Sustainable and Efficient Manganese-Catalyzed Imine Formation: a Step Further to One-Pot Bimetallic Synthesis of N-Heterocycles

• Autor(a) principal: Viduedo, Nuno André dos Santos
• Data de Publicação: 2021
• Tipo de documento: Dissertação
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: http://hdl.handle.net/10362/125915
• topic: Imines; N-heterocycles; Manganese catalysis; Palladium catalysis; Domínio/Área Científica::Engenharia e Tecnologia::Engenharia Química

Imine derivatives have long been described as exceptionally useful compounds in organic chemistry, being mostly recognized as key intermediates in the synthesis of nitrogen heterocycles, such as indoles and azaindoles. In fact, these two similar N-heterocyclic scaffolds are widely present in biologically active compounds, thus considered privileged nucleus in medicinal chemistry. Therefore, there is a great interest of the scientific community in developing new synthetic methodologies to efficiently obtain both imines and the corresponding heterocyclic structures. Recently, imine synthesis has been explored by acceptorless dehydrogenative coupling (ADC) of aromatic amines and primary alcohols, via manganese-catalyzed processes. In this thesis, several phosphine-free manganese(I) tricarbonyl complexes, bearing different bidentate ligands, were employed in order to find the most efficient ones for the ADC reaction of aniline and aminopyridine systems. In this context, manganese complexes bearing chelating di-triazole-based ligands proved to be the most appropriate. Additionally, reaction conditions were optimized to maximize imine formation. Interestingly, it was found that ADC reactions were efficiently catalyzed using 3 mol% of Mn-based catalyst loading, in the presence of potassium tert-butoxide and molecular sieves, achieving high yields (up to 99%) of a large variety of imines (more than 25), starting from aniline and aminopyridine derivatives. Next, imine synthesis from aromatic amines and secondary alcohols, mediated by Mn-catalysts, was explored, while we were getting closer to the creation of N-heterocycles synthetic routes. Reaction conditions were separately optimized for secondary alcohol oxidation and ketimine formation, yielding the desired products in 91% and 95%, respectively. Lastly, a bimetallic route, involving manganese and palladium catalysis, to achieve indoles and azaindoles, from simple and commercially available aromatic amines and alcohols, were established. This one-pot procedure, concerning 3 reaction steps, allowed the obtention of indole scaffold in a promising 30% yield. On the other hand, although only trace amounts of azaindoles were found, the studies performed led to interesting discoveries that could be very useful in the near future.