Palladium-Catalyzed Direct Arylation of 5-Halouracils and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted by TBAF
[Image: see text] The 1-N-benzyl-5-iodo(or bromo)uracil undergoes Pd-catalyzed [Pd(2)(dba)(3)] direct arylation with benzene and other simple arenes in the presence of TBAF in DMF without the necessity of adding any ligands or additives to give 5-arylated uracil analogues. The TBAF-promoted coupling...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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American Chemical
Society
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011569/ https://www.ncbi.nlm.nih.gov/pubmed/24724921 http://dx.doi.org/10.1021/jo500602p |
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author | Liang, Yong Gloudeman, Jennifer Wnuk, Stanislaw F. |
author_facet | Liang, Yong Gloudeman, Jennifer Wnuk, Stanislaw F. |
author_sort | Liang, Yong |
collection | PubMed |
description | [Image: see text] The 1-N-benzyl-5-iodo(or bromo)uracil undergoes Pd-catalyzed [Pd(2)(dba)(3)] direct arylation with benzene and other simple arenes in the presence of TBAF in DMF without the necessity of adding any ligands or additives to give 5-arylated uracil analogues. The TBAF-promoted coupling also occurs efficiently with electron rich heteroarenes at 100 °C (1 h) even with only small excess of heteroarenes. The protocol avoids usage of the arylboronic acid or stannane precursors for the synthesis of 5-(2-furyl, or 2-thienyl, or 2-pyrrolyl)uracil nucleosides, which are used as important RNA and DNA fluorescent probes. The fact that 1-N-benzyl-3-N-methyl-5-iodouracil did not undergo the TBAF-promoted couplings with arenes or heteroarenes suggests that the C4-alkoxide (enol form of uracil) facilitates coupling by participation in the intramolecular processes of hydrogen abstraction from arenes. TBAF-promoted arylation was extended into the other enolizable heterocyclic systems such as 3-bromo-2-pyridone. The π-excessive heteroarenes also coupled with 5-halouracils in the presence of Pd(OAc)(2)/Cs(2)CO(3)/PivOH combination in DMF (100 °C, 2 h) to yield 5-arylated uracils. |
format | Online Article Text |
id | pubmed-4011569 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | American Chemical
Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-40115692015-04-11 Palladium-Catalyzed Direct Arylation of 5-Halouracils and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted by TBAF Liang, Yong Gloudeman, Jennifer Wnuk, Stanislaw F. J Org Chem [Image: see text] The 1-N-benzyl-5-iodo(or bromo)uracil undergoes Pd-catalyzed [Pd(2)(dba)(3)] direct arylation with benzene and other simple arenes in the presence of TBAF in DMF without the necessity of adding any ligands or additives to give 5-arylated uracil analogues. The TBAF-promoted coupling also occurs efficiently with electron rich heteroarenes at 100 °C (1 h) even with only small excess of heteroarenes. The protocol avoids usage of the arylboronic acid or stannane precursors for the synthesis of 5-(2-furyl, or 2-thienyl, or 2-pyrrolyl)uracil nucleosides, which are used as important RNA and DNA fluorescent probes. The fact that 1-N-benzyl-3-N-methyl-5-iodouracil did not undergo the TBAF-promoted couplings with arenes or heteroarenes suggests that the C4-alkoxide (enol form of uracil) facilitates coupling by participation in the intramolecular processes of hydrogen abstraction from arenes. TBAF-promoted arylation was extended into the other enolizable heterocyclic systems such as 3-bromo-2-pyridone. The π-excessive heteroarenes also coupled with 5-halouracils in the presence of Pd(OAc)(2)/Cs(2)CO(3)/PivOH combination in DMF (100 °C, 2 h) to yield 5-arylated uracils. American Chemical Society 2014-04-11 2014-05-02 /pmc/articles/PMC4011569/ /pubmed/24724921 http://dx.doi.org/10.1021/jo500602p Text en Copyright © 2014 American Chemical Society |
spellingShingle | Liang, Yong Gloudeman, Jennifer Wnuk, Stanislaw F. Palladium-Catalyzed Direct Arylation of 5-Halouracils and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted by TBAF |
title | Palladium-Catalyzed Direct
Arylation of 5-Halouracils
and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted
by TBAF |
title_full | Palladium-Catalyzed Direct
Arylation of 5-Halouracils
and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted
by TBAF |
title_fullStr | Palladium-Catalyzed Direct
Arylation of 5-Halouracils
and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted
by TBAF |
title_full_unstemmed | Palladium-Catalyzed Direct
Arylation of 5-Halouracils
and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted
by TBAF |
title_short | Palladium-Catalyzed Direct
Arylation of 5-Halouracils
and 5-Halouracil Nucleosides with Arenes and Heteroarenes Promoted
by TBAF |
title_sort | palladium-catalyzed direct
arylation of 5-halouracils
and 5-halouracil nucleosides with arenes and heteroarenes promoted
by tbaf |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011569/ https://www.ncbi.nlm.nih.gov/pubmed/24724921 http://dx.doi.org/10.1021/jo500602p |
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