Aromaticity | EPFL Graph Search

In chemistry, aromaticity means the molecule has cyclic (ring-shaped) structures with pi bonds in resonance (those containing delocalized electrons). Aromatic rings give increased stability compared to saturated compounds having single bonds, and other geometric or connective non-cyclic arrangements with the same set of atoms. Aromatic rings are very stable and do not break apart easily. Organic compounds that are not aromatic are classified as aliphatic compounds—they might be cyclic, but only aromatic rings have enhanced stability. The term aromaticity with this meaning is historically related to the concept of having an aroma, but is a distinct property from that meaning. Since the most common aromatic compounds are derivatives of benzene (an aromatic hydrocarbon common in petroleum and its distillates), the word aromatic occasionally refers informally to benzene derivatives, and so it was first defined. Nevertheless, many non-benzene aromatic compounds exist. In living organisms

Access to Chiral Cyclopentane Scaffolds by Enantioselective Nickel-Catalyzed Annulations

Joachim Sven Ernst Ahlin

The cyclopentane scaffold has attracted much attention due to its ubiquity in numerous bioactive natural products such as prostaglandins and polyquinanes. However, despite a plethora of available procedures to access this motif, a lack of methods that rival the generality of the Diels-Alder reaction for the synthesis of six-membered rings represents an important gap. Thus, the development of protocols providing efficient access to functionalized chiral cyclopentanes from simple and readily accessible starting materials is highly desirable. In this respect, the tremendous advances in the development of nickel-catalyzed carbon-carbon bond-forming reactions, combined with the unique properties of N-heterocyclic carbenes have led to the development of new approaches to five-membered carbocyclic rings. These include nickel-catalyzed reductive couplings and reductive [3+2] cycloadditions. These strategies are attractive, as functionalized five-membered carbocyclic rings can be accessed from two simple pi-components without any changes in atom connectivity. Despite the recent development of numerous chiral N-heterocyclic carbenes and their successful application in various transition metal-catalyzed reactions, applications in asymmetric nickel catalysis remain scarce. This thesis describes the development of efficient enantioselective nickel-catalyzed methodologies for the formation of five-membered carbocycles from readily accessible and inexpensive starting materials, enabled by two novel chiral N-heterocyclic carbene ligands. First, the development of an intermolecular enantioselective nickel-catalyzed reductive [3+2] cycloaddition of unsaturated aromatic esters and internal alkynes for the synthesis of cyclopentenones is described. For this scalable methodology, a bulky chiral C1-symmetric N-heterocyclic carbene ligand was shown to facilitate the efficient asymmetric synthesis of cyclopentenones from a wide range of mesityl enoates and internal alkynes under mild conditions. Unsymmetrically substituted alkynes were incorporated in a regioselective fashion and the cyclopentenones were synthesized in high yields and enantioselectivity. As a second methodology for the construction of chiral cyclopentane scaffolds, an intermolecular diastereoselective and enantioselective nickel-catalyzed reductive three-component coupling of various aryl aldehydes, norbornene derivatives and silanes is described, which gives access to synthetically valuable silyl-protected indan-1-ols via an aromatic C(sp2)-H functionalization. A bulky chiral C2-symmetric N-heterocyclic carbene ligand possessing a 1,2-(dinaphthalen-1-yl)ethylene diamine scaffold provided the silylated indan-1-ols under mild and scalable conditions, as a single diastereoisomer, in high enantioselectivity and good regioselectivity in the case of meta-substituted aryl aldehydes.

EPFL2016

Nanoparticle - Ionic Liquid Based Catalytic Systems

Alena Karakulina

In recent years ionic liquids have emerged as an important class of compounds for the synthesis of metal nanoparticles. The significant advantage of using ionic liquids is their dual role of reaction solvent and nanoparticle stabilizer. The variability of ionic liquids enables their chemical properties to be tuned by the rational introduction of functional moieties. Metal nanoparticles and ionic liquids appear to be ideal complementary components for the construction of multifunctional catalytic systems. The development of multifunctional systems based on the combination of catalytically active nanoparticles and functionalized ionic liquids allows the integration of complex multi-step catalytic reactions in a one-pot process. The design of efficient metal nanoparticle ¿ functionalized ionic liquid catalysts is currently attracting much attention. The thesis is centered on the design, synthesis, characterisation and the catalytic applications of novel metal nanoparticle ¿ ionic liquid based catalytic systems. In the first chapter a general introduction to the field of metal nanoparticles immobilized in ionic liquids is presented, and the recent evolution of metal nanoparticle ¿ acidic ionic liquid multifunctional catalysts is reviewed. The second chapter covers the studies on chlorometallate ionic liquids. Lewis acidity of various chlorometallate systems was evaluated with respect to the speciation present in these systems. The speciation in chlorozincate ionic liquids was determined by different techniques. The obtained scale of Lewis acidity of the chlorometallate ionic liquids and the understanding of the speciation in these systems allowed accurate selection of the appropriate system for catalytic applications. The third and the fourth chapters describe the studies concerning the ability of the chlorometallate ionic liquids to function in a cooperative manner with rhodium nanoparticles in hydrogenation reactions. A novel bifunctional catalyst, consisting of rhodium nanoparticles dispersed in a Lewis acidic ionic liquid medium, was developed. In the third chapter the rhodium nanoparticle component of the catalyst is characterized. Subsequently, the combined bifunctional catalytic system was used to catalyse the hydrogenation of aromatic compounds and was found to exhibit excellent activity under mild conditions. In the fourth chapter, the high activity of the rhodium nanoparticle ¿ Lewis acidic ionic liquid catalyst the direct hydrogenation of challenging heteroarene substrates is demonstrated. Chlorozincate(II), chloroaluminate(III) and chlorogallate(III) ionic liquids were found to be effective as a second active component of the catalytic system. The chemoselective reduction of different quinolines, pyridines, benzofurans was performed at mild conditions ¿ 30 bar and 80-120°C and the corresponding heterocycles were obtained in high yields. The high selectivity of the catalyst and its tolerance to different functional groups was demonstrated on a broad range of substrates. The recyclability of the rhodium nanoparticle ¿ Lewis acidic ionic liquid catalyst was evaluated. The final chapter presents two reduced graphene oxide supported rhodium nanoparticle catalysts obtained in ionic liquid media via microwave-assisted and conventional thermal heating methods. The rhodium nanoparticle-reduced graphene oxide composites were characterized by different techniques. The catalytic performance of the rhodium nanoparticle-reduced graphene oxide composites was evaluated in the hydrogenation of quinoline compounds under mild conditions, i.e. 10 bar and 80°C. The advantages of the microwave-assisted ionic liquid synthesis for the production of highly efficient catalysts were demonstrated. The long-term stability of the catalyst obtained by microwave-assisted method was studied and the catalyst could be recycled several times without significant loss in activity and selectivity.

EPFL2016

"Palladium-Catalyzed Diamination of Alkynes in Synthesis of Tetracycles" and "Copper-Catalyzed Cyanoalkylation of Unactivated Alkenes"

Minh Tu Ha

The thesis deals with the development of transition metal-catalyzed difunctionalization of alkenes and alkynes, which can be categorized into two major topics: (1) palladium-catalyzed diamination of alkynes for the synthesis of tetracycles; (2) copper-catalyzed cyanoalkylation-initiated double functionalization of alkenes. The first part of this thesis describes the synthesis of free NH tetracyclic indoles by palladium-catalyzed diamination of triple bonds. In the presence of palladium catalyst, 1,2-diarylethynes bearing an N-methyl-N-[2-(methoxy-carbonyl)ethyl]amino and an aminocarbonyl/aminosulfonyl group at the ortho positions of the two aromatic rings underwent double cyclization in a highly ordered fashion to afford N-2-(methoxycarbonyl)ethylaed indolo[3,2-c]isoquinolinone or indolobenzothiazine S,S-dioxide with complete chemoselectivity. Subsequently, the N-[2-(methoxycarbonyl)ethyl] group is readily removed under basic conditions (DBU, DMF, 120 °C) to afford tetracycles with indolyl nitrogen unprotected. We subsequently developed a transition metal-free diamination process to access the tetracyclic quindolinones. In the presence of acetic acid and a hydride donor (Hantsch¿s ester) under oxygen atmosphere, double cyclization of 1,3-diarylprop-2-yn-1-ones bearing an N,N-dialkylated amino and an N-monoalkylated amino groups at ortho positions of aromatic rings occurred smoothly to provide tetracyclic quindolinones. In the second part of thesis, copper-catalyzed cyanoalkylative difunctionalization of alkenes with alkylnitriles as alkylative reagents was addressed. We developed catalytic conditions (copper salt, ligand, peroxide, base) that allowed us to convert unactivated alkenes to 1,2-difunctionalized alkanes or its cyclic variants. The domino process proceeded through following key elementary steps: a) generation of cyanolakyl radicals; b) addition of cyanoalkyl radical to unactivated double bond; c) interception of this adduct radical by a suitable reagent, or more frequently, oxidation of adduct radical to carbenium; d) trapping of the carbocation by an internal/or external nucleophile. By applying this strategy, a series of value-added molecules such as dihydroisobenzofurans, gamma-lactones, aziridines and gamma-azidobutyronitriles, were readily synthesized from simple alkenes.

EPFL2017

Access to Chiral Cyclopentane Scaffolds by Enantioselective Nickel-Catalyzed Annulations

Joachim Sven Ernst Ahlin

EPFL2016

"Palladium-Catalyzed Diamination of Alkynes in Synthesis of Tetracycles" and "Copper-Catalyzed Cyanoalkylation of Unactivated Alkenes"

Minh Tu Ha

EPFL2017

Nanoparticle - Ionic Liquid Based Catalytic Systems

Alena Karakulina

EPFL2016