Discovery of (1S,2S)-Cyclohexane-1,2-diamine

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Racemic and enantiomerically pure titanium(IV) complexes with ortho-bromo-para-methyl-substituted diaminobis(phenolato) ligands were prepared with NH-, NMe-, and bipyrrolidine-based diamino bridges through ligand-to-metal chiral induction. The hydrolytic stability of the complexes was evaluated, and their cytotoxicity was measured using HT-29 human colon cancer cells based on the MTT assay. All stereochemical forms of the NMe-based complexes, although demonstrating the highest hydrolytic stability, were biologically inactive. For the NH and bipyrrolidine-based active complexes, the pure enantiomers exhibited high cytotoxicity whereas the racemic mixtures were inactive, supporting the involvement of a polynuclear active species. The bipyrrolidine complexes appear to provide the best combination of hydrolytic stability and biological activity, presumably by minimizing steric bulk and consequently enabling biological accessibility. Racemic and optically pure phenolato titanium(IV) complexes were prepared with NH, NMe, and bipyrrolidine-based diamino bridges. The optically pure bipyrrolidine complexes provide the best combination of hydrolytic stability and biological activity, presumably by maintaining small enough steric bulk to enable biological accessibility.

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Polarized ketene dithioketals have been recognized as useful building blocks in many synthetic operations. In this work, a transition-metal-free annulations of 1,1-bis(thiomethyl)-2-nitroethylene with hydroxylalkylamines or alkyldiamines have been reported. This methodology provides a directed approach to N-heterocycles, e.g., imidazolidines, oxazolidines and benzoxazoles under microwave conditions. These compounds were evaluated as acetylcholinesterase inhibitors by using an enzyme immobilized capillary reactor-tandem mass spectrometry.

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Racemic as well as enantiomerically pure trans-1,1?-(cyclohexane-1,2-diyl)bis(imidazole N-oxides) were prepared from trans-cyclohexane-1,2-bis(methylidenamine) and 1,2-dione monooximes (alpha-hydroxyiminoketones). The enantiomeric purity of selected products was determined by means of 1H NMR spectroscopy in the presence of (+)-(R)-(tert-butyl)(phenyl)phosphonothioic acid as a chiral solvating agent. Deoxygenation by treatment with Raney-nickel led to the corresponding chiral bis-imidazoles.

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trans-1,2-Diaminocyclohexane functionalized mesoporous silica was applied as an ideal catalyst for asymmetric Michael addition of various nitroalkane derivatives. Short channels and plugs in the pore structure offered chiral enhancement in Michael addition. The Royal Society of Chemistry 2012.

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(Chemical Equation Presented) The 1,1?-binaphthyl macrocycle (S)-2 is found to be an excellent catalyst for the alkyne addition to aldehydes. In the presence of (S)-2 (20 mol %) and Me2Zn (2 equiv) in THF at room temperature, the addition of phenylacetylene to linear or branched aliphatic aldehydes and vinyl aldehydes gave various propargylic alcohols with 89-96% ee.

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A novel and efficient Zinc-catalyzed C?O cross-coupling reaction have been developed using phenols with activated iodoarenes to afford diaryl ether derivatives in moderate to good yields under moderate reaction conditions. The reaction proceeds through an in situ generated Zn/L-proline complex. The use of relatively nontoxic and ecofriendly Zn, cheap and easily available amino acid ligand L-proline makes a better alternative for the synthesis of diaryl ethers. The main advantage of our protocol is that we could activate a d10 metal for the cross-coupling reaction. The scope and limitations of this protocol are also investigated.

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Synthesis, crystal structure and spectra properties of enantiopure and corresponding racemic Cu(II)-dipyridine amido complexes are reported. The different coordination styles result in the unexpected chiral-unrelated color changes between chiral and racemic complexes.

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New macrocyclic dinucleating ligands have been easily synthesized by Schiff-base condensation reaction with the appropriate aldehyde and amine using the boric ion template method. The ligands have two N2O2 metal-binding sites which are doubly linked to each other with methylene spacers. The ligands chelate with Co2+, Cu2+ and Ni2+ to form dimetallic compounds in high yields.

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Chiral metal-organic frameworks have attracted interest for enantioselective separations and catalysis because of their high crystallinity and pores with tunable shapes, sizes, and chemical environments. Chiral frameworks of the type M2(dobpdc) (M = Mg, Mn, Fe, Co, Ni, Zn; dobpdc4- = 4,4?-dioxidobiphenyl-3,3?-dicarboxylate) seem particularly promising for potential applications because of their excellent stability, high internal surface areas, and strongly polarizing open metal coordination sites within the channels, but to date these materials have been isolated only in racemic form. Here, we demonstrate that when appended with the chiral diamine trans-1,2-diaminocyclohexane (dach), Mg2(dobpdc) adsorbs carbon dioxide cooperatively to form ammonium carbamate chains, and the thermodynamics of CO2 capture are strongly influenced by enantioselective interactions within the chiral pores of the framework. We further show that it is possible to access both enantiomers of Mg2(dobpdc) with high enantiopurity (?90%) via framework synthesis in the presence of varying quantities of d-panthenol, an inexpensive chiral induction agent. Investigation of dach-M2(dobpdc) samples following CO2 adsorption – using single-crystal and powder X-ray diffraction, solid-state nuclear magnetic resonance spectroscopy, and density functional theory calculations – revealed that the ammonium carbamate chains interact extensively with each other and with the chiral M2(dobpdc) pore walls. Subtle differences in the non-covalent interactions accessible in each diastereomeric phase dramatically impact the thermodynamics of CO2 adsorption.

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By utilizing the oxygen bridge in dimeric mu-oxo-titanium-salen complexes as an efficient cross-linkage, a series of robust chiral titanium coordination assemblies has been successfully fabricated with the ditopic bridging ligands derived from BINOL and salen derivatives via coordination polymerization, which are fully characterized by IR, elemental analysis, XRD and microscopic studies. Because of their insolubility in most organic solvents and water, these metal-organic assemblies can successfully function as robust self-supported chiral catalysts, allowing an asymmetric ring opening (ARO) of meso-epoxides with aliphatic amines. Remarkably, owing to the linkage effects and the cooperation of two kinds of chiral titanium moieties in the metal-organic assemblies, the self-supported chiral catalysts demonstrate extremely high stability. They not only show high tolerance towards various meso-epoxides and nucleophilic aliphatic amines, but also can be reused in more than 20 runs without obvious metal leaching and loss in yields and enantioselectivities. Furthermore, the self-supported catalyst accomplished a one-pot tandem olefin epoxidation and ARO of an epoxide sequence starting from the olefin, 30% hydrogen peroxide and benzylamine. In marked contrast, the reaction failed to work when using the two corresponding homogeneous catalysts under identical reaction conditions. Good yields and enantioselectivities were obtained by the robust self-supported catalyst, which clearly indicates the cooperative effects between two chiral moieties within the metal-organic assemblies. The two catalytic centers can perform their own duties without interference and this further supports our strategy for the self-supported catalyst design. (Figure presented.).

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