59227-02-0

A novel selective fragmentation of cycloalkanones by NaNO2/HCl has been established. The C-C bond cleavage reaction proceeds smoothly under mild conditions, selectively affording versatile keto acids or oxime acids. The methodology can streamline the synthesis of valuable chiral molecules and isocoumarins from readily available feedstocks.

We have recently reported the strong and confined, chiral acid-catalyzed asymmetric 'silicon-hydrogen exchange reaction'. One aspect of this transformation is that it enables access to enantiopure enol silanes in a tautomerizing σ-bond metathesis, via deprotosilylation of ketones with allyl silanes as the silicon source. However, until today, this reaction has not been applied to racemic, 2-substituted, cyclic ketones. We show here that these important substrates readily undergo a highly enantioselective kinetic resolution furnishing the corresponding kinetically preferred enol silanes. Mechanistic studies suggest the fascinating possibility of advancing the process to a dynamic kinetic resolution.

The present invention relates to an NMDA receptor antagonist and use thereof. The NMDA receptor antagonist is a compound as shown in the formula I, and pharmaceutically acceptable salts, enantiomers, diastereoisomers, tautomers, solvates, isotope substitutes, polymorphic substances, prodrugs or metabolites thereof, and in the formula, ring A, ring B and R2 are as described in the specification. The invention also provides pharmaceutical compositions containing the compounds, and applications of the compounds in preparation of drugs for treating or preventing NMDA receptor mediated diseases.

The invention relates to an aromatic compound, a preparation method and use of the aromatic compound, andspecifically discloses a compound represented by the following formula (I), or a tautomer or anenantiomer or a diastereomer or a racemate of the compound or a mixture of the compound or a pharmaceutically acceptable salt of the compound. The invention further discloses a preparation method ofthe compound and application of the compound in treating nervous systemdiseases.

Ylide-functionalized phosphine (YPhos) ligands allow the palladium-catalyzed α-arylation of alkyl ketones with aryl chlorides with record setting activity. Using a cyclohexyl-substituted YPhos ligand, a wide range of challenging ketone substrates was efficiently and selectively monoarylated under mild conditions. A newly designed YPhos ligand bearing tert-butyl groups on the coordinating phosphorus atom is already active at room temperature. The synthetic potential was demonstrated by gram-scale reactions and the succinct synthesis of ?-caprolactone derivatives.

Regioselective formation of vinylogous acyl sulfonates was accomplished via the allylic oxidation of the corresponding vinyl sulfonates. The reaction progressed through the agency of catalytic iron(III) chloride catalysis with tert-Butyl hydroperoxide (TBHP) as the stoichiometric oxidant. Tolerance of other functional groups, including some other allylic and benzylic sites, was observed.

The enantioselective protonation of silyl enol ethers was realized in the presence of a pentacarboxycyclopenta-1,3-diene-based chiral Bronsted acid catalyst with water as an achiral proton source to give the corresponding α-aryl ketones in good yields and up to 75percent ee.

A three-step sequence for the synthesis of α-arylated cyclohexanones and the most challenging cycloheptanones is reported. First, an efficient one-pot synthesis of β,β'-disubstituted benzylidene cycloalkanes (styrenes) using the palladium-catalyzed Barluenga reaction from readily available feedstock chemicals is described. Furthermore, an epoxidation followed by the House-Meinwald rearrangement (HMR) of spiro-epoxides is reported to produce a number of α-arylated cycloalkanones upon ring expansion. Reactions catalyzed by bismuth triflate underwent quasi-exclusively ring expansion for all substrates (electronically poor and rich), with yields ranging from 15% to 95%, thus demonstrating the difficulty of achieving ring enlargement for electron-deficient spiro-epoxides. On the other hand, by means of catalysis with aluminum trichloride, the rearrangement of spiro-epoxides proceeded typically in high yields and with remarkable regioselectivity on a broader substrate scope. In this case, a switch of regioselectivity was achieved for spiro-epoxides with electron-withdrawing substituents which enable the method to be successfully extended to some chemospecific arene shifts and the synthesis of aldehydes bearing a α-quaternary carbon. While the HMR has been extensively studied for smaller ring enlargement, we are pleased to report herein that larger cyclohexanones and cycloheptanones can be obtained efficiently from more sterically demanding trisubstituted spiro-epoxides bearing electron-releasing and electron-neutral arene substituents.

A p-toluenesulfonic acid catalyzed fluorination of α-branched ketones for the construction of fluorinated quaternary carbon centers has been developed, featuring a broad substrate scope, environmentally benign reaction conditions, and operational simplicity.

The regiocontrolled rearrangement of 1,2-diols has been achieved by controlling the loading of BF3·Et2O. Its applicability is showcased by the divergent synthesis of austrodoral, austrodoric acid, and 8-epi-11-nordriman-9-one, as well as a formal synthesis of siphonodictyal B and liphagal. A new light is shed on piancol-type rearrangements that will be useful in diversity-oriented synthesis of related natural products.

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"Fisching" for complexity: The chiral Bronsted acid (R)-STRIP catalyzes the asymmetric Fischer indolization of a range of monosubstituted cyclopentanones and cyclohexanones to give chiral fused indolines bearing a quaternary stereogenic center at the 3-position. The method has been extended to include substrates bearing a tethered nucleophile, thus allowing for enantioselective indolization/ring-closing cascades to complex propellanes featuring two vicinal quaternary stereocenters. Copyright

In this paper, we present an asymmetric alkylation of modified 2-arylcyclohexanones that employs a novel chiral ammonium bromide as a phase-transfer catalyst and an achiral auxiliary as a controller to improve the enantioselectivity to afford optically enriched products having a chiral quaternary carbon center.

Mineralocorticoid receptor antagonists, of which formula (1) is exemplary.

The application of chiral sulfinamides and achiral sulfonic acids as a cocatalyst system for enantioselective protonation reactions is described. Structurally simple, easily accessible sulfinamides were found to induce moderate-to-high ee's in the formation of 2-aryl-substituted cycloalkanones from the corresponding trimethylsilyl enol ethers.

The α-arylation of ketones with aryl halides catalyzed by the easily prepared and air-stable palladium complex (SIPr)Pd(Py)Cl2 (3) is described. Complex 3 displays high activity for a variety of aryl halides (activated, unactivated, and sterically hindered aryl halides) under mild conditions. Moreover, both aryl and alkyl ketones can be arylated. The α-arylation of some alkyl ketones can even be run at room temperature. The mono- or diarylated products of the unhindered dialkyl ketone 3-pentanone could be controlled by temperature and the ratio of ketones to aryl halides. Palladium-catalyzed α-ketone arylation of aryl and alkyl ketones with aryl halides is described. A total of 31 examples is presented with yields ranging from 45 to 95%.The mono- or diarylated product of the unhindered dialkyl ketone 3-pentanone could be controlled. Copyright

A highly enantioselective organocatalytic oxidative kinetic resolution (OKR) of racemic secondary alcohols has been accomplished using asymmetric organocatalysis. A panel of chirally modified 2-azaadamantane N-oxyls (AZADOs) exhibit superior catalytic act

Screening of the Roche compound library led to the identification of cis-N-(2-phenyl-cyclohexyl)-spiropiperidine 1 as structurally novel GlyT1 inhibitor. The SAR, which was developed in this series, resulted in the discovery of highly potent compounds displaying excellent selectivity against the GlyT2 isoform.

Two new p-alkoxycarbonylated palladium bis(phosphinite) PCP pincer complexes are easily prepared and for the first time evaluated as homogeneous catalysts in α-arylation of ketone enolates. Apart from the total absence of phenyl-aryl exchange by-products and significantly low catalyst loadings, the general α-arylation protocols described in this letter feature not only a broad applicability to a range of ketones and aryl bromides with marked electronic and steric differences but also the possibility to generate mono-diarylated products.

The invention relates to compounds of the general formula (I), wherein A-A is -CH2-CH2-, -CH2-CH2-CH2-, -CH2-0- or -0-CH2-; x is hydrogen or hydroxy; R1 is aryl or heteroaryl, unsubstituted or substituted by one or more substituents, selected from the group consisting of lower alkyl, lower alkoxy, halogen or trifluoromethyl; R2 is aryl or heteroaryl, unsubstituted or substituted by one or more substituents, selected from the group consisting of lower alkyl, lower alkoxy, halogen or trifluoromethyl, or is lower alkyl, -(CH2)n--cycloalkyl, -(CH2)n-CF3, -(CH2)p-0-lower alkyl, -(CH2)1,2-phenyl, optionally substituted by halogen, lower alkyl, lower alkoxy or trifluoromethyl, or is -(CH2)p-NRR", wherein W and R" form together with the N-atom a heterocyclic ring, selected from the group consisting of piperidine, morpholine, thiomorpholine or 1, I-dioxo thiomorpholine; R3, R4 are independently from each other hydrogen, lower alkyl, phenyl or benzyl; R5 is hydrogen, lower alkyl or benzyl; R6 is hydrogen or lower alkyl; n is 0, 1 or 2; and p is 2 or 3; and to pharmaceutically acceptable acid addition salts thereof for the treatment of psychoses, pain, neurodegenerative disfunction in memory and learning, schizophrenia, dementia and other diseases in which cognitive processes are impaired, such as attention deficit disorders or Alzheimer's disease.

The present invention relates to compounds of formula wherein A-B is —CH2—CH2—, —CH2—O— or —O—CH2—; X is hydrogen or hydroxy; R1 is aryl, optionally substituted by one or two substituents selected fro

Reaction of 3-butenyl β-keto esters or 3-butenyl α-aryl ketones with a catalytic amount of [PdCl2(CH3CN)2] (2) and a stoichiometric amount of Me3SiCl or Me3SiCl/ CuCl2 in dioxane at 25-70°C formed 2-substituted cyclohexanones in good yield with high regioselectivity. This protocol tolerated a number of ester and aryl groups and tolerated substitution at the allylic, enolic, and cis and trans terminal olefinic positions. In situ NMR experiments indicated that the chlorosilane was not directly involved in palladium-catalyzed hydroalkylation, but rather served as a source of HCl, which presumably catalyzes enolization of the ketone. Identification of HCl as the active promoter of palladium-catalyzed hydroalkylation led to the development of an effective protocol for the hydroalkylation of alkyl 3-butenyl ketones that employed sub-stoichiometric amounts of 2, HCl, and CuCl2 in a sealed tube at 70°C.

This application relates to phenyl-substituted 1,2,3,4-tetrahydrocarbazoles and to their use as anti-depressant agents useful in the treatment of mental depression of either endogenous or reactive nature.

4A-Aryl-cis-decahydroisoquinolines, such as N-phenethyl-4a-(m-hydroxyphenyl)-cis-decahydroisoquinoline, useful as analgesics.