Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones
Autor(a) principal: | |
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Data de Publicação: | 2016 |
Outros Autores: | |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10284/5215 |
Resumo: | We have studied the role of Cu+-phenantroline as a catalyst in the cyclization of N-aryl-enaminones using density-functional theory computations. The catalyst was found to bind the substrate upon deprotonation of its eneaminone, and to dramatically increase the acidity of the carbon adjacent to the ketone functionality. The deprotonation of this carbon atom yields a carbanion which attacks the aryl moiety, thereby closing the heterocycle in the rate-determining step. This C–C bond forming reaction was found to proceed much more rapidly when preceded by re-protonation of the substrate N-atom (which had lost H+ in the initial step). Hydride transfer to the catalyst then completes the indole synthesis, in a very fast step. The influence of Li+ and K+ on the regioselectivity of the cyclization of bromo-substituted analogues could not, however, be reproduced by our model. Alternative pathways involving either single-electron transfer from the catalyst to the substrate or ring cyclization without previous carbon α-deprotonation were found to be kinetically or thermodynamically inaccessible. |
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Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminonesC–C couplingCu(I) reactivityC–H bond activationWe have studied the role of Cu+-phenantroline as a catalyst in the cyclization of N-aryl-enaminones using density-functional theory computations. The catalyst was found to bind the substrate upon deprotonation of its eneaminone, and to dramatically increase the acidity of the carbon adjacent to the ketone functionality. The deprotonation of this carbon atom yields a carbanion which attacks the aryl moiety, thereby closing the heterocycle in the rate-determining step. This C–C bond forming reaction was found to proceed much more rapidly when preceded by re-protonation of the substrate N-atom (which had lost H+ in the initial step). Hydride transfer to the catalyst then completes the indole synthesis, in a very fast step. The influence of Li+ and K+ on the regioselectivity of the cyclization of bromo-substituted analogues could not, however, be reproduced by our model. Alternative pathways involving either single-electron transfer from the catalyst to the substrate or ring cyclization without previous carbon α-deprotonation were found to be kinetically or thermodynamically inaccessible.The Royal Society PublishingRepositório Institucional da Universidade Fernando PessoaBernardo, Carlos E. P.Silva, Pedro J.2016-03-01T15:12:53Z2016-01-01T00:00:00Z2016-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10284/5215engBernardo C.E.P., Silva P.J. (2016). Computational exploration of the reaction mechanism of the Cu+-catalysed synthesis of indoles from N-aryl enaminones.Royal Society Open Science. http://dx.doi.org/10.1098/rsos.150582. ISSN 2054-5703.2054-570310.1098/rsos.150582info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2022-09-06T02:04:32Zoai:bdigital.ufp.pt:10284/5215Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T15:42:04.325485Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones |
title |
Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones |
spellingShingle |
Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones Bernardo, Carlos E. P. C–C coupling Cu(I) reactivity C–H bond activation |
title_short |
Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones |
title_full |
Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones |
title_fullStr |
Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones |
title_full_unstemmed |
Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones |
title_sort |
Computational exploration of the reaction mechanism of the Cu+- catalysed synthesis of indoles from N-aryl enaminones |
author |
Bernardo, Carlos E. P. |
author_facet |
Bernardo, Carlos E. P. Silva, Pedro J. |
author_role |
author |
author2 |
Silva, Pedro J. |
author2_role |
author |
dc.contributor.none.fl_str_mv |
Repositório Institucional da Universidade Fernando Pessoa |
dc.contributor.author.fl_str_mv |
Bernardo, Carlos E. P. Silva, Pedro J. |
dc.subject.por.fl_str_mv |
C–C coupling Cu(I) reactivity C–H bond activation |
topic |
C–C coupling Cu(I) reactivity C–H bond activation |
description |
We have studied the role of Cu+-phenantroline as a catalyst in the cyclization of N-aryl-enaminones using density-functional theory computations. The catalyst was found to bind the substrate upon deprotonation of its eneaminone, and to dramatically increase the acidity of the carbon adjacent to the ketone functionality. The deprotonation of this carbon atom yields a carbanion which attacks the aryl moiety, thereby closing the heterocycle in the rate-determining step. This C–C bond forming reaction was found to proceed much more rapidly when preceded by re-protonation of the substrate N-atom (which had lost H+ in the initial step). Hydride transfer to the catalyst then completes the indole synthesis, in a very fast step. The influence of Li+ and K+ on the regioselectivity of the cyclization of bromo-substituted analogues could not, however, be reproduced by our model. Alternative pathways involving either single-electron transfer from the catalyst to the substrate or ring cyclization without previous carbon α-deprotonation were found to be kinetically or thermodynamically inaccessible. |
publishDate |
2016 |
dc.date.none.fl_str_mv |
2016-03-01T15:12:53Z 2016-01-01T00:00:00Z 2016-01-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10284/5215 |
url |
http://hdl.handle.net/10284/5215 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Bernardo C.E.P., Silva P.J. (2016). Computational exploration of the reaction mechanism of the Cu+-catalysed synthesis of indoles from N-aryl enaminones.Royal Society Open Science. http://dx.doi.org/10.1098/rsos.150582. ISSN 2054-5703. 2054-5703 10.1098/rsos.150582 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
The Royal Society Publishing |
publisher.none.fl_str_mv |
The Royal Society Publishing |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
repository.mail.fl_str_mv |
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1799130287243788288 |