- Kinetic resolution of racemic allylic alcoholsviairidium-catalyzed asymmetric hydrogenation: scope, synthetic applications and insight into the origin of selectivity
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Asymmetric hydrogenation is one of the most commonly used tools in organic synthesis, whereas, kinetic resolutionviaasymmetric hydrogenation is less developed. Herein, we describe the first iridium catalyzed kinetic resolution of a wide range of trisubstituted secondary and tertiary allylic alcohols. Large selectivity factors were observed in most cases (sup to 211), providing the unreacted starting materials in good yield with high levels of enantiopurity (ee up to >99%). The utility of this method is highlighted in the enantioselective formal synthesis of some bioactive natural products including pumiliotoxin A, inthomycin A and B. DFT studies and a selectivity model concerning the origin of selectivity are presented.
- Wu, Haibo,Margarita, Cristiana,Jongcharoenkamol, Jira,Nolan, Mark D.,Singh, Thishana,Andersson, Pher G.
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p. 1937 - 1943
(2021/02/22)
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- Catalytic asymmetric addition of aldehydes using organolithium reagents in the presence of commercial available chiral diol ligands
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An efficient method for the catalytic asymmetric additions to aldehydes using organolithium reagents and titanium(IV) isopropoxide in the presence of commercially available and relatively inexpensive diol ligands, such as (S)-BINOL or D-TADDOL has been developed. Good to excellent yields (up to 92%) and enantioselectivities (up to 94%) of the corresponding secondary alcohol products can be obtained following a simple procedure at relatively mild reaction temperatures.
- Zong, Hua,Huang, Huayin,Song, Ling
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supporting information
p. 1069 - 1074
(2016/10/11)
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- Catalytic enantioselective addition of alkyl grignard reagents to aliphatic aldehydes
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Herein, we report an efficient catalytic system for the enantioselective addition of alkyl Grignard reagents to a broad range of aliphatic aldehydes with good yields and enantioselectivities. Remarkably, the challenging methylmagnesium bromide (MeMgBr) can also be added to a variety of aliphatic aldehydes, providing versatile chiral methyl carbinol units with unprecedented yields and enantioselectivities in a simple one-pot procedure under mild conditions. Copyright
- Fernandez-Mateos, Emilio,Macia, Beatriz,Yus, Miguel
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supporting information
p. 1249 - 1254
(2013/06/27)
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- Synthesis of alcohols from m-fluorophenylsulfones and dialkylboranes: Application to the C14-C35 building block of E7389
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The reaction of m-fluorophenylsulfone anions with dialkylboranes, followed by alkaline hydroperoxide oxidation, yields alcohols in high yields. Optimization of the process, scope and limitation, and application to the synthesis of one of the C14-C35 building blocks of E7389, a right half analogue of halichondrin B, are reported.
- Liu, Lei,Henderson, James A.,Yamamoto, Akihiko,Bremond, Paul,Kishi, Yoshito
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p. 2262 - 2265
(2012/06/30)
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- A novel one-pot synthesis of secondary alcohols from esters
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Alkylation or vinylation by using organometallic reagents after partial reduction of carboxylic esters with LDBBA gave secondary alcohols, also involving allyl alcohols, without any isolation of intermediates in good yield (54-78%).
- Chae, Min Jung,Jeon, Ah Ram,Park, Jae Kyo,An, Duk Keun
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experimental part
p. 1718 - 1720
(2011/04/25)
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- Catalytic enantioselective addition of MeMgBr and other Grignard reagents to aldehydes
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Herein, we report an efficient catalyst for the challenging enantioselective addition of MeMgBr to aldehydes. Unprecedented yields and enantioselectivities are achieved in the reaction with a broad range of aldehydes. Moreover, a variety of Grignard reagents can be also added to aromatic and aliphatic aldehydes in good yields and enantioselectivities in a simple one-pot procedure under mild conditions.
- Fernandez-Mateos, Emilio,MacIa, Beatriz,Ramon, Diego J.,Yus, Miguel
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supporting information; experimental part
p. 6851 - 6855
(2012/01/03)
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- Construction of cyclopentyl carbinols from ω-tosyloxy-1-alkenyl boronate esters and grignard reagents
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Addition of RMgCl (R = n-Bu, Ph) to pinacol esters of 6-tosyloxy-l-alkenyl boronic acids at -78 °C gave the borates, which upon warming to room temperature underwent migration of R on boron to C(1) carbon and concomitant ring construction C-C bond formati
- Kobayashi, Yuichi,Asano, Moriteru,Kiyotsuka, Yohei
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scheme or table
p. 787 - 791
(2010/09/18)
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- Empirical method for predicting enantioselectivity in catalytic reactions: demonstration with lipase and oxazaborolidine
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We derived a novel equation capable of predicting the degree of enantioselectivity in a catalytic reaction without any knowledge of the reaction mechanism and/or the transition-state structure, and tested the validity of this equation by changing substrates systematically in the lipase or oxazaborolidine-catalyzed reactions. A good correlation was observed between the predicted and observed E values, and the stereochemistry of the products could be predicted correctly in most cases (28 out of 30).
- Ema, Tadashi,Ura, Norichika,Yoshii, Masataka,Korenaga, Toshinobu,Sakai, Takashi
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experimental part
p. 9583 - 9591
(2010/01/06)
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- Highly enantioselective 1,2-additions of various organolithium reagents to aldehydes
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Several asymmetric 1,2-additions of various organolithium reagents (methyllithium, n-butyllithium, phenyllithium, lithioacetonitrile, lithium n-propylacetylide, lithium phenylacetylide) to aldehydes are shown to result in decent to excellent enantiomeric excesses (65-98%) when performed in the presence of a chiral lithium amido sulfide. The chiral lithium amido sulfides invariably exhibited higher levels of enantioselectivity in all the reactions tested, compared to the structurally similar chiral lithium amido ethers and the chiral lithium amide without a chelating group.
- Granander, Johan,Eriksson, Jonas,Hilmersson, Goeran
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p. 2021 - 2027
(2007/10/03)
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- Chlorodimethylaluminum-promoted nucleophilic addition of lithium pentamethylcyclopentadienide to aliphatic aldehydes and DDQ-mediated carbon-carbon bond cleavage of the adducts providing the parent aldehydes
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Treatment of aliphatic aldehyde with lithium pentamethylcyclopentadienide in the presence of chlorodimethylaluminum provided the corresponding carbinol in excellent yield. The carbinol returns to the parent aldehyde and pentamethylcyclopentadiene by the a
- Uemura, Minoru,Yorimitsu, Hideki,Oshima, Koichiro
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p. 163 - 166
(2007/10/03)
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- Pentamethylcyclopentadienide in organic synthesis: Nucleophilic addition of lithium pentamethylcyclopentadienide to carbonyl compounds and carbon-carbon bond cleavage of the adducts yielding the parent carbonyl compounds
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Lithium pentamethylcyclopentadienide (C5Me5Li, Cp*Li) reacted with aromatic aldehyde to provide the corresponding carbinol in excellent yield. The carbinol returns to the parent aldehyde and pentamethylcyclopentadiene upon exposure to acid or due to heating. Chlorodimethylaluminum is essential as an additive to attain the nucleophilic addition of Cp*Li to aliphatic aldehyde. The carbinol derived from aliphatic aldehyde returns to the parent aldehyde and pentamethylcyclopentadiene by the action of a catalytic amount of 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ). The reversible addition/elimination of the Cp* group can represent a protection of aldehyde. Mechanistic details of the carbon-carbon bond cleavage are also disclosed.
- Uemura, Minoru,Yagi, Kazunari,Iwasaki, Masayuki,Nomura, Kenichi,Yorimitsu, Hideki,Oshima, Koichiro
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p. 3523 - 3535
(2007/10/03)
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- Nickel-catalyzed alkylation of aldehydes with trialkylboranes
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(Chemical Equation Presented) Nickel-catalyzed alkylation of aldehydes with trialkylboranes proceeds smoothly in the presence of a catalytic amount of 5-allyl-1,2,3,4,5-pentamethyl-1,3-cyclopentadiene or an excess of cesium carbonate to afford the corresponding secondary alcohols.
- Hirano, Koji,Yorimitsu, Hideki,Oshima, Koichiro
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p. 4689 - 4691
(2007/10/03)
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- Chiral lithium amido sulfide ligands for asymmetric addition reactions of alkyllithium reagents to aldehydes
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Six chiral amino sulfides have been synthesised from the amino acids phenylalanine, phenylglycine and valine. These amino sulfides were used as chiral ligands in the asymmetric addition of n-butyllithium and metyllithium to various aldehydes at low temperatures. The highest stereoselectivities were obtained with benzaldehyde, resulting in 1-phenyl-1-pentanol and 1-phenyl-1-ethanol in enantiomeric excesses of >98.5 and 95%, respectively. These stereoselectivities were significantly higher than those induced by the ether analogues.
- Granander, Johan,Sott, Richard,Hilmersson, Goeran
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p. 439 - 447
(2007/10/03)
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- A new convenient procedure to prepare organomanganese reagents from organic halides and activated manganese
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A new method to obtain activated manganese metal, especially attractive for large scale preparative organic chemistry, is described. The key point is the use of 2-phenylpyridine as electron carrier to reduce manganese chloride by lithium. The active manganese thus obtained was used to prepare various organomanganese reagents from organic halides. The reactivity of these reagents has been studied (acylation, 1,2- or 1,4-addition, alkylation and alkenylation).
- Cahiez, Gerard,Martin, Arnaud,Delacroix, Thomas
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p. 6407 - 6410
(2007/10/03)
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- Enantioselective butylation of aliphatic aldehydes by mixed chiral lithium amide/n-BuLi dimers
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The enantioselective butylation of aliphatic aldehydes with mixtures of n-butyllithium and chiral lithium amides in a diethyl ether-dimethoxymethane solvent mixture is described. Enantiomeric excesses ranging from 91 to 98.5% were observed for several aliphatic alcohols. The asymmetric butylation of the prochiral aldehydes proceeds much faster by the mixed lithium amide/n- BuLi complexes than by tetrameric n-BuLi.
- Arvidsson, Per I.,Davidsson, Oejvind,Hilmersson, Goeran
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p. 527 - 534
(2007/10/03)
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- The stereochemistry of the vinylogous Peterson elimination
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Base-induced eliminations of the vinylogous β-hydroxysilanes 7, 9, 11 and 12 are stereospecifically syn, giving largely the trans,trans-diene 8 from 7 and 11, the cis,trans-diene 10 from 9, and the trans,cis-diene 13 from 12. When a cis double bond is produced, it is selectively placed adjacent to the carbon atom that originally carried the hydroxy group. E2′ Reactions with silyl as the electrofugal group and acetate as the nucleofugal group, initiated by fluoride ion, are not stereospecific, but can be highly stereoselective in favour of the trans,trans-diene 8 when the carbon substituent at the silicon-bearing end is a cyclohexyl group and the double bond is cis, and in favour of the trans,cis-diene 13 when the carbon substituent at the silicon-bearing end is a methyl group and the double bond is trans. Attempts to use the Peterson reactions to make o-quinodimethanes stereospecifically failed, with no evidence of 1,4-elimination from the alcohols 40 and 41. The corresponding E2′ reaction from the esters using fluoride ion on the acetates or formates 46 and 47 gave stereoselectively the E,E-quinodimethane 48.
- Fleming, Ian,Morgan, Ian T.,Sarkar, Achintya K.
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p. 2749 - 2763
(2007/10/03)
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- Selectivity in Organic Group Transfer in Reactions of Mixed Diorganomanganese(II) and Triorganomanganate(II) with 2-Cyclohexen-1-one or Cyclohexanecarbaldehyde
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The unsymmetrical diorganomanganeses(II) (R1R2Mn) and magnesium triorganomanganates(II) (R21R2MnMgX) reacted with 2-cyclohexen-1-one to produce the 1,4-addition products in moderate to good yields. The approximate reactivity order obtained from the product distribution was CH2=CHCH2 > PhS > n-Bu > Ph > Me, Me3SiCH2, n-C6H13-CΞC. In contrast, the reactivity order for the addition of these reagents to cyclohexanecarbaldehyde was CH2=CHCH2 > Ph > Me > n-Bu > n-C6H13CΞC > Me3SiCH2.
- Yorimitsu, Hideki,Hayashi, Yasuhiro,Tang, Jun,Shinokubo, Hiroshi,Oshima, Koichiro
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p. 2297 - 2300
(2007/10/03)
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- Enantioselective addition of organocerium reagents to aldehydes -effects of TADDOL ligand structure
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A range of TADDOL organocerium reagents have been prepared and the effect of TADDOL structure on their enantioselective addition to aldehydes has been studied. Copyright
- Greeves, Nicholas,Pease, J. Elizabeth,Bowden, Martin C.,Brown, Stephen M.
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p. 2675 - 2678
(2007/10/03)
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- Enantioselective addition of tris(TADDOL) organocerium reagents to aldehydes
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A significant improvement in enantioselectivity (up to 92% ee) was achieved in butyl additions to a range of aldehydes with a novel tris(TADDOL) organocerium reagent.
- Greeves, Nicholas,Pease, J. Elizabeth
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p. 5821 - 5824
(2007/10/03)
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- Ti-TADDOLate-Catalyzed, Highly Enantioselective Addition of Alkyl- and Aryl-Titanium Derivatives to Aldehydes
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Toluene-ether or toluene-hexane solutions of aryl and alkyl triisopropoxy titanium reagents (free of Li, Mg, or Zn salts) are prepared from the corresponding Li or Grignard reagents and ClTi(OiPr)3, with careful removal of salts (centrifugation of LiCl or of dioxane*MgX2, and addition of 12-crown-4).The solutions of the organotitanium compounds are combined with one equiv. of an aldehyde and 0.2 equiv. of (R,R)-diisopropoxy-(α,α,α',α'-tetraphenyl-2,2-dimethyl-1,3-dioxolane-4,5-dimethanolato) titanium (Ti-TADDOLate 3) at dry-ice temperature.Warming up to room temperature leads to nucleophilic addition to the (Si)-face of the aldehydes with enantioselectivities as high as 99.5 : 0.5 (products 4-33 in Scheme 4).Functional groups or protecting groups and branching in the Ti-R group and in the aldehyde must be remote from the reacting centers.Aryl groups can be added to aldehydes by this method. - In contrast to all the enantioselective R2Zn additions to aldehydes, in which only one R-group is actually transferred, a twice as economic use is made of the originally employed R-metal reagent in the method described here. - A procedure for multigram preparation of the spiro-Ti-TADDOLate (2) employed for the in situ generation of catalyst (3) is described, and details of the determination of enantiomer ratios (er) by GC and NMR methods are given (Tab. 2, 3).The mechanistic interpretation of Ti-TADDOLate-mediated nucleophilic additions as derived previously (ref.4c) is also compatible with this monometallic variant of the method.
- Weber, Beat,Seebach, Dieter
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p. 7473 - 7484
(2007/10/02)
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- A study of methyl and tert-butyl as non migrating groups in the reaction of me(organyl)zinc and t-bu(organyl)zinc with aldehydes
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A series of mixed methyl (organyl) and tert-butyl(organyl)zincs were prepared by reaction of ZnCl2 with Grignard reagents. In the presence of salts t-butyl migrates to a lessor extent than methyl in the reaction with aldehydes. In the absence of salts both groups are comparable. BuZnMe prepared under salt-free conditions adds to benzaldehyde in 82.4% ee and in 85% yield, comparable to the reaction with distilled dibutylzinc.
- Laloe, Eric,Srebnik, Morris
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p. 5587 - 5590
(2007/10/02)
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- A new type of complex reagent, R4Pb / TiCl4
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Tetraalkllleads (R4Pb) reacted quite smoothly with aldehydes R'CHO in the presence of TiCl4 to produce the corresponding alcohols (RCHOHR′) in high to good yields. The reagent system, R4Pb/ TiCl4, exhibited high chemoselectivity; only aldehydes underwent the alkylation in the presence of ketones. Further, the new reagent exhibited high 1,2- and 1,3-asymmetric induction. The transfer order of alkyl groups in the reaction of aldehydes with mixed tetraalkylleads/TiCl4 was determined; Me>Et.i-Pr?n-Bu.
- Yamamoto, Yoshinori,Yamada, Jun-Ichi,Asano, Tetsuya
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p. 5587 - 5596
(2007/10/02)
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- Preparation of polyfunctional diorganomercurials and their transmetallation to diorganozincs. Applications to the preparation of optically active secondary alcohols
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Two new methods of preparation of functionalized diorganomercurials have been developed.The first method involves a substitution reaction of (ICH2)2Hg with zinc-copper reagents FG-RCu(CN)ZnI in THF/DMF at -60 deg C.Functional groups such as an ester, nitrile, ketone, phosphonate, halide, and boronic ester are tolerated in this reaction.The second method involves a reductive transmetallation between polyfunctional organozinc halides and mercurous chloride (Hg2Cl2).This very convenient procedure provides a rapid route to various functionalized diorganomercurials in good yields (61-89percent yield).The synthetic utility of these mercury organometallics is demonstrated.Their transmetallation with zinc dust (toluene, 80 deg C, 3-5 h) affords dialkylzincs which add enantioselectively to aldehydes in the presence of a catalytic amount (20 molpercent) of the norephedrine derivative 13.This transmetallation can also be used to prepare stereoselectively (E)-alkenylzinc halides (> 98percent E).Addition of Cl(H)ZrCp2 to (E)-5-chloropentenylzinc bromide in CH2Cl2 (25 deg C, 1 min) affords a 1,1-bimetallic of zinc and zirconium Cl(CH2)4CH(ZnBr)ZrCp2(Cl) which reacts stereoselectively with an aldehyde providing the (E)-disubstituted olefin (49percent yield; 100percent E).
- Rozema, Michael J.,Rajagopal, Duddu,Tucker, Charles E.,Knochel, Paul
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- Enantioselective Preparation of sec. Alcohols from Aldehydes and Dialkyl Zinc Compounds, Generated in situ from Grignard Reagents, Using Substoichiometric Amounts of TADDOL-Titanates
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Using the Schlenk trick (precipitation of MgX2 from etheral solutions by the addition of 1,4-dioxane) mixtures of a Grignard reagent RMgX (X = Cl, Br, I) and 0.5 equiv.ZnCl2 in Et2O can be converted to zinc alkyls R2Zn which in turn are added with enantioselectivities of up to 99:1 to aliphatic and aromatic aldehydes in the presence of Ti(OCHMe2)4 and a chiral titanate derived from an α,α,α',α'-tetraaryl-1,3-dioxolane-4,5-dimethanol (TADDOL).Grignard reagents containing remote double bonds, benzene rings, or acetal groups can also be employed.Different TADDOLs are compared with respect to their usefulness in this kind of enantioselective reactions.
- Bussche-Huennefeld, Joanna Linda v.,Seebach, Dieter
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p. 5719 - 5730
(2007/10/02)
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- DEPROTECTION OF BENZYL TYPE PROTECTING GROUPS FOR HYDROXY FUNCTIONS BY A PHOTOINDUCED SINGLE ELECTRON TRANSFER REACTION
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DMPM ethers were cleaved by a photo-induced single electron transfer reaction using dicyanoanthracene and anthraquinone as electron acceptors.A similar reaction occured when dimethoxynaphthylmethyl (DMNM) ethers were irradiated in the presence of dicyanob
- Nishida, Atsushi,Oishi, Satoshi,Yonemitsu, Osamu
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p. 2266 - 2268
(2007/10/02)
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- ASYMMETRIC SYNTHESIS via CHIRAL ACETAL TEMPLATES. 8. REACTIONS WITH ORGANOMETALLIC REAGENTS
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The titanium tetrachloride catalyzed coupling of organometallic reagents with chiral acetals 1 is shown to provide a convenient route for the preparation of a variety of chiral alcohols 4 of high optical purity.
- Lindell, Stephen D.,Elliott, John D.,Johnson, William S.
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p. 3947 - 3950
(2007/10/02)
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- NUCLEOPHILIC CLEAVAGES OF ACETALS USING ORGANOTITANIUM REAGENTS. A NEW SYNTHESIS OF CHIRAL ALCOHOLS
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A highly chemo- and stereoselective cleavage of acetals derived from (-)-(2R, 4R)-2,4-pentanediol with organotitanium reagents has been demonstrated.The reraction proceeds under mild condations in excellent yield and high chemoselectivity to give, after removel of auxiliary, the chiral alcohols of high enantiopurities.In addition, complexation of chiral acetals and TiCl4 followed by treatment with n-butyllithium also results in formation of the corresponding n-butylated alcohols with high stereoselectivity.
- Mori, Atsunori,Maruoka, Keiji,Yamamoto, Hisashi
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p. 4421 - 4424
(2007/10/02)
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