Palladium in azaheterocyclic synthesis: α-arylation of sulfones, domino processes and c-h carbene insertion reactions

• Autores: Ferran Pérez Janer
• Directores de la Tesis: Daniel Solé Arjó (dir. tes.)
• Lectura: En la Universitat de Barcelona ( España ) en 2018
• Idioma: español
• Tribunal Calificador de la Tesis: Roberto Sanz Díez (presid.), Pedro Romea Garcia (secret.), Anna Pla Quintana (voc.)
• Programa de doctorado: Programa de Doctorado en Química Orgánica por la Universidad de Barcelona
• Materias:
  • Química
    • Química orgánica
      • Compuestos heterocíclicos
      • Compuestos organometálicos
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• Resumen

  • Palladium in Azaheterocyclic Synthesis: α-arylation of sulfones, domino processes and C-H carbene insertion reactions Among transition metals used in organic chemistry, palladium has greatly contributed to the development of modern organic synthesis. This thesis is focused on the development of novel and efficient methodologies for the synthesis of nitrogen heterocycles employing palladium catalysed reactions. In this work, DFT calculations complement the experimental work in order to gather mechanistic insights of the reported transformations.

    In the first part of the thesis an exhaustive study of the intramolecular palladium catalysed α-arylation of sulfones is described. This metal-mediated process was successfully combined with conjugated additions to generate domino processes of two, three and four steps that allowed the synthesis of functionalised indoles and tetrahydroisoquinolines.

    From a mechanistic point of view, DFT calculations suggest that a concertated metalation-deprotonation process followed by reductive elimination is involved in the indole ring formation.

    Next, the intramolecular palladium catalysed α-arylation reaction was explored using nucleophiles derived from sulfonates, sulfonamides and phosphonates.

    Although feasible, these nucleophiles are less efficient in the intramolecular cyclization leading to the tetrahydroisoquinoline ring. Domino processes based on α-arylation/Michael addition reactions starting from sulfonates and sulfonamides using diverse Michael acceptors were also reported. Attempts to pursue domino process starting from phosphonates were unsuccessful.