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Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters

[Image: see text] An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regiosele...

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Autores principales: Wu, Jiufeng, Young, Claire M., Watts, Amy A., Slawin, Alexandra M. Z., Boyce, Gregory R., Bühl, Michael, Smith, Andrew D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278409/
https://www.ncbi.nlm.nih.gov/pubmed/35652512
http://dx.doi.org/10.1021/acs.orglett.2c01486
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author Wu, Jiufeng
Young, Claire M.
Watts, Amy A.
Slawin, Alexandra M. Z.
Boyce, Gregory R.
Bühl, Michael
Smith, Andrew D.
author_facet Wu, Jiufeng
Young, Claire M.
Watts, Amy A.
Slawin, Alexandra M. Z.
Boyce, Gregory R.
Bühl, Michael
Smith, Andrew D.
author_sort Wu, Jiufeng
collection PubMed
description [Image: see text] An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,β-unsaturated esters.
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spelling pubmed-92784092022-07-14 Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters Wu, Jiufeng Young, Claire M. Watts, Amy A. Slawin, Alexandra M. Z. Boyce, Gregory R. Bühl, Michael Smith, Andrew D. Org Lett [Image: see text] An enantioselective Michael addition of malonates to α,β-unsaturated para-nitrophenyl esters was achieved using the Lewis basic isothiourea HyperBTM, giving excellent levels of product enantioselectivity (up to >99:1 enantiomeric ratio) in good yields and with complete regioselectivity (>20:1 regioselectivity ratio) in the presence of alternative (phenyl ketone and ethyl ester) Michael acceptors. Density functional theory calculations indicate that N-acylation is rate-limiting. This constitutes a rare example of a highly enantioselective addition of simple, readily available malonates to α,β-unsaturated esters. American Chemical Society 2022-06-02 2022-06-10 /pmc/articles/PMC9278409/ /pubmed/35652512 http://dx.doi.org/10.1021/acs.orglett.2c01486 Text en © 2022 The Authors. Published by American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Wu, Jiufeng
Young, Claire M.
Watts, Amy A.
Slawin, Alexandra M. Z.
Boyce, Gregory R.
Bühl, Michael
Smith, Andrew D.
Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters
title Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters
title_full Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters
title_fullStr Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters
title_full_unstemmed Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters
title_short Isothiourea-Catalyzed Enantioselective Michael Addition of Malonates to α,β-Unsaturated Aryl Esters
title_sort isothiourea-catalyzed enantioselective michael addition of malonates to α,β-unsaturated aryl esters
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9278409/
https://www.ncbi.nlm.nih.gov/pubmed/35652512
http://dx.doi.org/10.1021/acs.orglett.2c01486
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