New methods for organocatalyzed asymmetric synthesis of spirocyclic pyrazolones from pyrazole-4,5-diones and n-boc protected pyrazolinone ketimines

  1. Gil Ordóñez, Marta
Supervised by:
  1. José María Andrés García Director
  2. Alicia Maestro Fernández Co-director

Defence university: Universidad de Valladolid

Fecha de defensa: 07 July 2023

Committee:
  1. Gonzalo Blay Llinares Chair
  2. Rubén Manzano San José Secretary
  3. José Antonio Fuentes García Committee member

Type: Thesis

Abstract

Pyrazole derivatives are an interesting class of heterocycles known for the wide range of applications they enable. Among all of them, spirocyclic pyrazolones and 4-amino-5-pyrazolone derivatives belong to a wide family of compounds with well-known pharmacological properties (antitumoral, analgesic). Due to this, chemists have devoted efforts to the asymmetric synthesis of these compounds. Whereas pyrazolin-5-ones and unsaturated pyrazolones have been extensively used as starting materials in asymmetric reactions, pyrazolin-4,5-diones and their corresponding N-Boc ketimines derivatives have hardly been used. On the other hand, asymmetric organocatalysis constitutes one of the most useful, effective and eco-friendly strategies for the asymmetric synthesis of organic compounds, and, because of this, it is a growing field. Consequently, the main objective in this Doctoral Thesis is the development of new methods for the asymmetric synthesis of spirocyclic pyrazolones and 4-amino-5-pirazolone derivatives from pyrazolin-4,5-diones and their N-Boc ketimines derivatives. Two different strategies will be used: covalent catalysis, by using chiral N-heterocyclic carbenes, and hydrogen bonding catalysis through the use of chiral bifunctional squaramides.