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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...

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Autores principales: 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.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2020
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.
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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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