Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation
Autor(a) principal: | |
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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 |
Resumo: | 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. |
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Eufrânio Nunes da Silva Júniorhttp://lattes.cnpq.br/5627593695811199Antônio Luiz BragaHugo Alejandro Gallardo OlmedoLuiz Cláudio de Almeida BarbosaEduardo Eliezer Albertohttp://lattes.cnpq.br/8640384578255856Renato Lúcio de Carvalho2022-10-19T15:25:31Z2022-10-19T15:25:31Z2022-08-04http://hdl.handle.net/1843/46387https://orcid.org/0000-0002-8515-9306This 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.Este trabalho apresenta a construção e desenvolvimento de uma nova metodologia para obtenção de compostos naftoquinoidais modificados via processos de ativação de ligação C(sp2)–H. Nesse contexto, foi explorada a capacidade de direção intrínseca das carbonilas, presentes nas naftoquinonas, em reações de arilação e anelação catalisadas por rutênio. Após sequenciais resultados negativos, expandiu-se para o uso de grupos diretores adicionados à estrutura quinoidal. A otimização do método levou à formação de quinonas policíclicas, com rendimentos moderados a ótimos, a partir de seus respectivos substratos, utilizando uma reação de anelação dupla catalisada por rutênio via um processo de ativação de ligação C(sp2)–H, na presença de um alcino interno, acetato de cobre-II e pivalato de sódio. Dois escopos foram desenvolvidos, e para o primeiro deles, diversos alcinos foram obtidos através de uma reação tipo Sonogashira, e subsequencialmente aplicados aos métodos otimizados, de onde onze produtos duplamente anelados foram obtidos e devidamente caracterizados. Um segundo escopo foi desenvolvido utilizando-se compostos quinoidais previamente sintetizados após sequenciais métodos de modificação estrutual, de onde sete produtos foram obtidos com sucesso. Um estudo complementar foi feito, onde foram explorados alcinos não-simétricos, alcenos e alcinos alquílicos, levando à formação de uma mistura de dois regioisômeros. A partir deste novo método, um total de vinte novos compostos foram obtidos com sucesso, dentre os quais quatorze tiveram suas estruturas corroboradas via difração de raios-X. Um mecanismo pôde der proposto com base em estudos da literatura e cálculos computacionais de energias relativas. Após a obtenção dos produtos finais, testes biológicos foram feitos para avaliar a atividade antitumoral de cada derivado contra a linhagem de célula cancerígena HL-60, dentre outras seis linhagens, porém com baixa atividade. Os resultados aqui apresentados foram publicados na Chemistry – A European Journal, além disso, vários artigos de revisão foram também produzidos a partir do conhecimento geral adquirido ao longo do desenvolvimento desta tese.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorINCT – Instituto nacional de ciência e tecnologia (Antigo Instituto do Milênio)Outra AgênciaengUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em QuímicaUFMGBrasilICEX - INSTITUTO DE CIÊNCIAS EXATAShttp://creativecommons.org/licenses/by-nc-nd/3.0/pt/info:eu-repo/semantics/openAccessQuímica orgânicaQuinonaCompostos policíclicosCompostos de rutênioRutênioCatáliseAgentes antineoplásicosRaios XDifraçãoCatalisadores de metais de transiçãoTestes biológicosRessonância magnética nuclearEspectro infravermelhoEspectrometria de massaCristalografiaQuinonesPolycyclic compoundsDouble-annulation reactionC–H activationRuthenium catalysisQuinonasCompostos policíclicosReação de anelação duplaAtivação de ligação C–HCatálise com rutênioRuthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activationAnelação dupla de quinonas catalisada por rutênio: explorando uma nova fronteira para obtenção de compostos policíclicos via ativação de ligação C-Hinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALTESE DE DOUTORADO - Renato Lúcio - 10.08.2022.pdfTESE DE DOUTORADO - Renato Lúcio - 10.08.2022.pdfVersão final da tese de doutorado corrigidaapplication/pdf27939106https://repositorio.ufmg.br/bitstream/1843/46387/1/TESE%20DE%20DOUTORADO%20-%20Renato%20L%c3%bacio%20-%2010.08.2022.pdff94614e01d5c0d6ccb55b84a8351e637MD51CC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.pt_BR.fl_str_mv |
Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation |
dc.title.alternative.pt_BR.fl_str_mv |
Anelação dupla de quinonas catalisada por rutênio: explorando uma nova fronteira para obtenção de compostos policíclicos via ativação de ligação C-H |
title |
Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation |
spellingShingle |
Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation Renato Lúcio de Carvalho 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 |
title_short |
Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation |
title_full |
Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation |
title_fullStr |
Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation |
title_full_unstemmed |
Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation |
title_sort |
Ruthenium-catalyzed double annulation of quinones: exploring a new frontier towards polycyclic compounds via C-H activation |
author |
Renato Lúcio de Carvalho |
author_facet |
Renato Lúcio de Carvalho |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Eufrânio Nunes da Silva Júnior |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/5627593695811199 |
dc.contributor.referee1.fl_str_mv |
Antônio Luiz Braga |
dc.contributor.referee2.fl_str_mv |
Hugo Alejandro Gallardo Olmedo |
dc.contributor.referee3.fl_str_mv |
Luiz Cláudio de Almeida Barbosa |
dc.contributor.referee4.fl_str_mv |
Eduardo Eliezer Alberto |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/8640384578255856 |
dc.contributor.author.fl_str_mv |
Renato Lúcio de Carvalho |
contributor_str_mv |
Eufrânio Nunes da Silva Júnior Antônio Luiz Braga Hugo Alejandro Gallardo Olmedo Luiz Cláudio de Almeida Barbosa Eduardo Eliezer Alberto |
dc.subject.por.fl_str_mv |
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 |
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 |
dc.subject.other.pt_BR.fl_str_mv |
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 |
description |
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. |
publishDate |
2022 |
dc.date.accessioned.fl_str_mv |
2022-10-19T15:25:31Z |
dc.date.available.fl_str_mv |
2022-10-19T15:25:31Z |
dc.date.issued.fl_str_mv |
2022-08-04 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/doctoralThesis |
format |
doctoralThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1843/46387 |
dc.identifier.orcid.pt_BR.fl_str_mv |
https://orcid.org/0000-0002-8515-9306 |
url |
http://hdl.handle.net/1843/46387 https://orcid.org/0000-0002-8515-9306 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.rights.driver.fl_str_mv |
http://creativecommons.org/licenses/by-nc-nd/3.0/pt/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by-nc-nd/3.0/pt/ |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.publisher.program.fl_str_mv |
Programa de Pós-Graduação em Química |
dc.publisher.initials.fl_str_mv |
UFMG |
dc.publisher.country.fl_str_mv |
Brasil |
dc.publisher.department.fl_str_mv |
ICEX - INSTITUTO DE CIÊNCIAS EXATAS |
publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais |
dc.source.none.fl_str_mv |
reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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UFMG |
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UFMG |
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