Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation

• Autor(a) principal: Renato Lúcio de Carvalho
• Data de Publicação: 2022
• Tipo de documento: Tese
• Idioma: eng
• Título da fonte: Repositório Institucional da UFMG
• Texto Completo: http://hdl.handle.net/1843/46387; https://orcid.org/0000-0002-8515-9306
• topic: Quinones; Polycyclic compounds; Double-annulation reaction; C–H activation; Ruthenium catalysis; Quinonas; Compostos policíclicos; Reação de anelação dupla; Ativação de ligação C–H; Catálise com rutênio; Química orgânica; Quinona; Compostos policíclicos; Compostos de rutênio; Rutênio; Catálise; Agentes antineoplásicos; Raios X; Difração; Catalisadores de metais de transição; Testes biológicos; Ressonância magnética nuclear; Espectro infravermelho; Espectrometria de massa; Cristalografia

This work presents the construction and development of a new methodology for the obtention of modified naphthoquinoidal compounds via a C(sp2)–H activation process. In this context, the intrinsic direction capability of the carbonyls, present in naphthoquinones, was explored towards arylation and annulation reactions mediated by ruthenium catalysis. After a sequence of failed results, we expanded this study to the use of directing groups added to the quinoidal structure. The optimization of this method led to the formation of polycyclic quinones, in moderate to optimum yields, from their respective substrates, using a ruthenium-catalyzed double-annulation reaction via a C(sp2)–H activation process, in the presence of an internal alkyne, copper-II acetate and sodium pivalate. Two scope sets were developed, and for the first one, several alkynes were obtained through a Sonogashira-type reaction, and subsequentially applied to the optimized methods, from which eleven double-annulated products were achieved and properly characterized. A second scope was developed using quinoidal compounds previously synthesized after sequential methods of structural modifications, from which seven products were successfully obtained. A complementary study was performed, in which nonsymmetrical alkynes, alkenes and alkyl-substituted alkynes were explored, leading to a mixture of regioisomers. From this method, a total of twenty new compounds were successfully obtained, from which fourteen had their structures corroborated via X-ray diffraction studies. A mechanism was proposed using literature studies and computational data based on relative energies. After obtaining the final products, biological assays were performed to evaluate the antitumoral activity of each derivative against HL-60 cancer cell lines, amongst six other cancer cell lines, however, presenting low activities. The results presented here were published in the Chemistry – A European Journal, furthermore, several review articles were produced using the general knowledge gathered along the development of this presented thesis.