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Diels–Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene
Reversing the regioselectivity of the renowned Diels–Alder reaction by overriding the usual thermodynamic and kinetic governing factors has always been a formidable challenge to synthetic organic chemists. Anthracenes are well-known to undergo [4 + 2]-cycloadditions with dienophiles at their 9,10-po...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814106/ https://www.ncbi.nlm.nih.gov/pubmed/36703384 http://dx.doi.org/10.1038/s42004-020-00407-9 |
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author | Huynh, Vinh Ngoc Leitner, Michael Bhattacharyya, Aditya Uhlstein, Lisa Kreitmeier, Peter Sakrausky, Patrick Rehbein, Julia Reiser, Oliver |
author_facet | Huynh, Vinh Ngoc Leitner, Michael Bhattacharyya, Aditya Uhlstein, Lisa Kreitmeier, Peter Sakrausky, Patrick Rehbein, Julia Reiser, Oliver |
author_sort | Huynh, Vinh Ngoc |
collection | PubMed |
description | Reversing the regioselectivity of the renowned Diels–Alder reaction by overriding the usual thermodynamic and kinetic governing factors has always been a formidable challenge to synthetic organic chemists. Anthracenes are well-known to undergo [4 + 2]-cycloadditions with dienophiles at their 9,10-positions (central ring) over 1,4-positions (terminal ring) guided by the relative aromatic stabilization energy of the two possible products, and also by harboring the largest orbital coefficients of the highest occupied molecular orbital (HOMO) at the 9,10-positions. We, herein, report a 1,4-selective [4 + 2]-cycloaddition strategy of 9,10-unsubstituted anthracenes by installing electron-donating substituents on the terminal rings which is heretofore unprecedented to the best of our knowledge. The developed synthetic strategy does not require any premeditated engagement of the 9,10-positions either with any sterically bulky or electron-withdrawing substituents and allows delicate calibration of the regioselectivity by modulating the electron-donating strength of the substituents on the terminal rings. Likewise, the regioselective functionalization of the terminal anthracene ring in electrophilic substitution reactions is demonstrated. A mechanistic rationale is offered with the aid of detailed computational studies, and finally, synthetic applications are presented. |
format | Online Article Text |
id | pubmed-9814106 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98141062023-01-10 Diels–Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene Huynh, Vinh Ngoc Leitner, Michael Bhattacharyya, Aditya Uhlstein, Lisa Kreitmeier, Peter Sakrausky, Patrick Rehbein, Julia Reiser, Oliver Commun Chem Article Reversing the regioselectivity of the renowned Diels–Alder reaction by overriding the usual thermodynamic and kinetic governing factors has always been a formidable challenge to synthetic organic chemists. Anthracenes are well-known to undergo [4 + 2]-cycloadditions with dienophiles at their 9,10-positions (central ring) over 1,4-positions (terminal ring) guided by the relative aromatic stabilization energy of the two possible products, and also by harboring the largest orbital coefficients of the highest occupied molecular orbital (HOMO) at the 9,10-positions. We, herein, report a 1,4-selective [4 + 2]-cycloaddition strategy of 9,10-unsubstituted anthracenes by installing electron-donating substituents on the terminal rings which is heretofore unprecedented to the best of our knowledge. The developed synthetic strategy does not require any premeditated engagement of the 9,10-positions either with any sterically bulky or electron-withdrawing substituents and allows delicate calibration of the regioselectivity by modulating the electron-donating strength of the substituents on the terminal rings. Likewise, the regioselective functionalization of the terminal anthracene ring in electrophilic substitution reactions is demonstrated. A mechanistic rationale is offered with the aid of detailed computational studies, and finally, synthetic applications are presented. Nature Publishing Group UK 2020-11-06 /pmc/articles/PMC9814106/ /pubmed/36703384 http://dx.doi.org/10.1038/s42004-020-00407-9 Text en © The Author(s) 2020 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Huynh, Vinh Ngoc Leitner, Michael Bhattacharyya, Aditya Uhlstein, Lisa Kreitmeier, Peter Sakrausky, Patrick Rehbein, Julia Reiser, Oliver Diels–Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene |
title | Diels–Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene |
title_full | Diels–Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene |
title_fullStr | Diels–Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene |
title_full_unstemmed | Diels–Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene |
title_short | Diels–Alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene |
title_sort | diels–alder reactions and electrophilic substitutions with atypical regioselectivity enable functionalization of terminal rings of anthracene |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814106/ https://www.ncbi.nlm.nih.gov/pubmed/36703384 http://dx.doi.org/10.1038/s42004-020-00407-9 |
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