- Enantioselective Allenoate-Claisen Rearrangement Using Chiral Phosphate Catalysts
-
Herein we report the first highly enantioselective allenoate-Claisen rearrangement using doubly axially chiral phosphate sodium salts as catalysts. This synthetic method provides access to β-amino acid derivatives with vicinal stereocenters in up to 95percent ee. We also investigated the mechanism of enantioinduction by transition state (TS) computations with DFT as well as statistical modeling of the relationship between selectivity and the molecular features of both the catalyst and substrate. The mutual interactions of charge-separated regions in both the zwitterionic intermediate generated by reaction of an amine to the allenoate and the Na+-salt of the chiral phosphate leads to an orientation of the TS in the catalytic pocket that maximizes favorable noncovalent interactions. Crucial arene-arene interactions at the periphery of the catalyst lead to a differentiation of the TS diastereomers. These interactions were interrogated using DFT calculations and validated through statistical modeling of parameters describing noncovalent interactions.
- Ellwart, Mario,Gensch, Tobias,Han, Seo-Jung,Lin, Hsin-Hui,Miró, Javier,Sigman, Matthew S.,Toste, F. Dean
-
supporting information
p. 6390 - 6399
(2020/04/27)
-
- Phosphine-Catalyzed Domino β/γ-Additions of Benzofuranones with Allenoates: A Method for Unsymmetrical 3,3-Disubstituted Benzofuranones
-
A phosphine-catalyzed domino process of benzofuranones with allenoates has been developed which furnishes highly functionalized unsymmetrical 3,3-disubstituted benzofuranones in synthetically useful yields. The mechanism for the transformation is a tandem β-umpolung/γ-umpolung process.
- Huang, Zhusheng,Yang, Xiuqin,Yang, Fulai,Lu, Tao,Zhou, Qingfa
-
supporting information
p. 3524 - 3527
(2017/07/17)
-
- Photoinduced Intermolecular [4+2] Cycloaddition Reaction for Construction of Benzobicyclo[2.2.2]octane Skeletons
-
A novel and efficient method for the synthesis of highly substituted benzobicyclo[2.2.2]octane skeletons has been explored. Under UV-light irradiation, o-divinylbenzenes underwent a pericyclic reaction to form the cyclic o-quinodimethane intermediates which were subsequently reacted with olefins through [4+2] addition to construct the benzobicyclo[2.2.2]octane skeletons in mild conditions. Gram scale reactions demonstrated the synthetic potential application of this protocol.
- Liu, Qiang,Wang, Junlei,Li, Dazhi,Yang, Chao,Xia, Wujiong
-
p. 1389 - 1402
(2017/02/10)
-
- Synthesis of 1,4-enamino ketones by [3,3]-rearrangements of dialkenylhydroxylamines
-
The synthesis of 1,4-enamino ketones has been achieved through the [3,3]-rearrangement of dialkenylhydroxylamines generated from the addition of N-alkenylnitrones to electron-deficient allenes. The mild conditions required for this reaction, and the simultaneous installation of a fluorenyl imine N-protecting group as a consequence of the rearrangement, avoid spontaneous cyclization of the 1,4-enamino ketones to form the corresponding pyrroles and allow for the isolation and controlled divergent functionalization of these reactive intermediates. The optimization, scope, and tolerance of the new method are discussed with demonstrations of the utility of the products for the synthesis of pyrroles, 1,4-diones, and furans.
- Pecak, Wiktoria H.,Son, Jongwoo,Burnstine, Amy J.,Anderson, Laura L.
-
supporting information
p. 3440 - 3443
(2014/07/21)
-
- Cross-dehydrogenative coupling reactions by transition-metal and aminocatalysis for the synthesis of amino acid derivatives
-
The direct approach: The title coupling reactions of N-aryl glycine esters with unmodified ketones occurred smoothly in the presence of tert-butyl hydroperoxide (TBHP) or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) under mild conditions (see scheme). The oxidant used for C-H activation determined the selectivity of the reactions for a particular type of ketone substrate. Copyright
- Xie, Jin,Huang, Zhi-Zhen
-
supporting information; experimental part
p. 10181 - 10185
(2011/02/27)
-
- Peptide ligation assisted by an auxiliary attached to amidyl nitrogen
-
New thiol-containing auxiliaries were developed for peptide ligation. They were placed at the amidyl N-atom in the second amino acid residue of a peptide fragment. With the new auxiliaries, peptide ligation could be conducted at non-Cys and non-Gly sites. Compared to other recently developed auxiliaries, an important feature of the present design was that the new auxiliaries were generally applicable and readily removable.
- Li, Juan,Cui, Hong-Kui,Liu, Lei
-
scheme or table
p. 1793 - 1796
(2010/06/13)
-
- New strategies for the design of folded peptoids revealed by a survey of noncovalent interactions in model systems
-
Controlling the equilibria between backbone cis- and trans-amides in peptoids, or N-substituted glycine oligomers, constitutes a significant challenge in the construction of discretely folded peptoid structures. Through the analysis of a set of monomeric peptoid model systems, we have developed new and general strategies for controlling peptoid conformation that utilize local noncovalent interactions to regulate backbone amide rotameric equilibria, including n→π*, steric, and hydrogen bonding interactions. The chemical functionalities required to implement these strategies are typically confined to the peptoid side chains, preserve chirality at the side chain N-α-carbon known to engender peptoid structure, and are fully compatible with standard peptoid synthesis techniques. Our examinations of peptoid model systems have also elucidated how solvents affect various side chain-backbone interactions, revealing fundamental aspects of these noncovalent interactions in peptoids that were largely uncharacterized previously. As validation of our monomeric model systems, we extended the scope of this study to include peptoid oligomers and have now demonstrated the importance of local steric and n→π* interactions in dictating the structures of larger, folded peptoids. This new, modular design strategy has guided the construction of peptoids containing 1-naphthylethyl side chains, which we show can be utilized to effectively eliminate trans-amide rotamers from the peptoid backbone, yielding the most conformationally homogeneous class of peptoid structures yet reported in terms of amide rotamerism. Overall, this research has afforded a valuable and expansive set of design tools for the construction of both discretely folded peptoids and structurally biased peptoid libraries and should shape our understanding of peptoid folding.
- Gorske, Benjamin C.,Stringer, Joseph R.,Bastian, Brent L.,Fowler, Sarah A.,Blackwell, Helen E.
-
scheme or table
p. 16555 - 16567
(2010/02/15)
-
- Alcohol-assisted phosphine catalysis: One-step syntheses of dihydropyrones from aldehydes and allenoates
-
This paper describes the phosphine-catalyzed annulation of methyl allenoate with various aromatic aldehydes to form 6-aryl-4-methoxy-5,6dihydro-2-pyrones. In this reaction, the addition of an alcohol was necessary to induce dihydropyrone formation, with the optimal agent being methanol. Moreover, the addition of n-butyllithium suppressed the formation of the noncyclized product, leading to the exclusive isolation of the dihydropyrone. This method provides an efficient, one-step route toward disubstituted dihydropyrones from simple, stable starting materials.
- Creech, Gardner S.,Kwon, Ohyun
-
p. 429 - 432
(2008/09/19)
-
- Synthesis of 13C-labeled γ-hydroxybutyrates for EPR studies with 4-hydroxybutyryl-CoA dehydratase
-
4-Hydroxybutyryl-CoA dehydratase from Clostridium aminobutyricum catalyses the reversible dehydration of its substrate 4-hydroxybutyryl-CoA (4-HB-CoA) to crotonyl CoA. The enzyme contains one [4Fe-4S]2+ cluster and one flavin adenine dinucleotide (FAD) molecule per homotetramer. Incubation of the enzyme with its substrate under equilibrium conditions followed by freezing at 77 K induced the EPR-spectrum of a neutral flavin semiquinone (g = 2.005, linewidth 2.1 mT), while at 10 K additional signals were detected. In an attempt to characterize these signals, 4-HB-CoA molecules specifically labeled with 13C have been synthesized. This was achieved via 13C- labeled γ-butyrolactones, which were obtained from 13C-labeled bromoacetic acids by efficient synthetic routes. Incubation of the 13C-labeled 4-hydroxybutyrate-CoA molecules with 4-hydroxybutyryl-CoA dehydratase did not lead to marked broadening of the signals.
- Naeser, Ulrike,Pierik, Antonio J.,Scott, Richard,Cinkaya, Irfan,Buckel, Wolfgang,Golding, Bernard T.
-
-
- Bromoacetyl bromide: A versatile and selective cleaving agent for ethers and acetals
-
It is shown that bromoacetyl bromide can be utilized for the selective cleavage of ethers and acetals in high yields. With cyclic ethers and acetals as starting materials, cleavage products are produced with two strategically positioned bromo substituents which may be exploited for selective extention of the carbon chain.
- Schneider, David F.,Viljoen, Murray S.
-
p. 721 - 728
(2007/10/03)
-
- Triazole derivatives
-
The present invention relates to triazole and imidazole derivatives of formula I and to their pharmaceutically acceptable acid addition salts. These compounds are NMDA receptor subtype blockers and are useful for the treatment of diseases related to the NMDA receptor.
- -
-
-
- In situ derivatization/solid-phase microextraction for the determination of haloacetic acids in water
-
An in situ derivatization solid-phase microextraction method has been developed for the determination of haloacetic acids (HAAs) in water. The analytical procedure involves derivatization of HAAs to their methyl esters with dimethyl sulfate, headspace sampling using solid-phase microextraction (SPME), and gas chromatography-ion trap mass spectrometry (GC/ITMS) determination. Parameters affecting both derivatization efficiency and headspace SPME procedure, such as the selection of the SPME coating, derivatization-extraction time and temperature, and ionic strength, were optimized. The commercially available Carboxen-poly(dimethylsiloxane) (CAR-PDMS) fiber appears to be the most suitable for the determination of HAAs. Moreover, the formation of HAA methyl esters was dramatically improved (up to 90-fold) by the addition of tetrabutylammonium hydrogen sulfate (4.7 μmol) to the sample as ion-pairing agent in the derivatization step. The precision of the in situ derivatization/HS-SPME/GC/ITMS method evaluated using an internal standard gave relative standard deviations (RSDs) between 6.3 and 11.4%. The method was linear over 2 orders of magnitude, and detection limits were compound-dependent, but ranged from 10 to 450 ng/L. The method was compared with the EPA method 552.2 for the analysis of HAAs in various water samples, and good agreement was obtained. Consequently, in situ derivatization/HS-SPME/GC/ITMS is proposed for the analysis of HAAs in water.
- Sarrion,Santos,Galceran
-
p. 4865 - 4873
(2007/10/03)
-
- Specific isotope enrichment of methyl methacrylate
-
A synthetic scheme has been developed to prepare methyl methacrylate specifically 13C-labelled at all different positions and in any combination of positions, from simple, commercially available starting materials. According to this scheme methyl (1-13C) and methyl (2-13C)methacrylate (1a and 1b) have been prepared with high label incorporation (99%).
- Werkhoven, Thekla M.,Van Nispen, Reinier,Lugtenburg, Johan
-
p. 2909 - 2914
(2007/10/03)
-
- 1-acyl-4-aliphatylaminopiperidine compounds
-
The invention relates to novel 1-acyl-4-aliphatylaminopiperidine compounds of STR1 formula (I), in which R1 is a benzoyl, naphthoyl or cycloalkanoyl radical which is unsubstituted or substituted by lower alkyl, lower alkoxy, halogen and/or trifluoromethyl; R2 is cycloalkyl or a phenyl or naphthyl radical which is unsubstituted or substituted by lower alkyl, lower alkoxy, halogen, nitro, cyano and/or trifluoromethyl; R3 and R4 together are lower alkylene or aza-, oxa- or thia-lower alkylene; or R3 is lower alkyl, lower alkoxy-lower alky, di-lower alkylamino-lower alkyl or a radical of the formula --(CH2)n --C(=O)--R5 (Ia); and R4 is hydrogen, lower alkyl or a radical of the formula --(CH2)n --C(=O)--R5 (Ia); R5 is (i) hydrogen, alkyl or alkyl which is substituted by halogen, lower alkoxy amino or amino substituted by lower alkyl, amino-lower alkyl, mono- or di-lower alkylaminoalkyl, lower alkanoyl, lower alkoxycarbonyl or lower alkylene or aza-, oxa- or thia-lower alkylene, (ii) hydroxyl, cycloalkoxy, lower alkoxy or lower alkoxy which is substituted by lower alkoxy, amino or amino substituted by lower alkyl, amino-lower alkyl, mono- or di-lower alkylamino-alkyl, lower alkanoyl, lower alkoxycarbonyl or lower alkylene or aza-, oxa- or thia-lower alkylene, or (iii) amino or amino substituted by lower alkyl, cycloalkyl, amino-lower alkyl, mono- or di-lower alkylaminoalkyl, lower alkanoyl, lower alkoxycarbonyl or lower alkylene or aza-, oxa- or thia-lower alkylene; X1 is methyelene, ethylene, a direct bond; a free or ketalized carbonyl group or a free or etherified hydroxymethylene group and n is 0 or 1, and their salts, processes for the preparation of the compounds according to the invention, pharmaceutical compositions containing these and their use as pharmaceutical active ingredients.
- -
-
-
- Scavenger assisted combinatorial process for preparing libraries of tertiary amine compounds
-
This invention relates to a novel solution phase process for the preparation of tertiary amine combinatorial libraries. These libraries have utility for drug discovery and are used to form wellplate components of novel assay kits.
- -
-
-
- An Intramolecular Element Effect in Nucleophilic Vimylic Substitution Reactions
-
Fluorochloro- and fluorobromoethenes CHX=CFX (X = Cl, Br) in reactions with sodium alkoxides RONa (R = Me, Et, i-Pr, t-Bu) in the corresponding alcohols afford the products of monosubstitution of both chlorine (bromine) and fluorine, as well as orthoesters XCH2C(OR)3 and esters XCH2COOR. The stereochemistry of the reactions and the intramolecular element effect are discussed.
- Shainyan,Danilevich
-
p. 188 - 192
(2007/10/03)
-
- Nucleophilic Substitution Reactions at Chloro-Substituted Ozonides and at a Chlorinated Dimeric Peroxide
-
Reactions of substituted 3-chloro- (2a-4a) and 3,5-dichloro-1,2,4-trioxolanes (9a, 10a) with AgBF4 in the presence of LiF gave the corresponding fluoro-substituted ozonides (2b - 4b and 9b and 10b).Substitutions of some of these chlorinated ozonides by the methoxy and by the acetoxy groups, and of 3,6-dichloro-3,6-dimethyl-1,2,4,5-tetroxane (22a) with the acetoxy group have been achieved too.
- Griesbaum, Karl,Schlindwein, Konrad
-
p. 8062 - 8066
(2007/10/03)
-
- Ozonides of Acyclic Olefins Having Mono- and Dichloro-Substituted Double Bonds
-
Ozonolyses of acyclic olefins containing 1,2-dichloro-substituted (4a,b) and monochloro-substituted double bonds (7a, b, 12) as well as two (4a, b, 7a, b) or one halomethyl group (12) attached to the double bond afford the corresponding ozonides as the first representatives of monocyclic chlorinated ozonides.Their stability decreases in order 5a, 5b > 8a, 8b > 13. - Key Words: Ozonides/ 1,2,4-Trioxolanes, 3-chloro-, 3,5-dichloro- / Polyethylene
- Griesbaum, Karl,Schlindwein, Konrad,Hilss, Michael
-
p. 1843 - 1848
(2007/10/02)
-
- REACTIONS OF HALOGEN FLUORIDES XII. REACTION OF BROMINE TRIFLUORIDE WITH BROMINE-CONTAINING ESTERS. A NEW METHOD FOR THE SYNTHESIS OF FLUOROALKYL 2-FLUOROACRYLATES
-
Being weak Lewis bases, esters reduce the reactivity of bromine trifluoride in the substitutive fluorination of organic bromine derivatives.For this reason the rate of the reaction of bromine trifluoride with bromine-containing esters depends not only on the electronic characteristics of the substituents at the reaction center but also on the basicity of the ester.As a rule, the selectivity of the reaction increases with increase in the basicity of the ester.The reaction of bromine trifluoride or chlorine monofluoride with fluoroalkyl 2,3-dibromopropionates can be used successfully for the synthesis of monomers (fluoroalkyl 2-fluoroacrylates).
- Kartashov, A. V.,Chuvatkin, N. N.,Boguslavskaya, L. S.
-
p. 2243 - 2248
(2007/10/02)
-
- Analyse structurale des derives fonctionnels des acides carboxyliques. Partie II. Halogeno et cyanoacetates de methyle
-
Methylene bending mode analysis and dipole moment determinations were carried out in solution (CCl4) for some methyl esters ΣCH2CO2Me with Σ =F(I), Cl(II), Br(III), I(IV), CN(V), in order to identify the conformers induced by ΣCH2 group rotating motion and determine their relation amounts.The results are consistent with the existence of two conformations; syn and anti for (I), syn and gauche for (II) and (III).Compounds (IV) and (V) occur almost exclusively in gauche and syn forms respectively.A theoretical study of compounds (I), (II) and (V) by P.C.I.L.O. methods and the Onsager formalism was performed.The collected data show that the conformers have the O-Me bond syn to the carbonyl.The calculated value of ΔE for the equilibrium between the syn and anti rotamers (Ea-Es =600 cal mol-1) is in good agreement with ΔH0298 estimated from the temperature-dependence studies (ΔE =158 cal mol-1).
- Maury, Catherine,Petrissans, Jean
-
p. 267 - 278
(2007/10/02)
-
- Phenoxypropanolamines and pharmaceutical use
-
Tertiary and secondary amines of the formulas STR1 wherein n is the integer 1 or 2, p0 R is hydrogen, lower-alkanoyl or phenyl-lower-alkanoyl, X1 is phenoxymethyl optionally mono-fluorinated or mono-chlorinated in the ortho-position, X2 is lower-alkyl, phenoxymethyl optionally mono-fluorinated or mono-chlorinated in the ortho-position or phenyl optionally monosubstituted by fluorine, chlorine, trifluoromethyl or lower-alkoxy, Y is hydrogen or methyl, and Z is a phenyl or thienyl residue substituted as hereinafter described, and the physiologically and pharmaceutically compatible salts are described. The compounds of formulas I and V-1 have catabolic activity and can be used for the treatment of obesity and diabetes mellitus or for the treatment of conditions which are associated with an increased protein breakdown, or as feed additives for fattening animals. The compounds of formulas I and V-1 can be prepared starting from corresponding primary amines.
- -
-
-
- Liquid Phase Carbonylation with Solid Catalyst. Carboxy Methylation of Dihalo Methane with Group VIII Metals Supported on Active Carbon
-
It was found that cobalt supported on active carbon showed an excellent catalytic activity for the carbonylation of dibromo methane in the liquid phase.For example, when the reaction was conducted under the conditions of 140 deg C, P (CO) = 31 atm, the yields of dimethyl malonate and bromomethyl acetate were 34.4percent and 22.2percent, respectively.Pd and Rh also showed catalytic activities.
- Yagita, Hiroshi,Kuwahara, Hiroyuki,Omata, Kohji,Fujimoto, Kaoru
-
p. 335 - 338
(2007/10/02)
-
- Substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives and anti-allergic use thereof
-
Leucotriene synthesis inhibiting substituted 4-(quinolin-2-yl-methoxy)phenyl-acetic acid derivatives of the formula STR1 R1 --represents a group of the formula STR2 wherein Y--represents a group of the formula STR3 Z--represents norbornyl, or represents a group of the formula STR4 and A and B are identical or different and denote hydrogen, lower alkyl or halogen, and salts thereof.
- -
-
-
- STRUCTURAL EFFECT ON THE MECHANISTIC PATHWAY OF THE DECOMPOSITION OF 3-ALKYL-1-ARYLTRIAZENES: A KINETIC STUDY
-
A kinetic study of the reaction between 3-alkyl-1-aryltriazenes and substituted acetic acids has been made in solvent acetone over the temperature range 21-37 deg C.Ea is 17.3 +/- 0.3 kcal mol-1 and log A is 10.3 +/- 0.1.Influence of the substituents on the reaction rate has been analyzed.The Hammett correlation with ? gave a ρ value of -0.96 for para-aryl substituted triazenes and +0.35 for meta- and para-substituted phenylacetic acid.The rate of decomposition of triazenes is also affected by changing the alkyl group.From these results a duality in mechanism is proposed; first, a simultaneous protonation and alkyl group expulsion to be the rate-determining step when R is tertiary, benzylic and possibly secondary.Secondly, a concerted mechanism for the protonation of nitrogen and cleavage of the N-R bond for primary alkyl groups.
- Laila, Abdulhameed A. R.
-
p. 453 - 456
(2007/10/02)
-
- The Ethyl Halides: Stable Neutral and Radical Cation Isomers where X = F, Cl, Br, I
-
The following isomers of the ethyl halide molecular ions have all been shown to be stable species in the gas phase: +.; +.; (ΔH0f = 1012 kJ mol-1); +. (ΔH0f = 971 kJ mol-1); +.; +. (ΔH0f = 1058 kJ mol-1); +. (ΔH0f = 995 kJ mol-1) and +..Neutralization-reionization mass spectrometry, employing Xe as the electron transfer target gas and O2 as the target gas for reionization, indicated that the ylides CH3ClCH2 and CH3BrCH2 could not be generated by such means.However, the species CH3CHClH, CH2CH2ClH and CH2CH2BrH ( and posibly CH3CHBr ) were unambiguously identified.
- Blanchette, Marcia C.,Holmes, John L.,Lossing, F. P.
-
p. 701 - 709
(2007/10/02)
-