This thesis describes the discovery of catalytic reactions that create carbon-carbon bonds stereoselectively between substrates bearing an alkene and organoboronic acids reagents. Chiral rhodium(I) catalysts were found to react with various meso-symmetrical substrates, thereby resulting in enantioselective desymmetrization reactions. The methodologies presented herein allow the rapid synthesis of several chiral functionalized molecules; including branched homoallylic alcohols, cyclopentenyl hydrazines, and ketohydrazines. The thesis is divided according to three main transformations: asymmetric allylic substitution of allylic carbonates, asymmetric ring-opening of [2.2.1]-diazabicyles, and carbonylation of alkenes or alkynes. Chapter 2 details the investigations of a ligand-controlled catalytic process to prepare either trans-2-arylcyclopent-3-enols (up to 94% ee), or trans-4-arylcyclopent-2-enols (up to 99% ee) as the major products starting from cyclic meso allylic dicarbonates. This rhodium-catalyzed methodology was extended to include linear allylic dicarbonates, thereby yielding chiral 2-arylbut-3-enols with up to 95% ee. An enantioselective desymmetrization of strained alkenes by ring-opening of meso bicyclic hydrazines is described in Chapter 3. The reaction allows one to prepare trans-2-arylcyclopent-3-enyl hydrazides with up to 99% ee. In addition, an enantioselective hydroarylation process was identified to yield 5-aryl-2,3-diazabicyclo[2.2.1]heptanes. Mechanistic investigations showed that the reaction proceeds via an unusual C-H activation/1,4-migration of the rhodium catalyst. Finally, Chapter 4 outlines the development of a mild catalytic acylation of pi systems. This mode of reactivity was optimized to promote the desymmetrization of [2.2.1]-diazabicycles via a formal allylic substitution with acyl anions as nucleophiles. The method yields densely functionalized trans-2-ketocyclopent-3-enyl hydrazides. In addition, preliminary studies demonstrate that the rhodium(I)-catalyzed acyl anion addition is also possible with other pi electrophiles. For example, with alkyne, it provided a synthesis of cyclopentenones that complements the Pauson-Khand reaction. Overall, the catalytic transformations reported herein give access to seven classes of products stereoselectively; starting from simple reagents.

This thesis describes the discovery of catalytic reactions that create carbon-carbon bonds stereoselectively between substrates bearing an alkene and organoboronic acids reagents. Chiral rhodium(I) catalysts were found to react with various meso-symmetrical substrates, thereby resulting in enantioselective desymmetrization reactions. The methodologies presented herein allow the rapid synthesis of several chiral functionalized molecules; including branched homoallylic alcohols, cyclopentenyl hydrazines, and ketohydrazines. The thesis is divided according to three main transformations: asymmetric allylic substitution of allylic carbonates, asymmetric ring-opening of [2.2.1]-diazabicyles, and carbonylation of alkenes or alkynes. Chapter 2 details the investigations of a ligand-controlled catalytic process to prepare either trans-2-arylcyclopent-3-enols (up to 94% ee), or trans-4-arylcyclopent-2-enols (up to 99% ee) as the major products starting from cyclic meso allylic dicarbonates. This rhodium-catalyzed methodology was extended to include linear allylic dicarbonates, thereby yielding chiral 2-arylbut-3-enols with up to 95% ee. An enantioselective desymmetrization of strained alkenes by ring-opening of meso bicyclic hydrazines is described in Chapter 3. The reaction allows one to prepare trans-2-arylcyclopent-3-enyl hydrazides with up to 99% ee. In addition, an enantioselective hydroarylation process was identified to yield 5-aryl-2,3-diazabicyclo[2.2.1]heptanes. Mechanistic investigations showed that the reaction proceeds via an unusual C-H activation/1,4-migration of the rhodium catalyst. Finally, Chapter 4 outlines the development of a mild catalytic acylation of pi systems. This mode of reactivity was optimized to promote the desymmetrization of [2.2.1]-diazabicycles via a formal allylic substitution with acyl anions as nucleophiles. The method yields densely functionalized trans-2-ketocyclopent-3-enyl hydrazides. In addition, preliminary studies demonstrate that the rhodium(I)-catalyzed acyl anion addition is also possible with other pi electrophiles. For example, with alkyne, it provided a synthesis of cyclopentenones that complements the Pauson-Khand reaction. Overall, the catalytic transformations reported herein give access to seven classes of products stereoselectively; starting from simple reagents.

This thesis discusses the preparation and use of transition-metal catalysts for selective organic chemical reactions. Specifically, two different matters have been studied; the asymmetric hydrogenation of carbon-carbon double bonds using N,P-ligated iridium catalysts and the metal-catalyzed transfer of small molecules from biomass to synthetic intermediates. In the first part of this thesis, chiral N,P-ligands were synthesized and evaluated in iridium catalysts for the asymmetric hydrogenation of non- and weakly functionalized alkenes (Papers I & II). The new catalysts were prepared via chiral-pool strategies and exhibited superior properties for the reduction of certain types of alkenes. In particular, some of the catalysts showed excellent activity and selectivity in the enantioselective reduction of terminal alkenes, and the preparation of a modular catalyst library allowed the asymmetric hydrogenation of a wide range of 1,1-disubstituted alkenes with unprecedented efficiency and enantioselectivity (Paper III). Methods for the selective preparation of chiral hetero- and carbocyclic fragments using iridium-catalyzed asymmetric hydrogenation as an enantiodetermining key step were also developed. A range of elusive chiral building blocks that have applications in pharmaceutical and natural-product chemistry could thus be conveniently prepared (Papers IV & V). The second part of this thesis deals with the catalytic decomposition of polysaccharides into sugar alcohols and the incorporation of their decomposition products into alkene substrates. Iridium-catalyzed dehydrogenative decarbonylation was found to decompose polyols into CO:H2 mixtures that could be used immediately in the ex situ low-pressure hydroformylation of styrene (Paper VI). The net process was thus the hydroformylation of alkenes with biomass-derived synthesis gas.

Thesis (Ph. D.)--University of Lund, 1995. / Published dissertation.

Thesis (Ph. D.)--University of Lund, 1995. / Published dissertation.

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This thesis concerns the development of novel catalytic approaches for the construction of stereocentres bearing a nitrogen atom. In 2011, the Dixon group reported a Ag(I)/cinchona-derived amino phosphine catalytic system for the activation of isocyanoacetates in asymmetric aldol and Mannich reactions. During this thesis work it was sought to extend the scope of this catalytic system to Mannich additions of other isocyanide pronucleophiles, then the focus was broadened to include Reformatsky and α-alkylation reactions of ketimine substrates. Chapter 1 gives an overview of the state of the art with particular emphasis on catalytic enantioselective additions to ketimines and the use of activated isocyanides as pronucleophiles. Chapter 2 describes the application of the Ag-catalysed enantio- and diastereoselective aldol reaction of isocyanoacetates to the concise asymmetric synthesis of the antibiotic chloramphenicol, which possesses a chiral stereodefined α-amino β-hydroxy motif. Chapter 3 details our efforts to expand the scope of the Ag(I)/amino phosphine catalytic system to the activation of more challenging isocyanides lacking an electron-withdrawing group in the α-position by investigating aldol and Mannich reactions of benzyl isocyanide. Chapter 4 describes how the scope of the Ag(I)/amino phosphine catalytic system was successfully extended to another pronucleophile, the versatile p-toluenesulfonylmethyl isocyanide (TosMIC). The first catalytic enantio- and diastereoselective addition of TosMIC to N-diphenylphosphinoyl (N-DPP) ketimines was developed, affording 2-imidazolines possessing two contiguous stereocentres with high yields and excellent levels of stereocontrol. Chapter 5 describes the development of a Ni(II)-catalysed Reformatsky reaction of N-DPP ketimines with ethyl bromoacetate and diethylzinc, providing racemic amines bearing a quaternary stereocentre in the α-position in good yields. Chapter 6 reports the serendipitous discovery of the α-alkylation of N-DPP ketimines with ethyl bromoacetate using visible light photoredox catalysis. The transformation, catalysed by ruthenium(II) and nickel(II) complexes under mild conditions, was optimised, its scope assessed and the mechanism investigated.

This PhD thesis is focused on the development of novel catalysis with low-oxidation main group species, mainly based on the group 13 element gallium, a relatively abundant, inexpensive, and low-toxic metal. Gallium in its stable high-oxidation state ‘+III’ is a commonly used Lewis acid catalyst in organic synthesis. In contrast, gallium in its less stable low-oxidation state ‘+I’ is under-explored, but may display both acceptor and donor properties at a single site (ambiphilicity). Based on the hypothesis that potentially ambiphilic gallium(I) –oxidatively generated in situ from gallium(0) using a silver salt– may activate both basic and acidic reagents, various gallium(I)-catalyzed carbon–carbon bond formations have been developed. These include catalytic C–O and C–B bond activations of electrophiles (acetals and aminals) and pro-nucleophiles (allyl and allenyl boronates), respectively. Gallium(III) and other metal Lewis acids have proved to be ineffective. These results represent the first catalytic use of gallium(0) in organic synthesis and a rare example of gallium(I) catalysis. The identity of the gallium(I) catalyst and its regeneration have been confirmed by 71Ga NMR analysis, and a reactive allyl–Ga(I) intermediate has been detected for the first time. In combination with 11B NMR and HRMS analyses, an SN1 reaction mechanism has been proposed. Importantly, the potential for asymmetric gallium(I) catalysis has been demonstrated using a chiral silver co-catalyst (40% ee). This gallium(I) chemistry has proved to be applicable to the catalytic activation of other electrophiles, including ethers or aldehydes, and pro-nucleophiles such as boranes, silanes, or tin-based reagents. Finally, the potential of a related low-oxidation aluminium catalyst has been explored for C–C bond formation.