No description available.

Since 2000 the organocatalytic synthesis has developed massively in a third pillar of asymmetric synthesis standing next to catalysis with metal complexes and enzymatic catalysis. Organocatalysts, due to their various activation modes which could be combined in domino reactions, offer a way for a synthesis of complex molecules from a simple starting material. This thesis deals with investigation of usage of chiral secondary amines as catalysts for asymmetric synthesis of cyclic compounds. The main part of research was devoted to development of organocatalytic method leading to synthesis of enantiomerically pure cyclopentanecarbaldehydes and nitrocyclopentanecarbaldehydes. We focused also on the organocatalytic preparation of cyclohexanecarbaldehydes. During this work we developed an asymmetric domino Michael addition/α- substitution reaction of 2-(2-bromoethyl)malonates resp. 1-bromo-3-nitropropane with various enals catalyzed by chiral secondary amine. In the first case cyclopentanecarbaldehydes were formed where two chiral centres were created. In second case nitrocyclopentanecarbaldehydes were formed where three chiral centres were created. Yields of such developed reaction protocol reach up to 74 % and the reaction proceeds with excellent diastereo- and enantioselectivity (up to 19:1 d.r. and...

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

In 1908, H. Emil Fisher attempted to prepare glycinal, an unprotected amino aldehyde, which he found to be inherently unstable and prone to polymerization. This instability arises from the propensity of amines to condense with aldehydes. Accordingly, amino aldehydes require protection of the amine functional group. On the contrary, aziridines do not condense with aldehydes; the aziridine ring-strain precludes the formation of an iminium ion. Predicated upon this orthogonal reactivity, a stable class of unprotected amino aldehydes has been prepared, and an in-depth investigation into their chemical reactivity has been undertaken. Reactions designed to utilize both their nucleophilic (amine) and electrophilic (aldehyde) centres have demonstrated their capacity to forge multiple bonds in a single transformation, and have been implemented in the synthesis of complex heterocycles and cyclic peptides.

This thesis describes research conducted since September 2006 in Prof. Robert Batey’s laboratory. The thesis is divided into four chapters. Chapter one presents a general introduction of domino reactions, sigmatropic rearrangements, and the allylic azide rearrangement. Several factors affecting the allylic azide rearrangement along with some respective examples are presented. Chapter two describes an efficient synthesis of azido unsaturated ester compounds using a microwave-assisted domino allylic azide / Johnson-Claisen rearrangement. The domino rearrangement reaction proceeds to give the azido ester compounds in good yield and excellent diastereoselectivity. The synthesis of vinyl epoxides and hydroxy allylic azides starting materials are also presented. In addition, other variants of Claisen rearrangements are briefly discussed. Chapter three describes a microwave-assisted domino allylic azide / Overman rearrangement process. The scope of the domino rearrangements, including an example involving an enantioenriched compound, is presented. The product of the domino rearrangements can be used as precursors to 1,2-vicinal diamines. Several functional group transformations and potential application of the product of the domino rearrangement are also described. Chapter four provides the synthesis of cis-2,5-disubstituted pyrrolidines from domino reduction / cyclization of γ-azido-α,β-unsaturated ketones. The overall process involves hydrogenation of the alkene and the azido group, followed by intramolecular cyclization and loss of H2O to form an imine, which is further reduced to give cis-2,5-disubstituted pyrrolidines. The reaction proceeds cleanly to give the products in high yield and with a very high diastereoselectivity ratio. In addition, the formation of pyrrolidinones via domino reduction / cyclication of γ-azido esters are also reported

This thesis describes research conducted since September 2006 in Prof. Robert Batey’s laboratory. The thesis is divided into four chapters. Chapter one presents a general introduction of domino reactions, sigmatropic rearrangements, and the allylic azide rearrangement. Several factors affecting the allylic azide rearrangement along with some respective examples are presented. Chapter two describes an efficient synthesis of azido unsaturated ester compounds using a microwave-assisted domino allylic azide / Johnson-Claisen rearrangement. The domino rearrangement reaction proceeds to give the azido ester compounds in good yield and excellent diastereoselectivity. The synthesis of vinyl epoxides and hydroxy allylic azides starting materials are also presented. In addition, other variants of Claisen rearrangements are briefly discussed. Chapter three describes a microwave-assisted domino allylic azide / Overman rearrangement process. The scope of the domino rearrangements, including an example involving an enantioenriched compound, is presented. The product of the domino rearrangements can be used as precursors to 1,2-vicinal diamines. Several functional group transformations and potential application of the product of the domino rearrangement are also described. Chapter four provides the synthesis of cis-2,5-disubstituted pyrrolidines from domino reduction / cyclization of γ-azido-α,β-unsaturated ketones. The overall process involves hydrogenation of the alkene and the azido group, followed by intramolecular cyclization and loss of H2O to form an imine, which is further reduced to give cis-2,5-disubstituted pyrrolidines. The reaction proceeds cleanly to give the products in high yield and with a very high diastereoselectivity ratio. In addition, the formation of pyrrolidinones via domino reduction / cyclication of γ-azido esters are also reported

Cette thèse a été consacrée tout d'abord à l'étude du premier procédé domino méthylénation-hydrogénation des aldéhydes et des cétones. Ce processus repose sur la combinaison d'un réactif gem-bimétallique [CH2(ZnI)2] et un catalyseur de Wilkinson (ClRh(PPh3)3) en présence d'hydrogène moléculaire.L'étendue et les limites de cette réaction ont été explorées. Ensuite, l’étude de la réaction de semi-hydrogénation antid'alcynes par catalyse homogène a permis d’accéder de façon stéréosélective aux alcènes (E) correspondants. Cette réaction a été développée en utilisant des réactifs commerciaux et peu couteux : Zn0, ZnI2 et Cl2Pd(PPh3)2sous1 atmosphère d’hydrogène moléculaire. Ces conditions sont à ce jour les plus douces utilisées pour cette réaction.Finalement, la préparation d’imidates par condensation de furfurylamine sur une variété d’iminoester, et la synthèse d’amidines par la condensation d’amines primaires sur les imidates précedemment obtenus, ont été réalisées. L’évaluation de l’activité anti-oxydante des nouveaux composés formés (imidates et amidines) a donnée des résultats prometteurs. / During this research, the firstmethylenation-hydrogenation domino process of aldehydes and ketones has been studied. This process is based on the combination of a gem-bimetallic reagent [CH2(ZnI)2] and a Wilkinson catalyst (ClRh(PPh3)3). The scope and limitations of this reaction have been explored.Furthermore, the semi-hydrogenation antiof internal alkynes by homogeneous catalysis allowed stereoselective access to the corresponding alkenes (E). This reaction was developed using commercially available and low expensive reagents: Zn0, ZnI2 and Cl2Pd(PPh3)2under H2 atmosphere. The use of easy handle and soft conditions had been first described.Finally, two synthetic routes were used to prepare imidates and amidines. The first were obtained from furfurylamine and iminoesters, while amidines were prepared from the condensation of primary amines on previous imidates. Evaluation of the antioxidant activity of these compounds gave promising results.

No description available.

A summary of research conducted since September 2007 at the University of Toronto in the laboratory of Professor Robert A. Batey is presented in this thesis, which is divided into four chapters. The first chapter contains a two-part introduction, where aryl- and aliphatic-Claisen rearrangements are discussed in part 1, and the nucleophilic addition of organoboron reagents to unsaturated C–N functionalities is described in part 2. Chapter 2 contains research involving synthetic and theoretical studies of aryl-Claisen rearrangements and other sigmatropic reactions. The work towards developing the lanthanide-catalyzed domino aryl-Claisen rearrangement for the synthesis of contiguous aryl–C(sp³) moieties is presented first. This is followed by computational studies involving E/Z-selectivity differences for the aryl-Claisen rearrangement, which was an issue noted for the domino aryl-Claisen reaction of a linear substrate. The mechanistic origins of E/Z-selectivity differences for the mono aryl-Claisen rearrangement, which was experimentally ambiguous for over 40 years, is resolved through computational methods. A theoretical analysis of selectivity differences for the allylic azide rearrangement is also described. The third section contains a discussion of Eu(fod)3-catalyzed aryl-Claisen rearrangements on vinyl bromide systems and preliminary studies involving application of the substrates in cross-coupling reactions, and other attempted mono- and domino sigmatropic rearrangements are presented in the fourth section. In chapter 3, the search for computational methods that can accurately predict experimental free energy of activation barriers for the aliphatic-Claisen rearrangement through benchmarking studies with a priori kinetic barrier and kinetic isotope effect data is described. Methods were found to predict new valid transition states and predict ΔG‡ values with a mean unsigned error of 0.3 kcal/mol relative to experimental values. In chapter 4, the development of new allylboration reaction is outlined, involving the double allylboration of nitriles and anhydrides, and initial studies towards the first aminoallylboration reactions of N-aluminoaldimines to form 1,2-diamines.

No description available.