- Novel syn intramolecular pathway in base-catalyzed 1,2-elimination reactions of β-acetoxy esters
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(Chemical Equation Presented) As part of a comprehensive investigation of electronic effects on the stereochemistry of base-catalyzed 1,2-elimination reactions, we observed a new syn intramolecular pathway in the elimination of acetic acid from β-acetoxy esters and thioesters. 1H and 2H NMR investigation of reactions using stereospecifically labeled tert-butyl (2R*,3R*)-3-acetoxy-2,3-2H2- butanoate (1) and its (2R*,3S*) diastereomer (2) shows that 23 ± 2% syn elimination occurs. The elimination reactions were catalyzed with KOH or (CH3)4-NOH in ethanol/water under rigorously non-ion-pairing conditions. By contrast, the more sterically hindered β-trimethylacetoxy ester produces only 6 ± 1% syn elimination. These data strongly support an intramolecular (Ei) syn path for elimination of acetic acid, most likely through the oxyanion produced by nucleophilic attack at the carbonyl carbon of the β-acetoxy group. The analogous thioesters, S-tert-butyl (2R*,3R*)-3-acetoxy-2,3- 2H2-butanethioate (3) and its (2R*,3S*) diastereomer (4), showed 18 ± 2% syn elimination, whereas the β-trimethylacetoxy substrate gave 5 ± 1% syn elimination. The more acidic thioester substrates do not produce an increased amount of syn stereoselectivity even though their elimination reactions are at the Elcb interface.
- Mohrig, Jerry R.,Carlson, Hans K.,Coughlin, Jane M.,Hofmeister, Gretchen E.,McMartin, Lea A.,Rowley, Elizabeth G.,Trimmer, Elizabeth E.,Wild, Andrew J.,Schultz, Steve C.
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- Stereospecificity of the reaction catalyzed by enoyl-CoA hydratase
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Enoyl-CoA hydratase catalyzes the stereospecific hydration of α,β- unsaturated acyl-CoA thiolesters. Hydration of trans-2-crotonyl-CoA to 3(S)- hydroxybutyryl-CoA proceeds via the syn addition of water and thus the pro-2R proton of 3(S)-hydroxybutyryl-CoA is derived from solvent. Incubation of 3(S)-hydroxybutyryl-CoA with enzyme in D2O results in the slow exchange of the pro-2S proton with solvent deuterium, in addition to the anticipated rapid exchange of the pro-2R proton. Further experiments have shown that the exchange of the pro-2S proton occurs in concert with the formation of the incorrect 3(R)-hydroxybutyryl-CoA enantiomer. The rate of 3(R)- hydroxybutyryl-CoA formation is 4 x 105-fold slower than the normal hydration reaction, but at least 1.6 x 106-fold faster than the non-enzyme- catalyzed reaction. This has allowed us to determine that the absolute stereospecificity for the enzyme-catalyzed reaction is 1 in 4 x 105. The initial formation of 3(R)-hydroxybutyryl-CoA is hypothesized to occur via the incorrect hydration of trans-2-crotonyl-CoA. Once formed, the 3(R)- hydroxybutyryl-CoA dehydrates to give cis-2-crotonyl-CoA. While the equilibrium constant for the hydration of trans-2-crotonyl-CoA to 3(S)- hydroxybutyryl-CoA is 7.5, the equilibrium constant for the hydration of cis- 2-crotonyl-CoA to 3(R)-hydroxybutyryl-CoA is estimated to be ~1000. To validate this reaction scheme, cis-2-crotonyl-CoA has been synthesized and characterized. These studies demonstrate that the enzyme is capable of catalyzing the epimerization of hydroxybutyryl-CoA.
- Wu, Wen-Jin,Feng, Yuguo,He, Xiang,Hofstein, Hilary A.,Raleigh, Daniel P.,Tonge, Peter J.
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- Vinylacidic Acid in the Reaction of Aza-Michael with 1-Ethylpyrazole
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Abstract: Commercial vinylacetic acid is a mixture of isomers of but-3-enoic andbut-2-enoic acids. It was shown that but-3-enoic acid undergoes isomerization inthe presence of a catalytic amount of 1-ethylpyrazole. The resulting Z- and E-isomersof but-2-enoic acid enter the aza-Michael reaction with pyrazole. The1H NMR analysis showed that by the end of theexperiment the ratio of unreacted Z- andE-isomers of but-2-enoic acid in thereaction mixture decreased by half (to 3 : 1), which pointed to a higherreactivity of the Z-isomer.
- Arzumanyan, A. M.,Attaryan, H. S.,Danagulyan, G. G.,Khachatryan, H. N.,Shahkhatuni, A. G.
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p. 1488 - 1490
(2020/10/02)
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- Dienolates of Cycloalkenones and α,β-Unsaturated Esters Form Diels–Alder Adducts by a Michael/Michael-Tandem Reaction Rather Than in One Step
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α,β-Unsaturated esters and lithium 1,3-dien-2-olates are known to furnish bicyclic lithium enolates by anionic Diels–Alder reactions. However, in principle, the respective products might form not only in a single step but also in two consecutive – or “tandem” – Michael additions, the first of which occurs intermolecularly, the second intramolecularly. Three cyclic lithium dienolates and four esters with a stereogenic Cα=Cβ bond reacted to give Diels–Alder adducts (10 times) or failed to react (2 times). Seven of the reactive combinations furnished adducts wherein the configuration of the former ester moiety had in part inverted. This precludes concerted pathways as their origins. This was a surprise since donors at C-2 of the 1,3-diene accelerate normal electron-demand Diels–Alder reactions in the order alkyl ⊕O? being a far better donor still, it is not obvious why the mechanism is non-concerted rather than concerted (and still more asynchronous).
- Loesche, Ann-Christine,Brückner, Reinhard
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supporting information
p. 562 - 573
(2018/12/11)
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- Ru-Based Catechothiolate Complexes Bearing an Unsaturated NHC Ligand: Effective Cross-Metathesis Catalysts for Synthesis of (Z)-α,β-Unsaturated Esters, Carboxylic Acids, and Primary, Secondary, and Weinreb Amides
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Despite notable progress, olefin metathesis methods for preparation of (Z)-α,β-unsaturated carbonyl compounds, applicable to the synthesis of a large variety of bioactive molecules, remain scarce. Especially desirable are transformations that can be promoted by ruthenium-based catalysts, as such entities would allow direct access to carboxylic esters and amides, or acids (in contrast to molybdenum-or tungsten-based alkylidenes). Here, we detail how, based on the mechanistic insight obtained through computational and experimental studies, a readily accessible ruthenium catechothiolate complex was found that may be used to generate many α,β-unsaturated carbonyl compounds in up to 81% yield and ≥98:2 Z/E ratio. We show that through the use of a complex bearing an unsaturated N-heterocyclic carbene (NHC) ligand, for the first time, products derived from the more electron-deficient esters, acids, and Weinreb amides (vs primary or secondary amides) can be synthesized efficiently and with high stereochemical control. The importance of the new advance to synthesis of bioactive compounds is illustrated through two representative applications: An eight-step, 15% overall yield, and completely Z-selective route leading to an intermediate that may be used in synthesis of stagonolide E (vs 11 steps, 4% overall yield and 91% Z, previously), and a five-step, 25% overall yield sequence to access a precursor to dihydrocompactin (vs 13 steps and 5% overall yield, formerly).
- Liu, Zhenxing,Xu, Chaofan,Del Pozo, Juan,Torker, Sebastian,Hoveyda, Amir H.
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supporting information
p. 7137 - 7146
(2019/05/10)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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Compounds of formula (I') and methods of their use and preparation, as well as compositions comprising compounds of formula (I').
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Page/Page column 263
(2018/06/30)
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- INHIBITORS OF BRUTON'S TYROSINE KINASE AND METHODS OF THEIR USE
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The present disclosure is directed to compounds of formula I and methods of their use and preparation, as well as compositions comprising compounds of formula I.
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Page/Page column 263
(2017/09/02)
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- Anticancer platinum complexes as non-innocent compounds for catalysis in aqueous media
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An efficient cyclization of alkyne-acids to enol-lactones catalyzed by anticancer platinum(ii) and platinum(iv) compounds is described. These compounds are not only DNA-binding complexes; they can also catalyze reactions in solvents such as acetone, methanol, water or blood plasma.
- Aleman, Jose,Del Solar, Virginia,Navarro-Ranninger, Carmen
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supporting information; experimental part
p. 454 - 456
(2010/04/30)
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- New reactions of anticancer-platinum complexes and their intriguing behaviour under various experimental conditions
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The anticancer platinum complexes here described react with organic substrates (such as acids, alkenes, alkynes) and catalyze transformations that can occur in biomolecules which contain unsaturated functions. We have analyzed the role of the platinum complexes in the observed reactions and studied the progress of the detected transformations upon variation of the reaction conditions. The Royal Society of Chemistry 2010.
- Aleman, Jose,Del Solar, Virginia,Cubo, Leticia,Quiroga, Adoracion G.,Navarro Ranninger, Carmen
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scheme or table
p. 10601 - 10607
(2011/01/05)
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- The detection of PHIP effects allows new insights into the mechanism of olefin isomerisation during catalytic hydrogenation
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PHIP (parahydrogen-induced polarisation) effects in the 1H NMR spectra of the products of Rh-complex-catalysed alkyne hydrogenation brings to light the fact that the cis-trans isomerisation of the formed olefin occurs through the formation of a σ-bonded intermediate stabilised by the reversible addition of a hydrogen molecule at the metal centre. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Viale, Alessandra,Santelia, Daniela,Napolitano, Roberta,Gobetto, Roberto,Dastru, Walter,Aime, Silvio
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experimental part
p. 4348 - 4351
(2009/02/08)
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- Hydrogen-free homogeneous catalytic reduction of olefins in aqueous solutions
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(Chemical Equation Presented) Herein we report a study involving the homogeneous catalytic reduction of unsaturated substrates in aqueous solutions or water-organic solvent mixtures. The reduction of olefins has been carried out in the presence of catalytic amounts of [Fe(CN)5NH3] 3- and excess of NH2OH, which under mild reaction conditions can be used to reduce carbon-carbon unsaturations without affecting carbonyl functionalities and aromatic rings. To explore the scope of the catalytic reduction, a wide variety of representative unsaturated substrates have been examined. The steric effects of the substituents on the carbon-carbon multiple bond as well as the regioselectivity and stereoselectivity of the catalyst have been studied. The deuterium kinetic isotope effect on the catalytic reduction of double bonds in olefins has been analyzed, and no significant kinetic isotope effect was found. Among the great advantages of this novel procedure for catalytic reduction are that hydrogen and high pressures are not needed, the catalyst is inexpensive and easily prepared, and water as well as water-organic solvent mixtures can be used as reaction media.
- Gaviglio, Carina,Doctorovich, Fabio
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p. 5379 - 5384
(2008/12/20)
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- MANUFACTURING METHOD OF ISOMERIZED PRODUCT OF ETHYLENICALLY UNSATURATED CARBOXYLIC ACID OR ESTER THEREOF
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PROBLEM TO BE SOLVED: To provide a method for selectively manufacturing an isomerized product of an ethylenically unsaturated monocarboxylic acid or esters thereof from the ethylenically unsaturated monocarboxylic acid or esters thereof without using a catalyst or an organic solvent. SOLUTION: The manufacturing method of the isomerized product of the ethylenically unsaturated monocarboxylic acid or esters thereof comprises transferring a double bond and selectively synthesizing a stereoisomer by causing the ethylenically unsaturated monocarboxylic acid or esters thereof to non-catalytically react in a reaction medium in a high temperature and high pressure state (a subcritical state or a supercritical state). Thus, the desired isomer is selectively manufactured in a short time in a one-step process without using the organic solvent. Moreover, waste or wastewater is hardly generated in the manufacturing processes.
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Page/Page column 6-8; 10
(2008/06/13)
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- METHOD FOR ISOMERIZING ORGANIC COMPOUND
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PROBLEM TO BE SOLVED: To provide a method for isomerizing a compound bearing a hydrocarbon group having a carbon-carbon double bond which permits transfer of the carbon-carbon double bond of the compound without using a catalyst or an organic solvent. SOLUTION: The method for isomerizing the compound comprises transferring the position of the carbon-carbon double bond by causing the compound bearing the hydrocarbon group having the carbon-carbon double bond to non-catalytically react in a reaction medium in a high-temperature and high-pressure state. Thus, the isomer having the double bond transferred is obtained in a short time in one step by pressing the compound bearing the hydrocarbon group having the carbon-carbon double bond into high-temperature high-pressure water as a reaction site at a high speed. Neither waste nor wastewater to dispose of is discharged from the manufacturing processes.
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(2008/06/13)
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- Synthesis and self-photooxygenation of alkenyl-linked [60]fullerene derivatives. A regioselective ene reaction
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(equation presented) Alkenyl-linked C60 derivatives undergo self-photooxygenation regioselectively, by the preferential abstraction of allylic hydrogens on the fullerene side of the double bond.
- Chronakis, Nikos,Vougioukalakis, Georgios C.,Orfanopoulos, Michael
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p. 945 - 948
(2007/10/03)
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- Tungsten(0) alkylidene complexes stabilized as pyridinium ylides: New aspects of their synthesis and reactivity
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The interaction of dihydropyridines with alkoxycarbene complexes of tungsten has been shown to lead to pyridinium ylid complexes: this transformation has now been applied to the synthesis of a hydroxyl-containing ylid complex by ring-opening of the pentacarbonyl (2-oxacyclopentylidene) tungsten(0) complex and to the synthesis of a series of chiral ylid complexes both from chiral and non-chiral carbene complexes by the use of dihydropyridines and dihydronicotines, respectively. The transfer of the alkylidene moiety of these complexes to nucleophilic olefins will be outlined and discussed. Especially relevant is the interaction of these pyridinium ylid complexes with unsaturated substrates such as dihydropyridines, enamines, and β-alkoxy bis(trimethyl-silyl) ketene acetals. This latter reaction leads to conjugated carboxylic acids, and has been be applied to a new synthesis of a honey bee pheromone, the queen substance.
- Rudler, Henri,Durand-Réville, Thomas
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p. 571 - 587
(2007/10/03)
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- Intermediates in the ene reactions of singlet oxygen and N-phenyl-1,2,4-triazoline-3,5-dione with olefins
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The reaction between singlet oxygen and cis- and trans-2-butene-1,1,1-d3 has been studied. The product isotope effects (k(H)/k(D)) were found to be 1.38 and 1.25, respectively. Similarly, N-phenyl-1,2,4-triazoline-3,5-dione (PTAD) reacts readily with these substrates and shows isotope effects that are larger (5.36, 1.29) but in the same direction. 2-Methyl-1-propene-3,3,3-d3 is unreactive with singlet oxygen but reacts easily with PTAD with a product isotope effect of 1.25. The intermolecular (kinetic) and intramolecular (product) isotope effects on the reactions of singlet oxygen with cis-1,4-diphenyl-2-butene were found to be 1.07 and 1.50, respectively. cis-Butene is 18 times more reactive with singlet oxygen than the trans isomer. Ene reactions for both singlet oxygen and PTAD probably proceed through the reversible formation of an intermediate with structural requirements similar to a perepoxide or aziridinium imide, respectively.
- Orfanopoulos,Smonou,Foote
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p. 3607 - 3614
(2007/10/02)
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- MODIFIED PHOTOBEHAVIOR OF CARBOXYLIC ACID DERIVATIVES INDUCED BY PROTONATION
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A series of carboxylic acid derivatives 1-6 containing a second interacting function have been converted into the corresponding O-protonated species or acylium ions upon treatment with 96percent sulfuric acid or oleum, respectively, at room temperature.The resulting stable cations have been spectroscopically characterized and submitted to irradiation.Cis-trans photoisomerization was observed in the ionic species derived from trans-crotonic, fumaric and maleic acids, and maleic anhydride.By contrast protonated crotonolactone 5a was found to be photostable.Finally, protonated α-bromobutyrolactone 6a was clean and efficiently dehydrohalogenated to 5a upon irradiation.Since the normal n ?* photoreactions of the uncharged carboxylic acid and their derivatives are inhibited under these conditions, protonation can be envisaged as a chemical selective method for photoprotection of the carboxy group.
- Amat, Ana M.,Asensio, Gregorio,Castello, Maria J.,Miranda, Miguel A.,Simon-Fuentes, Antonio
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p. 905 - 910
(2007/10/02)
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- Studies in Decarboxylation. Part 14. The Gas-phase Decarboxylation of But-3-enoic Acid and the Intermediacy of Isocrotonic (cis-But-2-enoic) Acid in its Isomerisation to Crotonic (trans-But-2-enoic) Acid
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At 593 K the complex system (A) is shown to be rapidly set up starting from any of the pure acids.Of particular crotonic acid isocrotonic acid but-3-enoic acid propene + CO2 (A) interest is the intermediacy of isocrotonic acid (the thermodynamically least stable of the three) in the interconversion of crotonic and but-3-enoic acids.A mechanism involving the enolic form of a carboxylic acid is proposed to account for this feature.The interconversion of crotonic and isocrotonic acids is much more rapid than that of their ethyl esters and a basis is proposed for the difference.Activation parameters relating to the decarboxylation of but-3-enoic acid are isolated by the flow technique.
- Bigley, David B.,Clarke, Michael J.
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