- Iron-Catalyzed Enantioselective Radical Carboazidation and Diazidation of α,β-Unsaturated Carbonyl Compounds
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Azidation of alkenes is an efficient protocol to synthesize organic azides which are important structural motifs in organic synthesis. Enantioselective radical azidation, as a useful strategy to install a C-N3 bond, remains challenging due to the inherently instability and unique structure of radicals. Here, we disclose an efficient enantioselective radical carboazidation and diazidation of α,β-unsaturated ketones and amides catalyzed by chiral N,N′-dioxide/Fe(OTf)2 complexes. An array of substituted alkenes was transformed to the corresponding α-azido carbonyl derivatives in good to excellent enantioselectivities, benefiting the preparation of chiral α-amino ketones, vicinal amino alcohols, and vicinal diamines. Control experiments and mechanistic studies proved the radical pathway in the reaction process. The DFT calculations showed that the azido transferred to the radical intermediate via an intramolecular five-membered transition state with the internal nitrogen of the Fe-N3 species.
- Liu, Wen,Pu, Maoping,He, Jun,Zhang, Tinghui,Dong, Shunxi,Liu, Xiaohua,Wu, Yun-Dong,Feng, Xiaoming
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supporting information
p. 11856 - 11863
(2021/08/16)
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- One-Pot Synthesis of Primary and Secondary Aliphatic Amines via Mild and Selective sp3 C?H Imination
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The direct replacement of sp3 C?H bonds with simple amine units (?NH2) remains synthetically challenging, although primary aliphatic amines are ubiquitous in medicinal chemistry and natural product synthesis. We report a mild and selective protocol for preparing primary and secondary aliphatic amines in a single pot, based on intermolecular sp3 C?H imination. The first C?H imination of diverse alkanes, this method shows useful site-selectivity within substrates bearing multiple sp3 C?H bonds. Furthermore, this reaction tolerates polar functional groups relevant for complex molecule synthesis, highlighted in the synthesis of amine pharmaceuticals and amination of natural products. We characterize a unique C?H imination mechanism based on radical rebound to an iminyl radical, supported by kinetic isotope effects, stereoablation, resubmission, and computational modeling. This work constitutes a selective method for complex amine synthesis and a new mechanistic platform for C?H amination.
- Comito, Robert J.,Ghosh, Subrata K.,Hu, Mengnan
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supporting information
p. 17601 - 17608
(2021/11/03)
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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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- Radical C?H-Amination of Heteroarenes using Dual Initiation by Visible Light and Iodine
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A novel light-induced C?H amination of heteroarenes can be accomplished with preformed iodine(III) reagents as the combined oxidant and nitrogen source. The reaction requires the use of a small amount of molecular iodine, which under photochemical activation generates in situ an iodine(I) reagent as the initiator of the radical amination reaction. A total of 32 examples exemplify the broad scope of the transformation. (Figure presented.).
- Lucchetti, Nicola,Tkacheva, Anastasia,Fantasia, Serena,Mu?iz, Kilian
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supporting information
p. 3889 - 3893
(2018/09/21)
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- Determining the predominant tautomeric structure of iodine-based group-transfer reagents by 17O NMR spectroscopy
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Cyclic benziodoxole systems have become a premier scaffold for the design of electrophilic transfer reagents. A particularly intriguing aspect is the fundamental II–IIII tautomerism about the hypervalent bond, which has led in certain cases to a surprising re-evaluation of the classic hypervalent structure. Thus, through a combination of 17O NMR spectroscopy at natural abundance with DFT calculations, we establish a convenient method to provide solution-phase structural insights for this class of ubiquitous reagents. In particular, we confirm that Shen’s revised, electrophilic SCF3-transfer reagent also adopts an "acyclic" thioperoxide tautomeric form in solution. After calibration, the approach described herein likely provides a more general and direct method to distinguish between cyclic and acyclic structural features based on a single experimental 17O NMR spectrum and a computationally-derived isotropic shift value. Furthermore, we apply this structural elucidation technique to predict the constitution of an electrophilic iodine-based cyano-transfer reagent as an NC–I–O motif and study the acid-mediated activation of Togni's trifluoromethylation reagent.
- Santschi, Nico,Pitts, Cody Ross,Jelier, Benson J.,Verel, René
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p. 2289 - 2294
(2018/09/14)
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- Metal-Free Oxidative Cross Coupling of Indoles with Electron-Rich (Hetero)arenes
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A new method for the synthesis of bi-heteroaryls is reported, based on the umpolung of indoles with benziodoxol(on)e hypervalent iodine reagents (IndoleBX). The oxidative coupling of IndoleBX with an equimolar amount of electron-rich benzenes, indoles, pyrroles, and thiophenes proceeded under mild transition-metal-free conditions. Functionalized non-symmetrical bi-indolyl heterocycles were accessed efficiently. Introduction of a new type of C2-substituted indole benziodoxole reagents further allowed extending the scope of the reaction to NH unprotected and C3-alkylated indoles. The obtained bi-heterocycles are important building blocks in synthetic and medicinal chemistry, and could be easily transformed into more complex heterocyclic systems.
- Caramenti, Paola,Nandi, Raj Kumar,Waser, Jerome
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supporting information
p. 10049 - 10053
(2018/07/29)
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- Divergent Access to (1,1) and (1,2)-Azidolactones from Alkenes using Hypervalent Iodine Reagents
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A versatile synthesis of azidolactones through azidation and cyclization of carboxylic acids onto alkenes has been developed. Based on either photoredox or palladium catalysis, (1,1) and (1,2) azido lactones can be selectively synthesized. The choice of catalyst and benziodoxol(on)e reagent serving as azide source was essential to initiate either a radical or Lewis acid mediated process with divergent outcome. These transformations were carried out under mild conditions using a low catalyst loading and gave access to a large scope of azido lactones.
- Alazet, Sébastien,Le Vaillant, Franck,Nicolai, Stefano,Courant, Thibaut,Waser, Jerome
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supporting information
p. 9501 - 9504
(2017/07/22)
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- Synthesis and Structure of Hypervalent Iodine(III) Reagents Containing Phthalimidate and Application to Oxidative Amination Reactions
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A new class of hypervalent iodine reagents containing phthalimidate was synthesized, and structurally characterized by X-ray analysis. The benziodoxole-based reagent displays satisfactory solubility in common organic solvents and is reasonably stable in solution as well as in the solid state. The reagent was used for the oxidative amination of the C(sp3)-H bond of N,N-dimethylanilines. In addition, the reagent was also applicable to oxidative amination with rearrangement of trialkylamines as well as enamines that were prepared in situ from secondary amines and aldehydes.
- Kiyokawa, Kensuke,Kosaka, Tomoki,Kojima, Takumi,Minakata, Satoshi
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p. 13719 - 13723
(2015/11/11)
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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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supporting information
p. 5832 - 5835
(2015/12/11)
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- Ethynylbenziodoxolones (EBX) as reagents for the ethynylation of stabilized enolates
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Herein, we report a detailed study on the electrophilic alkynylation of cyclic keto esters and amides with ethynylbenziodoxolone (EBX) reagents. The structure and stability of this class of reagents is first described more in details. Differential scannin
- Fernandez Gonzalez, Davinia,Brand, Jonathan P.,Mondiere, Regis,Waser, Jerome
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supporting information
p. 1631 - 1639
(2013/07/05)
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- One-pot synthesis of hypervalent iodine reagents for electrophilic trifluoromethylation
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Simplified syntheses suited for large scale preparations of the two hypervalent iodine reagents 1 and 2 for electrophilic trifluoromethylation are reported. In both cases, the stoichiometric oxidants sodium metaperiodate and tert-butyl hypochlorite have been replaced by trichloroisocyanuric acid. Reagent 1 is accessible in a one-pot procedure from 2-iodobenzoic acid in 72% yield. Reagent 2 was prepared via fluoroiodane 11 in a considerably shorter reaction time and with no need of an accurate temperature control.
- Matousek, Vaclav,Pietrasiak, Ewa,Schwenk, Rino,Togni, Antonio
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p. 6763 - 6768
(2013/07/26)
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- Gold-catalyzed regioselective synthesis of 2- and 3-alkynyl furans
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Chemical Matching: C2- or C3-alkynylated furans were selectively synthesized by using gold catalysis. Direct C-H alkynylation of furans was achieved with C2 selectivity, and a domino cyclization/alkynylation process starting from allenes gave C3-alkynylat
- Li, Yifan,Brand, Jonathan P.,Waser, Jerome
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supporting information
p. 6743 - 6747
(2013/07/26)
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- Azidation of β-keto esters and silyl enol ethers with a benziodoxole reagent
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The efficient azidation of β-keto esters and silyl enol ethers using a benziodoxole-derived azide transfer reagent is reported. The azidation of cyclic β-keto esters could be achieved in up to quantitative yields in the absence of any catalyst. In the case of less reactive linear β-keto esters and silyl enol ethers, complete conversion and good yields could be obtained by using a zinc catalyst.
- Vita, Maria Victoria,Waser, Jerome
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supporting information
p. 3246 - 3249
(2013/07/26)
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- Ethynyl benziodoxolones for the direct alkynylation of heterocycles: Structural requirement, improved procedure for pyrroles, and insights into the mechanism
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This report describes a full study of the gold-catalyzed direct alkynylation of indoles, pyrroles, and thiophenes using alkynyl hypervalent iodine reagents, especially the study of the structural requirements of alkynyl benziodoxolones for an efficient acetylene transfer to heterocycles. An improved procedure for the alkynylation of pyrroles using pyridine as additive is also reported. Nineteen alkynyl benziodoxol(on)es were synthesized and evaluated in the direct alkynylation of indoles and/or thiophenes. Bulky silyl groups as acetylene substituents were optimal. Nevertheless, transfer of aromatic acetylenes to thiophene was achieved for the first time. An accelerating effect of a methyl substituent in both the 3-and 6-position of triisopropylsilylethynyl-1,2-benziodoxol-3(1H)-one (TIPS-EBX) on the reaction rate was observed. Competitive experiments between substrates of different nucleophilicity, deuterium labeling experiments, as well as the regioselectivity observed are all in agreement with electrophilic aromatic substitution. Gold(III) 2-pyridinecarboxylate dichloride was also an efficient catalyst for the reaction. Investigations indicated that gold(III) could be eventually reduced to gold(I) during the process. As a result of these investigations, a π activation or an oxidative mechanism are most probable for the alkynylation reaction.
- Brand, Jonathan P.,Chevalley, Clara,Scopelliti, Rosario,Waser, Jerome
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supporting information; experimental part
p. 5655 - 5666
(2012/06/01)
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- Connecting binuclear Pd(III) and mononuclear Pd(IV) chemistry by Pd-Pd bond cleavage
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Oxidation of binuclear Pd(II) complexes with PhICl2 or PhI(OAc)2 has previously been shown to afford binuclear Pd(III) complexes featuring a Pd-Pd bond. In contrast, oxidation of binuclear Pd(II) complexes with electrophilic trifluoromethylating ("CF3 +") reagents has been reported to afford mononuclear Pd(IV) complexes. Herein, we report experimental and computational studies of the oxidation of a binuclear Pd(II) complex with "CF3 +" reagents. These studies suggest that a mononuclear Pd(IV) complex is generated by an oxidation-fragmentation sequence proceeding via fragmentation of an initially formed, formally binuclear Pd(III), intermediate. The observation that binuclear Pd(III) and mononuclear Pd(IV) complexes are accessible in the same reactions offers an opportunity for understanding the role of nuclearity in both oxidation and subsequent C-X bond-forming reactions.
- Powers, David C.,Lee, Eunsung,Ariafard, Alireza,Sanford, Melanie S.,Yates, Brian F.,Canty, Allan J.,Ritter, Tobias
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supporting information; experimental part
p. 12002 - 12009
(2012/09/08)
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- New hypervalent iodine reagents for electrophilic trifluoromethylation and their precursors: Synthesis, structure, and reactivity
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Several new five- and a six-membered heterocyclic monochloroiodanes, including two cationic species, were synthesized. Three of which were used for the preparation of corresponding trifluoromethylation reagents. These compounds were characterized by X-ray crystallography for a comparative structural study. A reactivity study on the trifluoromethylation of para-toluenesulfonic acid has been conducted in order to compare initial rates. Compounds having a longer I-O bond display a higher reactivity.
- Niedermann, Katrin,Welch, Jan M.,Koller, Raffael,Cvengro, Ján,Santschi, Nico,Battaglia, Philip,Togni, Antonio
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scheme or table
p. 5753 - 5761
(2010/09/18)
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- Recent advances in electrophilic CF3-transfer using hypervalent iodine(III) reagents
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The development of new methodologies for an efficient introduction of CF3 groups into complex molecules constitutes one of the most challenging tasks of modern organic chemistry. Recently, we reported the access to a new class of electrophilic CF3-transfer reagents based on hypervalent iodine. The versatile application of these reagents to C-centred nucleophiles, such as β-keto esters, silyl enol ethers and α-nitro esters, as well as to thiols and primary and secondary phosphines is described. Experiments with phenols afforded corresponding trifluomethylethers in very low yields. Schweizerische Chemische Gesellschaft.
- Kieltsch, Iris,Eisenberger, Patrick,Stanek, Kyrill,Togni, Antonio
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scheme or table
p. 260 - 263
(2009/04/07)
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- Novel 10-I-3 hypervalent iodine-based compounds for electrophilic trifluoromethylation
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The synthesis of a new family of 10-I-3 hypervalent iodine compounds is described in which the CF3 functionality participates directly in the hypervalent bond. These materials are accessible by nucleophilic ligand substitution at iodine using Me3SiCF3 in the presence of a substoichiometric amount of fluoride. The expected T-shaped geometry at iodine was verified by X-ray crystallographic analyses of three of the products (1-trifluoromethyl-1,2-benziodoxol-3-(1 H)-one and two substituted 1-trifluoromethyl-1,3-dihydro-1,2-benziodoxoles). Preliminary results for the direct electrophilic transfer of the trifluoromethyl moiety onto organic nucleophiles show modest reactivity in polar aprotic solvents under relatively mild conditions. The overall process can be understood as a formal umpolung of the CF3 group.
- Eisenberger, Patrick,Gischig, Sebastian,Togni, Antonio
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p. 2579 - 2586
(2008/02/04)
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- Organoiodinane Reagents for Phosphate Cleavage: Experimental and Computational Studies
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Several analogues of 1-oxido-1,2-benziodoxol-3(1H)-one, 1 (the valence tautomer of o-iodosobenzoate), were examined for the ability to cleave p-nitrophenyl diphenyl phosphate in aqueous micellar cetyltrimethylammonium chloride at pH 8.These included the 5
- Moss, Robert A.,Wilk, Boguslawa,Krogh-Jespersen, Karsten,Blair, John T.,Westbrook, John D.
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p. 250 - 258
(2007/10/02)
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