Copper-catalyzed asymmetric transformations with dihalogenated allylic compounds
- Autores: Andrea Chaves Pouso
- Directores de la Tesis: Martin Fañanas Mastral (dir. tes.)
- Lectura: En la Universidade de Santiago de Compostela ( España ) en 2025
- Idioma: inglés
- Tribunal Calificador de la Tesis: José Luis Vicario Hernando (presid.), María Dolores Pérez Meiras (secret.), Marcos García Suero (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencia y Tecnología Química por la Universidad de Santiago de Compostela y la Universidad de Vigo
- Materias:
- Enlaces
- Tesis en acceso abierto en: MINERVA
- Resumen
This doctoral thesis focuses on the development of copper-catalyzed asymmetric reactions involving alkyne allylboration with various allylic substrates, meso dibromocycloalkenes and geminal dichlorides, and the borylation of geminal dichlorides. These reactions use the catalytic generation of the LCu-Bpin complex. The thesis introduces a new copper-catalyzed methodology for the asymmetric allylboration of meso dibromocycloalkenes, leading to 1,4 dienes with up to three stereocenters and excellent regio, diastereo and enantioselectivity. By optimizing various parameters, including the use of a specific NHC sulfonate ligand and slow addition of the meso-compound, the reaction yields high enantioselectivity and efficient transformations, demonstrating broad applicability in creating optically active cyclic scaffolds. The second section develops a copper catalyzed alkyne allylboration using geminal dichlorides as electrophiles, which introduces a new challenge due to the formation of E Z isomers. The methodology efficiently generates 1,4 skipped dienes with an alkenylboronate, an alkenyl chloride and a bis-allylic stereocenters with excellent stereoselectivity. The study finds that the use of an NHC sulfonate ligand and a small counterion in the base, such as lithium tert butoxide, is key to controlling selectivity. The reaction tolerates a wide range of substrates and due to the presence of orthogonal functionalities we can modify the 1,4 diene in a selective manner. DFT calculations support the key presence of a metal cation bridge ligand-substrate interaction that is the key factor for the observed stereoselectivity outcome. In the final section, the thesis explores the asymmetric borylation of geminal dichlorides using copper catalysis, achieving chiral secondary boronic esters with control over the double bond configuration. Optimization of the NHC ligand and reaction conditions led to perfect stereoselectivity. The reaction also tolerates various functional groups and substrates. DFT calculations provided insights into the factors influencing stereoselectivity. These calculations revealed that the interaction between the proton at the alpha position of the gem dichloride and the pi electron density of the naphthalene unit of the chiral ligand is the primary factor to control the selectivity. Overall, the thesis advances the field of copper-catalyzed asymmetric transformations, providing new methodologies for the synthesis of complex, chiral molecules with high selectivity and functional versatility.
