<p> The reactions of methyllithium and phenyllithium with the iminium chloride, [(2R,3S)-2,3-dihydroxy-3-(6,7 -dimethoxy-3,4-dihydroisoquinolin-1-yl)]propionate hydrochloride, 34 as a means of preparing enantiomerically pure compounds are described. These reactions afford a single product in high yield. The nmr spectra of the products, 1-(1 ,2,3-trihydroxy-3,3-dimethylpropyl)-1 ,2,3,4-tetrahydro-6,7 -dimethoxy-1- methylisoquinoline 54 and 1-( 1,2,3-trihydroxy-3,3-diphenylpropyl)-1,2,3,4-tetrahydro-6,7- dimethoxy-1-phenylisoquinoline 62, are discussed and an explanation is given to account for the diastereoselectivity of the reaction. By this method, enantiomerically pure compounds bearing a quaternary centre at C-1 of the tetrahydroisoquinoline system may be prepared. Oxidative degradation of the hydroxylated side chain of compound 62 has led to the preparation of several other new compounds. </p> <p> The usefulness of the t-butoxycarbonyl group as a selective protecting group for nitrogen in the preparation of 2-t-butyloxycarbonyl-1,2,3,4-tetrahydro-1-(1,2,3- trihydroxy-3,3-dimethylpropyl)-6,7-dimethoxy-1-methylisoquinoline 59 is described. It has advantages over the ethoxycarbonyl group in that it not only selectively protects the amino group but also is easy to remove by short treatment with trifluoroacetic acid and water at room temperature. Treatment of 59 with sodium periodate afforded the aldehyde, 1-formyl-2-t-butyloxycarbonyl-1,2,3,4-tetrahydro-6,7-dimethoxy-1-methylisoquinoline, 60. An attempted oxidation of the aldehyde 60 to the acid is also described. </p> <p> A review of recent methods of inducing chirality at C-1 of the tetrahydroisoquinoline system is given in the Introduction. </p> / Thesis / Master of Science (MSc)

Le système spirocyclique (7,5) est un motif récurrent dans un certain nombre de produits naturels tels que les Micrandilactones ou les Rubriflordilactones. Ces structures polycycliques représentent un réel défi synthétique pour les chimistes organiciens puisqu'elles présentent au moins neuf centres stéréogènes dont plusieurs sont quaternaires. L'objectif principal de ce travail était de développer de nouvelles réactions de cycloaddition [3+2] et de les utiliser comme étape clé afin d'obtenir rapidement et efficacement le squelette polycylique de ces composés. La première partie de ces travaux a été consacrée au développement d'une réaction de cycloaddition [3+2] intra- et intermoléculaire mettant un jeu un nouveau partenaire dipolarophile, les γ-alkylidènes-buténolides. Cette étape clé conduit à la formation de cycloadduits hautement fonctionnalisés de façon rapide et efficace avec d'excellents rendements et de façon hautement chimio-, régio- et diastéréosélective. De plus, des calculs théoriques ont permis d'appréhender le mécanisme réactionnel entre un 2-diazo-1,3-cétoester et la protoanémonine catalysé par un sel de rhodium mis en jeu dans ce type de processus et ainsi d'expliquer les résultats obtenus.Dans une deuxième partie, deux approches aux cœurs ABC et CD de la micrandilactone C ont été développées mettant respectivement en jeu une cycloaddition [3+2] formellement intermoléculaire utilisant un lien de type acétal de silicium et suivie par une réaction de Diels Alder. Ainsi, le motif tétracyclique devrait être rapidement accessible après quelques aménagements de la voie de synthèse initiale. / The spiro (7, 5) ring system is a recurring structural moiety in numerous natural products such as Micrandilactones and Rubriflordilactones. In term of complexity, these polycyclic structures represent a synthetic challenge for organic chemist. Indeed, these molecules present at least nine stereogenic centres including several quaternary ones. The main goal of this work was to use unprecedented partners in the [3+2] cycloaddition reaction to obtain quickly and efficiently the polycyclic core of those natural products. The first part of these studies was dedicated to the development of an intra- and intermolecular [3+2] cycloaddition using for the first time a γ-alkylidene-butenolide dipolarophile. This approach provides rapid and facile access to highly functionalised polycyclic molecules along with excellent regio-, chemo- and stereoselectivities. In addition, thanks to computational studies an overall picture of the mechanism of the intermolecular rhodium catalysed [3+2] cycloaddition between 2-diazo-1,3-ketoester and protoanemonin was apprehended, and experimental results have been rationalised.Finally, two approaches to the ABC and CD cores of Micrandilactone C were developed using respectively a formal intermolecular [3+2] cycloaddition reaction in presence of a silicon acetal linker followed by a Diels Alder reaction. The ACDE tetracyclic moiety should be quickly accessible after few modifications of the initial strategy.