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Design of a genetic algorithm for the simulated evolution of a library of asymmetric transfer hydrogenation catalysts

A library of catalysts was designed for asymmetric-hydrogen transfer to acetophenone. At first, the whole library was submitted to evaluation using high-throughput experiments (HTE). The catalysts were listed in ascending order, with respect to their performance, and best catalysts were identified. In the second step, various simulated evolution experiments, based on a genetic algorithm, were applied to this library. A small part of the library, called the mother generation (GO), thus evolved from generation to generation. The goal was to use our collection of HTE data to adjust the parameters of the genetic algorithm, in order to obtain a maximum of the best catalysts within a minimal number of gen-erations. It was namely found that simulated evolution’s results depended on the selection of GO and that a random GO should be preferred. We also demonstrated that it was possible to get 5 to 6 of the ten best catalysts while investigating only 10% of the library. Moreover, we developed a double algorithm making this result still achievable if the evolution started with one of the worst GO.

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SULPHONYLAMINO DERIVATIVES FOR THE TREATMENT OF ALZHEIMER’S DISEASE

A compound of formula (I), wherein R1 is alkyl, alkenyl, cycloalkyl, cycloalkenyl, heterocycloalkyl, heterocycloalkenyl, aryl, heteroaryl, heteropolycyclyl or polycyclyl, any of which is optionally substituted with alkyl, heteroaryl, aryl or -O-aryl; R2 is alkyl, alkenyl or aryl, any of which is optionally substituted with hydroxy, halogen, aryl, heteroaryl, cycloalkyl, cycloalkenyl, -C(O)NH-aryl, heterocycloalkyl, heterocycloalkenyl, heteropolycyclyl or polycyclyl; R3 is hydrogen or aryl; R4is alkyl, alkenyl, alkoxy, alkylthio or aryl, any of which is optionally substituted with hydroxy, aryl, heteroaryl, cycloalkyl, cycloalkenyl, thioalkyl, heterocycloalkyl, heterocycloalkenyl, heteropolycyclyl or polycyclyl; R5 is hydrogen or an alkyl or alkenyl group optionally substituted with hydroxy, aryl, -C(O)O- alkyl or -C(O)NH- alkyl; or R4-C-R5 taken together form cycloalkyl, cycloalkenyl or polycyclyl, any of which is optionally substituted with alkyl or hydroxyalkyl; R6 is hydrogen, alkyl, -alkyl-aryl or -alkyl-heteroaryl; or a pharmaceutically-acceptable salt thereof.

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A new and highly efficient catalyst for the enantioselective Mukaiyama-Michael reaction between (E)-3-crotonoyl-1,3-oxazolidin-2-one and 2-trimethylsilyloxyfuran

The Mukaiyama-Michael reaction between 2-trimethylsilyloxyfuran and (E)-3-crotonoyl-1,3-oxazolidin-2-one has been stereoselectively catalysed by several optically active complexes based on bis(oxazoline) (box) or pyridine bis(oxazoline) (pybox) chiral ligands and metal cations. The catalysts derived from the newly synthesised 2,6-bis[(4?R,5?R)-diphenyl-1,3-oxazolin-2?-yl]pyridine and the triflates of EuIII, LaIII, CeIV were highly efficient: The diastereoselectivity was entirely anti and the enantioselectivity was excellent (ranging from 98 to > 99%). A mechanistic insight into the nature of the activated substrate-catalyst complex was inferred studying the lanthanum complexes with 1H and 13C NMR spectroscopy. Based on these results and on the crystallographic structure of the complex between pybox and La(OTf)3, a stereochemical model is proposed to rationalise the crucial role of the substituent in position 5, suitably placed to blind the Si-face of the coordinated reagent.

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Chiral CNN pincer palladium(II) complexes with 2-aryl-6-(oxazolinyl) pyridine ligands: Synthesis, characterization, and application to enantioselective allylation of isatins and suzuki-miyaura coupling reaction

A series of chiral 2-aryl-6-(oxazolinyl)pyridine (aryl = phenyl or 1-naphthyl) ligands 2a-f were conveniently prepared from commercially available 6-bromo-2-picolinaldehyde in two steps. Reaction of 2a-f with PdCl2 in toluene in the presence of sodium bicarbonate afforded the corresponding CNN pincer Pd(II) complexes 3a-f via aryl C-H bond activation of the related ligands. All of the new compounds have been fully characterized by elemental analysis (MS for ligands), 1H and 13C NMR, and IR spectra. In addition, the molecular structures of Pd(II) complexes 3c-f have been determined by X-ray single-crystal diffraction. The obtained chiral pincer catalysts were successfully used in the asymmetric allylation of isatins with allyltributyltin, giving the corresponding 3-allyl-3-hydroxyoxindoles in high yields with enantioselectivities of up to 86% ee. These pincers could also catalyze the asymmetric Suzuki-Miyaura coupling reaction to provide the axially chiral biaryl products in good yields with good stereoselectivities (up to 68% ee).

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A catalyst don’t appear in the overall stoichiometry of the reaction it catalyzes, but it must appear in at least one of the elementary reactions in the mechanism for the catalyzed reaction. 23190-16-1, Name is (1R,2S)-(?)-2-Amino-1,2-diphenylethanol, molecular formula is C6H5CH(NH2)CH(C6H5)OH. In a Article£¬once mentioned of 23190-16-1, SDS of cas: 23190-16-1

Asymmetric conjugate addition of ketones to beta-nitrostyrenes by means of 1,2-amino-alcohol-derived prolinamides as bifunctional catalysts

Different L-prolinamides 21, prepared from L-proline and chiral beta-amino alcohols are active bifunctional catalysts for the direct nitro-Michael addition of ketones to beta-nitrostyrenes. In particular, catalyst 21e, prepared from L-proline and (1S,2R?)-cis-1-amino-2-indanol, exhibits the highest catalytic performance working in polar aprotic solvents such as NMP, especially in the presence of 20 mol-% of acid additives such as p-nitrobenzoic acid or under microwave heating. High syn diastereoselectivities (up to 94 % de) and good enantioselectivities (up to 80 % ee) are obtained at room temp. Moreover, catalyst 21e can be easily recovered and reused. ESI-MS studies are used to characterize the intermediates assumed for the catalytic cycle. The stereochemical control attending Michael addition reactions between ketones and nitrostyrenes catalyzed by prolinamide derivatives 21 has been investigated with computational density functional methods. Transition-state energies for the rate-limiting C-C bond-forming step are calculated. Analysis of these structures indicates that hydrogen bonding plays an important role in catalysis, and that the energy barrier for Re-face attack to form syn-(4S,5R) products is lower than that for Si-face attack leading to syn-(4R,5S) products. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.

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The reaction rate of a catalyzed reaction is faster than the reaction rate of the uncatalyzed reaction at the same temperature.23190-16-1, Name is (1R,2S)-(?)-2-Amino-1,2-diphenylethanol, molecular formula is C6H5CH(NH2)CH(C6H5)OH. In a Article£¬once mentioned of 23190-16-1, Application In Synthesis of (1R,2S)-(?)-2-Amino-1,2-diphenylethanol

Biomimetic chirality sensing with pyridoxal-5?-phosphate

Pyridoxal-5?-phosphate (PLP) is introduced to a biomimetic indicator displacement assay for simultaneous determination of the absolute configuration, enantiomeric composition and concentration of unprotected amino acids, amino alcohols and amines. The chiroptical assay is based on fast imine metathesis with a PLP aryl imine probe to capture the target compound for circular dichroism and fluorescence sensing analysis. The substrate binding yields characteristic Cotton effects that provide information about the target compound ee and the synchronous release of the indicator results in a nonenantioselective off-on fluorescence response that is independent of the enantiomeric sample composition and readily correlated to the total analyte concentration.

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Synthesis and structure of novel chiral oxazolinylferrocenes and oxazolinylferrocenylphosphines, and their rhodium(I) -complexes

A variety of chiral oxazolinylferrocenes are prepared from either ferrocenecarboxylic acid or cyanoferrocene and chiral beta-amino alcohols. Highly diastereoselective ortho-lithiation (84 ? 99% de) of the oxazolinylferrocenes is accomplished with sec-butyllithium and the treatment of the lithiated compounds with an electrophile such as MeI, Ph2PCI or (PhSe)2 gives the corresponding ortho-substituted oxazolinylferrocenes. The molecular structure of (S,S)-[2-(4?-isopropyloxazolin-2?-yl)ferrocenyl]diphenylphosphine (10), (S,S)-2-phenylseleno-1-(4?-isopropyloxazolinyl)ferrocene (17), (S,R)-3-methyl-1-diphenylphosphino-2-(4?-isopropyloxazolinyl)ferrocene (18), and (S,S,S)-[2-(4?,5?-diphenyloxazolin-2?-yl)ferrocenyl]diphenylphosphine ((S,S,S)-DIPOF; 21) has been fully characterized by X-ray crystallography. In connection with their usefulness as chiral ligands for Rh(I)-catalyzed asymmetric hydrosilylation of ketones, the square planar transition metal complexes having oxazolinylferrocenylphosphines, such as [Rh(COD)(P-N)]BF4 and Rh(CO)(P-N)Cl (P-N = 10 or 21), are prepared by treatment of [Rh(COD)2]BF4 and [Rh(CO)2Cl]2 with 10 and 21, respectively, and all structures have been characterized spectroscopically and further confirmed by X-ray crystallography.

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Fine-tunable organocatalysts bearing multiple hydrogen-bonding donors for construction of adjacent quaternary and tertiary stereocenters via a michael reaction

The fine-tunable bifunctional amine/thiourea organocatalysts, relying on multipe hydrogen-bonding donors was investigated. A representative set of aryl and alkyl substituted nitroolefins were surveyed under the optimal experimental conditions. The trisubstituted carbon nucleophiles were examined with a 10 mol% of catalyst. The significant role of the multiple hydrogen-bonding donors played in the system was demonstrated through the control experiments using less bulky methylated (1R,2R,1’R,2’R)-II-E, (1R,2R,S)-II-F, and (1R,2R,R)-II-G as the catalyst under the optimized reaction condition. The fine tunable amine/thiourea organocatalysts, relying on multiple hydrogen-binding donors, showed excellent activity, diastereoselectivity, enantioselectivity, and structural scope in asymmetric Michael addition of alpha-substituted beta-ketoesters to nitroolefins.

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Enantioselective addition of diethylzinc to aldehydes catalyzed by titanium(IV) complexes of N-sulfonylated amino alcohols with two stereogenic centers

Bidentate N-sulfonylated amino alcohols with one or two stereogenic centers were prepared and applied as chiral ligands in the titanium(IV)-catalyzed asymmetric addition of diethylzinc to aldehydes, affording excellent enantioselectivities of up to 98% e.e.

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Iron-catalyzed asymmetric intramolecular cyclopropanation reactions using chiral tetramethyl-1,1?-spirobiindane-based bisoxazoline (TMSI-BOX) ligands

The versatile application of chiral bisoxazoline (BOX) ligands in diverse metal-catalyzed asymmetric reactions results in growing demand for novel BOX ligands containing different motifs. Herein, the successful development of a chiral spiro bisoxazoline ligand (TMSI-BOX) on the basis of the tetramethyl-1,1?-spirobiindane motif and bisoxazoline chelating units is described. The corresponding Fe complexes of TMSI-BOX proved to be excellent catalysts in the asymmetric intramolecular cyclopropanation reaction of diazo derivatives, providing synthetically versatile [3.1.0]bicycloalkane derivatives bearing two contiguous quaternary chiral centers with high enantiomeric purity.

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