- Simple primary β-amino alcohols as organocatalysts for the asymmetric Michael addition of β-keto esters to nitroalkenes
-
Simple primary β-amino alcohols act as an efficient organocatalysts in the asymmetric Michael addition of β-keto esters with nitroalkenes affording highly pure chiral Michael adducts. Also, both enantiomers of the adducts were obtained, depending on the specific catalyst used and reaction temperature.
- Begum, Zubeda,Sannabe, Haruka,Seki, Chigusa,Okuyama, Yuko,Kwon, Eunsang,Uwai, Koji,Tokiwa, Michio,Tokiwa, Suguru,Takeshita, Mitsuhiro,Nakano, Hiroto
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p. 203 - 209
(2021/02/09)
-
- Catalytic intramolecular hydroamination of aminoallenes using titanium complexes of chiral, tridentate, dianionic imine-diol ligands
-
Alkylation of d- or l-phenylalanine or valine alkyl esters was carried out using methyl or phenyl Grignard reagents. Subsequent condensation with salicylaldehyde, 3,5-di-tert-butylsalicylaldehyde, or 5-fluorosalicylaldehyde formed tridentate, X2/sub
- Sha, Fanrui,Mitchell, Benjamin S.,Ye, Christopher Z.,Abelson, Chase S.,Reinheimer, Eric W.,Lemagueres, Pierre,Ferrara, Joseph D.,Takase, Michael K.,Johnson, Adam R.
-
p. 9603 - 9616
(2019/07/09)
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- The Asymmetric Aza-silyl-Prins Reaction: Synthesis of Enantiopure Piperidines
-
The design and development of the first asymmetric aza-silyl-Prins reaction is reported, giving rise to valuable and diverse piperidines and pipecolic acid derivatives in both high yields and as single enantiomers. The creation of a novel chiral auxiliary-homoallylic amine for the aza-silyl-Prins reaction is essential to its success.
- Mittapalli, Ramana R.,Guesné, Sebastien J. J.,Parker, Robert J.,Klooster, Wim T.,Coles, Simon J.,Skidmore, John,Dobbs, Adrian P.
-
supporting information
p. 350 - 355
(2019/01/11)
-
- Hybrid-Type Squaramide-Fused Amino Alcohol Organocatalysts for Enantioselective Nitro-Aldol Reaction of Nitromethane with Isatins
-
A series of hybrid-type squaramide-fused amino alcohol (SFAA) catalysts were synthesized, and their catalytic efficiency in the enantioselective nitro-aldol reaction of various isatins with nitromethane has been described. This transformation afforded chiral 3-substituted 3-hydroxyoxindoles in excellent chemical yields (up to 99 %) with high enantioselectivities (up to 95 % ee). The resulting chiral 3-hydroxyoxindoles can be further used as synthetic precursors for the synthesis of several natural products that have a broad spectrum of fascinating biological activities.
- Chennapuram, Madhu,Subba Reddy,Seki, Chigusa,Okuyama, Yuko,Kwon, Eunsang,Uwai, Koji,Tokiwa, Michio,Takeshita, Mitsuhiro,Nakano, Hiroto
-
p. 1638 - 1646
(2017/04/06)
-
- NeoPHOX - A structurally tunable ligand system for asymmetric catalysis
-
A synthesis of new NeoPHOX ligands derived from serine or threonine has been developed. The central intermediate is a NeoPHOX derivative bearing a methoxycarbonyl group at the stereogenic center next to the oxazoline N atom. The addition of methylmagnesiu
- Padevět, Jaroslav,Schrems, Marcus G.,Scheil, Robin,Pfaltz, Andreas
-
supporting information
p. 1185 - 1195
(2016/07/06)
-
- Simple primary β-amino alcohol catalyzed enantioselective Diels-Alder reaction of 3-hydroxy-2-pyridones
-
The simple primary β-amino alcohol catalyzed Diels-Alder reaction of 3-hydroxy-2-pyridones as dienes with N-substituted maleimides to provide the highly substituted optically active isoquinuclidines as a single diastereomers in excellent enantioselectivities (up to 98%) with excellent chemical yields (up to 95%) was demonstrated. A range of simple β-amino alcohols were synthesized from the corresponding inexpensive amino acids and their catalytic activity was examined for this reaction.
- Takahashi, Toshihisa,Subba Reddy,Kohari, Yoshihito,Seki, Chigusa,Furuyama, Taniyuki,Kobayashi, Nagao,Okuyama, Yuko,Kwon, Eunsang,Uwai, Koji,Tokiwa, Michio,Takeshita, Mitsuhiro,Nakano, Hiroto
-
p. 5771 - 5776
(2016/12/03)
-
- Bisoxazolidine ligand and a catalyst using the same (by machine translation)
-
PROBLEM TO BE SOLVED: To establish a manufacturing method of a bisoxazolidine ligand and a catalytic reaction using the same.SOLUTION: There is provided a bisoxazolidine ligand represented by the formula (1) or (2). (1) (2), where Ris any of CH3, CH(CH3)2
- -
-
Paragraph 0024; 0125
(2017/03/08)
-
- Synthesis and applications in Henry reactions of novel chiral thiazoline tridentate ligands
-
Several novel chiral tridentate ligands containing thiazoline were efficiently synthesized from commercially available l=cysteine in high yield. These ligands were subsequently applied to the asymmetric Henry reaction of nitromethane and various aldehydes. It was found that the structures of the thiazoline ligands had a significant influence on the enantioselectivity. It was shown that the optimal catalyst for this reaction was a ligand complexed with CuCl, which was formed from chiral thiazoline with chiral aminoalcohol. At -20°C, with 10 mol% of this ligand, a product with (S)-configuration was isolated in 93% yield and 98% enantiomeric excess.
- Shi, Ye,Li, Yang,Sun, Jingbo,Lai, Qi,Wei, Chiyu,Gong, Zhiyong,Gu, Qiang,Song, Zhiguang
-
p. 661 - 667
(2015/09/28)
-
- A method for producing an optically active Alkylaminosulfonamide deriv. β-amino alcohol derivative and optically active
-
PROBLEM TO BE SOLVED: To provide a method for producing an optically active alkylaminosulfonamide derivative useful in pharmaceutical applications etc., and an optically active β-aminoalcohol derivative. SOLUTION: The optically active alkylaminosulf
- -
-
-
- Silyloxy Amino Alcohol Organocatalyst for Enantioselective 1,3-Dipolar Cycloaddition of Nitrones to α,β-Unsaturated Aldehydes
-
The catalytic activity of a simple amino alcohol that contains a bulky super silyl group [i.e., tris(trimethylsilyl)silyl (TTMSS)] bonded to the oxygen atom at the γ-position along with a primary amine moiety was examined in the enantioselective 1,3-dipolar cycloaddition of nitrones to α,β-unsaturated aldehydes. The organocatalyst successfully provided optically active isoxazolidines in good chemical yields (up to 86 %) with excellent diastereoselectivities (endo/exo, up to 96:4) and enantioselectivities (up to 97 % ee). Furthermore, the obtained isoxazolidines were easily converted into γ-amino diols that contain three contiguous stereogenic centers.
- Otsuki, Teppei,Kumagai, Jun,Kohari, Yoshihito,Okuyama, Yuko,Kwon, Eunsang,Seki, Chigusa,Uwai, Koji,Mawatari, Yasuteru,Kobayashi, Nagao,Iwasa, Tatsuo,Tokiwa, Michio,Takeshita, Mitsuhiro,Maeda, Atushi,Hashimoto, Akihiko,Turuga, Kana,Nakano, Hiroto
-
p. 7292 - 7300
(2015/11/25)
-
- Efficient asymmetric addition of diethylzinc to aldehydes using C 2-novel chiral pyridine β-amino alcohols as chiral ligands
-
A series of novel C2-symmetric chiral pyridine β-amino alcohol ligands have been synthesized from 2,6-pyridine dicarboxaldehyde, m-phthalaldehyde and chiral β-amino alcohols through a two-step reaction. All their structures were characterized by 1H NMR, 13C NMR and IR. Their enantioselective induction behaviors were examined under different conditions such as the structure of the ligands, reaction temperature, solvent, reaction time and catalytic amount. The results show that the corresponding chiral secondary alcohols can be obtained with high yields and moderate to good enantiomeric excess. The best result, up to 89% ee, was obtained when the ligand 3c (2S,2R)-2,2-((pyridine-2,6-diylbis(methylene)) bisazanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was used in toluene at room temperature. The ligand 3g (2S,2R)-2,2-((1,3-phenylenebis(methylene)) bis(azanediyl))bis(4-methyl-1,1-diphenylpentan-1-ol) was prepared in which the pyridine ring was replaced by the benzene ring compared to 3c in order to illustrate the unique role of the N atom in the pyridine ring in the inductive reaction. The results indicate that the coordination of the N atom of the pyridine ring is essential in the asymmetric induction reaction. Copyright
- Zhang, Weijie,Tang, Ruiren,Yu, Huirong,Gao, Shu
-
p. 545 - 551
(2014/07/07)
-
- Chiral Bis(oxazolidine)pyridine-copper-catalyzed enantioselective friedel-crafts alkylation of indoles with nitroalkenes
-
Catalytic asymmetric Friedel-Crafts reaction of indoles with nitroalkenes was catalyzed by the stereochemically tunable bis(oxazolidine)pyridine (PyBodine)-Cu(OTf)2 complex. Using the PyBodine(Val)-Cu(OTf) 2 catalyst gave the Friedel-Crafts ?adducts with highly enantioselective manner. For the 1,4-bis[(E)-2-nitrovinyl]benzene, the reaction proceeded in a meso-trick manner to give the chiral double Friedel-Crafts adduct with 97% enantiomeric excess. Georg Thieme Verlag Stuttgart New York.
- Sato, Toru,Arai, Takayoshi
-
p. 349 - 354
(2014/03/21)
-
- Ethynylbenziodoxolones (EBX) as reagents for the ethynylation of stabilized enolates
-
Herein, we report a detailed study on the electrophilic alkynylation of cyclic keto esters and amides with ethynylbenziodoxolone (EBX) reagents. The structure and stability of this class of reagents is first described more in details. Differential scannin
- Fernandez Gonzalez, Davinia,Brand, Jonathan P.,Mondiere, Regis,Waser, Jerome
-
p. 1631 - 1639
(2013/07/05)
-
- Design, synthesis, and applications of potential substitutes of t-Bu-phosphinooxazoline in Pd-catalyzed asymmetric transformations and their use for the improvement of the enantioselectivity in the Pd-catalyzed allylation reaction of fluorinated allyl enol carbonates
-
The design, synthesis, and applications of potential substitutes of t-Bu-PHOX in asymmetric catalysis is reported. The design relies on the incorporation of geminal substituents at C5 in combination with a substituent at C4 other than t-butyl (i-Pr, i-Bu, or s-Bu). Most of these new members of the PHOX ligand family behave similarly in terms of stereoinduction to t-Bu-PHOX in three palladium-catalyzed asymmetric transformations. Electronically modified ligands were also prepared and used to improve the enantioselectivity in the Pd-catalyzed allylation reaction of fluorinated allyl enol carbonates.
- Belanger, Etienne,Pouliot, Marie-France,Courtemanche, Marc-Andre,Paquin, Jean-Francois
-
scheme or table
p. 317 - 331
(2012/02/15)
-
- COMPOSITIONS AND METHODS FOR CYCLOFRUCTANS AS SEPARATION AGENTS
-
The present invention relates to derivatized cyclofructan compounds, compositions comprising derivatized cyclofructan compounds, and methods of using compositions comprising derivatized cyclofructan compounds for chromatographic separations of chemical species, including enantiomers. Said compositions may comprise a solid support and/or polymers comprising derivatized cyclofructan compounds.
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-
Page/Page column 45-49; 64
(2010/12/31)
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- Solid state NMR spectroscopy as a precise tool for assigning the tautomeric form and proton position in the intramolecular bridges of o-hydroxy schiff bases
-
Two analogous Schiff bases, (S,E)-2-((1-hydroxy-3-methyl-1,1-diphenylbutan- 2-ylimino)methyl)phenol (1) and (S,Z)-2-hydroxy-6-((1-hydroxy-3-methyl-1,1- diphenylbutan-2-ylamino)methylene)cyclohexa-2,4-dienone (2), exist in the solid state as phenol-imine and keto-amine tautomers, respectively. Their crystal structures were solved using the X-ray diffraction method. Sample 1 forms orthorhombic crystals of space group P2(1)2(1)2(1), while 2 forms monoclinic crystals of space group P2(1). In each sample, one molecule is in the asymmetric unit of the crystal structure. One-dimensional and two-dimensional solid state NMR techniques were used for structure assignment and for inspection of the 13C and 15N δii of the chemical shift tensor (CST) values. NMR study indicates that the span (Ω = δ11 - δ33) and the skew (κ = 3(δ22 - δiso/Ω) are extremely sensitive to change in the tautomeric form of the Schiff bases. Theoretical calculations of NMR shielding parameters for 1 and 2 and a model compound with reduced aliphatic residue were performed using the GIAO method with B3LYP functional and 6-311++g(d,p) basis sets. From comparative analysis of the experimental and theoretical parameters, it was concluded that the position of hydrogen in the intramolecular bridge has tremendous influence on 13C and 15N CST parameters. Inspection of Ω and κ parameters allowed for the establishment of the nature of the hydrogen bonding and the assignment of the equilibrium proton position in the intramolecular bridges in the solid state.
- Jaworska, Magdalena,Hrynczyszyn, Pawel B.,Welniak, Miroslaw,Wojtczak, Andrzej,Nowicka, Katarzyna,Krasinski, Grzegorz,Kassassir, Hassan,Ciesielski, Wlodzimierz,Potrzebowski, Marek J.
-
p. 12522 - 12530
(2011/02/28)
-
- Salicylaldimine based copper (II) complex: A potential catalyst for the asymmetric Henry reaction
-
The chiral ligand synthesized from L-diphenylvalinol and salicylaldehyde is found to catalyse the asymmetric Henry reaction with copper(II)acetate monohydrate. Various nitroaldols were formed with 77-95% ee and good yield. The mechanism for the formation of a particular enantiomer is also discussed. The enantioselection in the formation of the chiral nitroaldol is discussed in terms of steric bulkiness of the catalytic system.
- Ananthi, Nallamuthu,Balakrishnan, Umesh,Velmathi, Sivan
-
p. 370 - 379,10
(2020/09/16)
-
- CHIRAL TETRAAMINOPHOSPHONIUM SALTS, CATALYST FOR ASYMMETRIC SYNTHESIS AND METHOD FOR PRODUCING CHIRAL beta-NITROALCOHOL
-
A chiral tetraaminophosphonium salt represented by formula (1) and a method for producing chiral β-nitroalcohol comprising reacting an aldehyde or a ketone and a nitroalkane in the presence of the chiral tetraaminophosphonium salt represented by formula (
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-
Page/Page column 7
(2009/05/28)
-
- Orally Bioavailable Caffeic Acid Related Anticancer Drugs
-
The present invention concerns compounds and their use to treat cell proliferative diseases such as cancer. Compounds of the present invention display significant potency as inhibitors of Jak2/STAT3 pathways and downstream targets and inhibit the growth and survival of cancerous cell lines.
- -
-
Page/Page column 18
(2008/06/13)
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- Chiral tetraaminophosphonium salt-mediated asymmetric direct henry reaction
-
Chiral tetraaminophosphonium salts 1 possessing the phosphorus-centered [5.5]-spirocyclic core have been designed and synthesized in a single step from l-valine-derived diamine. The three-dimensional molecular structure was successfully verified by the si
- Uraguchi, Daisuke,Sakaki, Sawako,Ooi, Takashi
-
p. 12392 - 12393
(2008/03/30)
-
- Enantioselective ethylation of aldehydes using a regenerable polymer-supported N-picolylvalinol tridentate ligand
-
A supported pyridine-based tridentate chiral ligand has been prepared and evaluated for enantioselective addition of diethylzinc to aldehydes. The catalyst allowed the preparation of various chiral alcohols with the R configuration in good yields and enan
- Kelsen, Vinciane,Pierrat, Philippe,Gros, Philippe C.
-
p. 10693 - 10697
(2008/02/13)
-
- First enantioselective reductive amination of α-fluoroenones
-
From α-fluoroenones 2, a synthesis of (E) ketone oxime O-alkyl ethers 5 is reported with good to excellent yields. Then the first enantioselective reduction of these ketimines, via oxazaborolidine, is described with moderate to good enantiomeric excesses, leading to valuable chiral fluoroallylic amines 1.
- Dutheuil, Guillaume,Bailly, Laetitia,Couve-Bonnaire, Samuel,Pannecoucke, Xavier
-
-
- Enantioselective alkynylation of aromatic aldehydes catalyzed by new chiral oxazolidine ligands
-
New chiral oxazolidines were conveniently synthesized from natural amino acids in three simple steps with good yields. The use of chiral oxazolidine ligands for the enantioselective alkynylation of aldehydes provides a simple, practical and inexpensive me
- Kang, Yong-Feng,Wang, Rui,Liu, Lei,Da, Chao-Shan,Yan, Wen-Jin,Xu, Zhao-Qing
-
p. 863 - 865
(2007/10/03)
-
- The use of bifunctional catalyst systems in the asymmetric addition of alkynylzinc to aldehydes
-
The bifunctional ligand 2a showed a more enhanced reactivity than that of the corresponding amino alcohol ligand in the asymmetric addition of alkynylzinc to benzaldehyde. The bifunctional ligand 2a can catalyze the addition of phenylacetylene to various
- Kang, Yong-Feng,Liu, Lei,Wang, Rui,Yan, Wen-Jin,Zhou, Yi-Feng
-
p. 3155 - 3159
(2007/10/03)
-
- Enantioselective addition of diethylzinc to aldehydes catalyzed by chiral amino alcohols. Substituent effect and nonlinear effect
-
A new series of chiral β-amino alcohols derived from (S)-leucine, valine, and phenylalanine have been synthesized and evaluated as chiral catalysts for the enantioselective addition of diethylzinc to aldehydes. The β-amino alcohol (1c) possessing a isobutyl substituent and two phenethyl substituents on the carbinol carbon atom was found to be an efficient and optimal ligand to catalyze the diethylzinc addition with high enantioselectivity (up to 97% ee) and good yield. Furthermore, a strong (+)-nonlinear effect (asymmetric amplification) was observed in the enantioselective catalysis, providing high level of enantioselection (93% ee) by use of ligand 1c in 20% ee.
- Ohga, Takahiko,Umeda, Satoshi,Kawanami, Yasuhiro
-
p. 4825 - 4829
(2007/10/03)
-
- Highly effective and recyclable chiral auxiliaries: A study of the synthesis and use of three 4-isopropyl-5,5-diaryloxazolidin-2-ones
-
A series of three 5,5-diaryl substituted oxazolidin-2-ones (diphenyl, dinaphthyl and ditolyl) have been synthesised. Studies on the benzylation of the lithium enolates of N-acyl derivatives reveal that the yields obtained were sensitive to the method of quenching the reaction. This was particularly acute for the 5,5-diphenyl system where effective yields (69%) and high diastereoselectivities (dr 98 : 2) are only observed when the reactions were quenched into aqueous buffer. Methylation studies on the N-acyl derivatives showed that the most advantageous results (58-69%, dr ≥ 91 : 9) were only observed using the sodium enolates. The 5,5-ditolyl-4-isopropyloxazolidin-2-one proved to be more efficacious in terms of efficiency and diastereoselectivity (dr ≥ 97 : 3). Subsequent, simple alkaline hydrolyses of the alkylation products allowed for the high recovery and recyclability of the 5,5-diaryl substituted oxazolidin-2-ones without any deleterious endocyclic cleavage. In addition, the acyl portions were recovered in high yield from the alkaline hydrolyses without any evidence of racemisation.
- Alexander,Cook,Gibson,Kennedy
-
p. 1538 - 1549
(2007/10/03)
-
- Synthesis of optically-active benzylic amines; asymmetric reduction of ketoxime ethers with chiral oxazaborolidines
-
The preparation of novel optically active benzylic amines by the enantioselective reduction of phenone oximes using chiral oxazaborolidine is described. The choice of the chiral 1,2-amino alcohol (S)-diphenylvalinol as chiral inducer and that of the benzy
- Fontaine, Evelyne,Namane, Claudie,Meneyrol, Jerome,Geslin, Michel,Serva, Laurence,Roussey, Eliane,Tissandie, Stephanie,Maftouh, Mohamed,Roger, Pierre
-
p. 2185 - 2189
(2007/10/03)
-
- Studies on the asymmetric reduction of β-oximino methyl ether boronates: Reagent control, double diastereocontrol and transmitted remote asymmetric induction
-
High asymmetric induction (94% ee) could be obtained in the reduction of the achiral E-oxime ether boronate 5 with a homochiral oxazaborolidine 13-BH3-THF complex. Application of this homochiral reducing agent system to non-aromatic oxime ethers 21 produced low to moderate asymmetric induction. Application of the same homochiral reducing agent system to reduction of homochiral boronate E-oximes 3 and 4 produced extreme double diastereo-selection effects, i.e. 8 and 95% ee respectively, which demonstrated that remote asymmetry was being 'transmitted' by a suitable choice of a 'partner' molecule from the boronate moiety to the oxime during reduction. However, attempts to obtain direct remote asymmetric induction in the reduction of homochiral β-oximino boronate methyl ethers 3 and 4 to the corresponding amines produced zero, with for example BH3-THF complex, up to 28% ee with an Et3N-BH3-THF mixture (after oxidative boronate ester cleavage).
- Sailes, Helen E.,Watts, John P.,Whiting, Andrew
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p. 3362 - 3374
(2007/10/03)
-
- Synthesis of N-α-pyridylmethyl amino alcohols and application in catalytic asymmetric addition of diethylzinc to aromatic aldehydes
-
A series of novel chiral ligands 2a-2f were conveniently prepared from β-amino alcohols through a two-step reaction and applied to catalyze the enantioselective addition of diethylzinc to benzaldehyde. Among them, ligand 2c was found to show the best asym
- Wu, Yangjie,Yun, Hongying,Wu, Yusheng,Ding, Kuiling,Zhou, Ying
-
p. 3543 - 3552
(2007/10/03)
-
- A useful modification of the Evans auxiliary: 4-Isopropyl-5,5- diphenyloxazolidin-2-one
-
The 4-isopropyl-5,5-diphenyloxazolidinone (1) is readily prepared from (R)- or (S)-valine ester, PhMgBr, and ethyl chlorocarbonate. It has a melting point of ca. 250°, a low solubility in most organic solvents, and a C=O group which is sterically protected from nucleophilic attack. Thus, the soluble N-acyl-oxazolidinones (7-16) can be prepared from 1 with BuLi at temperatures around 0°instead of - 78°(Scheme 3), their Li enolates can be generated with BuLi, rather than with LDA, and deacylation in the final step of the procedure can be achieved with NaOH at ambient temperatures (Scheme 12), with facile recovery of the precipitating auxiliary 1 (filtering, washing, and drying). The following reactions of N-acyl-oxazolidinones from 1 have been investigated: alkylations (Scheme 4), aminomethylations and hydroxymethylations (Scheme 5), aldol additions (Schemes 6 and 7), Michael additions (Schemes 9 and 10), and a (4 + 2) cycloaddition (Scheme 11). The well-known features of reactions following the Evans methodology (yield, diastereoselectivity, dependence on conditions, counter ions, additives etc.) prevail in these transformations. Most products, however, have higher melting points and a much more pronounced crystallization tendency than those derived from conventional oxazolidinones, and can thus be purified by recrystallization, avoiding chromatography (Table 1). The disadvantage of 1 having a higher molecular weight (ca. 150 Da) than the non-phenyl-substituted auxiliary is more than compensated by the ease of its application, especially on large scale. A number of crystal structures of oxazolidinones derived from 1 and a TiCl4 complex of an oxazolidinone are described and discussed in view of the diastereoselective-reaction mechanisms.
- Hintermann, Tobias,Seebach, Dieter
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p. 2093 - 2126
(2007/10/03)
-
- A study of 4-substituted 5,5-diaryl oxazolidin-2-ones as efficacious chiral auxiliaries
-
A series of three 5,5-diaryl substituted oxazolidin-2-ones (diphenyl, dinaphthyl and ditolyl) have been prepared and shown to be particularly effective chiral auxiliaries to afford high yields and diastereoselectivities for alkylation and azidations of their N-acyl derivatives. The 5,5-ditolyl oxazolidin-2-one proved to be particularly efficacious in terms of diastereoselectivity, yield and solubility.
- Gibson, Colin L.,Gillon, Karen,Cook, Stuart
-
p. 6733 - 6736
(2007/10/03)
-
- 1-magnesiotetrahydroisoquinolyloxazolines as chiral nucleophiles in stereoselective additions to aldehydes: Auxiliary optimization, asymmetric synthesis of (+)-corlumine, (+)-bicuculline, (+)-egenine, and (+)-corytensine, and preliminary 13C NMR studies of 1-lithio- and 1-magnesiotetrahydroisoquinolyloxazolines
-
Transmetalation of 1-lithiotetrahydroisoquinolyloxazolines with magnesium halides affords Grignard reagents that add to aldehydes with up to 80% selectivity for one of the four possible diastereomeric products. An oxazoline chiral auxiliary derived from camphor provides an optimal blend of diastereoselectivity and isomer separability. Synthetic applications of the optimal auxiliary, patterned after a literature approach in the racemic series, comprise an improved (formal) synthesis of bicuculline, egenine, and corytensine, as well as an efficient synthesis of corlumine. Preliminary NMR studies show that both 1-lithio- and 1-magnesiotetrahydroisoquinolyloxazolines are dynamic mixtures in THF solution at low temperatures. The barrier to pyramidal inversion of the secondary Grignard reagent is in the 9.8-10.1 kcal/mol range, while an upper limit of about 8.2 kcal/mol can be assigned to the barrier to the organolithium inversion.
- Gawley, Robert E.,Zhang, Pingsheng
-
p. 8103 - 8112
(2007/10/03)
-
- Chemical Aspects of Metoprolol Metabolism. Asymmetric Synthesis and Absolute Configuration of the 3--1-(isopropylamino)-2-propanols, the Diastereomeric Benzylic Hydroxylation Metabolites
-
Asymmetric synthesis of 3--1-(isopropylamino)-2-propanol (2), the benzylic hydroxylation metabolite of metoprolol (1), is described, and the absolute configurations of the diastereomers were assigned.Ketone 3, prepared in a multistep synthesis, was reduced with a complex of (2S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol(9) and borane, yielding 2, with a ratio of 82:18 for the diastereomers.The absolute configurations 1'S,2S and 1'S2R were assigned for the diastereomers formed in excess on the basis of reductions on closely related alkyl phenyl ketones and the circular dichroism spectrum.Derivatization of the 1'-hydroxyl group of oxazolidinone 10 with a chiral Mosher acid chloride and the use of an HPLC procedure to resolve the resulting esters enabled us to determine the metabolic product stereoselectively for 2.In the presence of the rat liver microsomal fraction, the benzylic hydroxylation of 1 was highly product stereoselective favoring 1'R stereochemistry at the new asymmetric center in racemic 1 and in both enantiomers of 1.Determination of the stereochemistry of 2 will facilitate study of this polymorphically controlled metabolic process.
- Shetty, H. Umesha,Nelson, Wendel L.
-
-
- Asymmetric Synthesis Using Chirally Modified Borohydrides. Part 3. Enantioselective Reduction of Ketones and Oxime Ethers with Reagents Prepared from Borane and Chiral Amino Alcohols
-
The asymmetric reduction of aromatic and aliphatic ketones, halogeno ketones, keto esters, and ketone oxime ethers with reagents prepared from borane and chiral amino alcohols has been investigated.When α,α-diphenyl-β-amino alcohols, such as (2S,3R)-(-)-2-amino-3-methyl-1,1-diphenylpentanol (2d), were used as a chiral auxiliary, very high enantioselectivities (ca. 90percent e.e.) were obtained in the reduction of various ketones and oxime ethers.
- Itsuno, Shinichi,Nakano, Michio,Miyazaki, Koji,Masuda, Hirofumi,Ito, Koichi,et al.
-
p. 2039 - 2044
(2007/10/02)
-
- Asymmetric Reduction of Aromatic Ketones with the Reagent prepared from (S)-(-)-2-Amino-3-methyl-1,1-diphenylbutan-1-ol and Borane
-
Asymmetric reduction of prochiral aromatic ketones with the reagent prepared from (S)-(-)-2-amino-3-methyl-1,1-diphenylbutan-1-ol and borane afforded the corresponding aromatic secondary alcohols in high optical (94-100percent enantiomeric exces
- Itsuno, Shinichi,Ito, Koichi,Hirao, Akira,Nakahama, Seiichi
-
p. 469 - 470
(2007/10/02)
-