RT info:eu-repo/semantics/doctoralThesis
T1 C-H Functionalization of Arenes Enabled by Cooperating Pyridone-Type Ligands: More Selective Transformations and a Dual Ligand System for Milder Reaction Conditions
A1 Pinilla Martín, Cintya
A2 Universidad de Valladolid. Escuela de Doctorado
K1 Catalisis
K1 C-H Activation
K1 Activación C-H
K1 Cooperating ligands
K1 Ligandos cooperativos
K1 23 Química
AB The main goal of this thesis is to develop more sustainable and environmentally friend reaction conditions for the C-C coupling reactions. The formation of new C-C bond is a versatile tool in the synthesis of interesting compounds such as drugs, pesticides, cosmetics and so on. Several efforts have been made during the last decades in order to use the raw materials as reagents, avoiding their prefunctionalization. The new strategies require a C–H activation step in their mechanism but this is not easy due to the low reactivity of the C–H bonds. To achieve those high energy demanding processes, cooperating ligands have been developed with the role of assisting during the C–H activation of the reactants. The work in this thesis is focused on the use of cooperating ligands in C–C coupling reactions with C–H activation.The use of the ligand 2,2’-bipiridin-6(1H)-ona in the direct arylation of anilines allows to obtain the C-C coupling product in the aromatic ring without protecting the amino group, a commonly used strategy in the literature. The protection is necessary to avoid the amination product (C-N). In our approach, the protection and deprotection steps are not needed and achieving a more sustainable global process. The chemoselectivity is achieved due to the cooperating ligand that decrease the C-H activation energy of the aniline and disfavours the formation of the C-N coupling product. Moreover, the reaction is selective to the ortho coupling in primary anilines, and tolerates different electronic properties in the reagents.Milder conditions (30 ºC less) have been developed for the direct arylation of simple arenes by the use of a dual ligand system: the cooperating ligand 2,2’-bipiridin-6(1H)-ona together with tricyclohexylphosphine. The reaction tolerates different electronic properties in the reagents. The experimental and computational mechanistic studies show a possible bimetallic mechanism where the system 2,2’-bipiridin-6(1H)-ona/Pd cooperates in the C-H activation and the system PCy3/Pd is responsible of the oxidative addition and reductive elimination steps. The trasnmetallation step between two analogous species has been demonstrated experimentally.The cooperating ability of ligands with a similar scaffold to the ones that have demonstrated to be effective accelerating C-H functionalization reactions (2,2’-bipiridin-6(1H)-ona and mono protected amino acids). The new ligands are 6-hydroxypicolinic acid and amido-pyridine type ligands which synthesis is modular and their electronical and steric properties can be adapted to the requirements of the reaction. The ligand 6-hydroxypicolinic acid showed to be very effective in the C-H activation step by independent experiments. However, in the catalytic direct arylation of arenes did not give good results. The amido-pyridine ligands were less effective than the 6-hydroxypicolinic acid in the C-H activation step and almost no coupling product was observed when tested in the catalytic direct arylation of arenes or in other type of reactions with C-H activation of arenes. Results comparable to the reported ones were obtained only in the acetoxylation of alkyl-carboxylic acids. In conclusion, the ligand cooperation in the C–H activation is a necessary but not sufficient requirement for an efficient C–H functionalization. In any case, the proved ability of these ligands in the C–H activation step makes them suitable candidates to be considered when developing new catalytic C–H functionalization reactions.
YR 2024
FD 2024
LK https://uvadoc.uva.es/handle/10324/67150
UL https://uvadoc.uva.es/handle/10324/67150
LA eng
NO Escuela de Doctorado
DS UVaDOC
RD 24-nov-2024