Catalytic Stereoselective Borylative Transannular Reactions.

Medium-sized carbocycles containing an α,ß-unsaturated ketone moiety as Michael acceptor site and a ketone moiety as internal electrophilic site are ideal substrates to conduct Cu(I)-catalyzed conjugated borylation followed by electrophilic intramolecular trapping that results into a pioneer transannular borylative ring closing reaction. The relative configuration of three adjacent stereocenters is controlled, giving access to a single diastereoisomer for a wide range of substrates tested. Moreover, when a chiral ligand is incorporated, the reaction provides enantioenriched polycyclic products with up to 99 % ee.

Catalytic Enantioselective Transannular Morita-Baylis-Hillman Reaction.

Catalytic and enantioselective approaches to transannular reactions are very limited and mostly are based on chiral Lewis acid catalyzed pericyclic reactions. In this report, we present an efficient and straightforward methodology to access bicyclic carbo- and heterocyclic scaffolds combining different ring sizes through transannular Morita-Baylis-Hillman reaction catalyzed by a chiral enantiopure bifunctional phosphine. The reaction is remarkably wide in scope and enables the use of a variety of medium and large size ketoenone substrates leading to the final products in high yields and providing excellent stereocontrol in the formation of a quaternary stereogenic center at the ring fusion. Moreover, its potential as a general tool in organic synthesis has been highlighted through the accomplishment of the first enantioselective total synthesis of (-)-γ-gurjunene, a sesquiterpene natural product.

Catalytic Enantioselective Cloke-Wilson Rearrangement.

Racemic cyclopropyl ketones undergo enantioselective rearrangement to deliver the corresponding dihydrofurans in the presence of a chiral phosphoric acid as the catalyst. The reaction involves activation of the donor-acceptor cyclopropane substrate by the chiral Brønsted acid catalyst to promote the ring-opening event, thus generating a carbocationic intermediate that subsequently undergoes cyclization. Computational studies and control experiments support this mechanistic pathway.

Enantioselective Silver and Amine Co-catalyzed Desymmetrizing Cycloisomerization of Alkyne-Linked Cyclohexanones.

A silver(I) and amine co-catalyzed desymmetrization of 4-propargylamino cyclohexanones for the direct enantioselective synthesis of 2-azabicyclo[3.3.1]nonanes is described. Exploiting reactivity arising from dual activation of the pendant terminal alkyne by silver(I) and the ketone moiety through transient enamine formation, this synthetically relevant transformation is easy to perform, efficient and broad in scope. High enantioselectivity (up to 96 % ee) was achieved by exploiting a significant matching effect between the chirality of a cinchona alkaloid-derived aminophosphine ligand for the silver(I) salt and the 2-bis(aryl)methylpyrrolidine catalyst which was rationalized by DFT calculations. This allowed for the preparation of both enantiomers of the bicyclic product with near-identical stereocontrol.

Ipso-Borylation of Aryl Ethers via Ni-Catalyzed C-OMe Cleavage.

A Ni-catalyzed ipso-borylation of aryl ethers via C(sp(2))-OMe and C(sp(3))-OMe cleavage is described. The transformation is characterized by its wide substrate scope under mild conditions and an exquisite divergence in site selectivity that can be easily switched by selecting the appropriate boron reagent.

Room-temperature hydrohydrazination of terminal alkynes catalyzed by saturated abnormal N-heterocyclic carbene-gold(I) complexes.

A number of saturated abnormal N-heterocyclic carbene (NHC) complexes of gold, in combination with KBAr(F) 4 as activator, were successfully applied in the chemoselective addition of hydrazine to alkynes. The reaction proceeds even at room temperature, which was not possible to date with gold catalysts. The reaction can be applied to a number of substituted arylalkynes. With alkylalkynes the yields are low. The saturated abnormal NHC ligands are resistant to isomerization to the saturated normal NHC coordination mode under basic reaction conditions. Under acidic conditions, a simple protonation at the nitrogen atom not neighboring the carbene center was observed and unambiguously characterized by an X-ray crystal-structure analysis. Computational studies confirm that such an isomerization would be highly exothermic, the observed kinetic stability probably results from the need to shift two protons in such a process.

Enantioselective conjugate addition of nitro compounds to α,ß-unsaturated ketones: an experimental and computational study.

A series of chiral thioureas derived from easily available diamines, prepared from α-amino acids, have been tested as catalysts in the enantioselective Michael additions of nitroalkanes to α,ß-unsaturated ketones. The best results are obtained with the bifunctional catalyst prepared from L-valine. This thiourea promotes the reaction with high enantioselectivities and chemical yields for aryl/vinyl ketones, but the enantiomeric ratio for alkyl/vinyl derivatives is very modest. The addition of substituted nitromethanes led to the corresponding adducts with excellent enantioselectivity but very poor diastereoselectivity. Evidence for the isomerization of the addition products has been obtained from the reaction of chalcone with [D(3)]nitromethane, which shows that the final addition products epimerize under the reaction conditions. The epimerization explains the low diastereoselectivity observed in the formation of adducts with two adjacent tertiary stereocenters. Density functional studies of the transition structures corresponding to two alternative activation modes of the nitroalkanes and α,ß-unsaturated ketones by the bifunctional organocatalyst have been carried out at the B3LYP/3-21G* level. The computations are consistent with a reaction model involving the Michael addition of the thiourea-activated nitronate to the ketone activated by the protonated amine of the organocatalyst. The enantioselectivities predicted by the computations are consistent with the experimental values obtained for aryl- and alkyl-substituted α,ß-unsaturated ketones.

Highly diastereo- and enantioselective direct Barbas-List aldol reactions promoted by novel benzamidoethyl and benzamidopropyl prolinamides in water.

Four novel benzamido-functionalized prolinamides have been prepared and tested as organocatalysts for enantioselective aldol reaction of aldehydes and cyclic ketones in water. In particular, prolinamide derived from achiral ethylene diamine was the best catalyst leading to anti aldols in excellent diastereomeric (up to 98/2) and enantiomeric (up to 99/1) ratios, thereby showing that lateral amide functionalities might be a key issue for facilitating "in water" chemistry. These catalysts are cheaper and easier to prepare than those previously described.

Synthesis of both enantiomers of hemiesters by enantioselective methanolysis of meso cyclic anhydrides catalyzed by alpha-amino acid-derived chiral thioureas.

Both ureas and thioureas derived from L- or D-valine act as bifunctional organocatalysts able to induce the enantioselective alcoholysis of mono-, bi-, and tricyclic meso anhydrides. The desymmetrization occurs in near quantitative yields and excellent enantiomeric ratios (up to >99:<1) under low catalyst loading. Both enantiomers of the hemiesters can be directly obtained by changing the configuration of the catalyst.

Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones.

The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic entry to architecturally complex bicyclic ethereal frameworks. The mechanistic pathway and the origin of enantio- and diastereoselectivities has been uncovered using density functional theory (DFT) calculations.

Catalytic enantioselective domino Michael/transannular aldol reaction under bifunctional catalysis.

The enantioselective Michael reaction catalyzed by a bifunctional tertiary amine/squaramide has been used to trigger a Michael/transannular aldol cascade process that leads to densely substituted bicyclo[5.4.0]undecanes and in which three contiguous stereogenic centres, one of them a tertiary alcohol moiety, have been formed in a fully stereocontrolled fashion.

γ-Substituted Allenic Amides in the Phosphine-Catalyzed Enantioselective Higher Order Cycloaddition with Azaheptafulvenes.

Racemic γ-substituted allenes undergo enantioselective higher order [8 + 2]-cycloaddition with azaheptafulvenes using a chiral amino acid derived amidophosphine as catalyst, providing the corresponding azaazulenoid cycloadducts with excellent levels of regio-, diastereo-, and enantioselectivities. In this reaction, the activated allylic phosphonium ylide intermediate participates as the C2-component of the reaction, in contrast to the conventional reactivity of this type of zwitterionic intermediates as C3-components in cycloaddition reactions.

Catalytic synthesis of (E)-alpha,beta-unsaturated esters from aldehydes and 1,1-diethoxyethylene.

A practical and high yielding synthesis of alpha,beta-unsaturated esters from aldehydes and 1,1-diethoxyethylene was developed.

Enantioselective Silver-Catalyzed Cascade Synthesis of Fused Lactone and Lactam Oxazolines.

A new and highly stereoselective cascade reaction between isocyanoacetate esters and α-hydroxy and α-amino ketones has been developed. A cinchona alkaloid derived aminophosphine/silver(I) catalyst complex promoted the reaction and enabled the ready synthesis of fused bicyclic γ-lactone and γ-lactam oxazolines with high enantiocontrol (up to 99% ee).

MEBO: una nueva alternativa en el tratamiento de las quemaduras / MEBO: a new alternative in the treatment of the burns

Recientemente, estudios experimentales, así como experiencias clínicas soportan la creencia que las lesiones cicatrizan mejor en el medio húmedo creado por los vendajes oclusivos. En virtud de sus ingredientes activos y fórmula especial, MEBO aisla el lecho de la lesión de los factores invasivos medioambientales y reduce la pérdida de líquidos corporales, produce un efecto anti-inflamatorio y anti-edema, reduce el dolor tremendamente, controla la invasión por bacterias y hongos, mejora la cicrocirculación y así recupera a la células semi-viables y promueve cicatrización con mínimas ecaras y aceptables resultados estéticos. El objetivo del presente estudio fue explorar la efectividad terapéutica de MEBO en el manejo de las quemaduras...

MEBO: una nueva alternativa en el tratamiento de las quemaduras / MEBO: a new alternative in the treatment of the burns

Recientemente, estudios experimentales, así como experiencias clínicas soportan la creencia que las lesiones cicatrizan mejor en el medio húmedo creado por los vendajes oclusivos. En virtud de sus ingredientes activos y fórmula especial, MEBO aisla el lecho de la lesión de los factores invasivos medioambientales y reduce la pérdida de líquidos corporales, produce un efecto anti-inflamatorio y anti-edema, reduce el dolor tremendamente, controla la invasión por bacterias y hongos, mejora la cicrocirculación y así recupera a la células semi-viables y promueve cicatrización con mínimas ecaras y aceptables resultados estéticos. El objetivo del presente estudio fue explorar la efectividad terapéutica de MEBO en el manejo de las quemaduras... (AU)