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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...

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Autores principales: Bowen, Eleanor, Laidlaw, Gillian, Atkinson, Bethany C., McArdle-Ismaguilov, Timur A., Franckevičius, Vilius
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
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.
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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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