- Chemical space exploration of oxetanes
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This paper focuses on new derivatives bearing an oxetane group to extend accessible chemical space for further identification of kinase inhibitors. The ability to modulate kinase activity represents an important therapeutic strategy for the treatment of h
- Cou?ago, Rafael M.,Laufer, Stefan,de Sá Alves, Fernando Rodrigues
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- Retro-Corey-Chaykovsky Epoxidation: Converting Geminal Disubstituted Epoxides to Ketones
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Corey-Chaykovsky epoxidation has been widely applied in the conversion of aldehydes and ketones to epoxides with sulfonium and sulfoxonium ylides. The reverse transformation is realized for conversion of geminal disubstituted epoxides to ketones in the presence of DABCO in refluxing mesitylene. The method is a weak basic transformation from epoxides to ketones with loss of a methylene group and can be applied as an alternative strategy of the acid-catalyzed Meinwald rearrangement or oxidation for conversion of epoxides to carbonyl compounds.
- Li, Siqi,Li, Pingfan,Xu, Jiaxi
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- Mild Iridium-Catalysed Isomerization of Epoxides. Computational Insights and Application to the Synthesis of β-Alkyl Amines
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The isomerization of epoxides to aldehydes using the readily available Crabtree's reagent is described. The aldehydes were transformed into synthetically useful amines by a one-pot reductive amination using pyrrolidine as imine-formation catalyst. The reactions worked with low catalyst loadings in very mild conditions. The procedure is operationally simple and tolerates a wide range of functional groups. A DFT study of its mechanism is presented showing that the isomerization takes place via an iridium hydride mechanism with a low energy barrier, in agreement with the mild reaction conditions. (Figure presented.).
- Cabré, Albert,Cabezas-Giménez, Juanjo,Sciortino, Giuseppe,Ujaque, Gregori,Verdaguer, Xavier,Lledós, Agustí,Riera, Antoni
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supporting information
p. 3624 - 3631
(2019/07/10)
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- Biocatalytic Parallel Interconnected Dynamic Asymmetric Disproportionation of α-Substituted Aldehydes: Atom-Efficient Access to Enantiopure (S)-Profens and Profenols
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The biocatalytic asymmetric disproportionation of aldehydes catalyzed by horse liver alcohol dehydrogenase (HLADH) was assessed in detail on a series of racemic 2-arylpropanals. Statistical optimization by means of design of experiments (DoE) allowed the identification of critical interdependencies between several reaction parameters and revealed a specific experimental window for reaching an ′optimal compromise′ in the reaction outcome. The biocatalytic system could be applied to a variety of 2-arylpropanals and granted access in a redox-neutral manner to enantioenriched (S)-profens and profenols following a parallel interconnected dynamic asymmetric transformation (PIDAT). The reaction can be performed in aqueous buffer at ambient conditions, does not rely on a sacrificial co-substrate, and requires only catalytic amounts of cofactor and a single enzyme. The high atom-efficiency was exemplified by the conversion of 75 mM of rac-2-phenylpropanal with 0.03 mol% of HLADH in the presence of ~0.013 eq. of oxidized nicotinamide adenine dinucleotide (NAD+), yielding 28.1 mM of (S)-2-phenylpropanol in 96% ee and 26.5 mM of (S)-2-phenylpropionic acid in 89% ee, in 73% overall conversion. Isolated yield of 62% was obtained on 100 mg-scale, with intact enantiopurities. (Figure presented.).
- Tassano, Erika,Faber, Kurt,Hall, Mélanie
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supporting information
p. 2742 - 2751
(2018/07/29)
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- SUBSTITUTED [1,2,4]TRIAZOLE COMPOUNDS AND THEIR USE AS FUNGICIDES
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The present invention relates to compoundsof the formula (I) wherein the variables are defined in the description and claims, their preparation and uses thereof.
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Page/Page column 138; 139
(2014/07/08)
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- SUBSTITUTED 2-[PHENOXY-PHENYL]-1-[1,2,4]TRIAZOL-1-YL-ETHANOL COMPOUNDS AND THEIR USE AS FUNGICIDES
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The present invention relates to substituted 2-[phenoxy-phenyl]-1-[1,2,4]triazol-1-yl-ethanol compounds of formula I as defined in the description,and the N-oxides, and salts thereof, their preparation and intermediates for preparing them. The invention also relates to the use of these compounds for combating harmful fungi and seed coated with at least one such compound and also to compositions comprising at least one such compound.
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Page/Page column 84
(2014/06/23)
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- β-tert-Butyl aspartate as an organocatalyst for the asymmetric α-amination of α,α-disubstituted aldehydes
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The enantioselective α-amination reaction of α,α- disubstituted aldehydes can lead to a variety of enantioenriched amino aldehydes, amino alcohols, and amino acids. After screening a variety of amino acids and their derivatives, we identified a cheap, simple, commercially available aspartic acid derivative that can catalyze efficiently the reaction between α,α-disubstituted aldehydes and dialkyl azodicarboxylates. The reaction proceeds smoothly leading to the corresponding α-aminated adducts in moderate to quantitative yields and moderate to high enantioselectivities (up to 96% ee). Finally, the conversion of these adducts to α,α-disubstituted quaternary amino acids is also described.
- Theodorou, Alexis,Papadopoulos, Giorgos N.,Kokotos, Christoforos G.
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supporting information
p. 5438 - 5443
(2013/07/05)
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- Isomerization of terminal epoxides by a [Pd-H] catalyst: A combined experimental and theoretical mechanistic study
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An unusual palladium hydride complex has been shown to be a competent catalyst in the isomerization of a variety of terminal and internal epoxides. The reaction displayed broad scope and synthetic utility. Experimental and theoretical evidence are provided for an unprecedented hydride mechanism characterized by two distinct enantio-determining steps. These results hold promise for the development of an enantioselective variant of the reaction.
- Vyas, Devendra J.,Larionov, Evgeny,Besnard, Celine,Guenee, Laure,Mazet, Clement
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supporting information
p. 6177 - 6183
(2013/06/04)
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- Resolution of 2,2-disubstituted epoxides via biocatalytic azidolysis
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A practical procedure for the enzymatic resolution of 2-alkyl-2-aryl- disubstituted epoxides using the Codex HHDH P2E2 enzyme and sodium azide is reported. This method allowed the synthesis of novel regio-and enantioselective 1-azido-2-arylpropan-2-ols in
- Molinaro, Carmela,Guilbault, Audrey-Anne,Kosjek, Birgit
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supporting information; experimental part
p. 3772 - 3775
(2010/11/16)
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- BICYCLIC NITROIMIDAZOLES COVALENTLY LINKED TO SUBSTITUTED PHENYL OXAZOLIDINONES
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The current invention provides a series of bicyclic nitroimidazole- substituted phenyl oxazolidinones in which a bicyclic nitroimidazole pharmacophore is covalently bonded to a phenyl oxazolidinone, their pharmaceutical compositions, and the method of use of the compositions for prevention and treatment of bacterial infections. The bicyclic nitroimidazole-substituted phenyl oxazolidinones possess surprising antibacterial activity against wild- type and resistant strains of pathogens, and are therefore useful for the prevention, control and treatment of a number of human and veterinary bacterial infections caused by these pathogens, such as Mycobacterium tuberculosis.
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Page/Page column 99
(2009/10/22)
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- Polymer-supported thioanisole: A versatile platform for organic synthesis reagents
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A new cross-linked polystyrene-supported thioanisole reagent is reported. This reagent incorporates the flexible JandaJel cross-linker and can be treated with methyl trifluoromethanesulfonate to form the corresponding sulfonium salt. This salt can in turn be deprotonated to form a polymer-supported sulfur ylide that is able to react with aldehydes and ketones to form epoxides. The thioanisole reagent can also be oxidized to form an insoluble sulfoxide reagent that is useful in Swern oxidation reactions. In these reactions, the polymer-supported thioanisole-based reagents can be recovered, regenerated and reused.
- Choi, Matthew Kwok Wai,Toy, Patrick H.
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p. 2875 - 2879
(2007/10/03)
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- Microbiological transformations 43. Epoxide hydrolases as tools for the synthesis of enantiopure α-methylstyrene oxides: A new and efficient synthesis of (S)-ibuprofen
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Biohydrolysis of various α-methylstyrene oxide derivatives, differently substituted at the aromatic ring, was investigated using 10 epoxide hydrolases from different origins. Our results indicate that the enantioselectivity of these biohydrolyses strongly depends on the nature of the enzyme and of the substituent. Using some of these enzymes, this approach allows to prepare these epoxides in high optical purity. The potentiality to perform efficient preparative-scale resolution using such a biocatalyst was illustrated by the four-step synthesis of (S)-ibuprofen, a nonsteroidal antiinflammatory drug and household pain killer, one of the top-ten drugs sold worldwide. Using a combined chemoenzymatic strategy, we were thus able to set up a four-step enantioconvergent procedure allowing for the synthesis of this compound in optically pure form and with a 47% overall yield, including the resolution process, due to a possible recycling of the formed diol via chemical racemisation.
- Cleij,Archelas,Furstoss
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p. 5029 - 5035
(2007/10/03)
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- Solvent free synthetic procedure throughout reaction and separation: ylide reaction with alkyl aryl ketones in the absence of solvent followed by distillation to give 1-alkyl-1-aryloxiranes
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After heating a mixture of trimethylsulphonium iodide, tBuOK and an alkyl aryl ketone at 60-70 °C for 1-5 h, vacuum distillation gave the corresponding 1-alkyl-1-aryloxirane. The procedure was accomplished without using any solvent throughout the reaction and the separation.
- Toda, Fumio,Kanemoto, Kazuyuki
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p. 185 - 188
(2007/10/03)
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- Reactivity and selectivity in the oxidation of styrene derivatives, II studies on the oxidation of p-substituted α-methylstyrenes
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The liquid phase oxidation of p-substituted (Br-, Cl-, t-Bu-, MeO-, CF3-) α-methylstyrenes and of α,p-dimethoxystyrene 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 the epoxide formation and the parallel reactions amount to 19-48 kJ/mol. The epoxide selectivity increases with increasing temperature and concentration of olefine. The relative chain propagation constants kp (C=C) were determined by competitive oxidation with cumene. The kp(C=C) values of p-substituted α-methylstyrenes can be correlated by the Hammett equation with both σ and σ+ substituent constants.
- Suprun, Wladimir
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p. 231 - 237
(2007/10/03)
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- Reactions of 4-Substituted-2'-Halogenoacetophenones with Grignard Reagents
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The initial reaction of 4-substituted 2'-halogenoacetophenones with an excess of methyl Grignard reagent is shown to be an attack at the 1'-carbonyl to form a halohydrin salt.The various reactions which then follow are substituent dependent.In the 4-hydroxy case the only product is 1-(4-hydroxyphenyl)-2-methylpropan-2-ol (13) which arises via a -aryl shift with simultaneous elimination of magnesium halide.When the substituent is 4-methoxy, a second pathway becomes important involving epoxide formation and a subsequent -hydride migration to the benzylic position, or attack of the Grignard reagent at the benzylic carbon of the epoxide.When the substituent is 4-bromo, the reaction proceeds exclusively via the epoxide and, following a -hydride shift, leads to the isomeric butanols (33) and (34).The reasons underlying such diversity of reactivity are discussed.
- Crombie, Leslie,Hardy, Robert,Knight, David W.
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p. 1373 - 1380
(2007/10/02)
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