- Synthesis of Enantiomerically Pure β-Hydroxy Ketones via β-Keto Weinreb Amides by a Condensation/Asymmetric-Hydrogenation/Acylation Sequence
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An established route to enantiomerically pure β-hydroxy ketones proceeds through the asymmetric hydrogenation of β-keto esters, an ester/amide exchange, and the use of the resulting β-hydroxy amide for the acylation of an organometallic compound. We shortened this route by showing that β-keto Weinreb amides are hydrogenated with up to 99 % ee in the presence of [Me2NH2]+{[RuCl(S)-BINAP]2(μ-Cl)3}–(0.5 mol-%) at room temp./5 bar. These Weinreb amides were prepared by seemingly obvious yet unprecedented condensations of lithiated N-methoxy-N-methylacetamide with carboxylic chlorides (51–87 % yield). The resulting β-hydroxy Weinreb amides were used for the acylation of organolithium and Grignard reagents. They thus gave enantiomerically pure β-hydroxy ketones (28 examples). A selection of these compounds gave anti-1,3-diols after another C=O bond hydrogenation, or syn-1,3-diols by a Narasaka–Prasad reduction.
- Diehl, Julian,Brückner, Reinhard
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supporting information
p. 278 - 286
(2017/01/24)
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- Screening, substrate specificity and stereoselectivity of yeast strains, which reduce sterically hindered isopropyl ketones
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Towards the synthesis of sterically hindered optically active secondary alcohol 2, yeast strains (Candida floricola IAM 13115 and Trichosporon cutaneum IAM 12206) with si-face hydride attack on isopropyl phenylsulfonylmethyl ketone 1 were developed by scr
- Hiraoka, Chihiro,Matsuda, Masaaki,Suzuki, Yuya,Fujieda, Shigeo,Tomita, Mina,Fuhshuku, Ken-ichi,Obata, Rika,Nishiyama, Shigeru,Sugai, Takeshi
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p. 3358 - 3367
(2007/10/03)
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- The zirconium alkoxide-catalyzed aldol-tishchenko reaction of ketone aldols
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The aldol-Tishchenko reaction of ketone aldols as enol equivalents has been developed as an efficient strategy to furnish differentiated 1,3-anti-diol monoesters in one step. The thermodynamically unstable ketone aldols undergo a facile retro-aldolization to yield a presumed zirconium enolate in situ, which then undergoes the aldol-Tishchenko reaction in typically high yields and with complete 1,3-anti diastereocontrol. Evaluation of a broad range of metal alkoxides as catalysts and optimization of the reaction protocol led to a modified zirconium alkoxide catalyst with attenuated Lewis acidity and dichloromethane as solvent, which resulted in suppression of the undesired acyl migration to a large extent. Various ketone aldols have been prepared and subjected to the general process, giving rise to a broad range of differently substituted 1,3-anti-diol monoesters, which may be hydrolyzed to the corresponding 1,3-anti-diols.
- Schneider, Christoph,Hansch, Markus,Weide, Timo
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p. 3010 - 3021
(2007/10/03)
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- Ligands for asymmetric catalysis
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The subject invention relates to phosphine ligands that are useful for asymmetric reactions, especially as chiral ligands for catalytic asymmetric hydrogenation.
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- Enantioselective synthesis ofanti 1, 3-diols via ru(ii)-catalyzed hydrogénations
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The homogeneous ruthenium-catalyzed hydrogénation of new symmetrical 1, 3-diketones has been achieved with various ligands including SKEWPHOS and Me-DuPHOS. Complete conversions with enantiomeric and diastereomeric excesses up to 99% were obtained. This represents a new catalytic application of the chiral ligands above. Thieme Stuttgart.
- Blanc, Delphine,Ratovelomanana-Vidai, Virginie,Marinetti, Angela,Genêt, Jean-Pierre
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p. 480 - 482
(2007/10/03)
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- Chiral 1,2-bis(phosphetano)benzenes: Preparation and use in the Ru- catalyzed hydrogenations of carbonyl derivatives
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Chiral 1,2-bis(phosphetano)benzenes are readily prepared from accessible, optically pure 1,3-diol cyclic sulfates. Their ruthenium complexes catalyze the enantioselective hydrogenations of functionalized carbonyls with moderate-to-high enantiomeric excesses. High levels of diastereo- and enantioselectivity are achieved, especially in the hydrogenation of β-diketones to the corresponding anti-1,3-diols.
- Marinetti, Angela,Genet, Jean-Pierre,Jus, Sebastien,Blanc, Delphine,Ratovelomanana-Vidal, Virginie
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p. 1160 - 1165
(2007/10/03)
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- Stereocontrolled reductive amination of 3-hydroxy ketones
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syn-1,3-Aminoalcohols are synthesized in high diastereomeric excess by reductive amination of 3-hydroxyketones with sodium cyanoborohydride in the presence of benzylamine.
- Haddad, Mansour,Dorbais, Jerome,Larcheveque, Marc
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p. 5981 - 5984
(2007/10/03)
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- In search of open-chain 1,3-stereocontrol
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Methylation of methyl 4-phenylpentanoate 25 gives the diastereoisomers methyl (2RS,4SR)-2-methyl-4-phenylpentanoate 26 and methyl (2RS,4RS)- 2-methyl-4-phenylpentanoate 27 in a ratio of 44:56. The aldehydes 3-dimethyl(phenyl)silylbutanal 28, 3-dimethyl(ph
- Barbero, Asun,Blakemore, David C.,Fleming, Ian,Wesley, Robert N.
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p. 1329 - 1352
(2007/10/03)
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- Polychlorinated materials as a source of polyanionic synthons
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The reaction of dichloromethane (1a) or dichlorodideuteriomethane (1b) with an excess of lithium powder (1:7 molar ratio) and a catalytic amount of DTBB (5 mol%) in the presence of a carbonyl compound 2 (1:2 molar ratio) in THF at -40°C yields, after hydrolysis, the corresponding 1,3-diols 3 in moderate yields. The process is applied to other gem-dichlorinated materials such as 7,7-dichloro [4.1.0]heptane (4), 1,1-dichlorotetramethylcyclopropane (7) and dichloromethyl methyl ether (10), using pivalaldehyde as electrophile. Starting from 1,1,1-trichlorinated compounds or tetrachloromethane (14) and using chlorotrimethylsilane as electrophile at temperatures ranging between -80 and -90°C, the corresponding polysilylated compounds 15-17 are prepared applying the mentioned methodology.
- Guijarro, Albert,Yus, Miguel
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p. 1797 - 1810
(2007/10/03)
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- Asymmetric Synthesis of (3R,5R)- and (3S,5S)-2,6-Dimethylheptane-3,5-diol, useful C2 Chiral Auxiliaries
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(R,R)- and (S,S)-2,6-Dimethylheptane-3,5-diol, which are useful C2 chiral auxiliaries, have been both synthesized in high optical purity from 2,6-dimethylheptane-3,5-dione, by using as key step a Sharpless kinetic resolution.
- Jacoby, C.,Braekman, J.C.,Daloze, D.
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p. 753 - 756
(2007/10/02)
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- Dichloromethane as a source of the CH22-synthon: A combination of an arene-catalysed lithiation and a barbier-type reaction
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The reaction of dichloromethane 1 with an excess of lithium powder (1:7 molar ratio) and catalytic amount of 4,4'-di-tert-butylbiphenyl (5 mol %) in the presence of a carbonyl compound 2 (1:2 molar ratio) in tetrahydrofuran at -40°C yields, after hydrolysis, the corresponding 1,3-diols 3 in moderate yields. The process can be also applied to more complicated gem-dichloro derivatives such as 7,7-dichlorobicyclo[4.1.0]heptane 6 or methyl dichloromethyl ether 9.
- Guijarro, Albert,Vus, Miguel
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p. 253 - 256
(2007/10/02)
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- Chiral Organometallic Reagents, I. Stereoselective Exchange of Diastereotopic Bromine Atoms by Lithium in 1,1-Dibromo-3-(trimethylsilyloxy)alkanes
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Bromine-lithium exchange in 1,1-dibromo-3-(trimethylsilyloxy)alkanes 4 and 6 affords the carbenoids 8 and 14, which have been added to ketones, aldehydes, arylboronates, and silylating agents.Diastereoselectivity in the generation and trapping of the carb
- Hoffmann, Reinhard W.,Bewersdorf, Martin,Krueger, Michael,Mikolaiski, Wolfgang,Stuermer, Rainer
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p. 1243 - 1252
(2007/10/02)
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- Reduction of β-Hydroxy Ketones with Catecholborane. A Stereoselective Approach to the Synthesis of Syn 1,3-Diols
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The stereoselective reduction of acyclic β-hydroxy ketones to syn 1,3-diols may be achieved with the mild reducing agent catecholborane.In certain instances reaction stereoselectivity may be enhanced through rhodium(I) catalysis.
- Evans, David A.,Hoveyda, Amir H.
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p. 5190 - 5192
(2007/10/02)
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- Synthetically Useful β-Lithioalkoxides from Reductive Lithiation of Epoxides by Aromatic Radical Anions
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Epoxides are reductively cleaved by means of lithium 4,4'-di-tert-butylbiphenylide.Ethylene oxide itself cleaves to lithium 2-lithioethoxide (15) in less than 5 min at -95 deg C.Epoxides possessing one unsubstituted carbon atom reduce in a matter of minutes at -78 deg C.When both carbon atoms are monosubstituted, at least 1 h is required.Epoxides with one or with two geminal saturated substituents open mainly between the oxygen atom and the least substituted carbon atom.Ring opening in the other direction leads to an unstable β-lithioalkoxide which very rapidly forms an olefin.Acyclic 1,2-disubstituted epoxides yield only olefins.Cyclooctene oxide produces, after protonation, a 3:7 ratio of cyclooctanol and cyclooctene.Cyclohexene oxide gives a 3:1 ratio of cyclohexanol and cyclohexene.Vinyloxiranes, on the other hand, open at the most substituted C-O bond to produce an allylic anion associated with an alkoxide.The carbanionic centers of the resulting dianions add to the carbonyl groups of aldehydes and ketones; however, when a hydrogen atom is present on the carbon atom which is attached to both negatively charged atoms, some reduction of the carbonyl group competes with the nucleophilic addition.The allylic anions derived from vinyloxiranes, after treatment with titanium tetraisopropoxide or cerium(III) chloride, add to aldehydes mainly at the most or least substituted terminus, respectively.In the former case, the configuration of the resulting glycols is predominantly anti.A number of adducts of the dianions with conjugated unsaturated aldehydes and ketones can be converted to unsaturated cyclic 6-membered ring ethers in the presence of acid or methanesulfonyl chloride.
- Cohen, Theodore,Jeong, In-Howa,Mudryk, Boguslaw,Bhupathy, M.,Awad, Mohamed M. A.
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p. 1528 - 1536
(2007/10/02)
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- DIASTEREO-DIFFERENTIATING SIMMONS-SMITH REACTION USING A NEW CHIRAL AUXILIARY
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Diastereo-differentiating Simmons-Smith reactions of enol ethers of various ketones were carried out by using (3S,5S)-2,6-dimethyl-3,5-heptanediol as a new chiral auxiliary.The diastereomer excess of these reactions reached to be >99 percent.
- Sugimura, Takashi,Futagawa, Tohru,Yoshikawa, Masato,Tai, Akira
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p. 3807 - 3810
(2007/10/02)
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- INTRAMOLECULAR HYDROSILYLATIONS II: THE ANTI-SELECTIVE REDUCTION OF β-HYDROXYKETONES
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A study was made of the synthesis and intramolecular hydrosilylation of silyloxyketones (2) (Sheme 2).It was found that with a variety of Lewis acid catalysts, anti-selective hydrosilylation took place to give (3) and, after desilylation, (5).With SnCl4, the most effective and practical catalyst, ratios (3):(4) ranged between 40:1 and 120:1 for a number of substrates.An explanation for the stereoselectivity is proposed based on (Cl) as a transition state model.The result is an anti-selective reduction of β-hydroxyketones, summarised in Scheme 4.
- Anwar, S.,Davis, A.P.
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p. 3761 - 3770
(2007/10/02)
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- The Application of Difunctional Organosilicon Compounds to Organic Synthesis; 1,3-Asymmetric Induction in the Reduction of β-Hydroxy-ketones
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A number of β-hydroxy-ketones were reduced to anti-1,3-diols with diastereoisomeric excesses exceeding 95percent, by a method involving presumed intramolecular transfer of hydrogen from a silicon atom to the carbonyl carbon.
- Anwar, Saeed,Davis, Anthony P.
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p. 831 - 832
(2007/10/02)
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- THE DIRECTED REDUCTION OF Β-HYDROXY KETONES EMPLOYING Me4NHB(OAc)3
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The diastereoselective reduction of a range of acyclic β-hydroxy ketones with triacetoxyborohydride is described.In all cases, the anti 1,3-diol diastereomer is the principal product (eq 1).
- Evans, David A.,Chapman, Kevin T.
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p. 5939 - 5942
(2007/10/02)
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