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

• Ano de defesa: 2020
• Autor(a) principal: Bertallo, Camila Rodrigues de Souza
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Biblioteca Digitais de Teses e Dissertações da USP
• Palavras-chave em Português: 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
• Link de acesso: https://www.teses.usp.br/teses/disponiveis/60/60138/tde-29062021-154153/

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.