Development of a comprehensive study on base-controlled regioselective functionalization and Iridium-Catalysed Borylation of indolizines

Indolizines is an important bioisostere of indole being considered as privileged structure with application in pharmaceutical, agrochemical and material sciences field. In this context, the focus of this thesis was to develop new methodologies for the preparation of more complex indolizine scaffolds...

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Detalles Bibliográficos
Autor: Bertallo, Camila Rodrigues de Souza
Tipo de recurso: tesis doctoral
Estado:Versión publicada
Fecha de publicación:2020
País:Brasil
Institución:Universidade de São Paulo (USP)
Repositorio:Biblioteca Digital de Teses e Dissertações da USP
Idioma:inglés
OAI Identifier:oai:teses.usp.br:tde-29062021-154153
Acceso en línea:https://www.teses.usp.br/teses/disponiveis/60/60138/tde-29062021-154153/
Access Level:acceso abierto
Palabra clave:Acoplamento cruzado de Negishi
Acoplamento cruzado de Suzuki
Ativação C-H
C-H activation
C-H borilação
C-H borylation
Indolizinas
Indolizines
Metalação
Metalation
N-heterocíclicos
N-heterocycles
Negishi cross-coupling
Suzuki cross-coupling
Descripción
Sumario:Indolizines is an important bioisostere of indole being considered as privileged structure with application in pharmaceutical, agrochemical and material sciences field. In this context, the focus of this thesis was to develop new methodologies for the preparation of more complex indolizine scaffolds using different strategies such as (a) directed metalation using lithium bases and Mg bases complexed with LiCl and (b) C-H borylation using [Ir(OMe)(COD)]2 as catalyst. This work allowed the isolation of 39 new indolizine derivatives functionalized at C-2, C-3 or C-5 position in 48-95% yields through a base-controlled regioselective approach using lithium amides and TMPMgCl.LiCl. Over the last years, the direct C-H borylation of arenes and heteroarenes has become an attractive method for the preparation of functionalized derivatives that could be hardly to prepare through the traditional methods. However, whilst many heterocycles such as indole, azaindoles, pyridines, pyrroles and quinolines have been investigated, to the best of our knowledge this is the first time that a study has been conducted for indolizine. Seven new modified indolizines could be synthetized using this protocol.