- 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.
- Dong, Shunxi,Feng, Xiaoming,He, Jun,Liu, Wen,Liu, Xiaohua,Pu, Maoping,Wu, Yun-Dong,Zhang, Tinghui
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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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- Synthesis, Characterization, and Reactivity of a Hypervalent-Iodine-Based Nitrooxylating Reagent
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Herein, the synthesis and characterization of a hypervalent-iodine-based reagent that enables a direct and selective nitrooxylation of enolizable C?H bonds to access a broad array of organic nitrate esters is reported. This compound is bench stable, easy-
- Calvo, Roxan,Katayev, Dmitry,Le Tellier, Antoine,Nater, Darryl,Nauser, Thomas,Rombach, David
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supporting information
p. 17162 - 17168
(2020/07/31)
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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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- Synthesis, Characterization, and Reaction of a Both Inter- and Intramolecularly Coordinated Pseudocyclic Iodosylbenzene–Trifluoroacetic Acid Complexes
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An ortho-substituted ether-oxygen-coordinated pseudocyclic iodosylbenzene-trifluoroacetic acid (pcISB-TFA) complex was synthesized and characterized by X-ray crystallographic analysis. TFA suppresses the disproportionation by both coordination of the oxygen atom to the iodine(III) center through secondary bonding and by hydrogen bonding to the oxygen anion. This bench-stable reagent is highly soluble in common organic solvents and reacts with various organic substrates under mild reaction conditions to give the corresponding products in good yields.
- Yudasaka, Masaharu,Maruyama, Toshifumi,Yamaguchi, Eiji,Tada, Norihiro,Itoh, Akichika
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p. 550 - 556
(2018/02/09)
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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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- Silver-promoted (radio)fluorination of unsaturated carbamates via a radical process
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The intramolecular fluorocyclization of unsaturated carbamates is described here using a hypervalent iodine reagent in the presence of a silver catalyst. Both (hetero)aryl-substituted olefins and acrylamides can be utilized as effective substrates. Preliminary mechanistic investigations suggest that the reaction proceeds via a cyclization/1,2-(hetero)aryl migration/fluorination cascade involving an unusual radical process. Furthermore, starting from no-carrier-added [18F]TBAF, a simple one-pot, two-step cascade method was developed for the generation of 18F-labeled heterocycles with high radiochemical purity.
- Yang, Bin,Chansaenpak, Kantapat,Wu, Hongmiao,Zhu, Lin,Wang, Mengzhe,Li, Zibo,Lu, Hongjian
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supporting information
p. 3497 - 3500
(2017/03/30)
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- Synthesis of Multisubstituted Triphenylenes and Phenanthrenes by Cascade Reaction of o-Iodobiphenyls or (Z)-β-Halostyrenes with o-Bromobenzyl Alcohols through Two Sequential C-C Bond Formations Catalyzed by a Palladium Complex
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o-Bromobenzyl alcohol has been developed as a novel annulating reagent, bearing both nucleophilic and electrophilic substituents, for the facile synthesis of polycyclic aromatic hydrocarbons. A palladium/electron-deficient phosphine catalyst efficiently coupled o-iodobiphenyls or (Z)-β-halostyrenes with o-bromobenzyl alcohols to afford triphenylenes and phenanthrenes, respectively. The present cascade reaction proceeded through deacetonative cross-coupling and sequential intramolecular cyclization. An array of experimental data suggest that the reaction mechanism involves the equilibrium of 1,4-palladium migration.
- Iwasaki, Masayuki,Araki, Yasuhiro,Iino, Shohei,Nishihara, Yasushi
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p. 9247 - 9263
(2015/09/28)
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- Intramolecular fluorocyclizations of unsaturated carboxylic acids with a stable hypervalent fluoroiodane reagent
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A new class of fluorinated lactones was prepared by the intramolecular fluorocyclizations of unsaturated carboxylic acids by using the stable fluoroiodane reagent in combination with AgBF4. This unique reaction incorporates a cyclization, an aryl migration, and a fluorination all in one step. The fluoroiodane reagent, prepared easily from fluoride, can also be used without a metal catalyst to give moderate yields within just 1 hour, thus demonstrating that it is a suitable reagent for developing new 18F-labelled radiotracers for PET imaging. All in one: A new class of lactones containing a tertiary alkyl fluoride was prepared in high yields by using a stable fluoroiodane reagent. This unique reaction incorporates a cyclization, an aryl migration, and a fluorination all in one step.
- Geary, Gemma C.,Hope, Eric G.,Stuart, Alison M.
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supporting information
p. 14911 - 14914
(2016/02/05)
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- Structure-reactivity relationship of trifluoromethanesulfenates: Discovery of an electrophilic trifluoromethylthiolating reagent
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A family of electrophilic trifluoromethanesulfenates was prepared. Structure-reactivity relationship studies showed that the substituted groups on the aryl ring of the trifluoromethylthiolating reagent did not have an obvious influence on their reactivities. A simplified electrophilic trifluoromethylthiolating reagent 1c was then identified that can react with a wide range of nucleophiles such as Grignard reagents, arylboronic acids, alkynes, indoles, β-ketoesters, oxindoles, and sodium sulfinates under mild reaction conditions. A variety of functional groups were tolerated under these conditions.
- Shao, Xinxin,Xu, Chunfa,Lu, Long,Shen, Qilong
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p. 3012 - 3021
(2015/03/30)
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- General and practical formation of thiocyanates from thiols
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A new method for the cyanation of thiols and disulfides using cyanobenziodoxol(on)e hypervalent iodine reagents is described. Both aliphatic and aromatic thiocyanates can be accessed in good yields in a few minutes at room temperature starting from a broad range of thiols with high chemioselectivity. The complete conversion of disulfides to thiocyanates was also possible. Preliminary computational studies indicated a low energy concerted transition state for the cyanation of the thiolate anion or radical. The developed thiocyanate synthesis has broad potential for various applications in synthetic chemistry, chemical biology and materials science.
- Frei, Reto,Courant, Thibaut,Wodrich, Matthew D.,Waser, Jerome
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supporting information
p. 2662 - 2668
(2015/02/05)
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- An enantioselective formal synthesis of montelukast sodium
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A formal synthesis of the antiasthma drug montelukast sodium is described, wherein the key chiral diol intermediate was accessed with greater convergence of the C-C bond-forming steps as compared to previous routes. Improved synthetic efficiency was achie
- Bollikonda, Satyanarayana,Mohanarangam, Saravanan,Jinna, Rajender Reddy,Kandirelli, Venkata Kiran Kumar,Makthala, Laxman,Sen, Saikat,Chaplin, David A.,Lloyd, Richard C.,Mahoney, Thomas,Dahanukar, Vilas Hareshwar,Oruganti, Srinivas,Fox, Martin E.
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p. 3891 - 3901
(2015/06/02)
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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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- Palladium-catalyzed annulation of o-iodobiphenyls with o-bromobenzyl alcohols: Synthesis of functionalized triphenylenes via C-C and C-H bond cleavages
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Treatment of o-iodobiphenyls with o-bromobenzyl alcohols in the presence of cesium carbonate under palladium catalysis affords a series of highly substituted triphenylenes. The reaction involves two C-C bond formations and C-C and C-H bond cleavages. A combination of palladium and an electron-deficient phosphine ligand proves to be effective for both decarbonylative cross-coupling and intramolecular cyclization.
- Iwasaki, Masayuki,Iino, Shohei,Nishihara, Yasushi
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supporting information
p. 5326 - 5329
(2013/11/06)
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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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p. 12002 - 12009
(2012/09/08)
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- A conjunctive carboiodination: Indenes by a double carbopalladation- reductive elimination domino process
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Something gained, nothing lost: A Pd0-catalyzed domino intermolecular/intramolecular process terminated by carbohalogenation is reported. In this reaction, two new C-C bonds, one new C-I bond and one five-membered ring are formed in a single step, and all of the atoms in the starting materials are incorporated into the product (see scheme). Copyright
- Jia, Xiaodong,Petrone, David A.,Lautens, Mark
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supporting information
p. 9870 - 9872
(2012/10/30)
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- Phosphine/palladium-catalyzed syntheses of alkylidene phthalans, 3-deoxyisoochracinic acid, isoochracinic acid, and isoochracinol
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In this study we used sequential catalysis-PPh3-catalyzed nucleophilic addition followed by Pd(0)-catalyzed Heck cyclization-to construct complex functionalized alkylidene phthalans rapidly, in high yields, and with good stereoselectivities (E/Z ratios of up to 1:22). The scope of this Michael-Heck reaction includes substrates bearing various substituents around the alkylidene phthalan backbone. Applying this efficient sequential catalysis, we accomplished concise total syntheses of 3-deoxyisoochacinic acid, isoochracinic acid, and isoochracinol.
- Fan, Yi Chiao,Kwon, Ohyun
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supporting information; experimental part
p. 3264 - 3267
(2012/08/28)
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- Lipase-mediated resolution of substituted 2-aryl-propanols: Application to the enantioselective synthesis of phenolic sesquiterpenes
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A comprehensive study of the lipase-mediated resolution of substituted 2-aryl-propanols is reported. The latter alcohols were submitted to the irreversible acetylation catalyzed either by PPL, CRL, or lipase PS. The enantioselectivity of these transformations was dependent on the type of lipase used. The type of substituents and particularly their position on the aromatic ring strongly affected the selectivity of the reaction. The experiments described prove that PPL is the more versatile lipase catalyzing the acetylation with an enantiomeric ratio (E) value that ranges from 1 up to 144, depending on the substrate used. Conversely, the same transformations were catalyzed by CRL and lipase PS with an enantiomeric ratio value, which is always less than 5. The remarkable behavior of PPL was exploited in the large scale resolution of some substituted 2-aryl-propanols whose enantiomeric forms are relevant building blocks in the enantioselective synthesis of phenolic sesquiterpenes. By these means, the synthesis of (S)-turmeronol B and the formal syntheses of (R)-curcumene, (R)-curcuphenol, (R)-xanthorrhizol, and (R)-curcuhydroquinone were accomplished.
- Serra, Stefano
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experimental part
p. 619 - 628
(2011/07/08)
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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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- Evidence for divalent iodine (9-I-2) radical intermediates in the thermolysis of (tert-butylperoxy)iodanes. An unusually efficient deiodination of o-iodocumyl alcohols by cyclohexyl radicals
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1-(tert-Butylperoxy)-3,3-dimethyl-1H-1,2-benziodoxoles (2a and 2b) and 1-(tert-butylperoxy)-3,3-bis(trifluoromethyl)-5-methyl-1H-1,2-benziodo xole (2c) were prepared from chloroiodanes 1a-c and tert-butylhydroperoxide in the presence of potassium tert-butoxide in tetrahydrofuran. Products, kinetic data for the decomposition of 2 in cyclohexane, benzene, toluene, and acetonitrile (E(a) = 31.0 ± 1.0 kcal/mol, log A = 17.0 ± 0.5; 35-70 °C), and the increased rate of decomposition of 2c in benzene-d6 in the presence of a magnetic field (7 T) indicate that homolytic cleavage of the I-O bond in 2 with the formation of iodanyl (9-I-2) and tert-butylperoxyl radicals is the primary decomposition step. The nearly quantitative formation of iodocyclohexane during the decomposition of 2c in cyclohexane is due to the unexpected reaction of cyclohexyl radicals with 2-(2-iodo-5-methylphenyl)-1,1,1,3,3,3-hexafluoro-2-propanol, a primary decomposition product of 2c. The results of a separate study of the deiodination of o-iodocumyl alcohols (3) by cyclohexyl radicals are consistent with an S(H)2 type mechanism.
- Dolenc, Darko,Plesni?ar, Bo?o
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p. 2628 - 2632
(2007/10/03)
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- Unsaturated hydroxyalkylquinoline acids as leukotriene antagonists
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Compounds having the formula I: STR1 are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
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- Fluorinated hydroxyalkylquinoline acids as leukotriene antagonists
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Compounds having the formula I: STR1 are leukotriene antagonists and inhibitors of leukotriene biosynthesis. These compounds are useful as anti-asthmatic, anti-allergic, anti-inflammatory, and cytoprotective agents. They are also useful in treating angina, cerebral spasm, glomerular nephritis, hepatitis, endotoxemia, uveitis, and allograft rejection.
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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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