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An intramolecular Pauson-Khand reaction of various 3-alkynyl-1-alkylidenecyclic compounds was performed to give the corresponding [5.n.1.1,5] tricyclic compounds (n = 2-4). A facile construction of the core structure in cedrene terpenoids was also investigated in detail and formal total synthesis of alpha- and beta-cedrenes was accomplished.

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Hydroxyl-promoted reductive cyclization of enyne compounds catalyzed by Pd(OAc)2-BBEDA was explored and found to effect constructing the pyrindine framework with the alkylidene appendage. This methodology was applied to the stereoselective synthesis of (-)-4a,5-dihydrostreptazolin.

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A transition metal-free, regioselective C-5 trifluoromethylation of 2,3-dihydropyridin-4(1H)- ones (cyclic enaminones) with trimethyl(trifluoromethyl) silane (TMSCF3) was developed that proceeds under mild conditions at room temperature. This direct transformation was successful with both electron-rich and electron-deficient cyclic enamin- ACHTUNGTRENUNGones. This method bypasses substrate prefunctionalization and transition metal catalysis, and allows the convenient and direct access to a variety of medicinally important 3-trifluoromethylpiperidine derivatives. This chemistry also represents a rare example of a direct trifluoromethylation of an internal olefinic C-H bond. A radical mechanism is proposed for this reaction.

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(R,R)-1,2-Bis(tert-butylsulfinyl)benzene as an efficient and simple ligand can be applied in the rhodium-catalyzed asymmetric 1,4-addition of sodium tetraarylborate reagents to N-substituted 2,3-dihydro-4-pyridones and 4-quinolones. The reactions proceeded smoothly to provide the corresponding adducts in good yields (up to 92%) and excellent enantioselectivities (up to 99%) under mild conditions. (R,R)-1,2-Bis(tert-butylsulfinyl)benzene as a ligand can be applied in the rhodium-catalyzed asymmetric 1,4-addition of sodium tetraarylborates to N-substituted 2,3-dihydro-4-pyridones and 4-quinolones. The reactions proceeded smoothly to provide the corresponding adducts in good yields (up to 92%) and excellent enantioselectivities (up to 99%) under mild conditions. Copyright

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Allylic oxidation of heteroatom substituted cyclic alkenes by tert-butyl hydroperoxide (70% TBHP in water) using catalytic dirhodium caprolactamate [Rh2(cap)4] forms enone products with a variety of 2-substituted cyclic enamides and 3,4-dihyro-2H-pyrans. These reactions occur under mild reaction conditions, are operationally convenient to execute, and are effective for product formation with as low as 0.25 mol% catalyst loading. With heteroatom stabilization of the intermediate allylic free radical two sites for oxidative product formation are possible, and the selectivity of the oxidative process varies with the heteroatom when R = H. Cyclic enamides produce 4-piperidones in good yields when R = alkyl or aryl, but oxidation of 2H-pyrans also gives alkyl cleavage products. Alternative catalysts for TBHP oxidations show comparable selectivities but give lower product yields.

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Compounds of formula (I) 1are novel CNS active agents that are useful for treating pain and for treating other disorders associated with the cholinergic system.

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Eeny, meeny, miny.i? enaminones! Lactams and imides have been shown to consistently provide enantioselectivities substantially higher than other substrate classes previously investigated in the palladium-catalyzed asymmetric decarboxylative allylic alkylation. Several new substrates have been designed to probe the contributions of electronic, steric, and stereoelectronic factors that distinguish the lactam/imide series as superior alkylation substrates (see scheme). These studies culminated in marked improvements on carbocyclic allylic alkylation substrates. Copyright

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Readily available vinyl alanes are used in the Cu-catalyzed asymmetric conjugate addition reaction to N-substituted-2-3-dehydro-4-piperidones. The enhanced reactivity of recently developed and easily prepared phosphine amine ligands in combination with inexpensive Cu(II)naphtenate (CuNp) allows the introduction of a great variety of alkenyl, alkyl, and aryl aluminums in high enantioselectivity.

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Discovery of a series of pyrazolopiperidine sulfonamide based gamma-secretase inhibitors and its SAR evolution is described. Significant increases in APP potency on the pyrazolopiperidine scaffold over the original N-bicyclic sulfonamide scaffold were achieved and this potency increase translated in an improved in vivo efficacy.

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1,3-Disubstituted, enantiopure cyclohexanols have been prepared in very high diastereoselectivities and good yields by a concise one-pot method combining the enantioselective rhodium-catalyzed conjugate addition of arylboronic acids with indium-mediated allylation into a highly efficient one-pot reaction in aqueous media. Wiley-VCH Verlag GmbH & Co. KGaA, 2006.

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