- Triphosgene and DMAP as Mild Reagents for Chemoselective Dehydration of Tertiary Alcohols
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The utility of triphosgene and DMAP as mild reagents for chemoselective dehydration of tertiary alcohols is reported. Performed in dichloromethane at room temperature, this reaction is readily tolerated by a broad scope of substrates, yielding alkenes preferentially with the (E)-geometry. While formation of the Hofmann products is generally favored, a dramatic change in alkene selectivity toward the Zaitzev products is observed when the reaction is carried out in dichloroethane at reflux.
- Ganiu, Moshood O.,Cleveland, Alexander H.,Paul, Jarrod L.,Kartika, Rendy
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supporting information
p. 5611 - 5615
(2019/08/01)
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- Oxidation of Tertiary Aromatic Alcohols to Ketones in Water
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A new rosin-based amphiphile enables the oxidation of tertiary aromatic alcohols in water under mild conditions. The oxidation process is mediated by β-scission of alkoxy radicals. Our catalyst system including the surfactant, catalysts, and water can be easily recycled within the same reaction vial. (Figure presented.).
- Chen, Dengfeng,Zhang, Yuchen,Pan, Xingyu,Wang, Fei,Huang, Shenlin
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supporting information
p. 3607 - 3612
(2018/09/18)
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- On the effect of backbone modifications in 3,3-dimethyl-1-(trifluoromethyl)-3H-1λ3,2-benziodaoxole
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We report on the effect of small side-chain modifications to the structure of 3,3-dimethyl-1-(trifluoromethyl)-3H-1λ3,2-benziodaoxole (1b) on its reactivity, as expressed by the initial rate v0 in a model reaction, and show how the latter can be successfully correlated to an easily determined physical parameter p, a 13C NMR chemical shift. The relationship v0~ p is already present in the simplest starting material devoid of the hypervalent bond and the iodine core and, therefore, presents an interesting approach towards the future scaffold-optimization of this class of reagents. The reactivity of hypervalent-iodine-based trifluoromethylating agents, as expressed by the initial rate v0 in a model reaction, correlates to an easily determined physical parameter p, a 13C NMR chemical shift.
- Santschi, Nico,Matthey, Coraline,Schwenk, Rino,Otth, Elisabeth,Togni, Antonio
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supporting information
p. 1925 - 1931
(2015/03/18)
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- Examining the origin of selectivity in the reaction of racemic alcohols with chiral N-phosphoryl oxazolidinones
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A range of known and novel N-phosphoryl oxazolidinones and imidazolidinones were prepared and screened in the kinetic resolution of a range of racemic magnesium chloroalkoxides. Models are proposed to account for the enantioselectivity achieved based on a combination of chiral relay effects, generation of transient stereochemistry and the structure of the intermediate magnesium alkoxide.
- Crook, Samuel,Parr, Nigel J.,Simmons, Jonathan,Jones, Simon
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p. 1298 - 1308
(2015/01/09)
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- Factors affecting migration of tertiary alkyl groups in reactions of alkylboronic esters with bromomethyllithium
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The reactions of bromomethyllithium with tert-alkylboronic esters could be of great potential for the formation of quaternary carbon centers but often give poor yields/conversions. Calculations and experimental evidence show that tert-alkyl groups migrate less effectively than other types of alkyl group in such reactions and that O-migration competes. Furthermore, slow/incomplete capture of the bromomethyl reagent by the boronic ester is a problem in more hindered systems, and an additional competing reaction, possibly Li-Br exchange on the bromomethylborate species, also leads to lower yields of migrated products. Based on this, experimental protocols have been devised in which the competing reactions are largely suppressed, leading to higher conversions to migrated product for several substrates.
- Elliott, Mark C.,Smith, Keith,Heulyn Jones,Hussain, Ajaz,Saleh, Basil A.
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p. 3057 - 3064
(2013/06/27)
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- Added-metal-free catalytic nucleophilic addition of Grignard reagents to ketones
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On the basis of the investigation of the combinational effect of quaternary ammonium salts and organic bases, an added-metal-free catalytic system for nucleophilic addition reactions of a variety of Grignard reagents to diverse ketones in THF solvent has been developed to produce tertiary alcohols in good to excellent yields. By using tetrabutylammonium chloride (NBu4Cl) as a catalyst and diglyme (DGDE) as an additive, this system strongly enhances the efficiency of addition at the expense of enolization and reduction. NBu 4Cl should help to shift the Schlenk equilibrium of Grignard reagents to the side of dimeric Grignard reagents to favor the additions of Grignard reagents to ketones via a favored six-membered transition state to form the desired tertiary alcohols, and DGDE should increase the nucleophilic reactivities of Grignard reagents by coordination. This catalytic system has been applied in the efficient synthesis of Citalopram, an effective U.S. FDA-approved antidepressant, and a recyclable version of this catalytic synthesis has also been devised.
- Zong, Hua,Huang, Huayin,Liu, Junfeng,Bian, Guangling,Song, Ling
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experimental part
p. 4645 - 4652
(2012/07/03)
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- Zinc(ii)-catalyzed Grignard additions to ketones with RMgBr and RMgI
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Highly efficient alkylations and arylations of ketones with Grignard reagents (RMgBr and RMgI) have been developed using catalytic ZnCl2, Me3SiCH2MgCl, and LiCl. Tertiary alcohols were obtained in high yields with high chemoselectivities, while minimizing undesired side products produced by reduction and enolization.
- Hatano, Manabu,Ito, Orie,Suzuki, Shinji,Ishihara, Kazuaki
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supporting information; experimental part
p. 2674 - 2676
(2010/07/08)
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- Zinc(II)-catalyzed addition of grignard reagents to ketones
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(Figure presented) The addition of organometallic reagents to carbonyl compounds has become a versatile method for synthesizing tertiary and secondary alcohols via carbon-carbon bond formation. However, due to the lack of good nucleophilicity or the presence of strong basicity of organometallic reagents, the efficient synthesis of tertiary alcohols from ketones has been particularly difficult and, thus, limited. We recently developed highly efficient catalytic alkylation and arylation reactions to ketones with Grignard reagents (RMgX: R = alkyl, aryl; X = Cl, Br, I) using ZnCl2, Me3SiCH 2MgCl, and LiCl, which effectively minimize problematic side reactions. In principle, RMgBr and RMgI are less reactive than RMgCl for the addition to carbonyl compounds. Therefore, this novel method with homogeneous catalytic ZnCl2·Me3SiCH2MgCl·LiCl is quite attractive, since RMgBr and RMgI, which are easily prepared and/or commercially available, like RMgCl, can be applied successfully. As well as ketones and aldehydes, aldimines were effectively applied to this catalysis, and the corresponding secondary amines were obtained in high yield. With regard to mechanistic details concerning β-silyl effect and salt effect, in situ-prepared [R(Me3SiCH2)2Zn] -[Li]+[MgX2]m[LiCl]n (X = Cl/Br/I) is speculated to be a key catalytic reagent to promote the reaction effectively. The simplicity of this reliable ZnCl2·Me 3SiCH2MgCl·LiCl system in the addition of Grignard reagents to carbonyl compounds might be attractive for industrial as well as academic applications.
- Hatano, Manabu,Ito, Orie,Suzuki, Shinji,Ishihara, Kazuaki
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supporting information; experimental part
p. 5008 - 5016
(2010/10/04)
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- Phosphine-catalyzed reductions of alkyl silyl peroxides by titanium hydride reducing agents: Development of the method and mechanistic investigations
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(Figure presented) A method that allows for the reduction of protected hydroperoxides by employing catalytic amounts of phosphine is presented. The combination of a titanium(IV) alkoxide and a siloxane allowed for the chemoselective reduction of phosphine oxides in the presence of alkyl silyl peroxides. Subsequent reduction of the peroxide moiety by phosphine provided the corresponding silylated alcohols in useful yields. Mechanistic experiments, including crossover experiments, support a mechanism in which the peroxide group was reduced and the silyl group was transferred in a concerted step. Labeling studies with 17O-labeled peroxides demonstrate that the oxygen atom adjacent to the silicon atom is removed from the silyl peroxide.
- Harris, Jason R.,Haynes, M. Taylor,Thomas, Andrew M.,Woerpel
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supporting information; experimental part
p. 5083 - 5091
(2010/10/19)
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- Highly enantioselective arylation of aldehydes and ketones using AlArEt2(THF) as aryl sources
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A series of AlArEt2(THF) (Ar = Ph (la), 4-MeC6H 4 (1b), 4-MeOC6H 4 (1c), 4-Me 3SiC6H4 (1d), 2-naphthyl (le)) were synthesized from reactions of AlEt2Br(THF) with ArMgBr. In CDC13 solution, the 1H NMR spectra showed that AlArEt2(THF) compounds exist as a mixture of four species of formulas of AlAr xEt3-x (THF) (x = 0, 1, 2, or 3). AlArEt2(THF) compounds were found to be superior and atom-economic reagents for asymmetric aryl additions to organic carbonyls. Aryl additions of AlArEt2(THF) to aldehydes catalyzed by the titanium(IV) complex of (R)-H8-BINOL were efficient with a short reaction time of 1 h, affording aryl addition products as exclusive or main products in high yields and excellent enantioselectivities of up to 98% ee. Although ethyl additions to aldehydes occurred in minor extent, this study demonstrates that increasing the amount of AlArEt2(THF) from 1.2 to 1.4 or to 1.6 equiv significantly improved the aryl addition products of up to >99%. On the other hand, asymmetric arylations of AlArEt2(THF) to ketones employing a titanium(IV) catalyst of (S)-BINOL produced optically active tertiary alcohols exclusively in excellent enantioselectivities of up to 94% ee.
- Zhou, Shuangliu,Wu, Kuo-Hui,Chen, Chien-An,Gau, Han-Mou
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supporting information; experimental part
p. 3500 - 3505
(2009/09/30)
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- Kinetic resolution of hydroperoxides with enantiopure phosphines: Preparation of enantioenriched tertiary hydroperoxides
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An efficient reductive kinetic resolution strategy capable of accessing optically active tertiary hydroperoxides is reported. Readily accessible tertiary hydroperoxides are resolved with commercially available (R)- or (S)-xylyl-PHANEPHOS with selectivity factors as large as 37. The resulting bis(phosphine oxide) can be recycled in high yields. The isolated mono(phosphine oxide) intermediate resolved hydroperoxides with the same selectivity as the parent bisphosphine. Copyright
- Driver, Tom G.,Harris, Jason R.,Woerpel
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p. 3836 - 3837
(2008/02/13)
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- Highly efficient alkylation to ketones and aldimines with Grignard reagents catalyzed by zinc(II) chloride
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A highly efficient alkylation to ketones and aldimines with Grignard reagents in the presence of catalytic trialkylzinc(II) ate complexes derived from ZnCl2 (10 mol %) in situ was developed. This simple Zn(II)-catalyzed alkylation could minimize the well-known but serious problems with the use of only Grignard reagents, which leads to reduction and aldol side products, and the yield of desired alkylation products could be improved. Copyright
- Hatano, Manabu,Suzuki, Shinji,Ishihara, Kazuaki
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p. 9998 - 9999
(2007/10/03)
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- Highly alkyl-selective addition to ketones with magnesium ate complexes derived from Gignard reagents
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(Chemical Equation Presented) A highly efficient alkyl-selective addition to ketones with magnesium ate complexes derived from Grignard reagents and alkyllithiums is described. The nucleophilicity of R in R3MgLi is remarkably increased compared to that of the original RLi or RMgX, while the basicity of R3MgLi is decreased. Furthermore, a highly R-selective addition to ketones is demonstrated using RMe2MgLi in place of R 3MgLi.
- Hatano, Manabu,Matsumura, Tokihiko,Ishihara, Kazuaki
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p. 573 - 576
(2007/10/03)
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- Spiroiminodihydantoin is a major product in the photooxidation of 2′-deoxyguanosine by the triplet states and oxyl radicals generated from hydroxyacetophenone photolysis and dioxetane thermolysis
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(formula presented) Photolysis of hydroxyacetophenone and thermolysis of the corresponding dioxetane afford spiroiminodihydantoin rather than 4,8-dihydro-4-hydroxy-8-oxo-2′-deoxyguanosine (4-HO-8-oxodG) through the oxidation of 2′-deoxyguanosine (dG) by triplet-excited hydroxyacetophenone and the peroxyl radicals derived thereof by α cleavage and subsequent oxygen trapping. The structure of the spiroiminodihydantoin is assigned by the SELINQUATE NMR technique, which unequivocally establishes the spirocyclic connectivity.
- Adam, Waldemar,Arnold, Markus A.,Gruene, Matthias,Nau, Werner M.,Pischel, Uwe,Saha-Moeller, Chantu R.
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p. 537 - 540
(2007/10/03)
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- Reactivity and Selectivity in the Oxidation of Styrene Derivatives. IV. Studies on the Oxidation of Substituted β,β-Dimethylstyrenes
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The liquid phase oxidation of substituted (p-MeO-, p-Cl-, m-CF3-) 2-aryl-3-methyl-but-2-enes, of 1,1-diphenyl-2-methyl-propene, of 1-ethoxy-2-methyl-1-phenyl-propene and of 9-isopropylidene-fluorene with pure oxygen was investigated in chlorobenzene solution and in presence of cumene and of cumene hydroperoxide in the temperature range 65-125°C. The product yields were determined gaschromatographically. The differences of the activation energies of epoxide formation and the parallel reactions were calculated. They amount to 19-48 kJ/mol. The epoxide selectivity increases with increasing temperature and increasing concentration of olefin. The relative chain propagation constants (kpC=C) were determined by competitive oxidation with cumene. The kpC=C values of substituted β,β-dimethylstyrenes can be correlated by a LFE-relationship with the ionisation energies of the olefins.
- Suprun
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p. 247 - 255
(2007/10/03)
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- Samarium(II) triflate as a new reagent for the grignard-type carbonyl addition reaction
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On treatment of a THF solution of Sm(OTf)3 with 1 equiv of an organolithium or organomagnesium reagent at ambient temperature, the purple or deep green solution of the divalent samarium triflate [Sm(OTf)2] was readily obtained. For this preparation, s-BuLi was the most effective as was evidenced by the reduction of 2-phenylethyl iodide in the presence of HMPA. The Sm(OTf)2 reagent mediated the Grignard-type reaction effectively in THF/HMPA; alkylation and allylation of ketones or aldehydes with alkyl, allyl, or benzyl halides proceeded via organosamarium intermediates. Diastereoselectivity of the samarium-Grignard reaction was examined using 2-methylcyclohexanone, 4-tert-butylcyclohexanone, and 2-phenylpropanal and was found to be higher in each case than that with SmI2. With 2-methylcyclohexanone, for example, Sm(OTf)2 gave the greatest ratio of axial alcohol:equatorial alcohol = 99:1, and SmI2 gave a ratio of 91:9. Halides containing an ester or a silyl group were reactive in the Reformatsky- or Peterson-type reaction, respectively, using the Sm(OTf)2 reagent.
- Fukuzawa, Shin-Ichi,Mutoh, Keisuke,Tsuchimoto, Teruhisa,Hiyama, Tamejiro
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p. 5400 - 5405
(2007/10/03)
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- Electronic and steric effects on the solvation at the transition state in the solvolysis of some tertiary benzylic chlorides
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The deviation from linear relationship in the regression analyses using Grunwald-Winstein equation for tertiary benzylic chlorides 1-4 could be improved by increasing steric hindrance near the reaction site and/or by increasing electron-release of the substituent on aryl ring, which clearly demonstrates the importance of solvent intervention due to the solvation of cationic transition states in solvolysis.
- Liu, Kwang-Ting,Chen, Pang-Shao,Chiu, Pao-Feng,Tsao, Meng-Lin
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p. 6499 - 6502
(2007/10/02)
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- GRIGNARD REAGENTS AS POWDERS : PREPARATION AND REACTIVITY
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The TDA-1 chelating agent is able to complex Grignard reagents.This complexation leads to powders.The preparation is general and the complexes "RMgX/TDA-1" are easily prepared from every type of Grignard reagents.These solids are stable under nitrogen and can be titrated and used as Grignard reagents.The study of their chemical reactivity shows a behaviour comparable to that of conventional Grignard reagents, the rate of reactions however being decreased.Selective addition onto a mixture of aldehyde and ketone is possible.Interestingly the reactions can be performed in hydrocarbon solvents (toluene, light petroleum, cyclohexane).
- Boudin, Alain,Cerveau, Genevieve,Chuit, Claude,Corriu, Robert J.P.,Reye, Catherine
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p. 171 - 180
(2007/10/02)
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- AZO ANIONS IN SYNTHESIS. USE OF TRITYL- AND DIPHENYL-4-PYRIDYLMETHYLHYDRAZONES FOR REDUCTIVE C-C BOND FORMATION.
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The lithium salts of trityl- and diphenyl-4-pyridylmethyl-hydrazones of both aldehydes and ketones react with electrophiles (alkyl halides, aldehydes, ketones, crotonates) at low temperature to form C-trapped azo compounds; these intermediates decompose homolytically with loss of nitrogen below room temperature and can be diverted in a synthetically useful way to alkanes, alkenes, alcohols or saturated esters.
- Baldwin, Jack E.,Adlington, Robert M.,Bottaro, Jeffrey C.,Kolhe, Jayant N.,Newington, Ian M.,Perry, Matthew W. D.
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p. 4235 - 4246
(2007/10/02)
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- Thermolabile Hydrocarbons, XX. Synthesis, Structure, and Strain of Sym. Tetraalkyl-1,2-diarylethanes
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The syntheses of 18 1,1,2,2-tetraalkyl-1,2-diarylethanes 1 - 4 by dimerisation procedures starting with 10 - 13 are reported.In the absence of p-substituents X and with increasing alkyl side chains the α,p-dimers 6 or their aromatic counter parts 7 are obtained besides or instead of 1.The relationships between strain enthalpy Hs, bond lengths, bond angles, torsional angles, and rotational barrier are discussed on the basis of force field calculations.They are supported by two additional experimental structure determinations by X-ray diffraction.
- Kratt, Guenter,Beckhaus, Hans-Dieter,Lindner, Hans Joerg,Ruechardt, Christoph
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p. 3235 - 3263
(2007/10/02)
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- Stereochemistry of Aliphatic Carbocations, 15. Rearrangements in 2-Arylalkyl Systems
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Phenyl shifts from secondary to primary carbon proceed with virtually complete inversion at the migration origin, regardless whether they are induced by solvolysis of the aryl sulfonate 25 or by deamination of the amines 12, 17, 26, and 43.Sequential rearrangements (Ph, CH3 and Ph, H) are likewise stereo- and regiospecific.These results strongly support the intervention of phenonium ions.In contrast, the competitive alkyl shifts (deamination only) from benzylic to primary carbon produce but a small excess of inversion (Me 27percent, Et 13percent, iPr 20percent, tBu 3percent).Obviously, benzyl cations are the predominant intermediates.
- Kirmse, Wolfgang,Guenther, Bernd-Rainer,Loosen, Karin
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p. 2140 - 2153
(2007/10/02)
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