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Group VI metal-promoted endo-azacyclizations via alkyne-derived metal vinylidene carbenes

The molybdenum-promoted cycloisomerization of terminal alkynes tethered to nitrogen nucleophiles is described. Reaction of N-carbamoyl alkynylamines with (Et3N)Mo(CO)5 affords cyclic enecarbamates. Similarly, cyclization of 2-ethynylaniline gives the isomeric indole heterocycle, although N-3- butynylaniline affords the cyclic metal azacarbene product.

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Palladium-catalyzed asymmetric intermolecular cyclization

Domino cyclization: Alkylpalladium intermediates in an asymmetric Heck reaction were intercepted by a second alkene to give tricyclic products with high enantioselectivity (see scheme; Boc=tert-butoxycarbonyl). The method was applied to the asymmetric synthesis of a precursor of (-)-martinellic acid, a folk eye medicine in South America. Copyright

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Ruthenium-catalyzed hydroformylation/reduction of olefins to alcohols: Extending the scope to internal alkenes

In the presence of 2-phosphino-substituted imidazole ligands and Ru 3(CO)12 or Ru(methylallyl)2(COD) direct hydroformylation and hydrogenation of alkenes to alcohols takes place. In addition to terminal alkenes, also more challenging internal olefins are converted preferentially to industrially important linear alcohols in high yield (up to 88%) and regioselectivity (n:iso up to 99:1).

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Normal Alpha Olefin Synthesis Using Dehydroformylation or Dehydroxymethylation

The present invention discloses processes for producing normal alpha olefins, such as 1-hexene, 1-octene, 1-decene, and 1-dodecene in a multistep synthesis scheme from another normal alpha olefin. Also disclosed are reactions for converting aldehydes, primary alcohols, and terminal vicinal diols into normal alpha olefins.

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Use of metalated enecarbamates in the squarate cascade. Direct access to highly functionalized 2,4-cyclooctadienones by intramolecular interception of the mesocyclic dienolates

A new method for constructing highly functionalized eight-membered ring ketones, fused to one or two additional rings as desired, is reported.

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Synthesis and studies on gem-fluorinated 2-azabicyclo[n.1.0]alkanes

Three novel amines all possessing gem-difluorocyclopropane, secondary amino group and a fused aliphatic cycle were synthesized by difluorocyclopropanation of N-Boc protected enamides. The compounds were stable when amino group was blocked by protonation or acylation, but otherwise underwent fragmentation already at the room temperature. Chemical structure, physico-chemical properties and fragmentation mechanisms of the fluorinated amines are studied in details.

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Asymmetric Hydroformylation and Hydrocarboxylation of Enamides. Synthesis of Alanine and Proline

Carbonyltris(triphenylphosphine)hydridorhodium (1) catalyzed the hydroformylation of N-vinylimides in the presence of optically active 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(diphenylphosphino)butane (DIOP) or 2,3-O-isopropylidene-2,3-dihydroxy-1,4-bis(5H-dibenzophospholyl)butane (DIPHOL) to afford optically active alpha-amido aldehydes.Linear disubstituted N-vinylimides or -amides reacted very sluggishly, while the cyclic N-acyl-2-pyrroline (19) was very reactive.In the unsubstituted N-vinylimides moderate (20-40percent ee) asymmetric induction was observed.The optically active alpha-amido aldehydes were readily converted to the corresponding alpha-amino acids.Asymmetric hydrocarboxylation of the same substrates in the presence of bis(triphenylphosphine)palladium chloride (2) produced alpha-amido esters in low optical purity.

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Application of a catalytic asymmetric povarov reaction using chiral ureas to the synthesis of a tetrahydroquinoline library

A 2328-membered library of 2,3,4-trisubstituted tetrahydroquinolines was produced using a combination of solution- and solid-phase synthesis techniques. A tetrahydroquinoline (THQ) scaffold was prepared via an asymmetric Povarov reaction using cooperative catalysis to generate three contiguous stereogenic centers. A matrix of 4 stereoisomers of the THQ scaffold was prepared to enable the development of stereo/structure-activity relationships (SSAR) upon biological testing. A sparse matrix design strategy was employed to select library members to be synthesized with the goal of generating a diverse collection of tetrahydroquinolines with physicochemical properties suitable for downstream discovery.

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Asymmetric Hydrocyanation of Alkenes without HCN

A general and efficient rhodium-catalyzed asymmetric cyanide-free hydrocyanation of alkenes has been developed. Based on the asymmetric hydroformylation/condensation/aza-Cope elimination sequences, a broad scope of substrates including mono-substituted, 1,2-, and 1,1-disubstituted alkenes (involving natural product R- and S-limonene) were employed, and a series of valuable chiral nitriles are prepared with high yields (up to 95 %) and enantioselectivities (up to 98 % ee). Notably, the critical factor to achieve high enantioseletivies is the addition of catalytic amount of benzoic acid. This novel methodology provides an efficient and concise synthetic route to the intermediate of vildagliptin and anagliptin.

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Site-Selective Ni-Catalyzed Reductive Coupling of alpha-Haloboranes with Unactivated Olefins

A mild, chemo- and site-selective catalytic protocol that allows for incorporating an alkylboron fragment into unactivated olefins is described. The use of internal olefins enables C-C bond-formation at remote sp3 C-H sites, constituting a complementary and conceptually different approach to existing borylation techniques that are currently available at sp3 centers.

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