An asymmetric normal-electron-demand aza-Diels-Alder reaction via trienamine catalysis.

An asymmetric normal-electron-demand aza-Diels-Alder cycloaddition of 2-aryl-3H-indol-3-ones and 2,4-dienals was explored via trienamine catalysis of a chiral secondary amine. Multifunctional tricyclic polyhydropyrido[1,2-a]indoles were efficiently constructed in good stereoselectivity (up to 92% ee, >19 : 1 dr).

An asymmetric allylic alkylation-Smiles rearrangement-sulfinate addition sequence to construct chiral cyclic sulfones.

An asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates and ß-keto sulfones was investigated by the catalysis of modified cinchona alkaloids, whose products underwent a Smiles rearrangement-sulfinate addition cascade to furnish highly functionalized five-membered cyclic sulfones in moderate to excellent enantioselectivity and good diastereoselectivity after treatment with DBU.

Membranes and membrane processes for chiral resolution.

This critical review is devoted to an active field of research on chiral separation, membrane-based enantioseparation technique, which has potential for large-scale production of single-enantiomer compounds. Adsorption-type enantioselective membranes and membrane-assisted resolution systems with non-enantioselective solid membranes have attracted much attention recently. The principles and recent developments of both enantioselective liquid and solid membranes and membrane-assisted processes for chiral resolution will be summarized comprehensively in this review, in which the contents are of interest to a wide range of readers in a variety of fields from analytical, organic and medicinal chemistry, to pharmaceutics and materials, to process engineering for fabricating pharmaceuticals, agrochemicals, fragrances and foods, and so on (148 references).

Efficient method for the synthesis of polysubstituted benzenes by one-pot tandem reaction of vinyl malononitriles with nitroolefins.

The one-pot synthesis of polysubstituted benzene derivatives was achieved via vinylogous Michael addition of vinyl malononitriles and nitroolefins as the key step and a sequential tandem reaction. A series of complex aryl compounds such as biphenyls and terphenyls can be obtained with satisfactory yields.

Highly enantioselective michael addition of cyclic 1,3-dicarbonyl compounds to alpha,beta-unsaturated ketones.

[reaction: see text] The highly enantioselective Michael addition of 1,3-cyclic dicarbonyl compounds to alpha,beta-unsaturated ketones was reported to be catalyzed by an organic primary amine derived from quinine. A chiral anticoagulant drug, (S)-warfarin, was directly prepared in 96% ee, and other related important adducts were also obtained in excellent enantioselectivity (89-99% ee).

Asymmetric transfer hydrogenation catalysed by hydrophobic dendritic DACH-rhodium complex in water.

Hydrophobic Fréchet-type dendritic chiral 1,2-diaminocyclohexane-Rh(III) complexes have been applied in the asymmetric transfer hydrogenation of ketones in water using HCOONa as hydrogen source. The catalysts were found to be finely dissolved in the liquid substrates in the aqueous mixture and exhibited high catalytic activity and enantioselectivity (52-97% ee). The catalytic loading could be decreased to 0.01 mol% and good conversion was still obtained with excellent enantioselectivity. Moreover, the catalyst could be easily precipitated from the mixture by adding hexane and reused several times without affecting the high enantioselectivity.

Organocatalytic and direct asymmetric vinylogous Michael addition of alpha,alpha-dicyanoolefins to alpha,beta-unsaturated aldehydes.

The first highly regio-, chemo-, diastereo- and enantioselective direct vinylogous Michael addition of alpha,alpha-dicyanoolefins to alpha,beta-unsaturated aldehydes is described, employing readily available chiral alpha,alpha-diarylprolinol salts as iminium organocatalysts.

Copper(II)-mediated resolution of alpha-halo carboxylic acids with chiral O,O'-dibenzoyltartaric acid: spontaneous racemization and crystallization-induced dynamic resolution.

Herein we present a new example of coordination-mediated resolution of racemic acids by a chiral acid. The reaction of copper(II) acetate monohydrate, optically pure O,O'-dibenzoyltartaric acid (DBTA) and racemic alpha-bromo-2-chlorophenylacetic acid (HL1) in acetonitrile solution afforded a binuclear copper(II) complex with D-DBTA dianion, alpha-bromo-2-chlorophenylacetate and acetate as ligands. After decomposition of the complex with acid, the optically active acid ((R)-HL1) was obtained. Similarly, alpha-bromo-2-fluorophenylacetic acid (HL2), alpha-bromo-2-bromophenylacetic acid (HL3), alpha-chloro-2-chlorophenylacetic acid (HL4), alpha-chloro-2-fluorophenylacetic acid (HL5), alpha-bromophenylacetic acid (HL6), alpha-bromo-4-chlorophenylacetic acid (HL7), 2-bromopropionic acid (HL8) and 2-chloropropionic acid (HL9) were resolved by the same method. Satisfactory results were obtained for HL2 to HL5. For HL6 and HL7, only racemic acids were obtained. For the two alpha-halo aliphatic acids (HL8 and HL9), poor enantioselectivity was obtained. It is more interesting that three acids (HL1, HL2 and HL3) could spontaneously racemize in acetonitrile solution, which resulted in crystallization-induced dynamic resolution (CIDR) with greater than 50% yield.

Asymmetric direct vinylogous Michael reaction of activated alkenes to nitroolefins catalyzed by modified cinchona alkaloids.

[reaction: see text] The first organocatalytic and asymmetric direct vinylogous Michael reaction that employs the electron-deficient vinyl malononitriles as the nucleophilic species has been reported. The novel transformations exhibit exclusive gamma-selectivity and high diastereo- and enantioselectivity in the addition to nitroolefins, which give the multifunctional products with two vicinal chiral centers.

Transfer hydrogenation of activated C=C bonds catalyzed by ruthenium amido complexes: reaction scope, limitation, and enantioselectivity.

[reaction: see text] It was found that the chemoselectivity could be completely switched from C=O to C=C bonds in the transfer hydrogenation of activated alpha,beta-unsaturated ketones catalyzed by diamine-ruthenium complex. Moreover, this addition via metal hydride had been applied to the reduction of various activated olefins. The electron-withdrawing ability of functional groups substituted on C=C bonds at the alpha- or beta-position had strong influence on the reactivity. In addition, a wide variety of chiral diamine-Ru(II)-(arene) systems was investigated to explore the asymmetric transfer hydrogenation of prochiral alpha,alpha-dicyanoolefins. Two parameters had been systematically studied, (i) the structure of the N-sulfonylated chiral diamine ligands, in which several chiral diamines substituted on the benzene ring of DPEN were first reported, and (ii) the structure of the metal precursors, and high enantioselectivitiy (up to 89% ee) at the beta-carbon was obtained.

Synthesis of dendritic catalysts and application in asymmetric transfer hydrogenation.

Frechet-type core-functionalized chiral diamine-based dendritic ligands and hybrid dendritic ligands condensed from polyether wedge and Newkome-type poly(ether-amide) supported multiple ligands were designed and synthesized. The solubility of hybrid dendrimers was found to be finely controlled by the polyether dendron. The catalytic efficiency and recovery use of dendritic ruthenium complexes were compared in the transfer hydrogenation of acetophenone. The core-functionalized dendritic catalysts demonstrated much better recyclability, which verified the stabilizing effects of the bulky polyether wedge on the catalytically active complex. Moreover, the dendritic catalysts were applied in the asymmetric transfer hydrogenation of ketones, enones, imine, and activated olefin, and moderate to excellent enantioselectivitiy was achieved comparable to that of monomeric catalysts.

Highly efficient and recyclable heterogeneous asymmetric transfer hydrogenation of ketones in water.

A highly efficient heterogeneous asymmetric transfer hydrogenation of ketones in water was developed for the first time, which exhibited excellent enantioselectivities, distinct acceleration effect and remarkably high recyclabilities.

Multiple dendritic catalysts for asymmetric transfer hydrogenation.

The first and second generation multiple dendritic ligands based on chiral diamine were synthesized in a convergent approach and were well-characterized by NMR and MS techniques. Their ruthenium complexes prepared in situ had good solubility in the reaction medium (azeotrope of formic acid and triethylamine) and demonstrated high catalytic activity and enantioselectivity comparable to monomeric catalysts in the asymmetric transfer hydrogenation of ketones and imines. Quantitative yields and for some cases a slightly higher enantioselectivity (up to 98.7% ee) were obtained in the dendritic catalysis. Considering the high local catalyst concentrations at the periphery, diones were tested for the possible synergic reactivity between catalytic units at the surface, while no apparent differences were noted.

Enhanced in vivo activity of peptidase-resistant analogs of the insect kinin neuropeptide family.

The diuretic/myotropic insect kinin neuropeptides, which share the common C-terminal pentapeptide core FX(1)X(2)WG-NH(2), reveal primary (X(2)-W) and secondary (N-terminal to F) sites of susceptibility to peptidases bound to corn earworm (H. zea) Malpighian tubule tissue. Analogs designed to enhance resistance to tissue-bound peptidases, and pure insect neprilysin and ACE, demonstrate markedly enhanced in vivo activity in a weight gain inhibition assay in H. zea, and strong in vivo diuretic activity in the housefly (M. domestica). The peptidase-resistant insect kinin analog pQK(pQ)FF[Aib]WG-NH(2) demonstrates a longer internal residence time in the housefly than the native muscakinin (MK), and despite a difference of over 4 orders of magnitude in an in vitro Malpighian tubule fluid secretion assay, is equipotent with MK in an in vivo housefly diuretic assay. Aminohexanoic acid (Ahx) is shown to function as a surrogate for N-terminal Lys, while at the same time providing enhanced resistance to aminopeptidase attack. Peptidaese-resistant insect kinin analogs demonstrate enhanced inhibition of weight gain in larvae of the agriculturally destructive corn earworm moth. Potent peptidase resistant analogs of the insect kinins, coupled with an increased understanding of related regulatory factors, offer promise in the development of new, environmentally friendly pest insect control measures.