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An enantioselective electrophilic amination of 3-substituted-2-oxindoles is reported, using bis(2,2,2-trichloroethyl)azo-dicarboxylate and commercially available Cinchona alkaloid organocatalysts. The best results were obtained in the reaction of 3-aryl substrates, with high to excellent yields (75% to quantitative) and good stereoselectivity (64?77% ee). Facile reductive conversion of the protected 3-hydrazino fragment into the corresponding primary amine was also demonstrated, to expand the synthetic flexibility of asymmetric electrophilic amination with azo-dicarboxylic esters en route to enantioenriched 3-amino-2-oxindoles. The absolute configuration of 3-amino-3-phenyl-2-oxindole was independently established by electronic circular dichroism (ECD), combined with time-dependent density functional theory (TDDFT).

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A catalytic enantioselective synthesis of alpha-arylaminocyclobutanones from racemic alpha-hydroxycyclobutanone and a selection of N-alkylanilines has been established, via a tandem condensation/keto-enol tautomerization process reminiscent of the Amadori and Heyns rearrangements.

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alpha-exo-Methylene-gamma-butyrolactones and alpha-exo-methylene-delta-valerolactones constitute an important group of natural and bioactive products. An enantioselective halolactonization of dienoic acids using (DHQD)2PHAL catalyst is described. Various halogenated alpha-exo-methylene-gamma-butyrolactones and alpha-exo-methylene-delta-valerolactones were obtained in high yields and enantioselectivities. The resulting enantioenriched halogenated alpha-exo-methylene-lactones were found to exhibit significant tumor-inhibiting activities. (Figure presented.).

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Six highly enantiopure analogues of [2.2.2] were synthesized with five- or seven-membered rings in the (original) quinuclidine skeleton. Five of these compounds were prepared through epoxide opening by a secondary cyclic amine, providing the nor- and homoquinuclidine moieties through five- and six-membered ring formation. This method failed in the case of seven-membered ring formation, so for that particular ring size a different synthetic route starting from 3-quinuclidone was applied. The six novel analogues were examined as organocatalysts in four asymmetric conjugate addition reactions and the results compared with those of known cinchona alkaloid catalysts. This study shows that modification of the quinuclidine ring can have a substantial influence on catalyst activity and enantioselectivity. To acquire more insight into the characteristics of the new catalysts, the pKaHvalues were determined by means of fluorescence spectroscopy. Furthermore, relative reaction rates of conjugate thiol additions reactions catalyzed by these quinidine analogues were measured through polarimetry.

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Chiral Catalysts,
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(2R,3R,4S)-4-Amino-2,3-dihydroxyheptane-1,7-dioic acid, a common component of cyclic depsipeptide homophymines with anti-HIV activity, was synthesized as its orthogonally protected derivative from Fmoc-Glu(t-Bu)-OH in 6 steps. Osmium-catalyzed dihydroxylation of gamma-amino-Z-alpha,beta-unsaturated esters gave the dihydroxy esters with moderate diastereoselectivity. The stereochemistries of the amino acidswere determined by comparison of 1H NMR spectra.

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Two key improvements in the osmium-catalyzed asymmetric dihydroxylation have led to a simple procedure which is applicable to a wide range of olefins.

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A catalytic asymmetric brominative dearomatization reaction of benzofuran derivatives was achieved by using hydroquinidine 1,4-phthalazinediyl diether [(DHQ)2PHAL] as the catalyst and N-bromoacetamide (NBAc) as the brominating reagent. A series of brominated spiro[benzofuran-2,5?-oxazoles] bearing two contiguous stereogenic centers were obtained in high yields (up to 99%) with excellent enantioselectivity (up to 97% ee).

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Hydroquinine 2,5-diphenyl-4,6-pyrimidinediyl diether [(DHQ)2Pyr] catalyzed the regio-, diastereo-, and enantioselective addition of 4-substituted pyrazolones to isatin-derived nitroalkenes, providing a variety of chiral alkenylpyrazolone adducts containing a tetrasubstituted stereocenter bearing an oxindole moiety with excellent yields, regioselectivity, and diastereoselectivity, as well as a moderate enantioselectivity (up to 98 % yield, > 20:1 E/Z ratio dr and 78 % ee). The reaction harnesses a nitroalkene as an alkenylating agent through a Nucleophilic Vinylic Substitution (SNV) reaction.

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A new asymmetric synthesis of bicyclic pyrazolidinones through an alkaloid-catalyzed formal [3 + 2] cycloaddition of in situ generated ketenes and azomethine imines is described. The products were formed in good to excellent yields (52-99% for 17 examples), with good to excellent diastereoselectivity (dr 5:1 to 27:1 for 11 examples), and with excellent enantioselectivity in all cases (?96% ee). This method represents the first unambiguous example of an enantioselective reaction between ketenes and a 1,3-dipole.

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Enantioselective, desymmetrizing bromolactonization of alkynes

Asymmetric bromolactonizations of alkynes are possible using a desymmetrization approach. The commercially available catalyst (DHQD) 2PHAL promotes these cyclizations in combination with cheap NBS as a bromine source to give bromoenol lactones in high yield and with high enantioselectivity. The bromoenol lactone products, containing a tetrasubstituted alkene and a quaternary stereocenter, are valuable building blocks for synthetic chemistry.

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Chiral Catalysts,
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