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Catalytic Enantioselective Synthesis of α-Difunctionalized Cyclic Sulfones
[Image: see text] As saturated heterocyclic building blocks become increasingly popular in medicinal chemistry and drug discovery programs, expansion of the synthetic toolkit to novel stereofunctionalized heterocycles is a priority. Herein, we report the development of a palladium-catalyzed decarbox...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2022
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490805/ https://www.ncbi.nlm.nih.gov/pubmed/35801657 http://dx.doi.org/10.1021/acs.joc.2c01240 |
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author | Bowen, Eleanor Laidlaw, Gillian Atkinson, Bethany C. McArdle-Ismaguilov, Timur A. Franckevičius, Vilius |
author_facet | Bowen, Eleanor Laidlaw, Gillian Atkinson, Bethany C. McArdle-Ismaguilov, Timur A. Franckevičius, Vilius |
author_sort | Bowen, Eleanor |
collection | PubMed |
description | [Image: see text] As saturated heterocyclic building blocks become increasingly popular in medicinal chemistry and drug discovery programs, expansion of the synthetic toolkit to novel stereofunctionalized heterocycles is a priority. Herein, we report the development of a palladium-catalyzed decarboxylative asymmetric allylic alkylation reaction to access a broad range of enantioenriched α-difunctionalized 5- and 6-membered sulfones from easily accessible racemic starting materials. The allylic alkylation step was found to occur with high levels of enantioselectivity as a result of a palladium-mediated dynamic kinetic resolution of E/Z enolate intermediates. This methodology paves the way to hitherto unexplored stereodefined cyclic sulfones for medicinal chemistry applications. |
format | Online Article Text |
id | pubmed-9490805 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-94908052022-09-22 Catalytic Enantioselective Synthesis of α-Difunctionalized Cyclic Sulfones Bowen, Eleanor Laidlaw, Gillian Atkinson, Bethany C. McArdle-Ismaguilov, Timur A. Franckevičius, Vilius J Org Chem [Image: see text] As saturated heterocyclic building blocks become increasingly popular in medicinal chemistry and drug discovery programs, expansion of the synthetic toolkit to novel stereofunctionalized heterocycles is a priority. Herein, we report the development of a palladium-catalyzed decarboxylative asymmetric allylic alkylation reaction to access a broad range of enantioenriched α-difunctionalized 5- and 6-membered sulfones from easily accessible racemic starting materials. The allylic alkylation step was found to occur with high levels of enantioselectivity as a result of a palladium-mediated dynamic kinetic resolution of E/Z enolate intermediates. This methodology paves the way to hitherto unexplored stereodefined cyclic sulfones for medicinal chemistry applications. American Chemical Society 2022-07-08 2022-08-05 /pmc/articles/PMC9490805/ /pubmed/35801657 http://dx.doi.org/10.1021/acs.joc.2c01240 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 | Bowen, Eleanor Laidlaw, Gillian Atkinson, Bethany C. McArdle-Ismaguilov, Timur A. Franckevičius, Vilius Catalytic Enantioselective Synthesis of α-Difunctionalized Cyclic Sulfones |
title | Catalytic Enantioselective
Synthesis of α-Difunctionalized
Cyclic Sulfones |
title_full | Catalytic Enantioselective
Synthesis of α-Difunctionalized
Cyclic Sulfones |
title_fullStr | Catalytic Enantioselective
Synthesis of α-Difunctionalized
Cyclic Sulfones |
title_full_unstemmed | Catalytic Enantioselective
Synthesis of α-Difunctionalized
Cyclic Sulfones |
title_short | Catalytic Enantioselective
Synthesis of α-Difunctionalized
Cyclic Sulfones |
title_sort | catalytic enantioselective
synthesis of α-difunctionalized
cyclic sulfones |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9490805/ https://www.ncbi.nlm.nih.gov/pubmed/35801657 http://dx.doi.org/10.1021/acs.joc.2c01240 |
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