Investigations of Diels-Alder reactions in ionic liquids

Room temperature ionic liquids comprise an unique class of solvent composed of organic and inorganic-based ions that are molten under ambient conditions. They are characterised by high solvent polarity and low vapour pressure, and can be tailored to have specific physical and chemical properties. Consequently, there has been great interest in exploiting these attributes to accelerate and control organic reactions. One such reaction, the Diels-Alder reaction, is an important [4+2] cycloaddition reaction used extensively in the preparation of cyclic and heterocyclic compounds. Understanding the factors involved in the enhancing this reaction in ionic liquids remains a subject of intense interest and the centrepiece of the dissertation. The objective of the research is to explore the Diels-Alder cycloaddition reaction in ionic liquids, with a view of developing high effective reactions systems, that operate under mild reaction conditions. The role that ionic liquid media plays in facilitating the Diels-Alder reaction is discussed. A range of physical and chemical modes of activating the reaction are discussed including pressure, the application of Lewis acid catalysts, microwave irradiation and ultrasound sonication and a comparison on the various modes of activation is provided. Importantly, the results of this study can lead to a better understanding of the ionic liquids as well as their utilization for other organic reactions.

Synthetic chemistry with nitrous oxide and triazenes

Iris Roswitha Landman

Nitrous oxide (N2O) has gained much interest because of its physiological effects ("laughing gas") and its negative environmental impact ("greenhouse gas", "ozone-depleting substance"): It has a lifetime of more than 100 years in the atmosphere. Its persistent character shows how challenging it is to convert N2O into more valuable products. From a synthetic point of view, N2O has potential as diazo (N2) transfer reagent, but applications in synthetic organic chemistry are scarce. The main challenges are to capture N2O, avoid the loss of N2, and to overcome poor-selectivity and -yields. Herein, we describe two examples of the incorporation of two nitrogen atoms into the final product. Firstly, we use N2O as diazo transfer reagent in the preparation of triazolopyridines, which are valuable starting materials for heterocyclic compounds. The reactions can be performed under mild conditions and give synthetically interesting triazoles in moderate to good yields. Secondly, general methods to N1 acylated triazenes were missing previously. We developed routes to 1-acyl triazenes via acid-catalyzed hydration, or by gold- or iodine-catalyzed oxidation of 1-alkynyl triazenes. The latter compounds are prepared from N2O. The properties of the N1 acylated triazenes are distinct compared to other triazenes, displaying different physical and chemical properties. Under strong acidic conditions, 1-acyl triazenes act as acylation reagents. Finally, despite that triazene chemistry is known for more than 160 years, the preferred coordination site of acids still remained a matter of debate (N1, N2, or N3). In search of experimental evidence, we have analyzed triflic acid, B(C6F5)3, and PdCl2 adducts of triazenes by IR, NMR spectroscopy and single crystal X-ray crystallography. For all cases, we found the acid coordinating to the N1 atom of the triazene. This preference should be taken into account for future acid- and transition metal-catalyzed reactions with triazenes. Altogether, this thesis contributes to triazene chemistry and synthetic chemistry with N2O. In this way, we provide further evidence that N2O can be used as a diazo donor to get to synthetically interesting N-containing products.

EPFL2022

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

Transition metal-catalyzed carbon-carbon cross-coupling reactions using sulfonyl derivatives

The goal of this thesis was to find conditions to form C-C double bond and single bond using sulfonyl derivativies, which are arising from the Vogel's oxyallylation cascades. In a second chapter, it is shown that 2-methylprop-2-ene-1-sulfonyl fluorides can be easily prepared via the ene reaction of methallylsilanes and SO2 followed by halogenosis (NCS, then KF). In the presence of a base, aldehydes and 2-methylprop-2-ene-1-sulfonyl fluorides give mixture of (1Z)- and (1E)-1-aryl-3-methylbutadienes. Their (Z)→(E) isomerization by classical means fails or leads to their polymerization. We have discovered that SO2 can isomerize 1-aryl-3-methyl-1,3-dienes at low temperature, without formation of sulfolenes (cheletropic addition/elimination). Preliminary mechanistic studies suggest that SO2 add to the 1,3-dienes forming 1,4-diradical intermediates that are responsible for the (Z)→(E) isomerizations. In the third chapter, we have shown that arenesulfonyl chlorides are versatile electrophilic reagents for C-C cross-coupling reactions. Arene-, arylmethane- and alk-2-ene-1-sulfonyl chlorides undergo desulfitative Stille, carbonylative Stille, Negishi and Suzuki-Miyaura cross-coupling reactions. In these reactions the reactivity order is ArI> ArSO2Cl> ArBr> ArCl. Similarly, desulfitative Sonogashira-Hagihara cross-couplings of arenesulfonyl chlorides with aryl- and alkylacetylenes can be catalyzed by Pd2(dba)3/P(t-Bu)3/CuI. New conditions have been found for the desulfitative Mizoroki-Heck arylation and trifluoromethylation of mono- and disubustituted olefins with arenesulfonyl and trifluoromethanesulfonyl chlorides. This procedure allows one to obtain (E)-1,2-disubstituted alkenes with high stereoselectivity and 1,1,2-disubstituted alkenes with high (E)/(Z) stereoselectivity. If phosphine- and base-free conditions are required, 1 mol% {RhCl(C2H4)2} catalyses the desulfitative cross-coupling reactions. On the contrary to what has been reported for RuCl2(PPh3)2 catalyzed coupling reactions with sulfonyl chlorides, the palladium and rhodium desulfitative Mizoroki-Heck coupling reactions are not inhibited by radical scavenging agents. Moreover, sulfones that are formed from the sulfonylation of alkenes at 60°C can theoretically be envisaged as intermediates in all cross-coupling reactions. However we have shown that they are not desulfitated at higher temperatures in the presence of the Pd or Rh-catalysts. Alk-2-ene-1-sulfonamides can also undergo desulfamylating cross-coupling reaction with Grignard reagents in the presence of a nickel catalyst. In the fouth chapter, we have evaluated the possibility that silyl sulfinates can be used as nucleophilic partners to form C-C bond. Our preliminary results indicate that their hypothesis should be explored further. In a fifth chapter, we have contributed to the development of an efficient one-pot, three component syntheses of sulfonamides and sulfonic esters. We have demonstrated that the ene-reaction of sulfur dioxide with enoxysilanes can be stereoselective under conditions of kinetic control. As others in our laboratory, we have shown that the hetero-Diels-Alder addition of sulfur dioxide to 1-oxy or 1,3-dioxy-1,3-dienes generates zwitterions that add to enoxysilanes or allylsilanes giving silyl sulfinates that can be converted in the same pot into polyfunctional sulfones, sulfonamides or sulfonic esters. Intramolecular S-allylation of intermediate silyl sulfinates has allowed one to prepare new tetrahydro-2H-thiocine derivatives. Our key contribution has been to use enantiomerically enriched amines which has allowed one to obtain enantiomerically enriched polyfunctional sulfonamides.

EPFL2005