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Water versus solvent-free conditions for the enantioselective inter- and intramolecular aldol reaction employing l-prolinamides and l-prolinethioamides as organocatalysts

Organocatalysts 1, derived from L-proline and (1S,2R)-cis-l-aminoindan-2-ol or (R)-l-aminoin-dane, are evaluated as promoters in the direct asymmetric aldol reaction between ketones and aromatic aldehydes in the presence of water and under solvent-free reaction conditions. L-Prolinethioamides 1c and 1d exhibited higher enantioselectivity than the corresponding prolinamides 1a and 1b in the model aldol reaction between cyclohexanone and 4-nitro-benzaldehyde in the presence of 4-nitrobenzoic acid as cocatalyst. In particular, L-prolinethioamide 1d (5 mol%), derived from L-proline and (R)-1-amino-indane, is shown as the most efficient organocatalyst studied promoting the direct aldol reaction of cyclo-alkyl, alkyl, and a-functionalized ketones with aromatic aldehydes in the presence of water and under solvent-free reaction conditions employing only 2 equivalents of nucleophile. Generally, anft-aldol products are obtained in high yields and excellent diastereo- and enantioselectivities (up to > 98/2 until syn, up to 98% ee). Solvent-free conditions give slightly higher dr and ee than using water as solvent. In addition, organocatalyst Id can be easily recovered by extractive work-up and reused. Prolinethio-amide Id (5 mol%) in combination with 4-NO2C6H4CO2H (5 mol%) is also a very effective or-ganocatalytic system for the asymmetric solvent-free intramolecular Haj os-Parrish-Eder-Sauer-Wiechert reaction with comparable or higher levels of enantioselectivity (up to 88% ee) to other reported catalysts in organic solvents.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Fluoride anion recognition by a multifunctional urea derivative: An experimental and theoretical study

In this work we demonstrate the ability of a multifaceted N,N?-disubstituted urea to selectively recognize fluoride anion (F?) among other halides. This additional function is now added to its already reported organocatalytic and organogelator properties. The signaling mechanism relies on the formation of a charge-transfer (CT) complex between the urea-based sensor and F? in the ground state with a high association constant as demonstrated by absorption and fluorescence spectroscopy. The nature of the hydrogen bonding interaction between the sensor and F? was established by 1H-NMR studies and theoretical calculations. Moreover, the recovery of the sensor was achieved by addition of methanol.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Divergent Synthesis of Chiral Covalent Organic Frameworks

Featuring the simultaneous generation of a library of compounds from a certain intermediate, divergent synthesis has found increasing applications in the construction of natural products and potential medicines. Inspired by this approach, presented herein is a general strategy to introduce functionality, in a divergent manner, into covalent organic frameworks (COFs). This modular protocol includes two stages of covalent assembly, through which functional COFs can be constructed by a three-step transformation of a key platform molecule, such as 4,7-dibromo-2-chloro-1H-benzo[d]imidazole (DBCBI). Constructed herein are four types of chiral COFs (CCOFs) from DBCBI by nucleophilic substitution, Suzuki coupling, and imine formation. The unique array of eight isoframework CCOFs allowed investigation of their catalytic performance and structure?activity relationship in an asymmetric amination reaction.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Stereoselective dioxygenase-catalysed benzylic hydroxylation at prochiral methylene groups in the chemoenzymatic synthesis of enantiopure vicinal aminoindanols

Enantiopure benzylic alcohols containing two stereogenic centres in a cis- relationship result from stereoselective monohydroxylation of achiral 2- substituted indans in cultures of Pseudomonas putida UV4 and are used in the chemoenzymatic synthesis of both cis- and trans-aminoindanol enantiomers.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

Archives for Chemistry Experiments of (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol

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Development of a scalable synthesis of a GPR40 receptor agonist

Early process development and salt selection for AMG 837, a novel GPR40 receptor agonist, is described. The synthetic route to AMG 837 involved the convergent synthesis and coupling of two key fragments, (S)-3-(4-hydroxyphenyl) hex-4-ynoic acid (1) and 3-(bromomethyl)-4?-(trifluoromethyl)biphenyl (2). The chiral beta-alkynyl acid 1 was prepared in 35% overall yield via classical resolution of the corresponding racemic acid (¡À)-1. An efficient and scalable synthesis of (¡À)-1 was achieved via a telescoped sequence of reactions including the conjugate alkynylation of an in situ protected Meldrum’s acid derived acceptor prepared from 3. The biaryl bromide 2 was prepared in 86% yield via a 2-step Suzuki-Miyaura coupling-bromination sequence. Chemoselective phenol alkylation mediated by tetrabutylphosphonium hydroxide allowed direct coupling of 1 and 2 to afford AMG 837. Due to the poor physiochemical stability of the free acid form of the drug substance, a sodium salt form was selected for early development, and a more stable, crystalline hemicalcium salt dihydrate form was subsequently developed. Overall, the original 12-step synthesis of AMG 837 was replaced by a robust 9-step route affording the target in 25% yield.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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Exploiting molecular self-assembly: From urea-based organocatalysts to multifunctional supramolecular gels

We describe the self-assembly properties of chiral N,N?-disubstituted urea-based organocatalyst 1 that leads to the formation of hierarchical supramolecular gels in organic solvents at low concentrations. The major driving forces for the gelation are hydrogen bonding and pi-pi interactions according to FTIR and 1H NMR spectroscopy, as well as quantum-mechanical studies. The gelation scope could be interpreted based on Kamlet-Taft solvatochromic parameters. TEM, SEM, and AFM imaging revealed that a variety of morphologies including helical, laths, porous, and lamellar nanostructures could be obtained by varying the solvent. Experimental gelation tests and computational structural analysis of various structurally related compounds proved the existence of a unique set of molecular interactions and an optimal hydrophilic/hydrophobic balance in 1 that drive the formation of stable gels. Responses to thermal, mechanical, optical, and chemical stimuli, as well as multifunctionality were demonstrated in some model gel materials. Specifically, 1 could be used for the phase-selective gelation of organic solvent/water mixtures. The gel prepared in glycerol was found to be thixotropic and provided a sensitive colorimetric method for the detection of Ag I ions at millimolar concentrations in aqueous solution. Moreover, the gel matrix obtained in toluene served as a nanoreactor for the Friedel-Crafts alkylation of 1H-indole with trans-beta-nitrostyrene. Multifunctional gels: Urea-based organocatalyst 1 undergoes hierarchical self-assembly in organic solvents that leads to the formation of stable organogels. These materials show multistimuli responsive behaviors and multifunctional properties, including phase-selective gelation of organic solvent/water mixtures, colorimetric sensing of silver ions at millimolar concentrations, and operation as a nanoreactor for indole alkylation (see scheme).

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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In heterogeneous catalysis, catalysts provide a surface to which reactants bind in a process of adsorption. Recommanded Product: 126456-43-7, Name is (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol, belongs to chiral-nitrogen-ligands compound, is a common compound. Recommanded Product: 126456-43-7Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. In an article, authors is Balzano, Federica, once mentioned the new application about Recommanded Product: 126456-43-7.

Thiourea Derivative of 2-[(1 R)-1-Aminoethyl]phenol: A Flexible Pocket-like Chiral Solvating Agent (CSA) for the Enantiodifferentiation of Amino Acid Derivatives by NMR Spectroscopy

Thiourea derivatives of 2-[(1R)-1-aminoethyl]phenol, (1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol, (1R,2R)-(1S,2R)-1-amino-2,3-dihydro-1H-inden-2-ol, and (R)-1-phenylethanamine have been compared as chiral solvating agents (CSAs) for the enantiodiscrimination of derivatized amino acids using nuclear magnetic resonance (NMR) spectroscopy. Thiourea derivative, prepared by reacting 2-[(1R)-1-aminoethyl]phenol with benzoyl isothiocyanate, constitutes an effective CSA for the enantiodiscrimination of N-3,5-dinitrobenzoyl (DNB) derivatives of amino acids with free or derivatized carboxyl functions. A base additive 1,4-diazabicyclo[2.2.2]octane(DABCO)/N,N-dimethylpyridin-4-amine (DMAP)/NBu4OH) is required both to solubilize amino acid derivatives with free carboxyl groups in CDCl3 and to mediate their interaction with the chiral auxiliary to attain efficient differentiation of the NMR signals of enantiomeric substrates. For ternary systems CSA/substrate/DABCO, the chiral discrimination mechanism has been ascertained through the NMR determination of complexation stoichiometry, association constants, and stereochemical features of the diastereomeric solvates.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

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In heterogeneous catalysis, catalysts provide a surface to which reactants bind in a process of adsorption. Product Details of 126456-43-7, Name is (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol, belongs to chiral-nitrogen-ligands compound, is a common compound. Product Details of 126456-43-7Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. In an article, authors is , once mentioned the new application about Product Details of 126456-43-7.

Process for the syntehesis of (2R, 2-alpha-R, 3A) – 2- [1- (3, 5-bis(trifluoromethyl) phenyl) ethoxy] -3- (4-fluorophenyl) -1, 4-oxazine

The present invention is concerned with novel processes for the preparation of (2R, 2-alpha-R, 3a)-2-[1-[3,5-bis(trifluoromethyl)phenyl]ethoxy-3-(4-fluorophenyl)-1,4-oxazine. This compound is useful as an intermediate in the synthesis of compounds which possess pharmacological activity.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

Extracurricular laboratory:new discovery of (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol

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Highly Efficient and Robust Enantioselective Liquid?Liquid Extraction of 1,2-Amino Alcohols utilizing VAPOL- and VANOL-based Phosphoric Acid Hosts

The large-scale production of enantiopure compounds in a cost-effective and environmentally friendly manner remains one of the major challenges of modern-day chemistry. The resolution of racemates through enantioselective liquid?liquid extraction was developed as a suitable solution but has remained largely underused, owing to a lack of highly efficient and robust chiral hosts to mediate the process. This paucity of hosts can in part be attributed to a poor understanding of the underlying principles behind these processes hindering the design of more efficient selectors. A previously untested class of hosts, VAPOL and VANOL derived phosphoric acids, has been studied in depth for the efficient enantioselective liquid?liquid extraction of 1,2-amino alcohols. A systematic investigation of extraction parameters was conducted, revealing many key interactions and DFT calculations illustrate the binding modes for the 1:1 complexes that are involved in chiral recognition. The resulting, now-optimized, procedures are highly robust and easy to implement. They are also easily scalable, as demonstrated by U-tube experiments.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis

Some scientific research about C9H11NO

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In heterogeneous catalysis, catalysts provide a surface to which reactants bind in a process of adsorption. Computed Properties of C9H11NO, Name is (1S,2R)-1-Amino-2,3-dihydro-1H-inden-2-ol, belongs to chiral-nitrogen-ligands compound, is a common compound. Computed Properties of C9H11NOCatalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. In an article, authors is Dorsey, once mentioned the new application about Computed Properties of C9H11NO.

L-735,524: The design of a potent and orally bioavailable HIV protease inhibitor

A series of HIV protease inhibitors possessing a hydroxylaminepentanamide transition state isostere have been developed. Incorporation of a basic amine into the backbone of the L-685,434 (2) series provided antiviral potency combined with a highly improved pharmacokinetic profile in animal models. Guided by molecular modeling and an X-ray crystal structure of the inhibited enzyme complex, we were able to design L-735,524. This compound is potent and competitively inhibits HIV-1 PR and HIV-2 PR with K(i) values of 0.52 and 3.3 nM, respectively. It also stops the spread of the HIV-1(IIIb)-infected MT4 lymphoid cells at concentrations of 25-50 nM. To date, numerous HIV-PR inhibitors have been reported, but few have been studied in humans because they lack acceptable oral bioavailability. L-735,524 is orally bioavailable in three animals models, using clinically acceptable formulations, and is currently in phase II human clinical trials.

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Reference£º
Chiral nitrogen ligands in late transition metal-catalysed asymmetric synthesis¡ªI. Addressing the problem of ligand lability in rhodium-catalysed hydrosilations,
Nitrogen-Containing Ligands for Asymmetric Homogeneous and Heterogeneous Catalysis