Asymmetric induction on isocyanide-based transformations: development of stereoselective Ugi-type reactions

• Ano de defesa: 2023
• Autor(a) principal: Silva, Vitor Alcantara Fernandes da
• Orientador(a): Paixão, Márcio Weber
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: eng
• Instituição de defesa: Universidade Federal de São Carlos; Câmpus São Carlos
• Programa de Pós-Graduação: Programa de Pós-Graduação em Química - PPGQ
• Palavras-chave em Português: Organocatálise; Reação Multicomponente; Reação de Ugi; Hemiacetal; Isocianeto; Transformações estereosseletivas; Indução de assimetria; Ácido fosfórico quiral
• Palavras-chave em Inglês: Organocatalysis; Ugi reaction; Isocyanide; Multicomponent reaction; Stereoselective transformations; Asymmetric induction; Chiral Phosphoric Acid
• Área do conhecimento CNPq: CIENCIAS EXATAS E DA TERRA::QUIMICA::QUIMICA ORGANICA::SINTESE ORGANICA
• Link de acesso: https://repositorio.ufscar.br/handle/ufscar/18189

The design of new synthetic transformations that rapidly allow construction of structurally complex molecules from simple starting materials under both concepts of diversity and function-oriented syntheses is extremely desirable in contemporary organic chemistry. In this regard, multicomponent reactions (MCRs) appear as one of the most useful strategies for quickly generating structural diversity and molecular complexity. Among the vast repertoire of MCRs, isocyanide-based multicomponent reactions (IMCRs) stand out as a powerful approach to achieve highly functionalized molecules with elevated chemical efficiency, convergence and atom economy. As part of our ongoing interest in developing diastereoselective intramolecular I-MCRs based on chiral scaffolds, an efficient strategy has been established, which combines the stereocontrol of organocatalysis with the diversity-generating character of multicomponent reactions, leading to structurally unique cyclopentenyl frameworks containing two stereogenic centers. Based on our recent success into using hemiacetals in substrate-controlled I-MCR reactions, we have envisioned the development of an asymmetric Ugi-type Reaction with achiral hemiacetals using an organocatalytic Brønsted acid as the element of asymmetric induction. After a short screening of conditions, we found out that SPINOL-derived chiral phosphoric acids, especially with phenanthryl as substituent (59% yield, 66% ee), which was chosen as the best catalyst in this initial screening.