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Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone

Grignard reagents undergo conjugate addition to thiochromones catalyzed by copper salts to afford 2-substituted-thiochroman-4-ones, both 2-alkylthiochroman-4-ones and thioflavanones (2-arylthiochroman-4-ones), in good yields with trimethylsilyl chloride (TMSCl) as an additive. The best yields of 1,4...

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Autores principales: Bellinger, Tania J., Harvin, Teavian, Pickens-Flynn, Ti’Bran, Austin, Nataleigh, Whitaker, Samuel H., Tang Yuk Tutein, Mai Ling C., Hukins, Dabria T., Deese, Nichele, Guo, Fenghai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248974/
https://www.ncbi.nlm.nih.gov/pubmed/32370080
http://dx.doi.org/10.3390/molecules25092128
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author Bellinger, Tania J.
Harvin, Teavian
Pickens-Flynn, Ti’Bran
Austin, Nataleigh
Whitaker, Samuel H.
Tang Yuk Tutein, Mai Ling C.
Hukins, Dabria T.
Deese, Nichele
Guo, Fenghai
author_facet Bellinger, Tania J.
Harvin, Teavian
Pickens-Flynn, Ti’Bran
Austin, Nataleigh
Whitaker, Samuel H.
Tang Yuk Tutein, Mai Ling C.
Hukins, Dabria T.
Deese, Nichele
Guo, Fenghai
author_sort Bellinger, Tania J.
collection PubMed
description Grignard reagents undergo conjugate addition to thiochromones catalyzed by copper salts to afford 2-substituted-thiochroman-4-ones, both 2-alkylthiochroman-4-ones and thioflavanones (2-arylthiochroman-4-ones), in good yields with trimethylsilyl chloride (TMSCl) as an additive. The best yields of 1,4-adducts can be attained with CuCN∙2LiCl as the copper source. Excellent yields of 2-alkyl-substituted thiochroman-4-ones and thioflavanones (2-aryl substituted) are attained with a broad range of Grignard reagents. This approach works well with both alkyl and aromatic Grignard reagents, thus providing a unified synthetic approach to privileged 2-substituted thiochroman-4-ones and a potential valuable precursor for further synthetic applications towards many pharmaceutically active molecules. The use of commercially available and/or readily prepared Grignard reagents will expedite the synthesis of a large library of both 2-alkyl substituted thiochroman-4-ones and thioflavanones for additional synthetic applications.
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spelling pubmed-72489742020-06-10 Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone Bellinger, Tania J. Harvin, Teavian Pickens-Flynn, Ti’Bran Austin, Nataleigh Whitaker, Samuel H. Tang Yuk Tutein, Mai Ling C. Hukins, Dabria T. Deese, Nichele Guo, Fenghai Molecules Article Grignard reagents undergo conjugate addition to thiochromones catalyzed by copper salts to afford 2-substituted-thiochroman-4-ones, both 2-alkylthiochroman-4-ones and thioflavanones (2-arylthiochroman-4-ones), in good yields with trimethylsilyl chloride (TMSCl) as an additive. The best yields of 1,4-adducts can be attained with CuCN∙2LiCl as the copper source. Excellent yields of 2-alkyl-substituted thiochroman-4-ones and thioflavanones (2-aryl substituted) are attained with a broad range of Grignard reagents. This approach works well with both alkyl and aromatic Grignard reagents, thus providing a unified synthetic approach to privileged 2-substituted thiochroman-4-ones and a potential valuable precursor for further synthetic applications towards many pharmaceutically active molecules. The use of commercially available and/or readily prepared Grignard reagents will expedite the synthesis of a large library of both 2-alkyl substituted thiochroman-4-ones and thioflavanones for additional synthetic applications. MDPI 2020-05-01 /pmc/articles/PMC7248974/ /pubmed/32370080 http://dx.doi.org/10.3390/molecules25092128 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Bellinger, Tania J.
Harvin, Teavian
Pickens-Flynn, Ti’Bran
Austin, Nataleigh
Whitaker, Samuel H.
Tang Yuk Tutein, Mai Ling C.
Hukins, Dabria T.
Deese, Nichele
Guo, Fenghai
Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone
title Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone
title_full Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone
title_fullStr Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone
title_full_unstemmed Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone
title_short Conjugate Addition of Grignard Reagents to Thiochromones Catalyzed by Copper Salts: A Unified Approach to Both 2-Alkylthiochroman-4-One and Thioflavanone
title_sort conjugate addition of grignard reagents to thiochromones catalyzed by copper salts: a unified approach to both 2-alkylthiochroman-4-one and thioflavanone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7248974/
https://www.ncbi.nlm.nih.gov/pubmed/32370080
http://dx.doi.org/10.3390/molecules25092128
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