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A concise synthesis of highly functionalized dihydroquinolinones with excellent diastereoselectivities and enantioselectivities by sequential organocatalytic Michael—hemiaminalization/oxidation reactions under mild reaction conditions is presented.

Michael adducts [(III) and (V)] are synthesized in good yields and high enantioselectivities using a hydroquinine-based primary amine as catalyst.

A novel selective fluorination reaction of aromatic and olefinic ketoximes is developed using NSFI as fluorine source in the presence of a Pd-catalyst and KNO3 or AgNO3 as co-catalyst.

The reaction allows the formation of xanthenones and chromans with three contiguous stereocenters with high to excellent enantioselectivity and moderate to mostly excellent diastereoselectivity.

The organocatalytic Michael reaction of ketones with γ-monohalonitrodienes catalyzed by chiral prolinethiol ether under solvent-free conditions was developed. The described method represents a novel approach for accessing highly functionalized monohaloalkenes with α, β-stereocenters of up to >99% ee.

Novel SO 3 H-functionalized ionic liquids were successfully applied as catalysts for one-pot Fischer indole synthesis under microwave irradiation and in a water medium. Various types of indoles were prepared using single-carbonyl ketones/aldehydes or cyclohexandiones with aryhydrazine hydrochlorides in 86–96% yields in water under microwave irradiation. The indole products could be conveniently separated from the reaction mixture through filtration, and the catalytic system of [(HSO 3 -p) 2 im][CF 3 SO 3 ]/H 2 O could be reused directly without any treatment. The entire process is simple, time saving, and environmentally friendly.

Vinylation of benzylic C—H bond is achieved using a wide range of heterocyclic compounds as quinoxalines, quinolines, pyrazines and pyridines and DMA as a carbon source.

An efficient, organocatalytic enantioselective addition of cyclic diketones with β,γ-unsaturated α-keto esters has been developed that affords products in high yields (up to 95 %) and excellent enantioselectivity (up to >99 % ee) under mild conditions with a low catalyst loading (2.5 mol-%). The unsaturated α-keto esters are effectively coordinated and activated through hydrogen bonds with the squaramides and proved to be excellent hydrogen-bond acceptors in this asymmetric organocatalytic reaction. This reaction provides valuable and easy access to chiral Michael adducts, which are important moieties in the skeletons of biological and pharmaceutical molecules.

Cinchona-derived squaramide is an efficient catalyst for the asymmetric Michael addition of 1,3-dicarbonyl compounds to nitroolefins under solvent-free conditions.

A highly efficient organocatalytic synthesis of lapachol analogues from the Michael addition of naphthoquinone to various α,β-unsaturated ketones catalyzed by primary amines is presented. Good to high yields (up to 93 %) and high to excellent enantioselectivities (up to 98 % ee) were obtained for the target compounds. MS (ESI) provided evidence for the key intermediates in the proposed mechanism.

The first example of palladium-catalyzed direct ortho-nitration of aryl C—H bonds is presented.

An organocatalytic domino thia-Michael/ aldol condensation reaction of α, β-unsaturated aldehydes with 1, 4-dithiane-2,5-diol catalyzed by chiral diphenylprolinol TMS ether has been developed, which provides a new practical and direct route to chiral dihydrothiophenes with high yields (up to 90%) and excellent enantioselectivities (up to>99% ee). The catalytic mechanism of the domino reaction was further confirmed through the APCI-MS detection of proposed reaction intermediates.

The title reaction is catalyzed by a readily available cinchona-derived squaramide at low loading.

The structure of the chiral thioureido acid is optimized to give the Michael adducts, e.g. (III), (V) or (VII), in up to 98% d.e.

The first highly enantioselective organocatalytic Michael addition of 4-hydroxycoumarins is reported.

A highly enantioselective Michael reaction of aromatic ketones with nitroolefins was accomplished in the presence of a chiral bifunctional primary amine―thiourea catalyst and 4-nitrobenzoic acid as the co-catalyst; the corresponding adducts were obtained in excellent enantioselectivities (up to 99 % ee) and yields (up to 98 %). The catalytic mechanism of the Michael reaction was confirmed through the ESI-MS detection of proposed reaction intermediates and the 1 H NMR detection of hydrogen bonding between thiourea and the nitroolefins. DFT calculations showed that chiral moieties of the thiourea impacted the yields and enantioselectivities of the adducts remarkably, which corresponds to the observed experimental results.

Generally, amine-catalyzed enantioselective transformations rely on chiral enamine or unsaturated iminium intermediates. Herein, we report a protocol involving dual activation by an aromatic iminium and hydrogen-bonding. An enantioselective aza-Michael–Henry domino reaction of 2-aminobenzaldehydes with nitroolefins has been developed through this protocol using primary amine thiourea catalysts to provide a variety of 3-nitro-1,2-dihydroquinolines in moderate yields and with up to 90 % ee. The mechanism for the catalytic enantioselective reaction was confirmed by ESI mass spectrometric detection of the reaction intermediates. The products formed are substructures found in skeletons of important biological and pharmaceutical molecules.

The asymmetric tandem oxa-Michael-aldol reaction of salicylic aldehyde derivatives with α,β-unsaturated aldehydes catalyzed by a chiral amine/chiral acid organocatalytic system was investigated. The organocatalytic system of (S)-diphenylpyrrolinol trimethylsilyl ether with chiral shift reagent (S)-Mosher acid presented a synergistic effect in the improvement of reaction performance and offered an efficient steric effect in the transformation. The tandem oxa-Michael-aldol reaction proceeded with high yields (up to 90%) and with excellent ee values (up to 99%) to give the corresponding chromene derivatives. The structure of the chiral ammonium salt formed in situ and the corresponding mechanism were also studied by 1H NMR.

Novel SO3H-functionalized ionic liquids bearing two alkyl sulfonic acid groups in the imidazolium cations were designed and successfully applied as catalysts for the one-pot Fischer indole synthesis in water medium. The sequence of the catalytic activity observed in the transformation was in good agreement with the Bronsted acidity order determined by the Hammett method. Various types of indoles from single-carbonyl ketones/aldehydes and cyclohexandiones were provided in 68–96% yields using the catalytic system of [(HSO3-p)2im][HSO4]/H2O. The indole products could be conveniently separated from the reaction mixture by filtration and the dissolved catalyst could be regenerated by treatment with a strongly acidic cation exchange resin, which meant the whole process was performed in water without using any organic solvents.

Tiefsee-Diels-Alder-Reaktion: Die asymmetrische organokatalytische Diels-Alder-Reaktion zwischen Cyclohexenonen und aromatischen Nitroolefinen gelingt in Meerwasser und gesattigter Kochsalzlosung. Die Reaktion verlauft als saurekatalysierte Enaminaktivierung uber eine einstufige konzertierte Addition (siehe Schema).

An enantioselective oxa-Michael-Henry reaction of substituted salicylaldehydes with nitroolefins that proceeds though an aromatic iminium activation (AIA) has been developed by using a chiral secondary amine organocatalyst and salicylic acid as a co-catalyst. The corresponding 3-nitro-2H-chromenes were obtained in moderate-to-good yields with up to 91% ee under mild conditions. Based on the experimental results and ESI-mass spectrometric detection of the intermediates, a plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.

A novel and effective organocatalytic system consisting of pyrrolidinyl-thioimidazole and a chiral thioureido acid efficiently catalyzed the asymmetric Michael addition reactions of ketones to nitroolefins to afford the adducts with high diastereoselectivities (up to 99 : 1) and excellent enantioselectivities (up to 99% ee).

A series of trisubstituted alkenes containing (Z)-allylthio moieties as key structural units, that is, sodium (Z)-allyl thiosulfates, symmetrical di(Z-allyl) sulfides, and di(Z-allyl) disulfides, unsymmetrical diallyl sulfides were prepared in moderate to good yields via chemical transformations from the acetates of Baylis--Hillman adducts. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:188–198, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20394

The direct asymmetric Michael addition of ketones to nitroolefins catalyzed by 2-[(imidazol-2-ylthio)methyl]pyrrolidine, constructed from natural L-proline and imidazolylthio platforms, with salicylic acid as a co-catalyst has been developed to give the products in high yields (up to 95 %) and with excellent enantioselectivities (up to 99 % ee). The highly efficient catalytic performance may be attributed to the dual activation of the Michael substrates by the trifunctional organocatalysts and the co-catalyst salicylic acid, leading to the formation of a stable transition state complex through the synergic effect of hydrogen-bonding and electrostatic interactions. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Selective formation of (2E)‐2‐methylalk‐2‐enoates or 2‐methyl alkanoates could be achieved in moderate to good yields under mild conditions via Sm/HOAc/EtOH system–mediated reduction of Baylis–Hillman acetates depending on the amount of samarium consumed in the reactions.

Asymmetric Michael addition reactions of unmodified ketones to nitroalkenes were performed in PEGs catalyzed by novel pyrrolidinyl-thioimidazolium salts to give products in up to 97% yield and 99% enantioselectivity; ESI mass spectrometric detection for the first time gave evidence of the presence of the PEG-organocatalyst host-guest complex.

A three‐component asymmetric Mannich reaction of isovaleraldehyde, methyl ketones, and aromatic amines was efficiently synergistic catalyzed by amide‐task‐specific ionic liquids (AILs)/L‐proline under mild conditions. The corresponding asymmetric Mannich reaction adducts were obtained in moderate to high yields and stereo selectivity in all the cases tested. The product was easily isolated, and the remaining catalysis system can be readily recovered and reused at least three times without significant loss of catalytic activity and selectivity.

A novel class of pyrrolidine–pyridinium based organocatalysts has been developed and demonstrated to efficiently catalyze the asymmetric Michael addition reactions of unmodified cyclohexanone to nitroalkenes in the ionic liquid BMImBF 4 with up to 95% yield and nearly 100% ee. The catalytic system could be reused for four times and still retained high enantioselectivity. X-ray crystallographic analysis results suggested that a sterically hindered pyridinium moiety on the catalyst played an important role in the chiral induction.

A novel one-pot Fischer indole synthesis approach has been developed by using Bronsted acidic ionic liquids as dual solvent-catalysts. Yields of 83–97 % were obtained after reaction in BMImHSO4 at 70–110 °C in 0.5–6 h, and exclusive formation of 2,3-disubstituted indoles was observed in the reaction of alkyl methyl unsymmetrical ketones. The indoles produced could be conveniently separated from the reaction mixture without any volatile organic solvents, and the BMImHSO4 could be readily reused without efficiency loss after simple treatment involving only 1 equiv. of HCl for neutralization followed by filtration.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

(2004). WILLIAMSON REACTION IN IONIC LIQUIDS. Organic Preparations and Procedures International: Vol. 36, No. 2, pp. 156-161.