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Stereoselective Synthesis of Pyrroloquinolines by a Br¡ãnsted Acid Catalyzed [4+2]-Heterocyclization of Indole-7-Carbaldehydes, Anilines and Electron-Rich Alkenes

The pyrrolo[3,2,1-ij]quinoline heterocyclic core is found in the structure of a variety of compounds with interesting applications and then, new efficient and flexible strategies to construct this skeleton are required. Here, a new diastereoselective tetrafluoroboric acid (HBF4)-catalyzed three-component coupling reaction of 1H-indole-7-carbaldehyde derivatives, anilines and electron-rich alkenes to give pyrrolo[3,2,1-ij]quinolines is described. The reaction involves an unusual [4+2]-heterocyclization between an in situ formed imine and an alkene. The new catalytic method, where water is the only by-product, is efficient, robust and flexible, and allows for multigram-scale synthesis.

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Palladium-catalyzed, asymmetric Mizoroki-Heck reaction of benzylic electrophiles using phosphoramidites as chiral ligands

We report herein the first examples of asymmetric Mizoroki-Heck reactions using benzyl electrophiles. A new phosphoramidite was identified to be an effective chiral ligand in the palladium-catalyzed reaction. The reaction is compatible with polar functional groups and can be readily scaled up. Several cyclic olefins worked well as olefin components. Thirty-one examples are included.

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CHROMENONE DERIVATIVES

The invention concerns chromenone compounds of Formula I; or pharmaceutically-acceptable salts thereof, wherein each of R1, R2, R3, R4, R5, n and R6 has any of the meanings defined herein before in the description; processes for their preparation, pharmaceutical compositions containing them and their use in the manufacture of a medicament for use in the treatment of cell proliferative disorders.

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Synthesis of indoles via 6pi-electrocyclic ring closures of trienecarbamates

A new method for the preparation of indoles from readily available alpha-haloenones and alpha-(trialkylstannyl)enecarbamates is described. Following a Stille coupling, trienecarbamate 2 is electronically activated to undergo a facile 6pi-electrocyclic ring closure and subsequent oxidation to afford protected aniline 4. Upon deprotection and reductive amination, acid 5 underwent clean cyclization to N-acetylindole 6 (Ac2O, NEt3, 130 C). This method has been used to construct a variety of substituted indoles that are not easily prepared by conventional indole annelation methods. Copyright

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FUSED QUINOLINE DERIVATIVE AND USE THEREOF

The present invention aims at provision of a quinoline derivative having a neurokinin 2 (NK2) receptor antagonistic action and relates to a compound represented by the formula (I) wherein Rl is a hydrogen atom and the like; R2 is a hydrogen atom, a hydrocarbon group optionally having substituent(s) and the like; R3 is unsubstituted (i.e., absence), a hydrogen atom and the like; R4 and R5 are the same or different and each is a hydrogen atom, a hydrocarbon group optionally having substituent(s), and the like; R6is (cyclic group optionally having substituent(s)) -carbonyl, and the like; R7, R8, R9 and R10 are the same or different and each is a hydrogen atom, halogen and the like; or R7and R8, R8 and R9, and R9 and R10 may form a ring together with the adjacent carbon atoms; n is an integer of 1 to 5; — represents unsubstituted (i.e., absence) or a single bond; and — represents a single bond or a double bond, or a salt thereof, and the like.

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Synthesis of functionalised azepanes and piperidines from bicyclic halogenated aminocyclopropane derivatives

A series of 6,6-dihalo-2-azabicyclo[3.1.0]hexane and 7,7-dihalo-2-azabicyclo[4.1.0]heptane compounds were prepared by the reaction of dihalocarbene species with N-Boc-2,3-dihydro-1H-pyrroles or -1,2,3,4-tetrahydropyridines. Monochloro substrates were synthesised as well, using a chlorine-to-lithium exchange reaction. The behaviour of several aldehydes and ketones under reductive amination conditions with deprotected halogenated secondary cyclopropylamines was investigated, showing that this transformation typically triggers cyclopropane ring cleavage to give access to interesting nitrogen-containing ring-expanded products.

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SPIRO-1,1′-BIINDANE-7,7-BISPHOSPHINE OXIDES AS HIGHLY ACTIVE SUPPORTING LIGANDS FOR PALLADIUM-CATALYZED ASYMMETRIC HECK REACTION

The present invention relates to catalyst complexes comprising palladium (Pd) and at least one spiro-1,1 ‘-biindane-7,7’- bisphosphine oxide ligand as disclosed herein, and their use. The present invention is further directed to the asymmetric Pd-catalyzed covalent carbon-carbon single bond formation from aryl, heteroaryl and alkenyl triflates and halides and olefins utilising the said catalyst complexes.

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QUINOXALINE AND PYRIDOPYRAZINE DERIVATIVES AS PI3K-BETA INHIBITORS

The present invent ion relates to substituted quinoxaline and pyridopyrazine derivatives of Formula (I) wherein the variables have the meaning defined in the claims. The compounds according to the present inv ention are useful as pI3Kappabeta inhibitors. The invention further relates to pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.

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The synthesis of (+)-preussin and related pyrrolidinols by diastereoselective Paterno-Buechi reactions of chiral 2-substituted 2,3-dihydropyrroles

The N-alkoxycarbonyl substituted 2,3-dihydropyrroles 3 and 8 are converted to 2-benzyl-3-pyrrolidinols by the Paterno – Buechi reaction followed by hydrogenolysis. Since the addition of the photoexcited benzaldehyde at the unsaturated heterocycle proceeds in a syn fashion, the benzyl group at C-2 and the hydroxy group at C-3 of the product are cis oriented. The simple and facial diastereoselectivities of the Paterno -Buechi reaction were studied more closely and the relative configuration of the products was elucidated. The thermodynamically less stable endo product is formed as a result of simple diastereo-selection. The face differentiation in 2-substituted 2,3-dihydropyrroles is presumably due to the nonplanarity of these heterocycles, which forces attack of the carbonyl group on the face with the existing substituent. All-cis-pyrrolidinols are consequently formed after hydrogenolysis. Following this route, a total synthesis of the pyrrolidinol alkaloid (+)-preussin (1) was conducted, which yielded the target compound in a total yield of 11% over nine steps starting from L-pyroglutaminol (11).

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Delineating the possibilities for intramolecular interception of the squarate ester cascade through the use of metalated enecarbamates

Highly functionalized and annulated 2,4-cyclooctadienones are formed in a stereoselective manner by sequential treatment of squarate esters with a lithiated enecarbamate (six-membered ring or larger) and a cycloalkenyl-or 1-alkenyllithium reagent. The mechanistic details of this multistep process are presented. Particular attention is drawn to the step that involves intramolecular nucleophilic attack by a proximal oxido anion at the carbamate carbonyl and results in redirection of the cascade. This step is thwarted when five-membered cyclic enecarbamates are employed because of the excessive buildup of ring strain in the associated transition state.

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