- Enantioselective addition of dimethylzinc to α-keto esters
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The readily available (+)-N-Benzyl-(S)-mandelamide catalyzes the enantioselective addition of dimethylzinc to α-keto esters to give α-methyl-α-hydroxy esters containing stereogenic quaternary centers with moderate to good yields (56-87%). A good enantioselectivity of the reaction is obtained for aryl and heteroaryl keto esters. For these substrates ee values of 75-90% are obtained. The enantioselectivity is somewhat lower for the substrates bearing an aliphatic chain. Georg Thieme Verlag Stuttgart.
- Blay, Gonzalo,Fernandez, Isabel,Marco-Aleixandre, Alicia,Pedro, Jose R.
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- Catalytic asymmetric addition of dimethylzinc to α-ketoesters, using mandelamides as ligands
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A strategy based on the control of the electron-donating capabilities of the coordinating groups of the ligand has been applied in the catalytic asymmetric addition of organometallic reagents to ketoesters. Mandelamides having deprotonated alcohol and carboxyamido groups catalyzed the addition of dimethylzinc to α-ketoesters with good yields and ee (up to 90%).
- Blay, Gonzalo,Fernandez, Isabel,Marco-Aleixandre, Alicia,Pedro, Jose R.
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- Multicenter Strategy for the Development of Catalytic Enantioselective Nucleophilic Alkylation of Ketones: Me2Zn Addition to α-Ketoesters
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An array of heteroatoms is essential for the activity and enantioselectivity of the catalyst 2 in the addition of Me2Zn to α-ketoesters 1 (e.g. see equation). α-Hydroxyesters 3 were obtained with up to 96% ee in the presence of a catalytic amount of additive iPrOH, which serves to generate the catalytically active monomeric species (based on the observation of nonlinear effects).
- Funabashi, Ken,Jachmann, Markus,Kanai, Motomu,Shibasaki, Masakatsu
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- A concise synthesis of (S)-(+)-1-(4-{2-[bis-(4-fluorophenyl)methoxy]-ethyl} piperazin-1-yl)-2-phenylpropan-2-ol dimaleate
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(S)-(+)-1-(4-{2-[Bis-(4-fluorophenyl)methoxy]-ethyl}piperazin-1-yl) -2-phenylpropan-2-ol dimaleate was prepared in several steps from (S)-(+)-atrolactic acid by a process permitting synthesis of multigram quantities. With the information provided by asymmetric synthesis, the X-ray crystal structure was solved.
- Prisinzano, Thomas,Hsin, Ling-Wei,Folk, John E.,Flippen-Anderson, Judith L.,George, Clifford,Jacobson, Arthur E.,Rice, Kenner C.
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- Isothiourea-Catalyzed Acylative Kinetic Resolution of Tertiary α-Hydroxy Esters
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A highly enantioselective isothiourea-catalyzed acylative kinetic resolution (KR) of acyclic tertiary alcohols has been developed. Selectivity factors of up to 200 were achieved for the KR of tertiary alcohols bearing an adjacent ester substituent, with both reaction conversion and enantioselectivity found to be sensitive to the steric and electronic environment at the stereogenic tertiary carbinol centre. For more sterically congested alcohols, the use of a recently-developed isoselenourea catalyst was optimal, with equivalent enantioselectivity but higher conversion achieved in comparison to the isothiourea HyperBTM. Diastereomeric acylation transition state models are proposed to rationalize the origins of enantiodiscrimination in this process. This KR procedure was also translated to a continuous-flow process using a polymer-supported variant of the catalyst.
- Greenhalgh, Mark D.,Laina-Martín, Víctor,Neyyappadath, Rifahath M.,Qu, Shen,Smith, Andrew D.,Smith, Samuel M.
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p. 16572 - 16578
(2020/09/09)
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- Solvent-induced chirality switching in the enantioseparation of regioisomeric hydroxyphenylpropionic acids via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol
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The enantioseparation of three hydroxyphenylpropionic acid isomers via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol has been demonstrated. The racemates of all three acid isomers were successfully separated with high efficiency (0.56–0.84) after single crystallization. For 2-hydroxy-3-phenylpropionic acid 4, the configuration of the less-soluble salt was controlled by the crystallization solvent: the (R)-4 salt was crystallized from water, while 2-propanol afforded the (S)-4 salt. The chiral recognition mechanism of the three acids was discussed based on the crystal structures of the diastereomeric salts.
- Kodama, Koichi,Nagata, Jun,Kurozumi, Nobuhiro,Shitara, Hiroaki,Hirose, Takuji
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p. 460 - 466
(2017/03/23)
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- Enantioselective addition of organozinc reagents to carbonyl compounds catalyzed by a camphor derived chiral γ-amino thiol ligand
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In this article, the design and synthesis of the chiral camphor derived γ-amino thiol ligand 17 and its application in catalytic enantioselective carbon-carbon forming reactions through the addition of organozinc reagents to carbonyl compounds is described. The catalytic activity and enantioselectivity of ligand 17 is demonstrated in the enantioselective addition of various organozinc reagents to aldehydes and ketoesters, offering the corresponding alcohols in high yields and enantioselectivities. The role of the mercapto group in the highly enantioselective 1,2-addition reaction of organozincs to aldehyde is also discussed.
- Wu, Hsyueh-Liang,Wu, Ping-Yu,Cheng, Ying-Ni,Uang, Biing-Jiun
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p. 2656 - 2665
(2016/05/10)
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- Enantioselective fluorination of α-branched aldehydes and subsequent conversion to α-hydroxyacetals via stereospecific C-F bond cleavage
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The highly enantioselective fluorination of α-branched aldehydes was achieved using newly developed chiral primary amine catalyst 1. Furthermore, the C-F bond cleavage of the resulting α-fluoroaldehydes proceeded smoothly under alcoholic alkaline conditio
- Shibatomi, Kazutaka,Kitahara, Kazumasa,Okimi, Takuya,Abe, Yoshiyuki,Iwasa, Seiji
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p. 1388 - 1392
(2016/02/05)
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- Asymmetric Ti-crossed Claisen condensation: Application to concise asymmetric total synthesis of alternaric acid
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Asymmetric Ti-crossed Claisen condensation utilizing the dioxane-2,5-dione chiral template and its successful application to total synthesis of chiral alternaric acid are described.
- Nagase, Ryohei,Oguni, Yumiko,Ureshino, Satoko,Mura, Hiroaki,Misaki, Tomonori,Tanabe, Yoo
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p. 7001 - 7003
(2013/09/02)
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- Highly homogeneous stereocontrolled construction of quaternary hydroxyesters by addition of dimethylzinc to α-ketoesters promoted by chiral perhydrobenzoxazines and B(OEt)3
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A highly efficient enantioselective addition of Me2Zn to α-ketoesters, assisted by a chiral perhydro-1,3-benzoxazine ligand, is described. This novel catalytic system offers homogeneous elevated enantioselectivities in the preparation of α-hydroxyesters that bear a quaternary stereocenter, with a minor dependence on electronic and steric effects when aromatic, heteroaromatic, or aliphatic α-ketoesters are employed. The catalyst can be recovered and reused without loss of activity.
- Infante, Rebeca,Nieto, Javier,Andres, Celia
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scheme or table
p. 4375 - 4379
(2012/05/20)
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- Enantioselective alkynylation of carbonyl compounds with trimethoxysilylalkynes catalyzed by lithium binaphtholate
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Enantioselective alkynylation of aldehydes and ketones was accomplished using trimethoxysilylalkynes as alkynylating reagents and lithium 3,3′-diphenylbinaphtholate as a catalyst. Optically active propargylic alcohols were obtained in good to high chemica
- Ueda, Tomohiro,Tanaka, Kana,Ichibakase, Tomonori,Orito, Yuya,Nakajima, Makoto
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experimental part
p. 7726 - 7731
(2010/10/21)
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- A new type of oxidation-reduction condensation by the combined use of phenyl diphenylphosphinite and oxidant
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A new type of oxidation-reduction condensation of alcohols with sulfur, nitrogen, and oxygen nucleophiles by the combined use of phenyl diphenylphosphinite (PhOPPh2) and oxidants such as azides or diethyl azodicarboxylate (DEAD) are described. In these reactions, chiral secondary and tertiary alcohols are converted into the corresponding chiral sulfides, azides, esters and ethers under mild and neutral conditions with almost complete inversion of stereochemical configuration.
- Mukaiyama, Teruaki,Kuroda, Kiichi,Maruyama, Yuji
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scheme or table
p. 63 - 82
(2010/04/23)
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- Enantioselective synthesis of quaternary stereogenic centers through catalytic asymmetric addition of dimethylzinc to α-ketoesters with chiral cis-cyclopropane-based amide alcohol as ligand
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A new amino alcohol with a chiral cyclopropane backbone has been developed and used in the catalytic asymmetric diethylzinc addition to various types of α-ketoesters. This cyclopropane-based chiral amino alcohol shows moderate enantioselectivity in the ad
- Zheng, Bing,Hou, Shicong,Li, Zhiyuan,Guo, Hongchao,Zhong, Jiangchun,Wang, Min
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experimental part
p. 2125 - 2129
(2010/03/01)
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- Asymmetric addition of dimethylzinc to α-ketoesters catalyzed by (-)-MITH
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(Chemical Equation Presented) This investigation describes the catalytic asymmetric addition of dimethylzinc to α-ketoesters in the presence of (-)-MITH (5) and triethyl borate as an additive to give the corresponding chiral α-hydroxy esters with good yie
- Wu, Hsyueh-Liang,Wu, Ping-Yu,Shen, Ying-Ying,Uang, Biing-Jiun
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p. 6445 - 6447
(2008/12/22)
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- Enantioselective homoallyl-cyclopropanation of dibenzylideneacetone by modified allylindium halide reagents-rapid access to enantioenriched 1-styryl-norcarene
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Dibenzylideneacetone (8) reacts with in situ-generated allylindium halide reagents to yield the product of a homoallyl-cyclopropanation reaction: 2-(3″-butenyl)-1,1-bis[(E)-2′-phenylethenyl]cyclopropane (9), which proceeds via step-wise cleavage of the C{double bond, long}O bond and delivery of two allyl fragments from the reagent. A range of enantiomerically enriched ligands have been tested as stoichiometric asymmetric modifiers for this process. Enantiopure compounds such as cinchona alkaloids, ephedra, aminoalcohols and tartaric acid derivatives, which have proven of utility as asymmetric modifiers for the indium-mediated allylation of aldehydes and ketones, were very inefficient in the process 8→9. However, mandelic acid derivatives, in particular mandelates, were found to be of significant potential. The absolute stereochemistry of the cyclopropane 9 has been determined by degradation to 1,1-dicarboxymethyl-2-butylcyclopropane, converging with an independent enantioselective synthesis starting from hexene. Under optimised conditions, viz. using allylindium iodide reagents and working-up with aqueous Na2SO3 to avoid iodine-mediated polymerisation, (S)-9 can be generated in 86% yield and with (S)-methyl mandelate as modifier useful enantiopurity (94/6 er) was observed. The cyclopropane product ((S)-9) undergoes RCM using standard conditions to afford a norcarene unit ((1S,6S)-1-(E)-2′-(phenylethenyl)-bicyclo[4.1.0]hept-2-ene) without loss of enantiopurity.
- Lloyd-Jones, Guy C.,Wall, Philip D.,Slaughter, Jennifer L.,Parker, Alexandra J.,Laffan, David P.
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p. 11402 - 11412
(2007/10/03)
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- Stereospecific C-S bond formation from chiral tertiary alcohols by quinone-mediated oxidation-reduction condensation using alkyl diphenylphosphinites and its application to the synthesis of a chiral tertiary thiol
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Oxidation-reduction condensation between 2-sulfanyl-1,3-benzothiazole (Btz-SH) and the alkyl diphenylphosphinites 1, prepared from tertiary alcohols, proceeded smoothly in the presence of 2,6-di-t-butyl-1,4-benzoquinone (DBBQ) and the corresponding S-alky
- Ikegai, Kazuhiro,Pluempanupat, Wanchai,Mukaiyama, Teruaki
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p. 780 - 790
(2007/10/03)
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- Al-catalyzed enantioselective alkylation of α-ketoesters by dialkylzinc reagents. Enhancement of enantioselectivity and reactivity by an achiral Lewis base additive
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An Al-catalyzed enantioselective method for additions of Me2Zn and Et2Zn to α-ketoesters bearing aromatic, alkenyl, and alkyl substituents is disclosed. Transformations are promoted in the presence of a readily available amino acid-b
- Wieland, Laura C.,Deng, Hongbo,Snapper, Marc L.,Hoveyda, Amir H.
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p. 15453 - 15456
(2007/10/03)
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- Synthesis of enantioenriched tertiary benzylic alcohols via stereospecific lithiation of secondary benzyl carbamates - Design of dialkylcarbamates, cleavable under basic, mild conditions
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Enantiomerically enriched, secondary benzyl N-[2-(tert-butyldiphenylsilyloxy)ethyl]-N-isopropylcarbamates were prepared, lithiated, and stereospecifically substituted by several electrophiles. Deprotection under basic conditions furnished optically active tertiary benzylic alcohols and glycols or 2-hydroxy-2-arylalkanoic acid esters. In summary, the sequence achieves the stereospecific chain elongation of d1-synthons, derived from secondary benzyl alcohols.
- Derwing, Christoph,Hoppe, Dieter
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p. 149 - 154
(2007/10/03)
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- Stereoselective Protonation of Carbanions, 4. Enantioselective Protonation of Lactone Enolates
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The prochiral lithium enolates derived from the five-membered lactones rac-1 and rac-2 were protonated by 37 OH- and 21 NH-chiral proton sources in THF at -78 deg C.The enantioselectivities, determined directly from the reaction mixture by chiral HPLC, ar
- Gerlach, Uwe,Haubenreich, Thomas,Huenig, Siegfried
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p. 1969 - 1980
(2007/10/02)
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- Enantiomerically Pure Acetals in Organic Synthesis. 2. Diastereoselective Alkylation of Enantiomeric Lithio Alkyl Lactyl Tetrahydropyranosides and Related Enolates
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A concise approach for the rapid synthesis of enantiomerically pure α-alkylated derivatives of lactate esters and of other enantiomerically pure α-hydroxy esters is presented.This methodology, which makes use of enantiomeric lithium enolates prepared from diastereomeric tetrahydropyranyl ethers derived from alkyl lactates and other α-hydroxy esters, is used to prepare both enantiomers of frontalin from (S)-(-)-methyl lactate.
- Mash, Eugene A.,Fryling, James A.
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p. 1094 - 1098
(2007/10/02)
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- Chemoenzymatic Preparation of Atrolactic and Mosher's Acid using Aspergillus oryzae Protease
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Sterically demanding α-methyl- and α-trifluoromethyl-mandelic esters 5a and 6a were conveniently resolved on a large scale by a protease from Aspergillus oryzae leading to both enantiomers of atrolactic acid 5b and a precursor of Mosher's acid 6b in 75-88 percent e.e.Single recrystallisation led to optically pure material.
- Feichter, Clemens,Faber, Kurt,Griengl, Herfried
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p. 653 - 654
(2007/10/02)
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- (CAMPHORYLSULFONYL)IMINE DIANION IN THE SYNTHESIS OF NEW OPTICALLY PURE (CAMPHORYLSULFONYL)OXAZIRIDINE DERIVATIVES
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New, more efficient enantiomerically pure (camphorylsulfonyl)oxaziridines are prepared by mono alkylation of the dianion of (camphorylsulfonyl)imine at the carbon atom adjacent to the sulfonyl group.
- Davis, Franklin A.,Weismiller, Michael C.,Lal, G. Sankar,Chen, Bang Chi,Przeslawski, Robert M.
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p. 1613 - 1616
(2007/10/02)
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- HIGHLY ENANTIOSELECTIVE SYNTHESES OF α-HYDROXYACIDS USING N-BENZYL-4,4,7α-TRIMETHYL-TRANS-OCTAHYDRO-1,3-BENZOXAZINE AS A CHIRAL ADJUVANT
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Addition of Grignard and organolithium reagents to as well as hydride reduction of 2α-benzoyl-N-benzyl-4,4,7α-trimethyl-trans-octahydro-1,3-benzoxazine (2, Y = C6H5CO) and addition of phenylmagnesium bromide to the corresponding 2-acetyl analog (11) proceed in highly diastereoselective fashion to produce virrtually exclusively the diastereomer predicted on the basis of Cram's chelate rule if chelation involves the ring oxygen atom.Mild acid hydrolysis of the adducts followed by selective oxidation produces highly enantiomerically pure α-hydroxyacids with clean recovery of the chiral adjuvant.
- He, Xu-Chang,Eliel, Ernest L.
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p. 4979 - 4988
(2007/10/02)
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- Asymmetric Syntheses Based on 1,3-Oxathianes. 2. Synthesis of Chiral Tertiary α-Hydroxy Aldehydes, α-Hydroxy Acids, Glycols (RR'C(OH)CH2OH), and Carbinols (RR'C(OH)CH3) in High Enantiomeric Purity
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A chiral 1,3-oxathiane (5) prepared from (+)-pulegone in three steps is converted to diastereomerically pure equatorial 2-acyl derivatives by lithiation, condensation with aldehydes, and Me2SO oxidation.Reaction of the resulting ketones with Grignard reagents at -78 deg C again proceeds highly stereoselectively (diastereomer excess generally above 90percent) according to Cram's rule (cyclic model).The resulting tertiary carbinols when cleaved with NCS/AgNO3 give chiral tertiary α-hydroxy aldehydes, RR'C(OH)CHO, plus a mixture of epimeric sultines which may be readily reconverted to the starting oxathiane.The hydroxy aldehydes have been oxidized to chiral tertiary α-hydroxy acids, RR'C(OH)CO2H, and reduced to primary-tertiary glycols, RR'C(OH)CH2OH, and further to tertiary carbinols, RR'C(OH)CH3, all with over 90percent ee.The opposite enantiomers of these compounds (again >90percent ee) may be obtained by starting with a diastereomeric 1,3-oxathiane (6), also available from (+)-pulegone.The configurations of the chiral products may be deduced from the manner of preparation and the assumption that Cram's rule is valid and agree with prior assignments in the literature.
- Lynch, Joseph E.,Eliel, Ernest L.
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p. 2943 - 2948
(2007/10/02)
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- A NEW AND EFFECTIVE ASYMMETRIC SYNTHESIS OF 3-PHENYLALKANALS
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Highly optically active 3-phenylalkanals were obtained by the reaction of alkyl halides and a chiral homoenolate equivalent derived from the cinnamyl ether 3 and potassium diisopropylamide, followed by acidic hydrolysis.
- Mukaiyama, Teruaki,Hayashi, Hiroki,Miwa, Tetsuo,Narasaka, Koichi
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p. 1637 - 1640
(2007/10/02)
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