We successfully synthesize three different tertiary amine phosphinoamine ligands, which are 1-(2-(dicyclohexylphosphino)phenyl)pyrrole (L2), N-(2-(dicyclohexylphosphino)phenyl) morpholine (L3), and N-(2-(diisopropylphosphino)phenyl)morpholine (L4) separately. With another referenced ligand o-(dicyclohexylphosphino)biphenyl (L1) as comparison and test the reactivities toward palladium and nickel by in situ method with the four different ligands. We test Kumada-Corriu coupling reactivity of different nickel precursors to L1, L2 and L3, surprisingly, we find that under room temperature, reaction of NiCl2(DME) as precursor and TMEDA (1.1 equiv.) as ligand to replace phosphinoamine ligands (L1¡BL2¡BL3) can effectively couple iododecane with hexyllmagnesium bromide, and the catalytic condition possesses quite high selectivity. This new Ni-catalyzed cross-coupling reactions employing secondary isopropylmagnesium chloride have led to the exclusive formation of linear isomerized cross-coupling products due to reinsertion after rapid £]-H elimination.

The alkyl substitution effects and the hybridization effects on the rate of coupling of adsorbed hydrocarbon groups on Ag(111) have been investigated under ultrahigh vacuum by temperature programmed reaction/desorption (TPR/D). For these two different issues, two types of halide precursors were used. One is to form adsorbed fragments bearing C£\(sp3) and C£\-H, the other is to yield adsorbed fragments with different hybridized £\-carbons without C£\-H. The desired hydrocarbon groups were generated on Ag(111) by the thermal dissociation of the C-X (X = I or Br) bond in the corresponding halogenated compounds. Substitution of alkyl for hydrogen in the adsorbed alkyl groups systematically raises the coupling temperature. For example, 3-pentyl groups homo-couple at temperatures ~ 70 K higher than the ethyl homo-coupling reaction. The concept of ¡§geminal repulsion¡¨ can account for our experimental results while the size and the number of the alkyl substitution groups increase. Different hybridized C£\ (metal-bonded carbon) species cause various angle strain energies in the cyclic transition state for the coupling reaction. The C£\(sp) species (CH3C¡ÝC(ad) and (CH3)3SiC¡ÝC(ad)) have rather high coupling temperatures (~ 460 K) due to the unidirectional sp orbital and the stronger Ag-C(sp) bond in the transition state. The relative rates for homo-coupling as a function of the hybridization of the metal-bound carbon follow the trend sp3 > sp2 > sp on the Ag(111) surface. Lastly, we found that the isobutyl groups undergo a £]-hydride elimination instead of homo-coupling on the Ag(111) surface. It may be due to that isobutyl groups have a total of nine £]-hydogens among all the hydrocarbon groups, which makes this rare reaction pathway possibly occur on Ag(111).

La fonctionnalisation de liaisons C-H réputées peu réactives ouvre de nouvelles perspectives en synthèse organique. Une stratégie efficace consiste en l’utilisation d’un métal de transition. Les travaux de thèse présentés dans ce mémoire s’inscrivent dans ce contexte. Dans un premier temps, la réaction étudiée, catalysée par le palladium, vise à étendre une méthodologie mise au point au laboratoire, permettant la synthèse de benzocyclobutènes par activation intramoléculaire de liaisons C(sp3)-H de groupements méthyles benzyliques, à des composés non aromatiques. Plusieurs substrats ont été synthétisés pour être ensuite placés dans les conditions de la réaction d’activation C(sp3)-H, dans le but d’induire la formation du cyclobutène ou du cyclobutane désiré. Le processus n’est pas sélectif et de nombreux produits secondaires sont obtenus par des réactions péricyliques ou par des réarrangements suite à l’ouverture du palladacycle intermédiaire. Dans un deuxième temps, nos travaux ont permis de mettre à jour une nouvelle réaction de fonctionnalisation C(sp3)-H, catalysée par le palladium permettant l’arylation d’esters en position β par un mécanisme original. Les investigations portent sur l’optimisation complète de cette réaction, la compréhension du mécanisme et le développement d’une version énantiosélective prometteuse. Le mécanisme de cette réaction, confirmé par des calculs DFT réalisés en collaboration avec C. Kefalidis et E. Clot, se rapproche formellement de celui observé en α-arylation, puisqu’il repose sur la formation d’un énolate de palladium. La stratégie mise au point permet le couplage, dans des conditions douces, d’esters simples et commerciaux avec des halogénures d’aryles contenant un groupement électronégatif en position ortho, donnant ainsi accès à des intermédiaires de synthèse intéressants tels qu’un analogue de la phénylalanine ou des composés fluorés. / The direct functionalization of C-H bonds represents an atom- and step-economical alternative to more traditional synthetic methods based on functional group transformation, which often require multi-step sequences. In particular, transition-metal catalysis has recently emerged as a powerful tool to functionalize otherwise unreactive C-H bonds. In this context, we first investigated the extension of a methodology that has been developed in our laboratory for the synthesis of benzocyclobutenes via C(sp3)-H activation, to non aromatic compounds. Substrates have been synthesized in order to be evaluated in the reaction to form cyclobutenes or cyclobutanes. The process was not selective and several by-products were formed via pericylic reactions or rearrangements of the intermediate palladacycle. Our research has also focused on a conceptually new palladium catalyzed β-C-H arylation of carboxylic esters method. The investigations consisted of a complete optimization of the reaction conditions, an evaluation of the scope and elucidation of the mechanism. It was found that this type of [bêta]-arylation is mechanistically related to α-arylation because it involves the formation of a palladium-enolate. Computational studies (DFT calculations, C. Kefalidis et E. Clot) confirmed the proposed mechanism. Our strategy allowed a mild and efficient intermolecular arylation reaction from aryl halides bearing an ortho electronegative group, giving rise to a range of synthetically useful functionalized carboxylic esters such as phenylalanine analogues and new fluorinated building blocks.