- Novel synthesis method of oseltamivir
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The invention provides a novel synthesis method of oseltamivir. The synthesis method comprises the following steps: taking a compound (E)-2-(2-nitrovinyl) isoindoline-1,3-diketone and ethyl pyruvate as initial raw materials, and carrying out Michael addition reaction under the condition of catalysis of a thiourea catalyst to obtain a corresponding Michael addition product; then, subjecting the Michael addition product and (formyl methylene) triphenyl phosphine to a Wittig reaction and a Henry reaction in a pot so as to obtain a ring closing product; and forming an etherified product from the ring closing product and a trichloroacetonitrile intermediate, and performing reduction, acetylation and de-protection to obtain oseltamivir. The reaction route comprises six steps, raw materials used in each step of reaction are easy to obtain and not expensive, the operation is easy, the yield of each step of reaction is high, no heavy metal or azide is used in the whole synthesis process, and the method is green and safe and can be applied to industrial production.
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Paragraph 0093-0098
(2021/05/19)
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- Hybrid Peptide-Thiourea Catalyst for Asymmetric Michael Additions of Aldehydes to Heterocyclic Nitroalkenes
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Bifunctional organocatalysis combining covalent and noncovalent activation is presented. The hybrid peptide-thiourea catalyst features a N-terminal proline moiety for aldehyde activation and a thiourea unit for electrophile activation. This catalyst effec
- ?melová, Patrícia,Vargová, Denisa,?ebesta, Radovan
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p. 581 - 592
(2020/12/22)
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- Unified Synthesis of Polycyclic Alkaloids by Complementary Carbonyl Activation**
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A complementary dual carbonyl activation strategy for the synthesis of polycyclic alkaloids has been developed. Successful applications include the synthesis of tetracyclic alkaloids harmalanine and harmalacinine, pentacyclic indoloquinolizidine alkaloid nortetoyobyrine, and octacyclic β-carboline alkaloid peganumine A. The latter synthesis features a protecting-group-free assembly and an asymmetric disulfonimide-catalyzed cyclization. Furthermore, formal syntheses of hirsutine, deplancheine, 10-desbromoarborescidine A, and oxindole alkaloids rhynchophylline and isorhynchophylline have been achieved. Finally, a concise synthesis of berberine alkaloid ilicifoline B was completed.
- Christmann, Mathias,He, Guoli,List, Benjamin
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supporting information
p. 13591 - 13596
(2021/05/07)
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- Highly Acidic Conjugate-Base-Stabilized Carboxylic Acids Catalyze Enantioselective oxa-Pictet–Spengler Reactions with Ketals
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Acyclic ketone-derived oxocarbenium ions are involved as intermediates in numerous reactions that provide valuable products, however, they have thus far eluded efforts aimed at asymmetric catalysis. We report that a readily accessible chiral carboxylic acid catalyst exerts control over asymmetric cyclizations of acyclic ketone-derived trisubstituted oxocarbenium ions, thereby providing access to highly enantioenriched dihydropyran products containing a tetrasubstituted stereogenic center. The high acidity of the carboxylic acid catalyst, which exceeds that of the well-known chiral phosphoric acid catalyst TRIP, is largely derived from stabilization of the carboxylate conjugate base through intramolecular anion-binding to a thiourea site.
- Zhu, Zhengbo,Odagi, Minami,Zhao, Chenfei,Abboud, Khalil A.,Kirm, Helmi Ulrika,Saame, Jaan,L?kov, M?rt,Leito, Ivo,Seidel, Daniel
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supporting information
p. 2028 - 2032
(2019/12/24)
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- Catalyst Repurposing Sequential Catalysis by Harnessing Regenerated Prolinamide Organocatalysts as Transfer Hydrogenation Ligands
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A catalyst repurposing strategy based on a sequential aldol addition and transfer hydrogenation giving access to enantiomerically enriched α-hydroxy-γ-butyrolactones is described. The combination of a stereoselective, organocatalytic step, followed by an efficient catalytic aldehyde reduction induces an ensuing lactonization to provide enantioenriched butyrolactones from readily available starting materials. By capitalizing from the capacity of prolineamides to act as both an organocatalyst and a transfer hydrogenation ligand, catalyst repurposing allowed the development of an operationally simple, economic, and efficient sequential catalysis approach.
- Bourgeois, Frederic,Medlock, Jonathan A.,Bonrath, Werner,Sparr, Christof
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supporting information
p. 110 - 115
(2019/12/30)
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- A conjugate Lewis base-Br?nsted acid catalyst for the sulfenylation of nitrogen containing heterocycles under mild conditions
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Catalysts that contain a thiourea tethered to a carboxylic acid were found to affect the sulfenylation of indoles and other N-heterocycles on the hour time scale at room temperature. The mild nature of these conditions allowed for the incorporation of diverse functionalities into more complex heterocycles.
- Nalbandian, Christopher J.,Miller, Eric M.,Toenjes, Sean T.,Gustafson, Jeffery L.
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supporting information
p. 1494 - 1497
(2017/02/05)
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- Synthesis of pyrrolidine-3-carboxylic acid derivatives: Via asymmetric Michael addition reactions of carboxylate-substituted enones
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To concisely synthesize highly enantiomerically enriched 5-alkyl-substituted pyrrolidine-3-carboxylic acids, organocatalytic enantioselective Michael addition reactions of 4-alkyl-substituted 4-oxo-2-enoates with nitroalkanes have been developed. Using the developed reaction method, 5-methylpyrrolidine-3-carboxylic acid with 97% ee was obtained in two steps.
- Yin, Feng,Garifullina, Ainash,Tanaka, Fujie
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supporting information
p. 6089 - 6092
(2017/08/02)
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- NEW PROCESS
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The present invention relates to a new chemical synthesis, intermediates and catalysts useful for the preparation of the neprilysin (NEP) inhibitor sacubitril. It further relates to new intermediate compounds and their use for said new chemical synthesis
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Page/Page column 61; 66
(2017/06/02)
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- New simple primary amine-thiourea organocatalysts and their application in asymmetric conjugate addition
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A kind of simple primary amine-thiourea organocatalysts was developed. And their application in asymmetric conjugate addition of ketone to nitroalkene was investigated. In the presence of the new primary amine-thiourea, the conjugate addition of ketone to
- Yu, Lu,Li, Pengfei
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supporting information
p. 3697 - 3700
(2014/06/23)
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- Enantioselective [4 + 2] cycloaddition of cyclic N-sulfimines and acyclic enones or ynones: A concise route to sulfamidate-fused 2,6-disubstituted piperidin-4-ones
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A concise route to valuable sulfamate-fused 2,6-disubstituted piperidin-4-ones or 2,3-dihydropyridin-4(1H)-ones in good yield with high diastereo- and enantioselectivity is presented. The combination of chiral primary amine and o-fluorobenzoic acid efficiently promoted an asymmetric [4 + 2] cycloaddition reaction of N-sulfonylimines and enones or ynones. The cycloaddition reaction between cyclic N-sulfonylimines and ynones is first reported.
- Liu, Yong,Kang, Tai-Ran,Liu, Quan-Zhong,Chen, Lian-Mei,Wang, Ya-Chuan,Liu, Jie,Xie, Yong-Mei,Yang, Jin-Liang,He, Long
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supporting information
p. 6090 - 6093
(2014/01/06)
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- An efficient organocatalytic method for highly enantioselective michael addition of malonates to enones catalyzed by readily accessible primary amine-thiourea
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A practical and highly enantioselective Michael addition of malonates to enones catalyzed by simple and readily available bifunctional primary amine-thiourea derived from 1,2-diaminocyclohexane is reported. The addition of weak acids and elevated temperature (ca. 50 °C) improved the efficiency of the Michael reaction. This approach enables the efficient synthesis of 1,5-ketoesters with good yields, excellent enantioselectivities (up to 99% ee), and low loading (0.5-5 mol %) of simple chiral primary amine-thiourea catalysts, and is applicable in multigram scale synthesis.
- Dudzinski, Krzysztof,Pakulska, Anna M.,Kwiatkowski, Piotr
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supporting information; experimental part
p. 4222 - 4225
(2012/09/22)
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- A highly efficient asymmetric Michael addition of α,α- disubstituted aldehydes to maleimides catalyzed by primary amine thiourea salt
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The first highly efficient Michael addition of challenging α,α-disubstituted aldehydes to maleimides catalyzed by a simple bifunctional primary amine thiourea catalyst/benzoic acid system has been successfully developed to generate quaternary carbon cente
- Yu, Feng,Jin, Zhichao,Huang, Huicai,Ye, Tingting,Liang, Xinmiao,Ye, Jinxing
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experimental part
p. 4767 - 4774
(2010/11/20)
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- Highly effective and enantioselective α-amination of aldehydes promoted by chiral proline amide-thiourea bifunctional catalysts
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A series of secondary amine-thiourea catalysts derived from l-proline and chiral diamine were prepared and first applied to highly enantioselective amination of unmodified aldehydes with various azodicarboxylates in excellent yields (up to 99%) and enanti
- Fu, Ji-Ya,Huang, Qing-Chun,Wang, Qiao-Wei,Wang, Li-Xin,Xu, Xiao-Ying
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experimental part
p. 4870 - 4873
(2010/10/02)
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- Effective construction of quaternary stereocenters by highly enantioselective α-amination of branched aldehydes
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A highly efficient enantioselective α-amination of branched aldehydes with azadicarboxylates promoted by chiral proline-derived amide thiourea bifunctional catalysts was developed for the first time, affording the adducts bearing quaternary stereogenic centers with excellent yields (up to 99%) and enantioselectivities (up to 97% ee).
- Fu, Ji-Ya,Xu, Xiao-Ying,Li, Yan-Chun,Huang, Qing-Chun,Wang, Li-Xin
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supporting information; experimental part
p. 4524 - 4526
(2010/11/21)
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- Enantioselective, organocatalytic reduction of ketones using bifunctional thiourea-amine catalysts
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Prochiral ketones are reduced to enantioenriched, secondary alcohols using catecholborane and a family of air-stable, bifunctional thiourea-amine organocatalysts. Asymmetric induction is proposed to arise from the in situ complexation between the borane and chiral thiourea-amine organocatalyst resulting in a stereochemically biased boronate-amine complex. The hydride in the complex is endowed with enhanced nucleophilicity while the thiourea concomitantly embraces and activates the carbonyl.
- Li, De Run,He, Anyu,Falck
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supporting information; experimental part
p. 1756 - 1759
(2010/10/04)
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- Effective asymmetric Michael addition of acetone to nitroalkenes promoted by chiral proline amide-thiourea bifunctional catalysts
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A series of secondary amine-thiourea catalysts 1a-1d derived from L-proline and chiral diamine were prepared and successfully applied to the Michael addition of acetone to trans-nitroalkenes in excellent yields (up to 99%) and enantioselectivities (44-91%
- Wang, Qiao-Wei,Peng, Lin,Fu, Ji-Ya,Huang, Qing-Chun,Wang, Li-Xin,Xua, Xiaoying
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experimental part
p. 340 - 351
(2010/08/04)
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- Enantioselective catalytic α-alkylation of aldehydes via an S N1 pathway
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Primary aminothiourea derivatives are shown to catalyze enantioselective alkylation of α-arylpriopionaldehdyes with diarylbromomethane. Evidence for a stepwise, S N1 mechanism in the substitution reaction induced by anion binding to the catalyst is provided by catalyst structure-activity studies, kinetic isotope effects, linear free-energy relationship studies, and competition experiments.
- Brown, Adam R.,Kuo, Wen-Hsin,Jacobsen, Eric N.
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supporting information; experimental part
p. 9286 - 9288
(2010/11/03)
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- Asymmetric conjugate addition of carbonyl compounds to nitroalkenes catalyzed by chiral bifunctional thioureas
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Readily available chiral thioureas derived from cyclohexane-1,2-diamine were prepared and found to be highly effective organocatalysts for the conjugate addition of aldehydes and ketones to nitroalkenes. Excellent enantioselectivities and yields were obtained for a variety of aryl and heteroaryl nitroalkenes. The base additives are essential for good yields and excellent enantioselectivities in this transformation. Based on new experimental evidence, a modified catalytic mechanism was proposed to rationalize the important role of the base additives.
- Zhang, Xue-jing,Liu, Sheng-ping,Lao, Jin-hua,Du, Guang-jian,Yan, Ming,Chan, Albert S.C.
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experimental part
p. 1451 - 1458
(2009/10/23)
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- Chiral thiourea compounds and process for enantioselective reduction of ketones
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Chiral thioureas are effective catalysts for the borane reduction of prochiral ketones to optically active alcohols. A prochiral ketone may be reduced to an optically active alcohol in the presence of a substantially sub-stoichiometric amount of chiral thiourea. The asymmetric thiourea compound of the present invention may be produced according to a production method described herein.
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Page/Page column 6; Figure 4
(2009/10/18)
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- A simplified synthesis of Takemoto's catalyst
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A facile two-step procedure for the preparation of Takemoto's catalyst is reported. The thiourea moiety was obtained by condensation of 3,5-bis(trifluoromethyl)aniline with phenyl chlorothioformate and in situ substitution of phenol by trans-1,2-diaminocy
- Berkessel,Seelig
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experimental part
p. 2113 - 2115
(2009/12/25)
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- A reductase-mimicking thiourea organocatalyst incorporating a covalently bound NADH analogue: Efficient 1,2-diketone reduction with in situ prosthetic group generation and recycling
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A new class of bifunctional organocatalyst promotes the chemoselective reduction of diketone electrophiles at catalytic loadings in the presence of an inorganic co-reductant. The Royal Society of Chemistry.
- Procuranti, Barbara,Connon, Stephen J.
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p. 1421 - 1423
(2008/02/03)
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