditions. These reactions exhibit excellent reactivity and selectivity for unactivated 3° C-H bonds of various cycloalkanes and offer a powerful strategy for editing the stereochemical configurations of carbon scaffolds intractable to conventional methods. Mechanistic study suggests that the unique ability of N3? to serve as a catalytic H atom shuttle is critical to reversibly break and reform 3° C-H bonds with high efficiency and selectivity.
- Wang, Yaxin,Hu, Xiafei,Morales-Rivera, Cristian A.,Li, Guo-Xing,Huang, Xin,He, Gang,Liu, Peng,Chen, Gong
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supporting information
p. 9678 - 9684
(2018/07/21)
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- Heterotetracenes: Flexible Synthesis and in Silico Assessment of the Hole-Transport Properties
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Thienoacenes and furoacenes are among the most frequent molecular units found in organic materials. The efficient synthesis of morphologically different heteroacenes and the rapid determination of their solid-state and electronic properties are still challenging tasks, which slow down progress in the development of new materials. Here, we report a flexible and efficient synthesis of unprecedented heterotetracenes based on a platinum- and gold-catalyzed cyclization–alkynylation domino process using EthynylBenziodoXole (EBX) hypervalent iodine reagents in the key step. The proof-of-principle in silico estimation of the synthesized tetracenes’ charge transport properties reveals their strong dependence on both the position and nature of the heteroatoms in the ring system. A broad range of mobility is predicted, with some compounds displaying performance potentially comparable to that of state-of-the-art electronic organic materials.
- Li, Yifan,Gryn'ova, Ganna,Saenz, Felipe,Jeanbourquin, Xavier,Sivula, Kevin,Corminboeuf, Clémence,Waser, Jér?me
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supporting information
p. 8058 - 8065
(2017/06/19)
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- Enantioselective Copper-Catalyzed Oxy-Alkynylation of Diazo Compounds
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Enantioselective catalytic methods allowing the addition of both a nucleophile and an electrophile onto diazo compounds give a fast access into important building blocks. Herein, we report the highly enantioselective oxyalkynylation of diazo compounds usi
- Hari, Durga Prasad,Waser, Jerome
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supporting information
p. 8420 - 8423
(2017/07/06)
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- Gold-catalyzed domino cyclization-alkynylation reactions with EBX reagents: New insights into the reaction mechanism
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Gold-catalyzed domino processes constitute a useful alternative to C-H functionalization for the synthesis of functionalized (hetero)arenes. Herein, we report computational studies on the gold-catalyzed cyclization alkynylation of keto-allenes with ethyny
- Ghari, Hossein,Li, Yifan,Roohzadeh, Roohollah,Caramenti, Paola,Waser, Jerome,Ariafard, Alireza
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supporting information
p. 12257 - 12262
(2017/09/25)
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