- Alkylation of Aromatic Compounds with Optically Active Lactic Acid Derivatives: Synthesis of Optically Pure 2-Arylpropionic Acid Esters
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The alkylation of benzene with (S)-methyl 2-- or 2-(mesyloxy)propionate, in the presence of aluminum chloride, affords (S)-methyl 2-phenylpropionate in good chemical (50-80percent) and excellent optical yield (97percent as determined by rotation), with inversion of configuration at the attacking carbon atom.
- Piccolo, Oreste,Spreafico,Franca,Visentin, Giuseppina,Valoti, Ermanno
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Read Online
- Enantioselective α-Arylation of Ketones via a Novel Cu(I)-Bis(phosphine) Dioxide Catalytic System
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A novel catalytic system based on copper(I) and chiral bis(phosphine) dioxides is described. This allows the arylation of silyl enol ethers to access enolizable α-arylated ketones in good yields and enantiomeric excess up to 95%. Noncyclic ketones are amenable substrates with this method, which complements other approaches based on palladium catalysis. Optimization of the ligand structure is accomplished via rational design driven by correlation analysis. Preliminary mechanistic hypotheses are also evaluated in order to identify the role of chiral bis(phosphine) dioxides.
- Escudero-Casao, Margarita,Licini, Giulia,Orlandi, Manuel
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supporting information
p. 3289 - 3294
(2021/04/07)
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- Palladium-Catalyzed Asymmetric Markovnikov Hydroxycarbonylation and Hydroalkoxycarbonylation of Vinyl Arenes: Synthesis of 2-Arylpropanoic Acids
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Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium-catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom-economical approach to an array of 2-arylpropanoic acids including several commonly used non-steroidal anti-inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2-arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio- and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate-limiting step.
- Guan, Zheng-Hui,Ren, Zhi-Hui,Wang, Yuan,Yang, Hui-Yi,Yao, Ya-Hong,Zou, Xian-Jin
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supporting information
p. 23117 - 23122
(2021/09/18)
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- Synthetic method of chiral 2-aryl propionate
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The invention belongs to the technical field of chemical synthesis, and relates to a synthetic method of chiral 2-aryl propionate, in particular to enantioselective synthesis of 2-aryl propionate. Thesynthetic method comprises the following steps: adding a copper salt, a chiral phosphine ligand, a silicon-hydrogen compound (in terms of SiH), ROH and 2-aryl acrylate in a certain ratio into a reaction bottle, carrying out a reaction in a reaction solvent at -50 to 40 DEG C for 0.25-6 h, and successively performing hydrolyzing, liquid separating, extracting, washing, drying and column chromatography after the reaction is finished, thereby obtaining the target compound 2-aryl propionate. Compared with the prior art, the method has the advantages that the 2-aryl acrylate is reduced by adopting a Cu catalytic system, a catalyst, namely a Cu compound is low in price, and the limitation of hydrogen high-pressure reduction and a noble metal catalyst is broken through. Chiral 2-aryl propionic acid can be obtained through a simple hydrolysis reaction of 2-aryl propionate, and a part of the compounds of 2-aryl propionate are effective components of current commercially-available drugs suchas ibuprofen and naproxen.
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Paragraph 0039-0046
(2020/04/02)
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- Rhodium-Catalyzed Remote C(sp3)?H Borylation of Silyl Enol Ethers
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A rhodium-catalyzed remote C(sp3)?H borylation of silyl enol ethers (SEEs, E/Z mixtures) by alkene isomerization and hydroboration is reported. The reaction exhibits mild reaction conditions and excellent functional-group tolerance. This method is compatible with an array of SEEs, including linear and branched SEEs derived from aldehydes and ketones, and provides direct access to a broad range of structurally diverse 1,n-borylethers in excellent regioselectivities and good yields. These compounds are precursors to various valuable chemicals, such as 1,n-diols and aminoalcohols.
- Li, Jie,Qu, Shuanglin,Zhao, Wanxiang
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supporting information
p. 2360 - 2364
(2020/01/02)
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- Nickel/Photoredox-Catalyzed Asymmetric Reductive Cross-Coupling of Racemic α-Chloro Esters with Aryl Iodides
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A unique nickel/organic photoredox co-catalyzed asymmetric reductive cross-coupling between α-chloro esters and aryl iodides is developed. This cross-electrophile coupling reaction employs an organic reductant (Hantzsch ester), whereas most reductive cross-coupling reactions use stoichiometric metals. A diverse array of valuable α-aryl esters is formed under these conditions with high enantioselectivities (up to 94 %) and good yields (up to 88 %). α-Aryl esters represent an important family of nonsteroidal anti-inflammatory drugs. This novel synergistic strategy expands the scope of Ni-catalyzed reductive asymmetric cross-coupling reactions.
- Guan, Haixing,Mao, Jianyou,Walsh, Patrick J.,Zhang, Qianwen
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supporting information
p. 5172 - 5177
(2020/02/20)
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- Synthesis method of (S)-2-aryl propionate compound
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The invention discloses a synthesis method of a (S)-2-aryl propionate compound. The (S)-2-aryl propionate compound shown in the formula IV is obtained by taking a compound shown in a formula I and a compound shown in a formula II as raw materials and reacting under the conditions of a chiral ligand shown in a formula III, a nickel catalyst, a photocatalyst, a reducing agent and alkali under the condition of visible light. The method has the advantages of cheap and easily available raw materials, convenient generation, mild conditions, environmental protection and safety, the photocatalyst canbe recycled, the production cost is greatly reduced, the test operation is simple, less waste is generated, and the method can be developed into an industrial production method.
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Paragraph 0096-0099; 0120-0123
(2020/08/09)
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- Iron-catalysed enantioselective Suzuki-Miyaura coupling of racemic alkyl bromides
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The first iron-catalysed enantioselective Suzuki-Miyaura coupling reaction has been developed. In the presence of catalytic amounts of FeCl2 and (R,R)-QuinoxP?, lithium arylborates are cross-coupled with tert-butyl α-bromopropionate in an enantioconvergent manner, enabling facile access to various optically active α-arylpropionic acids including several nonsteroidal anti-inflammatory drugs (NSAIDs) of commercial importance. (R,R)-QuinoxP? is specifically able to induce chirality when compared to analogous P-chiral ligands that give racemic products, highlighting the critical importance of transmetalation in the present asymmetric cross-coupling system.
- Iwamoto, Takahiro,Okuzono, Chiemi,Adak, Laksmikanta,Jin, Masayoshi,Nakamura, Masaharu
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p. 1128 - 1131
(2019/01/28)
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- Cobalt-Catalyzed Enantioselective Negishi Cross-Coupling of Racemic α-Bromo Esters with Arylzincs
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The first cobalt-catalyzed enantioselective Negishi cross-coupling reaction, and the first arylation of α-halo esters with arylzinc halides, are disclosed. Employing a cobalt-bisoxazoline catalyst, various α-arylalkanoic esters were synthesized in excellent enantioselectivities and yields (up to 97 % ee and 98 % yield). A diverse range of functional groups, including ether, halide, thioether, silyl, amine, ester, acetal, amide, olefin and heteroaromatics is tolerated by this method. This method was suitable for gram-scale reactions, enabling the synthesis of (R)-xanthorrhizol with high enantiopurity. Radical clock experiments support the intermediacy of radicals.
- Liu, Feipeng,Zhong, Jiangchun,Zhou, Yun,Gao, Zidong,Walsh, Patrick J.,Wang, Xueyang,Ma, Sijie,Hou, Shicong,Liu, Shangzhong,Wang, Minan,Wang, Min,Bian, Qinghua
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supporting information
p. 2059 - 2064
(2018/02/14)
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- Ni-Catalyzed chemoselective alcoholysis of: N -acyloxazolidinones
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Although N-acyloxazolidinone-based (catalytic) asymmetric synthetic methodologies occupy an important position in modern organic synthesis, the catalytic cleavage of a chiral auxiliary remains underdeveloped. We report the Ni(cod)2/bipyr.-catalyzed alcoholysis of N-acyloxazolidinones to deliver esters. The reaction is broad in scope for both N-acyloxazolidinone substrates and alcohol nucleophiles, and displays good functional group tolerance and excellent chemoselectivity. A gram-scale methanolysis allowed the enantioselective synthesis of the C22-C26 segment of a close analogue of the potent immunosuppressant agent FK506.
- Huang, Pei-Qiang,Geng, Hui
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supporting information
p. 593 - 599
(2018/02/14)
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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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- Enantioselective Hydrogen Atom Transfer: Discovery of Catalytic Promiscuity in Flavin-Dependent 'Ene'-Reductases
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Flavin has long been known to function as a single electron reductant in biological settings, but this reactivity has rarely been observed with flavoproteins used in organic synthesis. Here we describe the discovery of an enantioselective radical dehalogenation pathway for α-bromoesters using flavin-dependent 'ene'-reductases. Mechanistic experiments support the role of flavin hydroquinone as a single electron reductant, flavin semiquinone as the hydrogen atom source, and the enzyme as the source of chirality.
- Sandoval, Braddock A.,Meichan, Andrew J.,Hyster, Todd K.
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p. 11313 - 11316
(2017/08/30)
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- Structural insights into the ene-reductase synthesis of profens
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Reduction of double bonds of α,β-unsaturated carboxylic acids and esters by ene-reductases remains challenging and it typically requires activation by a second electron-withdrawing moiety, such as a halide or second carboxylate group. We showed that profen precursors, 2-arylpropenoic acids and their esters, were efficiently reduced by Old Yellow Enzymes (OYEs). The XenA and GYE enzymes showed activity towards acids, while a wider range of enzymes were active towards the equivalent methyl esters. Comparative co-crystal structural analysis of profen-bound OYEs highlighted key interactions important in determining substrate binding in a catalytically active conformation. The general utility of ene reductases for the synthesis of (R)-profens was established and this work will now drive future mutagenesis studies to screen for the production of pharmaceutically-active (S)-profens.
- Waller,Toogood,Karuppiah,Rattray,Mansell,Leys,Gardiner,Fryszkowska,Ahmed,Bandichhor,Reddy,Scrutton
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p. 4440 - 4448
(2017/07/10)
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- Asymmetric Hydrogenation of α-Substituted Acrylic Acids Catalyzed by a Ruthenocenyl Phosphino-oxazoline-Ruthenium Complex
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Asymmetric hydrogenation of various α-substituted acrylic acids was carried out using RuPHOX-Ru as a chiral catalyst under 5 bar H2, affording the corresponding chiral α-substituted propanic acids in up to 99% yield and 99.9% ee. The reaction could be performed on a gram-scale with a relatively low catalyst loading (up to 5000 S/C), and the resulting product (97%, 99.3% ee) can be used as a key intermediate to construct bioactive chiral molecules. The asymmetric protocol was successfully applied to an asymmetric synthesis of dihydroartemisinic acid, a key intermediate required for the industrial synthesis of the antimalarial drug artemisinin.
- Li, Jing,Shen, Jiefeng,Xia, Chao,Wang, Yanzhao,Liu, Delong,Zhang, Wanbin
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supporting information
p. 2122 - 2125
(2016/06/01)
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- Stereoselective Ketone Rearrangements with Hypervalent Iodine Reagents
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The first stereoselective version of an iodine(III)-mediated rearrangement of arylketones in the presence of orthoesters is described. The reaction products, α-arylated esters, are very useful intermediates in the synthesis of bioactive compounds such as ibuprofen. With chiral lactic acid-based iodine(III) reagents product selectivities of up to 73 % ee have been achieved.
- Malmedy, Florence,Wirth, Thomas
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supporting information
p. 16072 - 16077
(2016/10/30)
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- Carbene-Catalyzed Dynamic Kinetic Resolution of Carboxylic Esters
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Carbene-catalyzed reaction of carboxylic esters has the potential to offer effective synthetic solutions that cannot be readily achieved by using the more conventional aldehyde-Type substrates. Here we report the first carbene-catalyzed dynamic kinetic resolution of α,α-disubstituted carboxylic esters with up to 99:1 er and 99% yield. The present study clearly illustrates the unique power of carbene-catalyzed reactions of readily available and easy to handle carboxylic esters.
- Chen, Xingkuan,Fong, Jacqueline Zi Mei,Xu, Jianfeng,Mou, Chengli,Lu, Yunpeng,Yang, Song,Song, Bao-An,Chi, Yonggui Robin
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supporting information
p. 7212 - 7215
(2016/07/06)
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- Solvolysis of formylphenyl esters by a bifunctional peptide catalyst
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An artificial hydrolytic system using a formylphenyl ester and a bifunctional peptide catalyst was developed. Controlling the spatial positions of the two functional groups, the amino group of proline and the imidazole of histidine in the peptide, was important for the reaction efficiency of hydrolysis. The application of this system to kinetic resolution was shown to be plausible.
- Akagawa, Kengo,Kudo, Kazuaki
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supporting information
p. 300 - 302
(2016/05/02)
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- P-Stereogenic pincer iridium complexes: Synthesis, structural characterization and application in asymmetric hydrogenation
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P-Stereogenic PNP type pincer iridium complexes PNPtBuMeIrH2Cl (3) and PNPtBuMeIrH3 (4) were synthesized in reasonable yields and characterized by 1H NMR, 13C NMR, 31P NMR, HRMS and/or single crystal X-ray diffraction. The ORTEP diagram shows that the coordination geometry around the iridium center of complex 3 is approximately octahedral. The chlorinated iridium complex (3) and/or the trihydride iridium complex (4) were used as catalysts in the asymmetric hydrogenation of ketones, olefins and quinoline to provide the desired products with up to 17% enantioselectivity.
- Yang, Zehua,Wei, Xuan,Liu, Delong,Liu, Yangang,Sugiya, Masashi,Imamoto, Tsuneo,Zhang, Wanbin
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- Cobalt-bisoxazoline-catalyzed asymmetric kumada cross-coupling of racemic α-bromo esters with aryl grignard reagents
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The first cobalt-catalyzed asymmetric Kumada cross-coupling with high enantioselectivity has been developed. The reaction affords a unique strategy for the enantioselective arylation of α-bromo esters catalyzed by a cobalt-bisoxazoline complex. A variety of chiral α-arylalkanoic esters were prepared in excellent enantioselectivity and yield (up to 97% ee and 96% yield). The arylated products were transformed into α-arylcarboxylic acids and primary alcohols without erosion of ee. The new enantioenriched α-arylpropionic esters synthesized herein are potentially useful in the development of nonsteroidal anti-inflammatory drugs. This method was conducted on gram-scale and applied to the synthesis of highly enantioenriched (S)-fenoprofen and (S)-ar-turmerone.
- Mao, Jianyou,Liu, Feipeng,Wang, Min,Wu, Lin,Zheng, Bing,Liu, Shangzhong,Zhong, Jiangchun,Bian, Qinghua,Walsh, Patrick J.
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supporting information
p. 17662 - 17668
(2015/02/02)
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- Simultaneous control of regioselectivity and enantioselectivity in the hydroxycarbonylation and methoxycarbonylation of vinyl arenes
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Using a family of novel mononuclear and dinuclear palladium complexes of phanephos ligands, the simultaneous control of regioselectivity and enantioselectivity in the hydroxycarbonylation and alkoxycarbonylation of styrene derivatives has been realised for the first time. The Royal Society of Chemistry 2013.
- Konrad, Tina M.,Durrani, Jamie T.,Cobley, Christopher J.,Clarke, Matthew L.
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supporting information
p. 3306 - 3308
(2013/06/05)
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- METAL-CATALYSED CARBONYLATION OF UNSATURATED COMPOUNDS
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The invention provides a method for the hydroxycarbonylation, alkoxycarbonylation, aryloxycarbonylation or thiocarbonylation of an unsaturated molecule. The method includes a hydroxycarbonylation, alkoxycarbonylation, aryloxycarbonylationor thiocarbonylation reaction on the unsaturated molecule in which a complex including a ligand comprising a [n,n′]cyclophane comprising two non-fused monocyclic aromatic rings bridged by two linear and aliphatic linkages, in which each of the non-fused monocyclic aromatic rings is substituted with a phosphorus atom-containing substituent, is used to catalyse the reaction.
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Page/Page column 13
(2012/07/27)
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- Enantioselective hydrogenation of α-substituted acrylic acids catalyzed by iridium complexes with chiral spiro aminophosphine ligands
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Highly active: Iridium complexes with chiral spiro aminophosphine ligands were synthesized and applied as catalysts for the asymmetric hydrogenation of α-substituted acrylic acids (see scheme). The complexes were highly active catalysts, showing turnover frequencies of up to 6000 h-1, and catalyst loadings could be reduced to 0.01 mol %. Copyright
- Zhu, Shou-Fei,Yu, Yan-Bo,Li, Shen,Wang, Li-Xin,Zhou, Qi-Lin
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supporting information; body text
p. 8872 - 8875
(2012/10/08)
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- Ene reductase-catalysed synthesis of (R)-profen derivatives
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Enantiomerically pure (R)-profen derivatives and intermediates are synthesised utilising the enzyme YqjM, an ene reductase from Bacillus subtilis. After optimisation of the reaction conditions, the chemoenzymatic approach was applied for the first time in the synthesis of (R)-flurbiprofen methyl ester. Copyright
- Pietruszka, Joerg,Schoelzel, Melanie
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p. 751 - 756
(2012/04/23)
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- Amino acid based chiral N-amidothioureas. Acetate anion binding induced chirality transfer
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N-Amidothioureas generated from amine-dimethylated natural l-phenylalanine and its d-enantiomer bearing a chiral carbon that is by 2 atoms or 3 chemical bonds away from the anion binding site establish chiral communication upon acetate anion binding to the thiourea moiety.
- Wang, Fang,He, Wen-Bin,Wang, Jin-He,Yan, Xiao-Sheng,Zhan, Ying,Ma, Ying-Ying,Ye, Li-Cai,Yang, Rui,Cai, Fu,Li, Zhao,Jiang, Yun-Bao
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supporting information; experimental part
p. 11784 - 11786
(2011/12/02)
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- Highly enantioselective hydroxycarbonylation and alkoxycarbonylation of alkenes using dipalladium complexes as precatalysts
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Joined at Pd: Novel palladium catalysts like 1, in which the planar-chiral phosphine acts as a bridging ligand, have been developed. These dimetallic complexes are highly enantioselective catalysts in the hydroxycarbonylation of alkenes, a reaction that has proven problematic over the years. PTSA=para-toluenesulfonic acid. Copyright
- Konrad, Tina M.,Fuentes, Jose A.,Slawin, Alexandra M. Z.,Clarke, Matthew L.
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supporting information; experimental part
p. 9197 - 9200
(2011/02/28)
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- Heavyweight "R-SMS-Phos" ligands in the olefins' hydrogenation arena
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"Chemical Equation Presented" A serles of enantiopure P-stereogenic 1,2-bis[(o-RO-phenyl)(phenyl)phosphino]ethane (R-SMS-Phos) ligands wherein R= i-Pr, i-Bu, tf-Bu, 3-Pen, and CH2TMS was assessed in the Rh(l)-catalyzed hydrogenation of an indic
- Zupancic, Borut,Mohar, Barbara,Stephan, Michel
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supporting information; experimental part
p. 1296 - 1299
(2010/06/15)
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- Kinetic resolution of (R,S)-pyrazolides containing substituents in the leaving pyrazole for increased lipase enantioselectivity
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With hydrolysis of (R,S)-azolides in water-saturated methyl tert-butyl ether (MTBE) via Candida antarctica lipase B (CALB) as the model system, (R,S)-pyrazolides containing a leaving 3-, 4- or 3,4-substituted-pyrazole moiety are selected as the best substrates for preparing various optically pure carboxylic acids containing an α-chiral center. Great improvements of enzyme activity for the (R)-enantiomers with excellent enantioselectivity (VR/VS > 100) are obtainable, if (R,S)-pyrazolides containing a leaving 3- or 3,4-substituted-pyrazole moiety are employed for the hydrolysis or alcoholysis by methanol in anhydrous MTBE. A detailed kinetic analysis for (R,S)-N-2-phenylpropionylpyrazoles indicates that a bulky 3-substituent such as 3-(3-bromophenyl) or 3-(2-pyridyl) in the leaving pyrazole moiety has profound effects on decreasing the nucleophilic attack and proton transfer of catalytic serine for the slow-reacting enantiomer in anhydrous MTBE, as well as that and substrate affinity for both enantiomers in water-saturated MTBE. The resolution platform is also successfully applied to the hydrolysis of (R,S)-pyrazolides in water-saturated cyclohexane via Candida rugosa lipase (Lipase MY) having opposite enantioselectivity to CALB.
- Wang, Pei-Yun,Wu, Chia-Hui,Ciou, Jyun-Fen,Wu, An-Chi,Tsai, Shau-Wei
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experimental part
p. 113 - 119
(2011/02/21)
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- Highly enantioselective hydrogenation of α-aryl-β-substituted acrylic acids catalyzed by Ir-SpinPHOX
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The enantioselective hydrogenation of a series of challenging substrates, α-aryl-β-substituted acrylic acids, was realized with high efficiency and enantioselectivity (up to 96%) under the catalysis of Ir(i) complex of Spiro-based P,N ligand, SpinPHOX.
- Zhang, Yi,Han, Zhaobin,Li, Fuying,Ding, Kuiling,Zhang, Ao
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supporting information; experimental part
p. 156 - 158
(2010/04/02)
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- Improvements of enzyme activity and enantioselectivity in lipase-catalyzed alcoholysis of (R,S)-azolides
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With Candida antarctica lipase B (CALB)-catalyzed alcoholysis of (R,S)-naproxenyl 1,2,4-triazolide at the optimal conditions (i.e. anhydrous MTBE as the solvent, and methanol as the acyl acceptor at 45°C) as the model system, the enzyme enantioselectivity
- Wu, An-Chi,Wang, Pei-Yun,Lin, Yi-Sheng,Kao, Min-Fang,Chen, Jin-Ru,Ciou, Jyun-Fen,Tsai, Shau-Wei
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experimental part
p. 235 - 241
(2010/11/04)
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- Pd-catalyzed deoxygenation of mandelate esters
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(Chemical Equation Presented) A new approach to the synthesis of phenylacetic acids and esters has been developed via the palladium-catalyzed deoxygenation of mandelate esters.
- Milne, Jacqueline E.,Murry, Jerry A.,King, Anthony,Larsen, Robert D.
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supporting information; experimental part
p. 445 - 447
(2009/04/10)
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- (R,S)-azolides as novel substrates for lipase-catalyzed hydrolytic resolution in organic solvents
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Azolides, that is, N-acylazoles, as versatile acylation reagents are well characterized in the literature, in which the azole structure can not only act as a better leaving group but also make the carbonyl carbon more electrophilic and susceptible to nucleophilic attack. It is therefore desirable to combine this unique property and lipase resolution ability in the development of a new resolution process for preparing optically pure carboxylic acids. With the Candida antarctica lipase B (CALB)-catalyzed hydrolysis of (R,S)-N- profenylazoles in organic solvents as the model system, (R,S)-N-profenyl-l,2,4- triazoles instead of their corresponding ester analogues were exploited as the best substrates for preparing optically pure profens, i.e., 2-arylpropionic acids. The structure-reactivity correlations for the (R,S)-azolides in water-saturated methyl tert-butyl ether (MTBE) at 45°C coupled with a thorough kinetic analysis were further employed for elucidating the rate-limiting formation of a tetrahedral adduct without C-N bond breaking or with moderate C-N bond breaking concerted with C-O bond formation in the acylation step. The advantages of easy substrate preparation, high enzyme reactivity and enantioselectivity, and easy recovery of the product and remaining substrate by aqueous extraction demonstrate the potential of using (R,S)-azolides as novel substrates for the enzymatic resolution process.
- Wang, Pei-Yun,Chen, Ying-Ju,Wu, An-Chi,Lin, Yi-Sheng,Kao, Min-Fang,Chen, Jin-Ru,Ciou, Jyun-Fen,Tsai, Shau-Wei
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supporting information; scheme or table
p. 2333 - 2341
(2009/12/27)
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- Highly regioselective palladium-catalyzed methoxycarbonylation of styrene using chiral ferrocene- and biphosphole-based ligands
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The methoxycarbonylation of styrene has been studied using Pd(OAc)2/L/acid catalytic systems with L being chiral ferrocene- and biphosphole-based ligands. Good activities are obtained in mild conditions. Chemoselectivities and regioselectivitie
- Diab, Lisa,Gouygou, Maryse,Manoury, Eric,Kalck, Philippe,Urrutigo?ty, Martine
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p. 5186 - 5189
(2008/12/20)
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- Felkin-Anh selectivity in Rh(bisoxazolinylphenyl)-catalyzed reductive aldol coupling reaction: asymmetric synthesis of stereotriads
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The catalytic reductive aldol coupling of 2-phenylpropionaldehyde and acrylate derivatives with rhodium-bisoxazolinyl catalysts resulted in high Felkin-Anh selectivity (β,γ-syn) up to 98% accompanied by α,β-anti diastereoselectivity and high enantiomeric excesses up to 99%.
- Hashimoto, Toru,Ito, Jun-ichi,Nishiyama, Hisao
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p. 9408 - 9412
(2008/12/22)
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- Structure and mechanism of an unusual malonate decarboxylase and related racemases
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A study was conducted to investigate the structure and mechanism of the arymalonate decarboxylase (AMDase), or malonate decarboxylase and related racemases. The AMDase is an unusual malonate decarboxylase, as it does not require biotin, or any other co-factors for activity and does not involve formation of a malonyl thioester-enzyme intermediate. It was found that the sequence of the AMDase shows similarity to the Glu and Asp rasmases. The fact that the AMDase and related Asp/Glu racemases do not require Mg2+, or any other co-factor, which might stabilize the postulated enediolate intermediate, made them unique enzymes for conducting investigations. It was also found that the homochiral carboxylic acid products of the AMDase are potentially valuable chiral precursors for the synthesis of pharmaceuticals and other products.
- Okrasa, Krzysztof,Levy, Colin,Hauer, Bernhard,Baudendistel, Nina,Leys, David,Micklefield, Jason
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supporting information; scheme or table
p. 6609 - 6613
(2009/07/18)
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- Asymmetric intermodular heck-type reaction of acyclic alkenes via oxidative palladium(II) catalysis
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Herein, we report an asymmetric intermolecular Heck-type reaction of acyclic alkenes by using a palladium-pyridinyl oxazoline diacetate complex under oxidative palladium(II) catalysis conditions. A premade palladium-ligand complex afforded higher enantioselectivities than a corresponding premixed palladium-ligand system, while offering enhanced asymmetric induction when compared to known intermolecular Heck-type protocols.
- Yoo, Kyung Soo,Park, Chan Pil,Yoon, Cheol Hwan,Sakaguchi, Satoshi,O'Neill, Justin,Jung, Kyung Woon
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p. 3933 - 3935
(2008/02/11)
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- CHIRAL LIGANDS USED IN TRANSITION METAL CATALYSTS FOR ASYMMETRIC ADDITION REACTIONS ESPECIALLY HYDROGENATION
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Ligands of the formula (I) secondary phosphine-Q-P(=O)HR1 (I) in the form of mixtures of diastereomers or pure diastereomers, in which secondary phosphine is a secondary phosphine group with hydrocarbon radicals or heterohydrocarbon radicals as substituents; Q is a bivalent bisaryl or bisheteroaryl radical with an axial chiral centre to which the two phosphorus atoms are bonded in the ortho positions to the bisaryl or bisheteroaryl bridge bond, or Q is a bivalent ferrocenyl radical with a planar chiral centre or without a planar chiral centre, to which the phosphorus atom of the secondary phosphine is bonded directly or via a C1-C4-carbon chain to a cyclopentadienyl ring, the -P*(=O)HR1 group is bonded either on the same cyclopentadienyl ring in ortho position to the bonded secondary phosphine or on the other cyclopentadienyl ring; P* is a chiral phosphorus atom, and R1 is a hydrocarbon radical, a heterohydrocarbon radical or a ferrocenyl radical, where R1 is a ferrocenyl radical with a planar chiral centre when Q is a ferrocenyl radical without a planar chiral centre. Metal complexes of these ligands are homogeneous catalysts for asymmetric addition reactions, particularly hydrogenations.
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Page/Page column 40-43
(2008/06/13)
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- Systematic study of the asymmetric methoxycarbonylation of styrene catalyzed by palladium systems containing chiral ferrocenyl diphosphine ligands
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We present the first systematic study of the Pd-catalyzed asymmetric methoxycarbonylation of styrene in the presence of chiral ferrocenyl phosphine ligands. The reaction conditions were optimized, and a screening of different catalyst precursors was performed. A number of 1,1′-bis(phosphino) ferrocenes of the Mandyphos, Josiphos, Walphos, and Taniaphos types were tested in combination with [PdCl2(NCPh)2], in the presence of TsOH as the acid source. These systems afforded high enantioselectivities, although the regioselectivity of the reaction was found to be in favor of the (undesired) linear ester. The catalytic system made with the Josiphos ligand 1 gave rise to an enantiomeric excess (ee) of 86%.
- Godard, Cyril,Ruiz, Aurora,Claver, Carmen
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p. 1610 - 1622
(2007/10/03)
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- Introduction of single mutation changes arylmalonate decarboxylase to racemase
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The introduction of only one mutation based on the estimated reaction mechanism endowed arylmalonate decarboxylase with a racemase activity, which catalyses racemisation of α-arylpropionates. The Royal Society of Chemistry 2006.
- Terao, Yosuke,Miyamoto, Kenji,Ohta, Hiromichi
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p. 3600 - 3602
(2008/09/20)
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- Asymmetric hydroesterification of styrene using catalysts with planar-chiral ferrocene oxazoline ligands
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Chiral P,N-ferrocene ligands, 1-diphenylphosphino-1′-[(S)-4-isopropyl-2.5-oxazolinyl]-2′-(S p)-(trimethylsilyl)-ferrocene and its diastereomer, and 1-diphenylphosphino-1′-[(S)-4-isopropyl-2.5-oxazolinyl]-2′(S p)-(diphenylphosphino)-ferrocene and its diastereomer were used in the palladium-catalyzed asymmetric hydroesterification of styrene. The role of these ligands, which contain central, axial, and planar chirality, on the stereochemical outcome was investigated. A significant effect of using CuCl2 as a co-catalyst on the reaction was observed. Excellent regioselectivity (b/n >99:1) with low ee (28%) was obtained in the presence of CuCl2; moderate enantioselectivity (64% ee) but low regioselectivity (b/n, 40/60) was obtained in the absence of CuCl2.
- Wang, Lailai,Kwok, Wai Him,Chan, Albert S. C.,Tu, Tao,Hou, Xuelong,Dai, Lixin
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p. 2291 - 2295
(2007/10/03)
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- Single enantiomer free-radical chemistry - Lewis acid-mediated reductions of racemic halides using chiral non-racemic stannanes
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Additions of one to two equivalents of Lewis acids that include magnesium salts to free-radical reduction reactions involving ester functionalized radicals and (1R,2S,5R)-menthyldiphenyltin hydride 4, bis((1R,2S,5R)-menthyl) phenyltin hydride 5, tris((1R,
- Dakternieks, Dainis,Perchyonok, V. Tamara,Schiesser, Carl H.
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p. 3057 - 3068
(2007/10/03)
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- Microbial deracemization of α-substituted carboxylic acids: Substrate specificity and mechanistic investigation
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A new enzymatic method for the preparation of optically active α-substituted carboxylic acids is reported. This technique is called deracemization reaction, which provides us with a route to obtain the enantiomerically pure compounds, theoretically in 100% yield starting from the racemic mixture. This means that the synthesis of a racemate is almost equal to the synthesis of the optically active compound, and this concept is entirely different from the commonly accepted one in the asymmetric synthesis. Using the growing cell system of Nocardia diaphanozonaria JCM3208, racemates of 2-aryl- and 2-aryloxypropanoic acid are deracemized smoothly and (R)-form-enriched products are recovered in high chemical yield (>50%). In addition, using optically active starting compounds and deuterated derivatives as well as inhibitors, we have disclosed the fact that a new type of enzyme takes part in this biotransformation, and that the reaction proceeds probably via the same mechanism as that in rat liver.
- Kato, Dai-Ichiro,Mitsuda, Satoshi,Ohta, Hiromichi
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p. 7234 - 7242
(2007/10/03)
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- A Practical NMR-Based High-Throughput Assay for Screening Enantioselective Catalysts and Biocatalysts
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Two NMR-based approaches for highthroughput screening of enantioselective catalysts and biocatalysts are described. One version makes use of pseudo-enantiomers or pseudo-meso-compounds based on 13C-labeling. A throughput of at least 1400 ee determinations per day is possible by using an appropriate flow-through cell and an autosampler. The other approach is based on traditional diastereomer formation using a chiral reagent or complexing agent. The ee values are accurate to within ±2% and ±5% of the true values.
- Reetz, Manfred T.,Eipper, Andreas,Tielmann, Patrick,Mynott, Richard
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p. 1008 - 1016
(2007/10/03)
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- Method for homogeneous enantioselective hydrogenation using catalytic ferrocenyl bis-phosphine complexes
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The present invention is relative to a method for the homogeneous, catalytic, enantioselective hydrogenation of compounds of the general formula (I) with the aid of compounds of the general formula (II) The use of the hydrogenated derivatives in organic synthesis.
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Page column 4, 7
(2008/06/13)
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- Microbial deracemization of alpha-substituted carboxylic acids.
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An enzyme system of Nocardia diaphanozonaria JCM 3208 catalyzes the inversion of the chirality of various alpha-substituted carboxylic acids, such as 2-phenylpropanoic acid and 2-phenoxypropanoic acid derivatives, via a novel deracemization reaction.
- Kato, Dai-ichiro,Mitsuda, Satoshi,Ohta, Hiromichi
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p. 371 - 373
(2007/10/03)
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- Catalytic enantioselective protonation of lithium ester enolates generated by conjugate addition of arylthiolate to enoates
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A chiral ligand, a catalytic amount of lithium cation, and no chiral proton source: These are features of the present asymmetric addition-protonation of propenoates with 2-trimethylsilylbenzenethiol. The reaction is catalyzed by a combination of lithium 2-trimethylsilylbenzenethiolate and the chiral ligand 1. Desulfurization of the product affords 2-substituted propanoates with high ee values and without racemization. Furthermore, 1 can be recovered quantitatively for reuse.
- Nishimura, Katsumi,Ono, Masashi,Nagaoka, Yasuo,Tomioka, Kiyoshi
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p. 440 - 442
(2007/10/03)
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- Enantioselective enolate protonation with chiral anilines: Scope, structural requirements, and mechanistic implications
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High enantioselectivity has been demonstrated in the protonation of N,N- diisopropyl amides (Table, 1, entries 1-4, 7, and 10-13) derived from certain β,γ unsaturated acids. Depending on double bond geometry and the degree of substitution at the γ-carbon, γ-protonation can be a competing reaction in the case of the aliphatic substrates 12, 14b, 14d, and 18. The evidence is most consistent with a mechanism that involves proton transfer from 1a to a mixed aggregate consisting of enolate 4a and the lithiated amide 5, but direct proton transfer from 1a to the enolate is not ruled out.
- Vedejs,Kruger,Lee,Sakata,Stec,Suna
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p. 4602 - 4607
(2007/10/03)
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- Enantioselective protonation of silyl enol ethers and ketene disilyl acetals with Lewis acid-assisted chiral Bronsted acids: Reaction scope and mechanistic insights
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Enantioselective protonation is a potent and efficient way to construct chiral carbons. Here we report details of the reaction using Lewis acid-assisted chiral Bronsted acids (chiral LBAs). The 1:1 coordinate complex of tin tetrachloride and optically active binaphthol ((R)- or (S)-BINOL) can directly protonate various silyl enol ethers and ketene disilyl acetals to give the corresponding α-aryl ketones and α-arylcarboxylic acids, respectively, with high enantiomeric excesses (up to 98% ee). A catalytic version of enantioselective protonation has also been achieved using stoichiometric amounts of 2,6-dimethylphenol and catalytic amounts of monomethyl ether of optically active BINOL in the presence of tin tetrachloride. This protonation is also effective for producing α-halocarbonyl compounds (up to 91% ee). DFT calculations on the B3LYP/LANL2DZ level show that the conformational structure of the chiral LBA and the orientation of activated proton on (R)-BINOLs are important for understanding the absolute stereochemistry of the products.
- Nakamura, Shingo,Kaneeda, Masanobu,Ishihara, Kazuaki,Yamamoto, Hisashi
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p. 8120 - 8130
(2007/10/03)
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- A practical new chiral controller for asymmetric Diels-Alder and alkylation reactions
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(formula presented) The enantiomerically pure hydroxy sulfones (+)- and (-)-2 have been prepared from 1,2-epoxycyclohexane by a simple and practical procedure. The acrylate esters of these alcohols undergo BCl3-catalyzed Diels-Alder reactions with a variety of dienes at -78 to -55°C in CH2Cl2 or C7H8 with high dienophile face selectivity (Table 1). The chiral esters so formed are readily cleaved with recovery of the controllers (+)- or (-)-2. Esters of (+)- and (-)-2 can be converted to Z-polassium enolates and alkylated with high face selectivity.
- Sarakinos, Georgios,Corey
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p. 1741 - 1744
(2008/02/11)
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- Catalytic asymmetric carbon-carbon bond forming reactions: Preparation of optically enriched 2-aryl propionic acids by a catalytic asymmetric hydroboration-homologation sequence
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A new catalytic asymmetric one-carbon homologation strategy has been developed which employs a rhodium catalyzed asymmetric hydroboration followed by homologation with LiCHCl2 and oxidation to generate 2-arylpropionic acids of high enantiomeric purity.
- Chen, Austin C.,Ren, Li,Crudden, Cathleen M.
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p. 611 - 612
(2007/10/03)
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