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Allenes are very important chemical reagents in organic synthesis. Due to their high reactivity, they have been extensively used to carry out a variety of unique and effective chemical transformations including but not limited to ionic and free radical additions and transition metal catalyzed cyclizations. As the chemistry of this group of compounds is explored further and their applications expanded there is a need to develop alternative and cost effective methods for their synthesis. Our approach involves the synthesis of allenes from oxa-bicyclo-alkan-2-ones by methyllithium induced Eschenmoser fragmentation of the bicyclotosylhydrazone derivatives.

A novel method for asymmetric synthesis of α-hydroxy ketone with excellent regio- and stereoselectivity has been established by the systematic investigation of asymmetric dihydroxylation of allenes. The efficiency of kinetic resolution of racemic allenes was also investigated by using the AD reaction on both 1,3-disubstituted and trisubstituted allenes. Steric effects, electronic effects and allene substitution are also discussed. Aziridines were formed by copper-catalyzed intramolecular nitrene addition to alkenes. The carbamate group was used as the tether between the alkene and the nitrene. Subsequent nucleophilic attack of the aziridine was accomplished using RSH, R2NH, N3-,or ROH as the nucleophile. This addition was found to be regio- and stereoselective. This methodology has provided a new strategy for the stereoselective construction of three adjacent functional groups, in particular the 1,2 diamino-3-hydroxy unit. The rhodium-catalyzed intramolecular aziridination of allenic N-sulfonyloxy carbamates has been established. Efficient ring opening of these bicyclic compounds may provide synthetic utility in organic chemistry. The intramolecular aziridination of allenic sulfamate esters was tested on a single example to afford in situ a ring opened product.

This thesis describes our examination of the reactivity of allenylpalladium intermediates generated from the reaction of palladium(0) with propargylic electrophiles. Chapter 1 provides a general overview of the literature reported to date concerning the nature and reactivity of allenylpalladium intermediates. The coupling of a variety of propargylic electrophiles with aryl boronic acids to form allenes is examined in Chapter 2. However, when employing diastereomerically pure electrophiles, some erosion of stereochemistry was observed in the allene products. This effect was examined further, and epimerisation of the allene product was found to be the origin of the loss of stereochemistry. Evidence for the species likely responsible for this epimerisation is presented. The serendipitous formation of tetrahydrofurans (THFs) from propargylic 7-membered cyclic carbonates prompted an in-depth examination of this reactivity, as described in Chapter 3. The reaction of these cyclic carbonates was rendered stereoselective and the stereochemical outcome of the reaction elucidated. The methodology was extended to propargylic acyclic carbonates which allowed the formation of tetrahydropyrans (THPs). The effect of ring-size and substituents on the cyclisations was examined, culminating in the formation of two rings in a single step from diol-containing bis-carbonates. Chapter 4 describes the extension of this methodology to the formation of azacyclic products. This built upon foundation work conducted by a Part II student within the group, and further improved the selectivity of the reaction. Two diverse azacyclic skeletons could be formed from the same substrate by the employment of different bidentate phosphine ligands, and a variety of substrates were examined under these conditions. Chapter 5 draws general conclusions and sets out possible future directions for the methodology, and full experimental details are outlined in Chapter 6.

This thesis describes the synthesis and reactivity of previously unprecedented bicyclic methylene aziridines via rhodium(II) catalysed cyclisation of α-allenic N-tosyloxycarbamates. These aziridines undergo reaction with organocuprates to give cis- disubstituted oxazolidinones by nucleophillic attack at the vinylic centre; plausible mechanisms for this process are discussed. Similar rhodium(II) catalysed cyclisations of β-allenic sulfamates afford cyclic enamines, aminocyclopropanes or bicyclic methylene aziridines; the product ratio depends on the allene substitution pattern. Suitably-designed substrates undergo trapping of the proposed intermediate amino allyl cation by internal nucleophiles or by cycloaddition. Finally, thermally-induced intramolecular cycloadditions of γ-allenic azides are described that give triazolines or [1,2,3]-triazoles.

The thesis describes synthesis and reactions of allene azides tethered to various functional groups and the application of the discovered cascade transformations towards the synthesis of radianspene J model system. Chapter 1 covers reactions of simple allene azides containing alkyl and cycloalkyl substituents. Thermal rearrangements of these substrates delivered isocyanides and azadienes via the proposed azatrimethylenemethane (ATMM) intermediates. On the other hand, vinylidenecyclopropanes (VDCPs) gave dramatically different products, as described in Chapter 2. A phenyl-substituted VDCP was transformed into an unstable polycyclic compound by a divinylcyclopropane rearrangement. Chapter 3 discusses allene azides tethered to furan, N-substituted pyrroles, and E- and Z-dienes. Depending on the structure of the starting material, products of formal (3+4)- or (2+3)-cycloaddition were formed. Finally, an application of the discovered cyclisation cascade towards total synthesis is described in Chapter 4. A model system of radianspene J was assembled using a key transannular cycloaddition of a macrocyclic allene.

The development of the interrupted Nazarov cyclization of allenyl vinyl ketones is presented. The intermediate oxyallyl cation, derived from an allenyl vinyl ketone, may be trapped efficiently by a divergent array of nucleophilic species generating functionalized cyclopent-2-enone products. Allenyl vinyl ketones are also a versatile source of cyclic molecules via a tandem reaction sequence terminated via reaction with acyclic dienes, cyclic dienes, aza-heterocycles, electron-rich alkenes, or styrenes by the formation of an additional ring by a [4 + 3] and/or [3 + 2] cyclization or by the formation of one additional carbon-carbon bond. The bicyclic compounds generated by these processes are densely substituted, and would be difficult to access as succinctly in other ways. The products of these interrupted Nazarov reactions generally reflect excellent regio- and stereoselectivity in the trapping reaction. In some instances, equilibrating conditions were shown to enhance the proportion of one product at the expense of another or to provide a different carbon skeleton. This process appears fairly general, and can be conducted with unsubstituted or alkyl, aromatic, or heteroaromatic allenyl vinyl ketones. The exceptional affinity of allenyl vinyl ketones to undergo interrupted Nazarov reactions is likely a result of the increased longevity of the intermediate oxyallyl cation, due in part to the increased resonance stabilization provided by the allene unit. The high regioselectivity noted in the trapping process was computationally and experimentally confirmed to be a result of a localization of the positive charge in the intermediate oxyallyl cation. The application of this recently developed methodology towards the synthesis of the natural product (+)-roseadione is also described. The tandem Nazarov/[4 + 3] cascade of allenyl vinyl ketones provides a unique manner in which to access the tricyclic core of this cyclooctanoid natural product, a molecule which, to date, has never been synthesized.

Les molécules polycycliques, et notamment les éthers spirocycliques, sont des structures présentant un fort intérêt dans le domaine de la chimie des parfums. Cette thèse est dédiée au développement de nouvelles cycloisomérisations de dérivés d’éthers d’énol catalysées par le triflate de bismuth(III). Une étude bibliographique a ainsi été consacrée aux réactions de cyclisation catalysées par Bi(OTf)3. Une réaction de cycloisomérisation d’éthers d’énol alléniques permettant la formation rapide de produits cyclopenténiques et dihydrofuraniques a été développée. Des dérivés oxaspirocycliques ont été obtenus à partir de substrats trifonctionnels possédant un éther d’énol cyclique et une fonction alcool additionnelle. La chimiodivergence de ces réactions a été étudiée avec l’activation préférentielle de l’allène par des catalyseurs à base d’or(I) menant à d’autres structures cyclopenténiques. Une réaction de double cyclisation a été développée donnant un accès privilégié à des produits polycycliques pontés comportant un motif oxaspirocyclique. Des études mécanistiques ont été effectuées et une nouvelle cyclisation tandem impliquant un transfert d’hydrure-1,5 a été étudiée. La réaction de double cyclisation de dérivés du campholénal énantioenrichis a ensuite été développée pour la formation de bis-éthers tétracycliques et de cétones tricycliques. La plupart de ces nouveaux composés présentent des notes remarquables, principalement dans les familles olfactives aromatiques et boisées. / Polycyclic compounds and more specifically, spirocyclic ethers are of particular interest in fragrance chemistry. This thesis is dedicated to the development of new cycloisomerisations of enol ether derivatives by bismuth(III) triflate catalysis. In this way, a bibliographic study has been carried out on cyclisations catalysed by bismuth(III) triflate. A cycloisomerisation of allenic enol ethers has been developed for the straightforward synthesis of cyclopentene and dihydrofuran derivatives. New oxaspirocyclic compounds have been obtained starting from trifunctional substrates containing a cyclic enol ether and an additional hydroxyl group. The chemodivergence of this reaction has been studied by means of gold(I) catalysis to access different cyclopentenic structures via the preferential activation of the allene. A double cyclisation reaction has been developed leading to bridged polycyclic compounds featuring an oxaspirocyclic moiety. Mechanistic studies have been performed and a tandem cyclisation involving a 1,5-hydride shift has been studied. The double cyclisation of enantioenriched campholenic aldehyde derivatives has been investigated for the formation of tetracyclic diethers and tricyclic ketones. Most of the new compounds presented interesting notes, mainly in the aromatic and woody olfactory family.

No description available.

Le présent mémoire a pour sujet le développement d’une méthode rapide et efficace vers la production d’allènes hautement substitués à partir de dérivés cyclopropaniques électrophiles énantioenrichis. L’avancement de méthodes synthétiques intéressantes pour la production asymétrique de ces dérivés de cyclopropane-1,1-diesters sera également présenté. Dans un premier temps, les différentes méthodes de synthèses des cyclopropanes activés seront abordées, ainsi que leur utilisation dans la préparation de molécules plus complexes. Par la suite, les techniques précédentes de préparation asymétrique des allènes seront introduites, démontrant ainsi la difficulté de leur accessibilité. Le développement d’une méthode fiable pour la synthèse de cyclopropane-1,1-diesters utilisant les ylures d’iodonium sera présenté. Finalement, l’accessibilité à plusieurs types d’allènes hautement substitués par l’utilisation de cuprates sera détaillée. Dans une seconde partie, il sera davantage question de l’accessibilité des cyclopropane-1,1-diesters énantioenrichis. Ces derniers sont d’un intérêt particulier, car ils constituent le point de départ de notre méthodologie précédente. Le développement d’une méthode pouvant être utilisée à grande échelle et à faible coût a donc été explorée. Les deux derniers chapitres présenteront donc les tentatives de générer ces cyclopropanes activés par résolution cinétique ou encore par l’hydrogénation asymétrique des cyclopropènes correspondants. / The subject of this present M.Sc. thesis is the developpement of an efficient and fast methodology toward the production of highly substituted allenes using enantioenriched cyclopropanes derivatives. The development of new synthetic methodologies in the production of these enantioenriched cyclopropan-1,1-diesters will be presented. First, the various methodologies for the preparation of activated cyclopropanes will be discussed along with their uses in the synthesis of more complex molecules. Then, the precedents in the field of asymmetric allenes synthesis will be introduced. The developpement of a viable method for the synthesis of cyclopropane-1,1-diesters using iodonium ylides will be presented. Finally, the accessibility of different highly substituted allenes by the used of cuprates will be detailed. In a second part, we will elaborate on the accessibility of the enantioenriched cyclopropane-1,1-diesters derivatives. These compounds are interesting, because they are used as starting materials in the previous methodology of allenes synthesis. This methodology has to be usable in large scale and at small cost. The last two chapters of this thesis will present the alternatives strategies for the preparation of these activated cyclopropanes by either kinetic resolution or the asymmetric hydrogenation of cyclopropenes.