Gold(i)-catalyzed stereoselective polycyclizations
- Autores: Zhouting Rong
- Directores de la Tesis: Antonio M. Echavarren Pablos (dir. tes.)
- Lectura: En la Universitat Rovira i Virgili ( España ) en 2017
- Idioma: español
- Tribunal Calificador de la Tesis: Mercedes Amat Tusón (presid.), Arjan Kleij (secret.), José Manuel González Díaz (voc.)
- Programa de doctorado: Programa de Doctorado en Ciencia y Tecnología Química por la Universidad Rovira i Virgili
- Materias:
- Enlaces
- Tesis en acceso abierto en: hdl.handle.net TDX
- Resumen
Gold(I)-catalyzed cycloisomerizations of 1,n-enynes as well as the reactions of these substrates with many nucleophiles allow the construction of complex carbo- and heterocyclic compounds by the selective activation of the alkyne in the presence of many other functional groups. These transformations have been used as the key steps in the total synthesis of diverse natural products.
Our group has been contributing to the development of gold(I)-catalyzed reactions for the construction of complex molecules and applying these methods to the total synthesis of natural products. Although there are some precedents on gold catalyzed polycyclizations, the scope and limit of gold catalysis have not been well explored. Moreover, the methods that have been developed usually require substrates with an internal nucleophile such as acid, alcohol, amide, phenol or aromatic rings. The use of alkene as the internal nucleophile, which allows the formation of steroid-like product, has never been achieved.
After condition screening, we found that a cationic gold(I) catalyst enabled this reaction. The scope of this transformation was explored and was found that 1,5-enynes bearing electron-rich aromatic rings, hydroxyl groups and alkenes are appropriate substrates for this transforamtion. 1-bromo-1,5-enynes were also found to polycyclize under the same conditions as terminal 1,5-enynes to give vinylbromide compounds which can be further transferred into other derivatives. The asymmetric version of this transformation was also investigated. It was found that the best enantioselectivity was given by using (R)-MeO-DTB-BIPHEP as the chiral ligand. The best ee was 54%. While the use of chiral ligands were not successful, a chiral camphorsultam auxiliary was found to be the most efficient auxiliary to promote the asymmetric transformation of this polycyclization. This camphorsultam auxiliary can be easily installed and removed and provide the polycycles in good diastereoselectivity. This is the first example of camphorsultam auxiliary enabled gold catalyzed trransformation and it showed good potential on promoting other gold catalyzed reactions.
