Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides

The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst tu...

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Autores principales: Arokianathar, Jude N., Hartley, Will C., McLaughlin, Calum, Greenhalgh, Mark D., Stead, Darren, Ng, Sean, Slawin, Alexandra M. Z., Smith, Andrew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588318/
https://www.ncbi.nlm.nih.gov/pubmed/34770741
http://dx.doi.org/10.3390/molecules26216333
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author Arokianathar, Jude N.
Hartley, Will C.
McLaughlin, Calum
Greenhalgh, Mark D.
Stead, Darren
Ng, Sean
Slawin, Alexandra M. Z.
Smith, Andrew D.
author_facet Arokianathar, Jude N.
Hartley, Will C.
McLaughlin, Calum
Greenhalgh, Mark D.
Stead, Darren
Ng, Sean
Slawin, Alexandra M. Z.
Smith, Andrew D.
author_sort Arokianathar, Jude N.
collection PubMed
description The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er).
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spelling pubmed-85883182021-11-13 Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides Arokianathar, Jude N. Hartley, Will C. McLaughlin, Calum Greenhalgh, Mark D. Stead, Darren Ng, Sean Slawin, Alexandra M. Z. Smith, Andrew D. Molecules Article The isothiourea-catalyzed enantioselective 1,6-conjugate addition of para-nitrophenyl esters to 2,6-disubstituted para-quinone methides is reported. para-Nitrophenoxide, generated in situ from initial N-acylation of the isothiourea by the para-nitrophenyl ester, is proposed to facilitate catalyst turnover in this transformation. A range of para-nitrophenyl ester products can be isolated, or derivatized in situ by addition of benzylamine to give amides at up to 99% yield. Although low diastereocontrol is observed, the diastereoisomeric ester products are separable and formed with high enantiocontrol (up to 94:6 er). MDPI 2021-10-20 /pmc/articles/PMC8588318/ /pubmed/34770741 http://dx.doi.org/10.3390/molecules26216333 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Arokianathar, Jude N.
Hartley, Will C.
McLaughlin, Calum
Greenhalgh, Mark D.
Stead, Darren
Ng, Sean
Slawin, Alexandra M. Z.
Smith, Andrew D.
Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides
title Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides
title_full Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides
title_fullStr Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides
title_full_unstemmed Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides
title_short Isothiourea-Catalyzed Enantioselective α-Alkylation of Esters via 1,6-Conjugate Addition to para-Quinone Methides
title_sort isothiourea-catalyzed enantioselective α-alkylation of esters via 1,6-conjugate addition to para-quinone methides
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8588318/
https://www.ncbi.nlm.nih.gov/pubmed/34770741
http://dx.doi.org/10.3390/molecules26216333
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