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Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines
Transition metal-catalyzed C–H functionalization and decarboxylative coupling are two of the most notable synthetic strategies developed in the last 30 years. Herein, we connect these two reaction pathways using bases and a simple Pd-based catalyst system to promote a para-selective C–H functionaliz...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192790/ https://www.ncbi.nlm.nih.gov/pubmed/32152476 http://dx.doi.org/10.1038/s41557-020-0428-1 |
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author | de Azambuja, Francisco Yang, Ming-Hsiu Feoktistova, Taisiia Selvaraju, Manikandan Brueckner, Alexander C. Grove, Markas A. Koley, Suvajit Cheong, Paul Ha-Yeon Altman, Ryan A. |
author_facet | de Azambuja, Francisco Yang, Ming-Hsiu Feoktistova, Taisiia Selvaraju, Manikandan Brueckner, Alexander C. Grove, Markas A. Koley, Suvajit Cheong, Paul Ha-Yeon Altman, Ryan A. |
author_sort | de Azambuja, Francisco |
collection | PubMed |
description | Transition metal-catalyzed C–H functionalization and decarboxylative coupling are two of the most notable synthetic strategies developed in the last 30 years. Herein, we connect these two reaction pathways using bases and a simple Pd-based catalyst system to promote a para-selective C–H functionalization reaction from benzylic electrophiles. Experimental and computational mechanistic studies suggest a pathway involving an uncommon Pd-catalyzed dearomatization of the benzyl moiety followed by a base-enabled rearomatization through a formal 1,5-hydrogen migration. This reaction complements “C–H activation” strategies that convert inert C–H bonds into C–metal bonds prior to C–C bond formation. Instead, this reaction exploits an inverted sequence and promotes C–C bond formation prior to deprotonation. These studies provide an opportunity to develop general para-selective C–H functionalization reactions from benzylic electrophiles and show how new reactive modalities may be accessed with careful control of reaction conditions. |
format | Online Article Text |
id | pubmed-7192790 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
record_format | MEDLINE/PubMed |
spelling | pubmed-71927902020-09-09 Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines de Azambuja, Francisco Yang, Ming-Hsiu Feoktistova, Taisiia Selvaraju, Manikandan Brueckner, Alexander C. Grove, Markas A. Koley, Suvajit Cheong, Paul Ha-Yeon Altman, Ryan A. Nat Chem Article Transition metal-catalyzed C–H functionalization and decarboxylative coupling are two of the most notable synthetic strategies developed in the last 30 years. Herein, we connect these two reaction pathways using bases and a simple Pd-based catalyst system to promote a para-selective C–H functionalization reaction from benzylic electrophiles. Experimental and computational mechanistic studies suggest a pathway involving an uncommon Pd-catalyzed dearomatization of the benzyl moiety followed by a base-enabled rearomatization through a formal 1,5-hydrogen migration. This reaction complements “C–H activation” strategies that convert inert C–H bonds into C–metal bonds prior to C–C bond formation. Instead, this reaction exploits an inverted sequence and promotes C–C bond formation prior to deprotonation. These studies provide an opportunity to develop general para-selective C–H functionalization reactions from benzylic electrophiles and show how new reactive modalities may be accessed with careful control of reaction conditions. 2020-03-09 2020-05 /pmc/articles/PMC7192790/ /pubmed/32152476 http://dx.doi.org/10.1038/s41557-020-0428-1 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article de Azambuja, Francisco Yang, Ming-Hsiu Feoktistova, Taisiia Selvaraju, Manikandan Brueckner, Alexander C. Grove, Markas A. Koley, Suvajit Cheong, Paul Ha-Yeon Altman, Ryan A. Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines |
title | Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines |
title_full | Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines |
title_fullStr | Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines |
title_full_unstemmed | Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines |
title_short | Connecting remote C–H bond functionalization and decarboxylative coupling using simple amines |
title_sort | connecting remote c–h bond functionalization and decarboxylative coupling using simple amines |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192790/ https://www.ncbi.nlm.nih.gov/pubmed/32152476 http://dx.doi.org/10.1038/s41557-020-0428-1 |
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