- Rapid, One-Step Synthesis of α-Ketoacetals via Electrophilic Etherification
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Herein, we report a rapid, one-step synthesis of α-ketoacetals via electrophilic etherification of α-alkoxy enolates and monoperoxyacetals. Methyl, primary, and secondary α-ketoacetals were obtained in 44-63% yields from tetrahydropyranyl substrates; usin
- Paris, Timothy J.,Schwartz, Chris,Sundall, Eric,Willand-Charnley, Rachel
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p. 14797 - 14811
(2021/10/20)
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- Tandem Acid/Pd-Catalyzed Reductive Rearrangement of Glycol Derivatives
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Herein, we describe the acid/Pd-tandem-catalyzed transformation of glycol derivatives into terminal formic esters. Mechanistic investigations show that the substrate undergoes rearrangement to an aldehyde under [1,2] hydrogen migration and cleavage of an oxygen-based leaving group. The leaving group is trapped as its formic ester, and the aldehyde is reduced and subsequently esterified to a formate. Whereas the rearrangement to the aldehyde is catalyzed by sulfonic acids, the reduction step requires a unique catalyst system comprising a PdII or Pd0 precursor in loadings as low as 0.75 mol % and α,α′-bis(di-tert-butylphosphino)-o-xylene as ligand. The reduction step makes use of formic acid as an easy-to-handle transfer reductant. The substrate scope of the transformation encompasses both aromatic and aliphatic substrates and a variety of leaving groups.
- Ciszek, Benjamin,Fleischer, Ivana,Kathe, Prasad,Schmidt, Tanno A.
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supporting information
p. 3641 - 3646
(2020/03/25)
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- Iron-Catalyzed Methylation Using the Borrowing Hydrogen Approach
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A general iron-catalyzed methylation has been developed using methanol as a C1 building block. This borrowing hydrogen approach employs a Kn?lker-type (cyclopentadienone)iron carbonyl complex as catalyst (2 mol %) and exhibits a broad reaction scope. A variety of ketones, indoles, oxindoles, amines, and sulfonamides undergo mono- or dimethylation in excellent isolated yields (>60 examples, 79% average yield).
- Polidano, Kurt,Allen, Benjamin D. W.,Williams, Jonathan M. J.,Morrill, Louis C.
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p. 6440 - 6445
(2018/07/25)
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- Mechanistic Insight into Additions of Allylic Grignard Reagents to Carbonyl Compounds
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Allylic Grignard reagents exhibit high reactivity and low selectivity in additions to carbonyl compounds. Additions of allylic Grignard reagents to carbonyl compounds were investigated using prenylmagnesium chloride as a mechanistic probe. When the carbonyl group is relatively unhindered, the addition proceeds through a six-membered transition state with allylic transposition. This process generally occurs with no diastereoselectivity because the reaction rates approach the diffusion limit. With hindered ketones, however, this pathway is disfavored, and the addition proceeds through a transition state resembling that of other Grignard reagents.
- Bartolo, Nicole D.,Woerpel
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p. 10197 - 10206
(2018/09/06)
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- Additions of Organomagnesium Halides to α-Alkoxy Ketones: Revision of the Chelation-Control Model
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The chelation-control model explains the high diastereoselectivity obtained in additions of organometallic nucleophiles to α-alkoxy ketones but fails for reactions of allylmagnesium halides. Low diastereoselectivity in ethereal solvents results from no chelation-induced rate acceleration. Additions of allylmagnesium bromide to carbonyl compounds are diastereoselective using CH2Cl2 as the solvent even though rate acceleration is still absent. Stereoselectivity likely arises from the predominance of the chelated form in solution. Therefore, a revised chelation-control model is proposed.
- Read, Jacquelyne A.,Yang, Yingying,Woerpel
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supporting information
p. 3346 - 3349
(2017/07/13)
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- Sodium iodide-catalyzed direct α-alkoxylation of ketones with alcohols via oxidation of α-iodo ketone intermediates
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The direct α-alkoxylation of ketones with alcohols via a sodium iodide-catalyzed oxidative cross-coupling has been developed. This protocol enables a range of alkyl aryl ketones to cross couple with an array of alcohols in synthetically useful yields. The mechanistic studies provided solid evidence supporting that an α-iodo ketone was a key reaction intermediate, being converted into an α-alkoxylated ketone via further oxidation to a hypervalent iodine species rather than a common nucleophilic substitution, and was generated from the ketone starting material via a radical intermediate. These new mechanism insights should have an effect on the design of iodide-catalyzed oxidative cross-coupling reactions between nucleophiles.
- Zhu, Cuiju,Zhang, Yuanfei,Zhao, Huaiqing,Huang, Shijun,Zhang, Min,Su, Weiping
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p. 331 - 338
(2015/02/19)
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- Oxidative iodination of carbonyl compounds using ammonium iodide and oxone
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A simple, efficient, mild, and regioselective method for oxyiodination of carbonyl compounds has been reported by using NH4I as the source of iodine and Oxone as an oxidant. Various carbonyl compounds such as aralkyl ketones, aliphatic ketones (acyclic and cyclic), and β-keto esters proceeded to the respective α-monoiodinated products in moderate to excellent yields. Unsymmetrical aliphatic ketones reacted smoothly yielding a mixture of 1-iodo and 3-iodo ketones with the predominant formation of 1-iodoproduct.
- Marri, Mahender Reddy,MacHarla, Arun Kumar,Peraka, Swamy,Nama, Narender
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supporting information; experimental part
p. 6554 - 6559
(2012/01/02)
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- Product studies and laser flash photolysis on alkyl radicals containing two different β-leaving groups are consonant with the formation of an olefin cation radical
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1-Bromo-2-methoxy-1-phenylpropan-2-yl (3) and 2-methoxy-1-phenyl-1-diphenylphosphatopropan-2-yl (4) were generated under continual photolysis from the respective PTOC precursors in a mixture of acetonitrile and methanol. The radicals undergo heterolytic fragmentation of the substituent in the β-position to generate the olefin cation radical (5). Z-2-Methoxy-1-phenylpropene (15) is the major product formed in the presence of 1,4-cyclohexadiene, and is believed to result from hydrogen atom transfer to the oxygen of the olefin cation radical, followed by deprotonation. Laser flash photolysis experiments indicate that reaction between 5 and 1,4-cyclohexadiene occurs with a rate constant of ~6 × 105 M-1 s-1. 2,2-Dimethoxy-1-phenylpropane (18) is observed as a minor product. Laser flash photolysis experiments place an upper limit on methanol trapping of 5 at k 3 M-1 s-1 and do not provide any evidence for the formation of reactive intermediates other than 5. The use of two PTOC precursors containing different leaving groups to generate a common olefin cation radical enables one to utilize product analysis to probe for the intermediacy of other reactive intermediates. The ratio of 15:18 is dependent upon hydrogen atom donor concentration, but is independent of the PTOC precursor. These observations are consistent with the proposal that both products result from trapping of 5 that is formed via heterolysis of 3 and 4.
- Bales,Horner,Huang,Newcomb,Crich,Greenberg
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p. 3623 - 3629
(2007/10/03)
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- Novel cerium(IV) ammonium nitrate mediated transformation of styrenes to α-methoxy acetophenones
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Styrenes when treated with a methanolic solution of CAN underwent a novel transformation to α-methoxy acetophenones presumably via a radical cation.
- Nair, Vijay,Nair, Latha G.,Panicker, Sreeletha B.,Sheeba,Augustine, Anu
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p. 584 - 585
(2007/10/03)
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- Stereoselectivities in AgBF4-catalyzed and photoinduced phenyl- rearrangement of 2-chloropropiophenone
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(S)-2-Phenylpropionic acid was stereoselectively obtained by the AgBF4- catalyzed phenyl-rearrangement of (S)-2-chloropropiophenone dimethyl acetal, while the photoirradiation of (S)- or (R)-2-chloropropiophenone afforded partially racemized (S)-or (R)-2-phenylpropionic acid, respectively. An intramolecular S(N)2 mechanism is suggested for the former rearrangement. The latter result is indicative of the intervention of an ion or radical intermediate in the photoinduced phenyl-rearrangement.
- Usui, Satoshi,Matsumoto, Takeshi,Ohkubo, Katsutoshi
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p. 9755 - 9758
(2007/10/03)
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- A facile synthesis of secondary α-alkoxy or α-acetoxy aromatic ketones
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The treatment of HNIB with aromatic ketones and subsequent solvolysis using alcohol or acetic acid in one-pot system makes it possible to give corresponding secondary α-alkoxy or α-acetoxy ketones in high yields.
- Lee, Jong Chan,Hong, Taiyoung
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p. 4085 - 4090
(2007/10/03)
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- Photochemistry of substituted propiophenones: An interesting α-and aryl substituents effect on their photobehaviour
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Photochemistry of different α-substituted and phenyl-substituted propiophenones in methanol is investigated with a view to delineate the substituent effect with a special reference tu their rearrangement to α-arylpropanoic acids, an important class of nonsteroidal antiinflammatory agents. The results thus obtained bringsforth an important element of their reactivityprofile i.e. the α-chloro-substituent in combination with nuclear alkyl substituents (para>meta) favours 1,2-arylmigration leading to the synthetically useful reaction for α-arylpro panoic acids.
- Sonawane, Harikisan R.,Bellur, Nanjundiah S.,Nazeruddin
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p. 11281 - 11294
(2007/10/02)
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- Enzymes in Organic Synthesis: Lipase Catalyzed Resolution of Secondary α-Ketoalcohols
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Resolution of several α-ketoalcohols of synthetic value using lipase as a catalyst is described.
- Duh, Tsai-Hui,Wang, Yi-Fong,Wu, Ming-Jung
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p. 1793 - 1794
(2007/10/02)
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- Chelates as intermediates in nucleophilic additions to alkoxy ketones according to Cram's rule (cyclic model)
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Chelates have been considered intermediates in the often highly stereoselective reactions of α-alkoxy and similarly substituted ketones for over 30 years,10 but without mechanistic evidence. It is now shown, by stop-flow ("rapid injection") NMR kinetics,15 that the specific rates of reaction of ketones C6H5COCH(OR)CH3 with Me2Mg, where R = (i-Pr)3 ("TIPS"), t-BuPh2Si, t-BuMe2Si, Et3Si, Me3Si, and Me, parallel the diastereoselectivity of the reaction; i.e., the fastest reacting compound (R = Me) is the one which gives the highest proportion of the product predicted by Cram's chelate rule. The major product of the slowest reacting compound (R = TIPS) is not in accord with Cram's chelate rule, and this compound reacts at the same specific rate as the parent, C6H5COCH2CH3. This is in accord with earlier work indicating that TIPSO does not chelate. Compounds intermediate in the series react at intermediate rates and give the two diastereomeric products in proportions which can be calculated by assuming two competing reactions (cf. Figure 2): one proceeding via the chelated transition states giving the product predicted by the chelate rule and one not involving chelation which gives the same product composition as the R = TIPS compound. Direct steric effects on carbonyl reactivity due to the remote bulky silyloxy substituents have been excluded by the study of carbon analogues bearing similar bulky groups. Thus, the kinetic effect in the above series appears to be due to steric hindrance to chelation; hence, the parallel of specific rate and stereoselectivity demonstrates that high stereoselectivity is associated with strong chelation, as postulated by Cram and Kopecky in 1959.10.
- Chen, Xiangning,Hortelano, Edwin R.,Eliel, Ernest L.,Frye, Stephen V.
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p. 1778 - 1784
(2007/10/02)
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- Chelation of 2-substituted-1-lithoxides: Structural and energetic factors of relevance to synthetic organic chemistry
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A number of lithium 2-(methylamino)-, 2-(dimethylamino)-, 2-methoxy-, and 2-(isopropylthio)-substituted-1-phenyl-1-propoxides were studied as models for asymmetric synthetic strategies for which lithium chelation between two electronegative atoms has frequently been invoked. The heats of formation of these alkoxides were determined by deprotonating the alcohols with lithium bis(trimethylsilyl)amide in a solution calorimeter. Aggregation numbers for the substituted alcohols and their corresponding lithium alkoxides were obtained with freezing point depression and vapor pressure osmometry in THF, benzene, and dioxane. In several cases, solution structures were obtained through 1H, 6Li, and 2D 6Li-1H NOE (HOESY) NMR spectroscopy. Solid-state structures of lithium (+)-N-methylpseudoephedrate and (-)-N-methylephedrate (+)-N-methylpseudoephedrate and (-)-N-methylephedrate (as the benzene solvate) were obtained by X-ray crystallography, and both were found to be present as tetramers in which the dimethylamino nitrogen atoms were coordinated to the lithium cations to form five-membered chelate rings. The lithium alkoxides were either tetramers or hexamers in nonpolar solvents; however, the alkoxides' solution structures were very complex in THF as evidenced by several 6Li resonances observed in the 6Li NMR spectra at low temperatures. Intramolecular lithium chelation was found to occur in each alkoxide in dioxane and benzene. The enthalpies of chelational stabilization were estimated by comparing their heats of deprotonation with those of nonchelatable 2-alkyl-substituted analogues. The stabilization enthalpies ranged from 5 to 11 kcal/mol per alkoxide molecule.
- Nichols, Michael A.,McPhail, Andrew T.,Arnett, Edward M.
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p. 6222 - 6233
(2007/10/02)
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- Hypervalent iodine oxidation of silyl enol ethers under Lewis acid conditions in methanol. A general route to α-methoxy ketones
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Hypervalent iodine oxidation of various silyl enol ethers (aromatic, heteroaromatic, aliphatic) using iodosobenzene-boron trifluoride etherate in methanol leads to α-methoxylation of ketones in high yields. The scope and mechanism of the reaction are discussed.
- Moriarty, Robert M.,Prakash, Om,Duncan, Michael P.,Vaid, Radhe K.,Musallam, Hikmat A.
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p. 150 - 153
(2007/10/02)
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- MECHANISM FOR THE OXIDATIVE CLEAVAGE OF ELECTRON-DEFICIENT ACETYLENES WITH ALKALINE HYDROGEN PEROXIDE.
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4-Phenyl-3-butyn-2-one was effectively cleaved by alkaline hydrogen peroxide to afford benzoic and acetic acids. The rate ratio for the addition of HOO** minus and HO** minus resulted in k//H//O//O-/k//H//O- equals 1400, which is comparable to that of benzylideneacetone. The major reaction of the cleavage proceeds via benzoylacetone. As a minor pathway, alpha -keto oxirene intermediate is formed and rearranges only to alpha -benzoylproprionate in a different way from the corresponding diketo carbene. alpha //-Keto esters are found to be converted by HOO** minus to alpha -alkoxy ketones via a novel oxidative substitution of ester group. The mechanism is discussed on the basis of oxirene intermediate inconvertible to keto carbene.
- Sawaki,Inoue,Ogata
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p. 1133 - 1138
(2007/10/02)
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- SILVER ASSISTED REARRANGEMENT OF PRIMARY AND SECONDARY α-BROMO-ALKYLARYLKETONES
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The silver assisted rearrangement of primary and secondary α-bromo-alkylarylketones is reported for the first time.The influence of the acidity on the reaction selectivity is discussed.
- Giordano, Claudio,Castaldi, Graziano,Casagrande, Francesco,Abis, Luigi
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p. 1385 - 1386
(2007/10/02)
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- A NEW METHOD FOR THE SYNTHESIS OF α-ARYLALKANOIC ACIDS BY THE USE OF 1,2-REARRANGEMENT OF THE ARYL GROUP
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A simple synthetic method of α-arylalkanoic acids was accomplished by the use of a novel 1,2-rearrangement of the aryl group and this method was applied to the syntheses of some biologically important subtances.
- Tsuchihashi, Gen-ichi,Kitajima, Koji,Mitamura, Shuichi
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p. 4305 - 4308
(2007/10/02)
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- The Allopolarization Principle and its Applications, IV. Substituent Effects in the Methylation of Enolate Anions
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The ratio of O- and C-methylated products in the reaction of the sodium salts of acetophenones 1, propiophenones 3, phenylacetones 5, β-dicarbonyl compounds 12, α-cyanocarbonyl compounds 13, acetaldehyde, propionaldehyde, and diethylketone with dimethyl sulfate, methyl iodide, and trimethyl phosphate in HMPTA has been determined with regard to the effect of substituents.In some cases the influence of solvents, concentration and temperature has also been studied.
- Gompper, Rudolf,Vogt, Hans-Hubert
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p. 2866 - 2883
(2007/10/02)
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- Chemistry of O-Alkyl Selenoesters. Reaction with Triethylphosphine
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The reaction between triethylphosphine and a number of aliphatic and aromatic selenoesters under oxygen-free conditions have been investigated.The purple intermediate formed in the reaction with the aliphatic selenoesters was quenched with atmospheric oxygen and gave the corresponding esters, whereas quenching with methyl iodide gave the corresponding 1-alkoxy-1-iodoalkyltriethylphosphonium iodides (13)-(16).The 1-alkoxy-1-iodoalkyltriethylphosphonium iodides gave the 1-alkoxyalkyltriethylphosphonium iodides (17)-(20) upon treatment with methanol, and treatment with benzaldehyde at -70 deg C gave α-alkoxyalkyl phenyl ketones (22)-(25).The reaction between the selenobenzoates and triethylphosphine gave α-dialkoxy-stilbenes and -dibenzyls.When the reaction was carried out in cyclohexene 7-alkoxy-7-phenylbicycloheptanes were formed.The presence of benzaldehyde in the reaction mixture led to α-alkoxystilbenes.An explanation for these different reactions is presented.
- Hansen, Per-Egil
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p. 1627 - 1634
(2007/10/02)
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