- Room Temperature Cu-Catalyzed N-Arylation of Oxazolidinones and Amides with (Hetero)Aryl Iodides
-
N,N′-Bis(pyridin-2-ylmethyl)oxalamide (BPMO) was found to be an apposite promoter for the Cu-catalyzed N-arylation of oxazolidinones and primary and secondary amides with (hetero)aryl iodides at room temperature. Excellent chemoselectivity reached between
- Bhunia, Subhajit,De, Subhadip,Ma, Dawei
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supporting information
(2022/02/09)
-
- Preparation method of oxazolidinone compound
-
The preparation method comprises the following steps 1): dissolving aromatic amino acid in methanol, dissolving the aromatic amino acid in methanol, heating up to 50 - 60 °C heat preservation 1 - 2h, 2) reducing: adding a catalytic amount of lithium salt in ethanol water as a solvent. 3) Ring-closing: toluene is used as a solvent, a reduction product and diethyl carbonate are added to 100 °C, a sodium methoxide solution is added dropwise, and the product is obtained after completion of the dropwise addition and after-treatment and purification after completion of the normal pressure distillation to the temperature of 100 °C heat preservation. The lithium salt is introduced to participate in the reaction, sodium borohydride is selected as a solvent, sodium borohydride is completely dissolved, and the lithium salt can be free from the compound to improve the reaction activity, so that the use amount of sodium borohydride is reduced to 2 equivalent, and the production cost is remarkably reduced.
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Paragraph 0044; 0049-0050
(2021/11/10)
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- Synthesis of Aminomethylene- gem-bisphosphonates Containing an Aziridine Motif: Studies of the Reaction Scope and Insight into the Mechanism
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A broad range of N-carbamoylaziridines were obtained and then treated by the diethyl phosphonate anion to afford α-methylene-gem-bisphosphonate aziridines. Study of the reaction's scope and additional experiments indicates that the transformation proceeds via a new mechanism involving the chelation of lithium ion. This last step is crucial for the reaction to occur and disfavors the aziridine ring-opening. A phosphonate-phosphate rearrangement from a α-hydroxybisphosphonate aziridine intermediate is also proposed for the first time. This reaction provides a simple and convenient method for the synthesis of a highly functionalized phosphonylated aziridine motif.
- Cheviet, Thomas,Peyrottes, Suzanne
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p. 3107 - 3119
(2021/02/05)
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- Atomically Dispersed High-Density Al–N4 Sites in Porous Carbon for Efficient Photodriven CO2 Cycloaddition
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Highly active catalysts that can directly utilize renewable energy (e.g., solar energy) are desirable for CO2 value-added processes. Herein, aiming at improving the efficiency of photodriven CO2 cycloaddition reactions, a catalyst composed of porous carbon nanosheets enriched with a high loading of atomically dispersed Al atoms (≈14.4?wt%, corresponding to an atomic percent of ≈7.3%) coordinated with N (AlN4 motif, Al–N–C catalyst) via a versatile molecule-confined pyrolysis strategy is reported. The performance of the Al–N–C catalyst for catalytic CO2 cycloaddition under light irradiation (≈95% conversion, reaction rate = 3.52 mmol g?1 h?1) is significantly superior to that obtained under a thermal environment (≈57% conversion, reaction rate = 2.11 mmol g?1 h?1). Besides the efficient photothermal conversion induced by the carbon matrix, both experimental and theoretical analysis reveal that light irradiation favors the photogenerated electron transfer from the semiconductive Al–N–C catalyst to the epoxide reactant, facilitating the formation of a ring-opened intermediate through the rate-limiting step. This study not only provides an advanced Al–N–C catalyst for photodriven CO2 cycloaddition, but also furnishes new insight for the rational design of superior photocatalysts for diverse heterogeneous catalytic reactions in the future.
- Yang, Qihao,Peng, Huaitao,Zhang, Qiuju,Qian, Xu,Chen, Xu,Tang, Xuan,Dai, Sheng,Zhao, Jiajun,Jiang, Kun,Yang, Qiu,Sun, Jian,Zhang, Linjuan,Zhang, Nian,Gao, Honglin,Lu, Zhiyi,Chen, Liang
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- Novel chiral stationary phases based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin combining cinchona alkaloid moiety
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Novel chiral selectors based on 3,5-dimethyl phenylcarbamoylated β-cyclodextrin connecting quinine (QN) or quinidine (QD) moiety were synthesized and immobilized on silica gel. Their chromatographic performances were investigated by comparing to the 3,5-dimethyl phenylcarbamoylated β-cyclodextrin (β-CD) chiral stationary phase (CSP) and 9-O-(tert-butylcarbamoyl)-QN-based CSP (QN-AX). Fmoc-protected amino acids, chiral drug cloprostenol (which has been successfully employed in veterinary medicine), and neutral chiral analytes were evaluated on CSPs, and the results showed that the novel CSPs characterized as both enantioseparation capabilities of CD-based CSP and QN/QD-based CSPs have broader application range than β-CD-based CSP or QN/QD-based CSPs. It was found that QN/QD moieties play a dominant role in the overall enantioseparation process of Fmoc-amino acids accompanied by the synergistic effect of β-CD moiety, which lead to the different enantioseparation of β-CD-QN-based CSP and β-CD-QD-based CSP. Furthermore, new CSPs retain extraordinary enantioseparation of cyclodextrin-based CSP for some neutral analytes on normal phase and even exhibit better enantioseparation than the corresponding β-CD-based CSP for certain samples.
- Zhu, Lunan,Zhu, Junchen,Sun, Xiaotong,Wu, Yaling,Wang, Huiying,Cheng, Lingping,Shen, Jiawei,Ke, Yanxiong
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p. 1080 - 1090
(2020/05/25)
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- Synthesis of pyrroloindolines through formal [3 + 2]-cycloaddition of indoles with chiral N-2-acetamidoacrylyl oxazolidinones
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Chiral N-2-acetamidoacrylyl oxazolidinones were produced and reacted with indoles under Lewis acid conditions to generate hexahydropyrrolo[2,3-b]indole products in a formal [3 + 2] cycloaddition process. Optimal conditions included the use of tin(IV) chloride in methylene chloride at 0 °C. Pyrroloindoline products were obtained from various indoles with shorter reaction times (12 hr) up to 91% yield with high, >20:1 exo selectivity. A mechanism involving reversible conjugate addition followed by an enamine lone-pair-iminium capture, tautomerization, and tin-enolate protonation accounts for the selectivity. The method enables selective applications to pyrroloindoline targets and further refinement with chiral catalysts.
- Smith, Isaac T.,Neeley, Jared B.,Brinley, Tanner D.,Fullmer, Peter R.,Andrus, Merritt B.
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supporting information
(2020/05/01)
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- Towards the Sarpagine-Ajmaline-Macroline Family of Indole Alkaloids: Enantioselective Synthesis of an N-Demethyl Alstolactone Diastereomer
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the strategy involving the use of functionalized tetrahydro-6H-cycloocta[b]indol-6-one is reported as a key intermediate for synthesis of members of the sarpagine-ajmaline-macroline family of monoterpene indole alkaloids. The desired tricycle was synthesized through the following key steps: 1) Evans’ syn-selective aldolization; 2) Liebeskind–Srogl cross-coupling using the phenylthiol ester of 3-chloropropanoic acid as a surrogate of acrylic thioester for the synthesis of 2,3-disubstituted indoles; and 3) ring-closing metathesis (RCM) for the formation of the eight-membered ring. An N-allylation followed by intramolecular 1,4-addition was planned for synthesis of the vobasine class of natural products. However, attempted cyclizations under a diverse set of conditions involving anionic, radical, and organopalladium/organonickel species failed to produce the bridged ring system. On the other hand, esterification of the pendant primary alcohol function with acetoacetic acid, followed by intramolecular Michael addition, afforded the desired tetracycle with excellent diastereoselectivity. Subsequent functional group manipulation and transannular cyclization of the amino alcohol afforded the N(1)-demethyl-3,5-diepi-alstolactone. We believe that the same synthetic route would afford the alstolactone should the amino alcohol with appropriate stereochemistry be used as the starting material.
- Dagoneau, Dylan,Wang, Qian,Zhu, Jieping
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supporting information
p. 4866 - 4873
(2020/04/15)
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- Auxiliary-controlled diastereoselective synthesis of a syn C-6-epimer of the ADAM 10 inhibitor GI254023X
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ADAM10 is a cell surface-expressed metalloprotease involved in various cell adhesion and proteolytic processes, in which biological studies have linked an over-expression of ADAM10 to the development and progression of various types of diseases including cancer. GI254023X is a hydroxamate metalloprotease inhibitor known for ADAM10 activity inhibition, but for which structure-activity based biological information for assessing anti-tumour and anti-inflammatory activity is lacking. In this work, an Evans’ asymmetric boron aldol reaction was used to synthesise a syn C-6-epimer of GI254023X intended for biological evaluation against the natural inhibitor.
- Nair, Shankari,Zeevaart, Jan Rijn,Hunter, Roger
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- One-pot synthesis of oxazolidinones and five-membered cyclic carbonates from epoxides and chlorosulfonyl isocyanate: Theoretical evidence for an asynchronous concerted pathway
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The one-pot reaction of chlorosulfonyl isocyanate (CSI) with epoxides having phenyl, benzyl and fused cyclic alkyl groups in different solvents under mild reaction conditions without additives and catalysts was studied. Oxazolidinones and five-membered cyclic carbonates were obtained in ratios close to 1:1 in the cyclization reactions. The best yields of these compounds were obtained in dichloromethane (DCM). Together with 16 known compounds, two novel oxazolidinone derivatives and two novel cyclic carbonates were synthesized with an efficient and straightforward method. Compared to the existing methods, the synthetic approach presented here provides the following distinct advantageous: being a one-pot reaction with metal-free reagent, having shorter reaction times, good yields and a very simple purification method. Moreover, using the density functional theory (DFT) method at the M06-2X/6-31+G(d,p) level of theory the mechanism of the cycloaddition reactions has been elucidated. The further investigation of the potential energy surfaces associated with two possible channels leading to oxazolidinones and five-membered cyclic carbonates disclosed that the cycloaddition reaction proceeds via an asynchronous concerted mechanism in gas phase and in DCM.
- Demir, Esra,Sari, Ozlem,?etinkaya, Yasin,Atmaca, Ufuk,Erdem, Safiye Sa?,?elik, Murat
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p. 1805 - 1819
(2020/11/07)
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- Sequencing of Sequence-Defined Oligourethanes via Controlled Self-Immolation
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Sequence-defined polymers show promise for biomimetics, self-assembly, catalysis, and information storage, wherein the primary structure begets complex chemical processes. Here we report the solution-phase and the high-yielding solid-phase syntheses of discrete oligourethanes and methods for their self-immolative sequencing, resulting in rapid and robust characterization of this class of oligomers and polymers, without the use of MS/MS. Crucial to the sequencing is the inherent reactivity of the terminal alcohol to "unzip" the oligomers, in a controlled and iterative fashion, releasing each monomer as a 2-oxazolidinone. By monitoring the self-immolation reaction via LC/MS, an applied algorithm rapidly produces the sequence of the oligourethane. Not only does this process provide characterization of structurally complex molecules, it works as a reader of molecular information.
- Anslyn, Eric V.,Coronado, Jaime N.,Dahlhauser, Samuel D.,Escamilla, P. Rogelio,Glass, Samuel A.,Moor, Sarah R.,Rapagnani, Rachel M.,Saunders, Douglas P.,Shei, Jasper S.,Vandewalle, Abigail N.,York, Jordan T.
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supporting information
p. 2744 - 2749
(2020/03/10)
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- Controllable Intramolecular Unactivated C(sp3)-H Amination and Oxygenation of Carbamates
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Dual catalyst-controlled intramolecular unactivated C(sp3)-H amination and oxygenation of carbamates merging visible-light photocatalysis and earth-abundant transition metal catalysis have been reported. Useful amino alcohol and diol derivatives could be selectively obtained from readily available tertiary alcohol derivatives. The possible mechanisms have been proposed via a 1,5-HAT process followed by Lewis acid-controlled cyclization. The nickel and zinc catalysts inhibit the formation of oxygenation and amination products, respectively. An interesting phenomenon of chirality transfer is also observed.
- Guo, Qihang,Ren, Xiang,Lu, Zhan
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supporting information
p. 880 - 884
(2019/05/16)
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- Synthesis of a diastereomer of the marine macrolide lytophilippine A
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The synthesis of a diastereomer of lytophilippine A required 22 longest linear steps using known building blocks. Cross-metathesis/asymmetric aldol addition and regioselective esterification/ring-closing metathesis served as efficient combi tools for scaffold construction. Detailed NMR investigations in different solvent (systems) provide evidence for a deep-seated configurational misassignment of the molecule named lytophilippine A.
- Klüppel, André,Gille, Annika,Karayel, Ceren Ester,Hiersemann, Martin
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supporting information
p. 2421 - 2425
(2019/03/29)
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- Concise and Additive-Free Click Reactions between Amines and CF3SO3CF3
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Trifluoromethyl trifluoromethanesulfonate has proved to be an excellent reservoir of difluorophosgene and a promising click ligation for amines in the preparation of urea derivatives, heterocycles, and carbamoyl fluorides under metal- and additive-free conditions. The reactions are rapid, efficient, selective, and versatile, and can be performed in benign solvents, giving products in excellent yields with minimal efforts for purification. The characteristics of the reactions meet the requirements of a click reaction. The use of trifluoromethyl trifluoromethanesulfonate as a click reagent is advantageous over other “CO” sources (e.g., TsOCF3, PhCO2CF3, CsOCF3, AgOCF3, and triphosgene) because this reagent is readily accessible; easy to scale up; and highly reactive, even under metal- and additive-free conditions. It is anticipated that CF3SO3CF3 will be increasingly as important as SO2F2 as a click agent in future drug design and development.
- Song, Hai-Xia,Han, Zhou-Zhou,Zhang, Cheng-Pan
-
supporting information
p. 10907 - 10912
(2019/08/02)
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- PROCESS FOR PREPARING OPTICALLY PURE (R)-4-N-PROPYL-DIHYDROFURAN-2(3H)-ONE
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The present invention discloses a process for preparing optically pure (R)-4-n-propyl-dihydrofuran-2(3H)-one, belonging to the field of chemical synthesis. According to the process, optically pure (S)-3-n-pentanoyl-4-substituted oxazol-2-one is used as a starting material, and after alkylation, reduction, cyano hydrolysis, lactonization, the product optically pure (R)-4-n-propyl-dihydrofuran-2(3H)-one is given. The preparation process has the advantages of easy availability of raw materials, low price, high yield, high optical purity of product, simple reaction conditions and simple operations.
- -
-
Paragraph 0100-0102
(2019/12/10)
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- Synthesis of new C3 symmetric amino acid- and aminoalcohol-containing chiral stationary phases and application to HPLC enantioseparations
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We recently reported a new C3-symmetric (R)-phenylglycinol N-1,3,5-benzenetricarboxylic acid-derived chiral high-performance liquid chromatography (HPLC) stationary phase (CSP 1) that demonstrated better results as compared to a previously described N-3,5-dintrobenzoyl (DNB) (R)-phenylglycinol-derived CSP. Over a decade ago, (S)-leucinol, (R)-phenylglycine, and (S)-leucine derivatives were used as the starting materials of 3,5-DNB-based Pirkle-type CSPs for chiral separation. In this study, three new C3-symmetric CSPs (CSP 2, 3, and 4) were prepared by combining the ideas and results mentioned above. Here we describe the synthetic procedures and applications of the new C3-symmetric CSPs (CSP 2–CSP 4).
- Yu, Jeongjae,Armstrong, Daniel W.,Ryoo, Jae Jeong
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- Access towards enantiopure α,α-difluoromethyl alcohols by means of sulfoxides as traceless chiral auxiliaries
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A new methodology to access enantiopure α,α-difluoromethyl alcohols is hereby being described. The strategy relies on the use of an enantiopure aryl α,α-difluoromethyl sulfoxide employed as chiral and removable auxiliary for the stereoselective difluoromethylation of carbonyl derivatives. The obtained α,α-difluoro-β-hydroxysulfoxides displayed unprecedented diastereomeric ratios.
- Batisse, Chloé,Panossian, Armen,Hanquet, Gilles,Leroux, Frédéric R.
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supporting information
p. 10423 - 10426
(2018/09/21)
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- New preparation method of brivaracetam
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The present invention relates to a new preparation method of brivaracetam, According to the new preparation method, a chiral compound represented by a formula III and (S)-2-aminobutyramide or a salt thereof are subjected to a condensation reaction in the presence of a condensing agent to obtain a compound represented by a formula IV and having two chiral centers; a hydroxy protecting group R1 is removed to obtain a compound represented by a formula V; the compound represented by the formula V and a chlorinating reagent are subjected to a chlorinating reaction to obtain a compound represented by a formula VI; the compound represented by the formula VI is subjected to a substitution reaction in the presence of an alkaline agent, and ring closure is performed to obtain a formula I. Accordingto the present invention, the structure represented by the formula I contains two chiral centers, the intermediate compound represented by the formula IV has two chiral centers, and the chiral centersare not changed during a series of the reactions until the final product is generated; and with the method, the high optical purity brivaracetam can be directly obtained without the separation with the chiral chromatography, and the method is suitable for industrial production.
- -
-
Paragraph 0173; 0174; 0175; 0176
(2018/11/04)
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- Direct Lewis Acid Catalyzed Conversion of Enantioenriched N-Acyloxazolidinones to Chiral Esters, Amides, and Acids
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The identification of Yb(OTf)3 through a multivariable high-throughput experimentation strategy has enabled a unified protocol for the direct conversion of enantioenriched N-acyloxazolidinones to the corresponding chiral esters, amides, and carboxylic acids. This straightforward and catalytic method has shown remarkable chemoselectivity for substitution at the acyclic N-acyl carbonyl for a diverse array of N-acyloxazolidinone substrates. The ionic radius of the Lewis acid catalyst was demonstrated as a key driver of catalyst performance that led to the identification of a robust and scalable esterification of a pharmaceutical intermediate using catalytic Y(OTf)3.
- Stevens, Jason M.,Parra-Rivera, Ana Cristina,Dixon, Darryl D.,Beutner, Gregory L.,Delmonte, Albert J.,Frantz, Doug E.,Janey, Jacob M.,Paulson, James,Talley, Michael R.
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p. 14245 - 14261
(2019/01/03)
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- Synthesis and stereochemical assignment of geraniol- and nerol-derived Cygerol enantiomers
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The enantiomers (up to 99% ee) of both geraniol- and nerol-derived 2-cyclohexyl-5,9-dimethyldeca-4,8-dienoic acid, the active ingredient of the wound healing medication Cygerol, were prepared via a low-temperature alkylation, basic hydrolysis, derivatization with (S)-4-benzyloxazolidin-2-one and chromatographic separation steps. The absolute configuration of stereocenters in the antipodes having an (E)- or (Z)-geometry of the internal double bond was determined based on characteristic 1H NMR signals of the corresponding (S)-4-benzyloxazolidin-2-one-derived imides and on conversion to the known diethyl (S)-2-cyclohexylsuccinate and (S)-2-cyclohexylbutane-1,4-diol with reported specific rotations.
- Sukhanova, Anna A.,Puchkin, Ilya A.,Vasil'ev, Andrei A.,Zlotin, Sergei G.
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p. 1834 - 1841
(2017/11/20)
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- Continuous Flow Synthesis of Carbonylated Heterocycles via Pd-Catalyzed Oxidative Carbonylation Using CO and O2 at Elevated Temperatures and Pressures
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A continuous-flow Pd-catalyzed oxidative carbonylation protocol utilizing CO and O2 gas for the synthesis of carbonylated heterocycles is described. The optimization of temperature, pressure, CO/O2 ratio, catalyst loading, and reaction time resulted in process intensified conditions for this transformation. The optimized continuous flow conditions (120 °C, 20 bar pressure, 24 min residence time) were used to prepare a number of benzoxazolone, 2-benzoxazolidinone, and other biologically and synthetically important five- and six-membered carbonylated heterocycles in good overall yield and purity (14 examples). The continuous-flow process enables the safe and scalable oxidative carbonylation using CO/O2 under elevated pressures and temperatures.
- Chen, Yuesu,Hone, Christopher A.,Gutmann, Bernhard,Kappe, C. Oliver
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p. 1080 - 1087
(2017/07/26)
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- A 4-substituted-2-oxazolidinone cyclization method
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The invention discloses a cyclization method of 4-substituted-2-oxazolidone. The method is implemented through the following steps: (1) acylation: acylating chiral alkamine in a toluene solvent by adopting chloro-formate in the presence of potassium carbonate, so as to obtain chiral alkamine acylate; (2) cyclization: carrying out cyclization reaction through taking PEG-400 as a phase transfer catalyst, thereby obtaining 4-substituted-2-oxazolidone. Compared with the prior art, the cyclization method disclosed by the invention has the advantages that the adopted phase transfer catalyst is low in cost and is free of risk, reacting steps are reduced, the cost is reduced, and the conditions are mild, so that the method is suitable for industrial production.
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-
Paragraph 0016-0018
(2017/02/24)
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- Iron-Catalyzed Diastereoselective Synthesis of Unnatural Chiral Amino Acid Derivatives
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An iron-catalyzed diastereoselective synthesis of unnatural chiral (S)-α-amino acids with γ-quaternary carbon centers has been developed. The protocol uses inexpensive iron salt as the catalyst, readily available 2-phthaloyl acrylamide and alkenes as the starting materials, and phenylsilane as the reductant, and the reactions were performed well in mixed solvent of 1,2-dichloroethane and ethylene glycol at room temperature. The method shows some advantages including simple and wide substrates, mild conditions, high diastereoselectivity, and easy workup procedures.
- Zhang, Hao,Li, Haifang,Yang, Haijun,Fu, Hua
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supporting information
p. 3362 - 3365
(2016/07/26)
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- (Enantio)selective Hydrogen Autotransfer: Ruthenium-Catalyzed Synthesis of Oxazolidin-2-ones from Urea and Diols
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A novel strategy for the synthesis of oxazolidin-2-ones from vicinal diols and urea is described. In this heterocycle synthesis, two different C?O and C?N bonds are sequentially formed in a domino process consisting of nucleophilic substitution and alcohol amination. The use of readily available starting materials and the good atom economy render this process environmentally benign. While this transformation is already highly chemo- and regioselective, we also developed the first asymmetric version of this method using (R)-(+)-MeO-BIPHEP as the chiral ligand.
- Pe?a-López, Miguel,Neumann, Helfried,Beller, Matthias
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supporting information
p. 7826 - 7830
(2016/07/07)
-
- Syntheses of (+)-30-epi-, (-)-6-epi-, (±)-6,30-epi-13,14-Didehydroxyisogarcinol and (±)-6,30-epi-Garcimultiflorone A Utilizing Highly Diastereoselective, Lewis Acid-Controlled Cyclizations
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The first syntheses of 13,14-didehydroxyisogarcinol (6) and garcimultiflorone A (5) stereoisomers are reported in six steps from a commercially available phloroglucinol. Lewis acid-controlled, diastereoselective cationic oxycyclizations enabled asymmetric syntheses of (-)-6-epi-6 and (+)-30-epi-6. A similar strategy enabled production of the meso-dervied isomers (±)-6,30-epi-6 and (±)-6,30-epi-5. Finally, a convenient strategy for gram scale synthesis was developed utilizing diastereomer separation at a later stage in the synthesis that minimized the number of necessary synthetic operations to access all possible stereoisomers.
- Boyce, Jonathan H.,Eschenbrenner-Lux, Vincent,Porco, John A.
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supporting information
p. 14789 - 14797
(2016/11/18)
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- Chemoselective room temperature E1cB N-N cleavage of oxazolidinone hydrazides from enantioselective aldehyde α-hydrazination: Synthesis of (+)-1,4-dideoxyallonojirimycin
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Room temperature E1cB N-N cleavage of oxazolidinone hydrazides via N-alkylation with diethyl bromomalonate and potassium or caesium carbonate as base in acetonitrile is presented. The new method has a much improved chemoselectivity, which is illustrated by a concise total synthesis of the piperidine iminosugar (+)-1,4-dideoxyallonojirimycin.
- Ferreira, Jasmin,Rees-Jones, Sophie C. M.,Ramaotsoa, Valerie,Msutu, Ath'enkosi,Hunter, Roger
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p. 1545 - 1549
(2016/02/09)
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- Pd-catalyzed reductive cleavage of N-N bond in dibenzyl-1-alkylhydrazine-1,2-dicarboxylates with PMHS: Application to a formal enantioselective synthesis of (R)-sitagliptin
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An environmentally benign approach involving Pd-catalyzed reductive N-N bond cleavage in dibenzyl-1-alkylhydrazine-1,2-dicarboxylates leading to the synthesis of N-(tert-butoxy)carbamates under very mild conditions has been described. PMHS serves as an inexpensive source of hydride in MeOH/deionized H2O medium. This protocol has been successfully applied in the formal synthesis of (R)-sitagliptin, an anti-diabetic drug.
- Dey, Soumen,Gadakh, Sunita K.,Ahuja, Brij Bhushan,Kamble, Sanjay P.,Sudalai, Arumugam
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supporting information
p. 684 - 687
(2016/01/26)
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- A simple and efficient approach to the N-amination of oxazolidinones using monochloroamine
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Chiral nonracemic N-amino cyclic carbamates (ACCs) are important auxiliaries for certain asymmetric transformations. In the past they have been synthesized from oxazolidinones using methods that require the preparation and use of non-atom economical aminating agents that can be difficult to prepare, and often strong bases. In what follows we describe a mild and operationally simple method for the direct N-amination of oxazolidinones that use NH2Cl derived from commercial bleach.
- Huynh, Uyen,Uddin, Md. Nasir,Wengryniuk, Sarah E.,McDonald, Stacey L.,Coltart, Don M.
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p. 4799 - 4802
(2016/10/05)
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- Enantioselective synthesis of putative lipiarmycin aglycon related to fidaxomicin/tiacumicin B
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An enantioselective synthesis of a putative lipiarmycin aglycon was accomplished and features: 1) Brown's enantioselective alkoxyallylboration and allylation of aldehydes, 2) chain elongation by iterative Horner-Wadsworth-Emmons olefination, 3) Evans' aldol reaction and 4) an enediene ring-closing metathesis. A neighboring-group-assisted chemoselective reductive desilylation was uncovered in this study and was instrumental to the realization of the present synthesis.
- Erb, William,Grassot, Jean-Marie,Linder, David,Neuville, Luc,Zhu, Jieping
-
supporting information
p. 1929 - 1932
(2015/02/19)
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- A Facile, Six-Step Process for the Synthesis of (3 S,5 S)-3-Isopropyl-5-((2 S,4 S)-4-isopropyl-5-oxo-tetrahydrofuran-2-yl)-2-oxopyrrolidine-1-carboxylic Acid tert -Butyl Ester, the Key Synthetic Intermediate of Aliskiren
-
A facile, six-step process for the synthesis of (3S,5S)-3-isopropyl-5-((2S,4S)-4-isopropyl-5-oxotetrahydro- furan-2-yl)-2-oxopyrrolidine-1-carboxylic acid tert-butyl ester from (S)-4-benzyloxazolidin-2-one 2 in an overall 50% yield is reported. The key transformations include: a highly efficient diastereoselective epoxidation, Lewis acid-catalyzed ring-opening with bromide, an SN2 reaction using NaN3, and a tandem reduction-cyclization reaction.
- Pan, Xianhua,Xu, Siyao,Huang, Rui,Yu, Wansheng,Liu, Feng
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p. 611 - 617
(2015/06/30)
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- Asymmetric synthesis approach of enantiomerically pure spiro-indenoquinoxaline pyrrolidines and spiro-indenoquinoxaline pyrrolizidines
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An efficient, one-pot, four-component procedure for the synthesis of a small library of novel chiral spiro-indenoquinoxaline pyrrolidines and chiral spiro-indenoquinoxaline pyrrolizidines with high regio-, diastereo- (up to 96 dr), and enantioselectivity (up to 99% ee), through a 1,3-dipolar cycloaddition reaction of azomethine ylides and an optically active cinnamoyl-crotonoyl oxazolidinone is described. This methodology was very simple and was utilized to construct complex products from simple starting materials. The process was carried out in aqueous ethanol as an eco-friendly solvent and in the absence of any Lewis acids catalysts. The oxazolidinone chiral auxiliary was removed through a non-destructive protocol. The reaction mechanism is discussed on the basis of the assignment of the absolute configuration of the cycloadducts and using quantum mechanical calculations. The regio- and stereoselectivity were described on the basis of transition states' stabilities and global and local reactivity indices of the reactants. The results of the theoretical calculations are in agreement with the experimental outcomes.
- Shahrestani, Naeimeh,Salahi, Farbod,Tavakoli, Niloofar,Jadidi, Khosrow,Hamzehloueian, Mahshid,Notash, Behrouz
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p. 1117 - 1129
(2015/10/28)
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- MACROCYCLIC PICOLINAMIDE COMPOUNDS WITH FUNGICIDAL ACTIVITY
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The invention relates to compounds of macrocyclic picolinamides of Formula I suitable to control or prevent growth of fungi.
- -
-
Paragraph 0087
(2015/04/15)
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- C- and N-Selective Grignard Addition Reactions of α-Aldimino Esters in the Presence or Absence of Zinc(II) Chloride: Synthetic Applications to Optically Active Azacycles
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Highly practical synthetic methods were developed for the C- and N-selective Grignard addition reactions of N-4-MeOC6H4-protected α-aldimino esters in the presence or absence of zinc(II) chloride. Diastereoselective C-alkyl addition, tandem C-alkyl addition-N-alkylation, and some transformations to synthetically useful optically active azacycles were demonstrated. (Chemical Equation Presented).
- Hatano, Manabu,Yamashita, Kenji,Ishihara, Kazuaki
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p. 2412 - 2415
(2015/05/27)
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- Catalytic fluoride triggers dehydrative oxazolidinone synthesis from CO2
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Herein, catalytic fluoride (F-) is demonstrated to be a trigger for dehydrative immobilization of atmospheric pressure CO2, such that reaction of CO2 with β-amino alcohols derived from natural amino acids gives optically pure oxazolidinones in high yields. A synergistic combination of fluoride and organosilicon agents (e.g., Bu4NF + Ph3SiF or siloxanes) enhances the catalytic activity and functional group compatibility. This system lies at the interface between homogenous and heterogeneous catalysis, and may prove useful for the development of recoverable/reusable siloxane-based CO2 immobilization materials. This journal is
- Takada, Yuki,Foo, Siong Wan,Yamazaki, Yusuke,Saito, Susumu
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p. 50851 - 50857
(2015/02/19)
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- Asymmetric synthesis of 3,3,5,5-tetrasubstituted 1,2-dioxolanes: Total synthesis of epiplakinic acid F
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The first enantioselective total synthesis of epiplakinic acid F (1) was achieved through a pivotal step involving a radical-mediated asymmetric peroxidation of vinylcyclopropanes with molecular oxygen to construct highly substituted 1,2-dioxolanes. Subsequent conversions of the chiral 1,2-dioxolanes led to total synthesis of epiplakinic acid F (1) and the confirmation of its absolute configuration. The enantiomer of epiplakinic acid F methyl ester (2) was also prepared. This journal is the Partner Organisations 2014.
- Tian, Xiang-Yin,Han, Jian-Wei,Zhao, Qiong,Wong, Henry N. C.
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supporting information
p. 3686 - 3700
(2014/06/09)
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- Synthesis of salicylic acid-based 1,3,4-oxadiazole derivatives coupled with chiral oxazolidinones: Novel hybrid heterocycles as antitumor agents
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A series of novel salicylic acid-based 1,3,4-oxadiazoles derivatives coupled with chiral oxazolidinones were synthesized to screen for their in vitro antitumor activity against five human cancer cell lines. Some of these compounds showed good antitumor activities with IC50values ranging from 31.19-57.21 μM. Among the tested compounds 11, 15, 19,23,24, and 34 showed broad-spectrum antitumor activity against all the cell lines. In particular, compound 19 revealed remarkable antitumor activity with IC50 = 31.19-41.87 μM. A431 was the most sensitive cell line against all the compounds studied, followed by HeLa, MCF-7, A549 and HepG2. Structures of newly synthesized compounds were confirmed by IR,1 H NMR, 13C NMR and HRMS spectral data
- Murty,Penthala, Raju,Nath, Lekshmi R.,Anto, Ruby John
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p. 1133 - 1142
(2015/03/31)
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- PROCESS FOR THE PREPARATION OF A FLUOROLACTON DERIVATIVE
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A novel process for the preparation of a fluorolactone derivative of the formula (I) and of its acylated derivative of formula (V) wherein R1 stands for a hydroxy protecting group is described. The acylated fluorolactones of formula (V), particularly the benzoyl derivative with R1 =benzyl are important precursors for the synthesis of prodrug compounds which have the potential to be potent inhibitors of the Hepatitis C Virus (HCV) NS5B polymerase.
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Page/Page column 8; 9
(2014/07/23)
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- Amidation of esters with amino alcohols using organobase catalysis
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A catalytic protocol for the base-mediated amidation of unactivated esters with amino alcohol derivatives is reported. Investigations into mechanistic aspects of the process indicate that the reaction involves an initial transesterification, followed by an intramolecular rearrangement. The reaction is highly general in nature and can be extended to include the synthesis of oxazolidinone systems through use of dimethyl carbonate.
- Caldwell, Nicola,Campbell, Peter S.,Jamieson, Craig,Potjewyd, Frances,Simpson, Iain,Watson, Allan J. B.
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p. 9347 - 9354
(2014/12/11)
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- THIOARYL DERIVATIVES AS GPR120 AGONISTS
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The present invention relates to thioaryl derivatives of Formula 1 as defined in the specification, a method for preparing the same, a pharmaceutical composition comprising the same and use thereof. The thioaryl derivatives of Formula 1 according to the present invention promote GLP-1 formation in the gastrointestinal tract and improve insulin resistance in macrophages, pancreas cells, etc. due to anti-inflammatory action, and can accordingly be effectively used for preventing or treating diabetes, complications of diabetes, inflammation, obesity, non-alcoholic fatty liver, steatohepatitis or osteoporosis.
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Paragraph 1017-1018
(2014/05/24)
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- Directed orthometalation and the asymmetric total synthesis of N -deoxymilitarinone A and torrubiellone B
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A diverted total synthesis (DTS) approach to the total synthesis of pyridone alkaloids N-deoxymilitarinone A (8) and torrubiellone B (10) has been developed. The common intermediate 14 was first assembled by a dual directed orthometalation process using a methoxymethyl group as directed metalation group. Other crucial steps include the assembly of polyenes under aldol condensation for DTS using general and concise strategy and diastereoselective synthesis of the syn-dimethyl array by an Evans aldol reaction.
- Ding, Feiqing,William, Ronny,Leow, Min Li,Chai, Hua,Fong, Jacqueline Zi Mei,Liu, Xue-Wei
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supporting information
p. 26 - 29
(2014/01/23)
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- Collective synthesis of 4-hydroxy-2-pyridone alkaloids and their antiproliferation activities
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A collective synthesis of 4-hydroxy-2-pyridone alkaloids - specifically, pretenellin B, prebassianin B, farinosone A, militarione D, pyridovericin, and torrubiellone C - has been achieved. Key steps include using a strategic convergent method to synthesize the densely substituted pyridone key intermediate by Suzuki-Miyaura cross-coupling reaction, a divergent synthesis approach of target molecules by aldol condensation of pyridone intermediate with homologous aldehydes, and an iterative synthesis of homologous aldehydes with all-trans-polyene backbones. Interestingly, among the six tumor cell lines investigated, torrubiellone C was found to induce potent and apoptotic inhibitory activities on Jurkat T cells with IC50 values of 7.05 μM. Hence, this approach could potentially contribute to the synthesis of bioactive small-molecule libraries as well as drug discovery.
- Ding, Feiqing,Leow, Min Li,Ma, Jimei,William, Ronny,Liao, Hongze,Liu, Xue-Wei
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supporting information
p. 2548 - 2554
(2014/10/15)
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- Easy access to evans' oxazolidinones. Stereoselective synthesis and antibacterial activity of a new 2-oxazolidinone derivative
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An interesting new approach was developed for the synthesis of Evans' chiral auxiliaries with excellent yields. In turn, another new stereoselective and efficient strategy has also allowed for the preparation of a 2-oxazolidinone derivative in 34% overall yield from the Morita-Baylis-Hillman adduct. The antibacterial activity of this oxazolidinone was tested against Staphylococcus aureus strains isolated from animals with mastitis infections.
- Diaz, Gaspar,De Freitas, Michelle A.A.,Ricci-Silva, Maria E.,Diaz, Marisa A.N.
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p. 7429 - 7439
(2014/07/08)
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- Tosvinyl and besvinyl as protecting groups of imides, azinones, nucleosides, sultams, and lactams. Catalytic conjugate additions to tosylacetylene
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The use of the 2-(4-methylphenylsulfonyl)-ethenyl (tosvinyl, Tsv) group for the protection of the NH group of a series of imides, azinones (including AZT), inosines, and cyclic sulfonamides has been examined. The Tsvprotected derivatives are obtained in excellent yields by conjugate addition to tosylacetylene (ethynyl p-tolyl sulfone). The stereochemistry of the double bond can be controlled at will: with only 1 mol % of Et3N or with catalytic amounts of NaH, the Z stereoisomers are generated almost exclusively, while the E isomers are obtained using a stoichiometric amount of DMAP. Analogous phenylsulfonylvinyl-protected groups (with the besvinyl or Bsv group instead of Tsv) are obtained stereospecifically by reaction with (Z)- or (E)-bis(phenylsulfonyl)ethene. For lactams and oxazolidinones, this last method is much better. The Tsv and Bsv groups are stable in the presence of non-nucleophilic bases and to acids. They can be removed highly effectively via a conjugate addition-elimination mechanism using pyrrolidine or sodium dodecanethiolate as nucleophiles.
- Petit, Elena,Bosch, Llus,Font, Joan,Mola, Laura,Costa, Anna M.,Vilarrasa, Jaume
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p. 8826 - 8834
(2015/01/08)
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- Dehydrative synthesis of chiral oxazolidinones catalyzed by alkali metal carbonates under low pressure of CO2
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Dehydrative synthesis of oxazolidinones from amino alcohols and CO 2 was achieved in the presence of alkali metal carbonates such as Cs2CO3 as catalyst. It is noteworthy that 1 atm of CO 2 is enough for the reaction to proceed and no special dehydrating agent is required in this system. A mechanstic study showed that the OH of amino alcohol acts as nucleophile and the OH in the carbamic acid moiety is liberated during the cyclization process.
- Foo, Siong Wan,Takada, Yuki,Yamazaki, Yusuke,Saito, Susumu
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supporting information
p. 4717 - 4720
(2013/08/23)
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- Synthesis and biological evaluation of paleo-soraphens
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Synthesis can provide molecules such as paleo-soraphens A and B (see scheme) that are genetically encoded but not obtained from the natural source. Although it is unclear whether this is part of an evolutionary process or the consequence of the chemical synthesis, the biological evaluation of these genetically encoded natural products can shed light on how natural products are structurally optimized with respect to their biological profile. Copyright
- Lu, Hai-Hua,Raja, Aruna,Franke, Raimo,Landsberg, Dirk,Sasse, Florenz,Kalesse, Markus
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supporting information
p. 13549 - 13552
(2014/01/06)
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- AROMATIC KETONE SYNTHESIS WITH AMIDE REAGENTS AND RELATED REACTIONS
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A method of preparing an aryl carbonyl or aryl thiocarbonyl compound, comprises reacting an N-(nitroaryl)-amide or N-(nitroaryl)-thioamide with an aromatic ring, with a superacid catalyst, to produce the aryl carbonyl or aryl thiocarbonyl compound. The superacid is present in an amount of at most 8 equivalents in proportion to the N-(nitroaryl)-amide or N-(nitroaryl)-thioamide. A method of preparing aryl amide or aryl thioamide, comprises reacting an N-(nitroaryl)-carbamide or N-(nitroaryl)-thiocarbamide with an aromatic ring, with a superacid catalyst, to produce the aryl amide or aryl thioamide.
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Paragraph 0045
(2013/10/22)
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- Ethyl imidazole-1-carboxylate (EImC) as a carbonylating agent: Efficient synthesis of oxazolidin-2-ones from amino alcohols
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Various substituted oxazolidin-2-ones were synthesized from the corresponding amino alcohols using ethyl imidazole- 1-carboxylate (EImC). Highly substituted and sterically hindered amino alcohols and amino alcohols having a free hydroxy group were cyclized to oxazolidin-2-ones efficiently. This method is simple and produces oxazolidin-2-ones in very good yield.
- Veeraswamy,Reddy, K. Indrasena,Ragavan, R. Venkat,Yennam, Satyanarayana,Jayashree
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p. 109 - 111
(2013/03/14)
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- Nucleophile-catalyzed additions to activated triple bonds. protection of lactams, imides, and nucleosides with MocVinyl and related groups
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Additions of lactams, imides, (S)-4-benzyl-1,3-oxazolidin-2-one, 2-pyridone, pyrimidine-2,4-diones (AZT derivatives), or inosines to the electron-deficient triple bonds of methyl propynoate, tert-butyl propynoate, 3-butyn-2-one, N-propynoylmorpholine, or
- Mola, Laura,Font, Joan,Bosch, Lluis,Caner, Joaquim,Costa, Anna M.,Etxebarria-Jardi, Gorka,Pineda, Oriol,De Vicente, David,Vilarrasa, Jaume
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p. 5832 - 5842
(2013/07/26)
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- Double molecular recognition with aminoorganoboron complexes: Selective alcoholysis of β-dicarbonyl derivatives
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Double duty: Aminoorganoboron (AOB) complexes recognize alcohol and β-dicarbonyl units, and thereby facilitate chemo- and site-selective alcoholysis of the latter (see scheme). The complex activates both reaction partners. This strategy enables C-C, C-N, and C-O bond cleavage in addition/elimination reactions under near neutral pH conditions and provides a new method for functional group conversions. Copyright
- Oishi, Shunsuke,Saito, Susumu
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supporting information; experimental part
p. 5395 - 5399
(2012/06/18)
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- Desulfurization-oxygenation of chiral 1,3-thiazolidine-2-thiones and 1,3-oxazolidine-2-thiones using propylene oxide and microwave irradiation
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An efficient method for the desulfurization-oxygenation of 1,3-thiazolidine-2-thiones and 1,3-oxazolidine-2-thiones using propylene oxide and employing microwave irradiation is described. This strategy of oxygenation of the thiocarbonyl group provides an attractive methodology to prepare chiral 1,3-thiazolidin-2-ones and 1,3-oxazolidin-2-ones from the corresponding precursors in good yields. Copyright
- Minor-Villar, Leticia,Tello-Aburto, Rodolfo,Olivo, Horacio F.,Fuentes, Aydee,Romero-Ortega, Moises
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p. 2835 - 2839
(2013/02/21)
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