Nous nous sommes tout d'abord intéressés à la version catalytique intermoléculaire de la 1,2-diamination des éthers allyliques et en avons développé une première version. Cette réaction emploie des quantités catalytiques de Palladium(II) en tant que catalyseur et est totalement régio- et stéréosélective. Cela représente une avancée importante dans le domaine de la 1,2-difonctionnalisation oxydante des alcènes. Nous avons par la suite optimisé et simplifié cette procédure, ce qui a permis la diamination des éthers allyliques par le biais d'un seul équivalent d'alcène et un unique oxydant. Cette réaction emploie des quantités catalytiques de Palladium(II) en tant que catalyseur et est à nouveau totalement régio- et stéréosélective en utilisant cette fois-ci des conditions douces, compatibles avec un grand nombre de fonctions chimiques. Le domaine d'activité de cette réaction a été élargi aux alcènes aliphatiques avec des rendements modérés voir bons grâce à l'utilisation d'une source d'azote plus acide: la tertrafluorophthalimide. Finalement, nous nous sommes intéressés et avons développé la première diamination 1-4 intermoléculaire et générale des diènes. Cette réaction emploie des réactifs financièrement très accessibles comme CuBr2 et la saccharine et procède encore une fois de manière régiosélective avec des conditions de réaction douces. Ceci représente, cette fois-ci, une avancée considérable dans le domaine des difonctionnalisations oxydante en position 1,4 des dienes. Des études concernant les mécanismes de ces réactions ainsi qu'un développement encore plus poussé de ces réactions sont en cours. / We have first been interested in the 1,2-intermolecular diamination of allylic ethers and managed to develop a first version. This reaction employs catalytic amounts of palladium(II) compounds as catalyst source and proceeds with complete regio- and stereoselectivity. It represents a significant advance in oxidative 1,2-difunctionalization of alkenes. Then we have realized an optimization and simplification of the procedure allowing the diamination of allylic ethers through the use of only one equivalent of alkene and one oxidant. The reaction employs catalytic amounts of palladium(II) compounds as catalyst source and proceeds again with complete regioselectivity in mild conditions compatible with a large number of chemical functions. The scope of the reaction has been enlarged to aliphatic alkenes with moderate to good yields using the more acidic nitrogen source tetrafluorophthalimide. Finally, we have been interested in, and then realized, the first general intermolecular 1,4-diamination of dienes. The reaction employs economic reagents such as CuBr2 and saccharin and proceeds with complete regioselectivity under mild conditions. It represents this time a significant advance in oxidative 1,4-difunctionalization of dienes. Work in order to understand the underlying mechanisms as well as to develop further these reactions is ongoing.

We have first been interested in the 1,2-intermolecular diamination of allylic ethers and managed to develop a first version. This reaction employs catalytic amounts of palladium(II) compounds as catalyst source and proceeds with complete regio- and stereoselectivity. It represents a significant advance in oxidative 1,2-difunctionalization of alkenes. Then we have realized an optimization and simplification of the procedure allowing the diamination of allylic ethers through the use of only one equivalent of alkene and one oxidant. The reaction employs catalytic amounts of palladium(II) compounds as catalyst source and proceeds again with complete regioselectivity in mild conditions compatible with a large number of chemical functions. The scope of the reaction has been enlarged to aliphatic alkenes with moderate to good yields using the more acidic nitrogen source tetrafluorophthalimide. Finally, we have been interested in, and then realized, the first general intermolecular 1,4-diamination of dienes. The reaction employs economic reagents such as CuBr2 and saccharin and proceeds with complete regioselectivity under mild conditions. It represents this time a significant advance in oxidative 1,4-difunctionalization of dienes. Work in order to understand the underlying mechanisms as well as to develop further these reactions is ongoing.

Cette thèse décrit le développement de nouvelles réactions de difonctionnalisation catalytique d’oléfines impliquant des transferts de nitrène médiés par des complexes de dirhodium(II).La première partie de ce manuscrit s’articule autour de la réactivité d’alcènes riches en électrons, c’est-à-dire substitués par un hétéroatome. L’application des conditions de transfert de nitrène catalytiques a permis la fonctionnalisation oxydante des positions C2 et C3 de l’indole. En utilisant cette stratégie, il est donc possible d’effectuer formellement des réactions d’oxyamination intermoléculaire et de diamination intramoléculaire. Dans ce dernier cas, le motif indoline formé étant présent dans certains produits naturels, la synthèse totale de la Pestalazine B a pu être initiée. Le champ d’application de ces réactions a été étendu aux énamides en collaboration avec le groupe du Professeur Isabelle Gillaizeau.La seconde partie de ce travail concerne le développement de la réaction d’oxyamination d’oléfines aromatiques et aliphatiques. Le champ d’application de cette réaction a été étudié en détail tandis que des expériences témoins et des analyses RMN ont permis de proposer un mécanisme original.Enfin, dans un dernier temps, nous avons démontré que par extension du concept, l’application des transferts de nitrène catalytiques permet de réaliser des réactions de diamination intermoléculaire d’oléfines. / This manuscript describes the development of new reactions for the difunctionalization of alkenes that involve dirhodium(II)-catalyzed nitrene transfers.The first part of the studies focuses on the reactivity of electron-rich alkenes, i.e. substituted by a heteroatom. The application of catalytic nitrene transfers has led to the development of oxidative conditions for the difunctionalization of the 2,3-π-bond of indolic derivatives. The strategy, thus, has allowed to perform formal reactions of intermolecular oxyamination and intramolecular diamination. The latter gives access to indoline skeleton found in the structure of several natural products such as Pestalazine B, the total synthesis of which has been initiated. The scope of intermolecular oxyamination has then been extended successfully to enamides in collaboration with the group of Professor Isabelle Gillaizeau.The second part of the experimental work has been aimed at applying the catalytic oxyamination to aromatic and aliphatic alkenes. The scope of the reaction has been extensively studied while test experiments and NMR analysis have allowed to propose an unexpected mechanism based on the Lewis acid character of the metallanitrene.Finally, the scope of catalytic nitrene transfers has been extended to the intermolecular diamination of alkenes with the development of bis(arenesulfonyl)imide-type reagents.

This Thesis reports the synthesis and reactions of new hydrazide, alkoxyimide and benzimidamide complexes (L)Ti=NX (X = NAr2, NOtBu or C(Ar)NO^tBu; L = dianionic supporting ligand or ligand set). The work is supported by DFT calculations which are used to rationalise the reaction outcomes observed and, in one case, the bonding in alkoxyimide complexes. <b>Chapter One</b> provides a background to hydrazide complexes, starting with their relevance to nitrogen fixation. In addition, Group 4 imide, alkylidene hydrazide and alkoxyimide complexes are also reviewed. The Chapter focuses in particular on the synthesis, structure, and stoichiometric and catalytic reactions of these complexes with unsaturated substrates. <b>Chapter Two</b> describes the development of the virtually unexplored 1,2-diamination reaction. The substrate scope and isolation of the vinylamine products are discussed. The protonation of the vinylimide complex Ti(N2N^Me){NC(Ph)C(Me)NPh2}(py) and the overall diamination reaction itself is then explored through an in-depth experimental and computational study. <b>Chapter Three</b> details the synthesis of cyclopentadienyl-amidinate supported alkoxyimide complexes. The first detailed reactivity study, supported by structural and computational studies, of any alkoxyimide complex is reported. Novel reactivity at Ti=Nα and, in one instance, Nα–Oβ reductive bond cleavage is observed. <b>Chapter Four</b> describes the reactivity of the benzimidamide complex Cp*Ti{PhC(NⁱPr)2}{NC(Ar^F5)NO^tBu} with a range of substrates including heterocumulenes, aldehydes, isonitriles and B(Ar^F5)3. Novel reactivity at Ti=Nα, and 3-component coupling is presented, and the experimental results supported by structural and computational studies. <b>Chapter Five</b> presents full experimental procedures and characterising data for the new complexes reported.

The thesis entitled “Studies on the Stereoselective Geminal and Vicinal Heterodifunctionalization of Alkenes” consists of three chapters. Chapter 1: Part A: Bromonium Ion Mediated Stereoselective Geminal Aminooxygenation of Vinylarenes In this part (part-A) of Chapter 1, the development and mechanistic studies of the first method for the non-Wacker intermolecular geminal aminooxygenation of vinylarenes (styrenes) has been presented (Scheme 1). Sheme 1 The role of the substituent on controlling the competitive vicinal and geminal addition pathways has been studied. It was found that the unsubstituted amino alcohol takes both the vicinal addition pathways, whereas, the introduction of substituent on the aminoalcohols was found to favour only the geminal addition route (Scheme 2). Scheme 2 The diastereomeric alkenes were found to show stereoconvergence on the product formation. The migration of the phenyl group in the semipinacol rearrangement was confirmed by deuterium labeling studies. This highly stereoselective oxidative geminal addition is found to involve a semipinacol rearrangement (Scheme 3). Scheme 3 Chapter 1: Part B: Bromonium Ion Mediated Stereoselective Anti-Markovnikov Geminal Diamination and Dioxygenation of Vinylarenes In this part (part-B) of Chapter 1, the development of a facile straightforward method for the stereoselective intermolecular geminal diamination of vinylarenes under the bromonium ion mediated conditions is discussed (Scheme 4). Scheme 4 The addition of unsubstituted diamine was found to follow both geminal and vicinal addition routes, while the introduction of the substituent on the diamine was found to favour only geminal addition (Scheme 5). Scheme 5 The stoichiometric geminal dioxygenation of vinylarenes using 1,2 and 1,3 -diols was also found to work well. The substituent on the nucleophile and the nucleophilicity of the heteroatom was found to control the competitive geminal and vicinal addition pathways. The stereoselectivity of geminal dioxygenation is dependent on the ring size of the product formed and on the position of the stereo-inducing substituent. Unlike the unsubstituted diamine and the unsubstituted aminoalcohol, irrespective of the substituents attached to it, the 1,2-diols furnished only the geminal addition product (Scheme 6). Scheme 6 Interestingly, the α-methyl substituted 1,3-diols provided the corresponding 2,4-disubstituted 1,3-dioxanes with very high stereoselectivity. The β-propyl substituted 1,3-diol gave the 2,5-disubstituted 1,3-dioxane as a mixture of diastereomers (Scheme 7). Scheme 7 The phenyl migration in the semi-pinacol rearrangement in the geminal addition process was confirmed from the deuterium labelling studies (Scheme 8). Scheme 8 Chapter 1: Part C: Straightforward Synthesis of 1,3-Dioxolan-4-ones through Geminal Difunctionalization of Vinylarenes The development of a straightforward method for the synthesis of important chiral synthon, 1,3-dioxolan-4-ones by the geminal addition of α-hydroxy carboxylic acids to vinylarenes has been presented in the final part of this chapter (part-C, Chapter 1) (Scheme 9). Scheme 9 The effect of substituents on the α-hydroxy carboxylic acid on controlling the stereoselectivity of the reaction has been studied. In the case of α-hydroxy carboxylic acid derived from isoleucine containing the chiral substituent at the α position, it exclusively forms a single diastereomer of the corresponding 1,3-dioxolan-4-one (Scheme 10). Scheme 10 The reactions of α-hydroxy carboxylic acids with styrenes containing a variety of substituents have been found to work well, including the styrenes containing the electron withdrawing groups and the β-substituted styrenes. The migration of the phenyl group in the semi-pinacol rearrangement in the geminal oxidative reaction has been confirmed by deuterium labelling studies (Scheme 11). Scheme 11 Simple carboxylic acids are found to form only the vicinal addition products on reaction with styrenes. However, the alcohols under the same conditions formed only the geminal addition product, thereby demonstrating the role of nucleophilicty of heteroatom being added that control the competitive vicinal and geminal addition pathways (Scheme 12 Scheme 12 Chapter 2: Reagent-Switch Controlled Metal-Free Geminal Difunctionalization of Vinylarenes In this Chapter, the development of two new methods for the geminal oxyamination of vinylarenes and the detailed studies to understand their mechanism are presented. A novel reagent-switch for the control of migrating group by controlling the two independent, distinct pathways of the two reagent systems has been reported for this geminal addition (Scheme 13). Scheme 13 We have developed the first general method for the geminal diamination of vinylarenes with excellent stereoselectivity mediated by a hypervalent iodine reagent (Scheme 14). Scheme 14 This method is also found to be very efficient for the stoichiometric metal-free geminal dioxygenation of vinylarenes (Scheme 15). Scheme 15 The substituent on the nucleophile and the nucleophilicity of the heteroatom was found to control the competitive geminal and vicinal addition pathways. Chapter 3: Studies on the Synthesis of Enantiopure Morpholine Derivatives Mediated by Dimethyl (Methylthio) Sulfonium Triflate (DMTST) In this chapter, the development of a sulfonium ion mediated cylco-etherification methodology for the construction of biologically important molecules such as morpholines, morpholine carboxylates and morpholine methylthio ethers in good yields under mild conditions using DMTST has been presented. This method was also found to work well for the synthesis of 1,4-oxazepane (Scheme 16). (For figures pl refer the abstract pdf file)

<p>Total synthesis of massarinolin A, purpurlides B, D, E, 2,3-deoxypurpurolide C, phleghenrines A and B were finished. A halogen bond promoted michael addiation was discovered during mechanism study toward diamination of allenes. Computational chemsitry study conducted toward the selectivity of 2+2 reaction supported the proposed key reaction during total synthesis of gibberellic acid 18.</p>

Au cours de ce travail de nouvelles méthodes pour la formation de liaison C-N ont été développées. Dans la première partie de cette thèse une application de catalyse métal-ligand bifonctionnelle pour la réaction énantiosélective aza-Michael est démontrée. Dans la deuxième partie nous présentons le travail sur les cyclisations, en utilisant des alcaloïdes du quinquina facilement disponibles, comme catalyseurs des plus prometteurs, fournissant des β-amino-acides d’indoline avec jusqu'à 98% ee. Parmi eux, l’hydroquinidine ressort du lot comme étant le catalyseur donnant le meilleur excès énatiomérique. La troisième partie est liée à l'élaboration d'un nouveau processus intermoléculaires de diamination de styrènes, diènes et triènes, utilisant des bis-sulfonylimides comme source d'azote, en combinaison avec le diacétate de iodosobenzène, qui fournit une approche intéressante et efficace de diamines vicinales biologiquement et chimiquement important. La réaction peut être effectuée à température ambiante sans avoir besoin de protection par atmosphère inerte. / The concept of metal-ligand bifunctionality was successfully applied for an enantioselective aza-Michael reaction by employing well-defined ruthenium amido complexes. The catalyst was optimised and the corresponding chiral indoline β-amino acid derivatives were obtained with high enantioselectivities. Next, a straightforward enantioselective bifunctional organocatalytic approach was also developed. Employing hydroquinidine as catalyst the corresponding cyclic products were obtained in excellent enantioselectivities and quantitative yields. These compounds can be selectively deprotected and applied to peptide synthesis. Finally, we have developed unprecedented diamination reactions of styrenes, butadienes and hexatrienes employing easily accessible hypervalent iodine(III) reagents under robust reaction conditions. The first examples of the metal-free 1,2-diamination of butadienes were demonstrated and this oxidation methodology was further extended to the highly attractive 1,4 installation of two nitrogen atoms within a single step.