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Diastereoselective Radical 1,4-Ester Migration: Radical Cyclizations of Acyclic Esters with SmI(2)
[Image: see text] Reductive cyclizations of carbonyl compounds, mediated by samarium(II) diiodide (SmI(2), Kagan’s reagent), represent an invaluable platform to generate molecular complexity in a stereocontrolled manner. In addition to classical ketone and aldehyde substrates, recent advances in rad...
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/PMC9377304/ https://www.ncbi.nlm.nih.gov/pubmed/35858251 http://dx.doi.org/10.1021/jacs.2c05972 |
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author | Morrill, Charlotte Péter, Áron Amalina, Ilma Pye, Emma Crisenza, Giacomo E. M. Kaltsoyannis, Nikolas Procter, David J. |
author_facet | Morrill, Charlotte Péter, Áron Amalina, Ilma Pye, Emma Crisenza, Giacomo E. M. Kaltsoyannis, Nikolas Procter, David J. |
author_sort | Morrill, Charlotte |
collection | PubMed |
description | [Image: see text] Reductive cyclizations of carbonyl compounds, mediated by samarium(II) diiodide (SmI(2), Kagan’s reagent), represent an invaluable platform to generate molecular complexity in a stereocontrolled manner. In addition to classical ketone and aldehyde substrates, recent advances in radical chemistry allow the cyclization of lactone and lactam-type substrates using SmI(2). In contrast, acyclic esters are considered to be unreactive to SmI(2) and their participation in reductive cyclizations is unprecedented. Here, we report a diastereoselective radical 1,4-ester migration process, mediated by SmI(2), that delivers stereodefined alkene hydrocarboxylation products via radical cyclization of acyclic ester groups in α-carbomethoxy δ-lactones. Isotopic labeling experiments and computational studies have been used to probe the mechanism of the migration. We propose that a switch in conformation redirects single electron transfer from SmI(2) to the acyclic ester group, rather than the “more reactive” lactone carbonyl. Our study paves the way for the use of elusive ketyl radicals, derived from acyclic esters, in SmI(2)-mediated reductive cyclizations. |
format | Online Article Text |
id | pubmed-9377304 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-93773042022-08-16 Diastereoselective Radical 1,4-Ester Migration: Radical Cyclizations of Acyclic Esters with SmI(2) Morrill, Charlotte Péter, Áron Amalina, Ilma Pye, Emma Crisenza, Giacomo E. M. Kaltsoyannis, Nikolas Procter, David J. J Am Chem Soc [Image: see text] Reductive cyclizations of carbonyl compounds, mediated by samarium(II) diiodide (SmI(2), Kagan’s reagent), represent an invaluable platform to generate molecular complexity in a stereocontrolled manner. In addition to classical ketone and aldehyde substrates, recent advances in radical chemistry allow the cyclization of lactone and lactam-type substrates using SmI(2). In contrast, acyclic esters are considered to be unreactive to SmI(2) and their participation in reductive cyclizations is unprecedented. Here, we report a diastereoselective radical 1,4-ester migration process, mediated by SmI(2), that delivers stereodefined alkene hydrocarboxylation products via radical cyclization of acyclic ester groups in α-carbomethoxy δ-lactones. Isotopic labeling experiments and computational studies have been used to probe the mechanism of the migration. We propose that a switch in conformation redirects single electron transfer from SmI(2) to the acyclic ester group, rather than the “more reactive” lactone carbonyl. Our study paves the way for the use of elusive ketyl radicals, derived from acyclic esters, in SmI(2)-mediated reductive cyclizations. American Chemical Society 2022-07-20 2022-08-03 /pmc/articles/PMC9377304/ /pubmed/35858251 http://dx.doi.org/10.1021/jacs.2c05972 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 | Morrill, Charlotte Péter, Áron Amalina, Ilma Pye, Emma Crisenza, Giacomo E. M. Kaltsoyannis, Nikolas Procter, David J. Diastereoselective Radical 1,4-Ester Migration: Radical Cyclizations of Acyclic Esters with SmI(2) |
title | Diastereoselective
Radical 1,4-Ester Migration: Radical
Cyclizations of Acyclic Esters with SmI(2) |
title_full | Diastereoselective
Radical 1,4-Ester Migration: Radical
Cyclizations of Acyclic Esters with SmI(2) |
title_fullStr | Diastereoselective
Radical 1,4-Ester Migration: Radical
Cyclizations of Acyclic Esters with SmI(2) |
title_full_unstemmed | Diastereoselective
Radical 1,4-Ester Migration: Radical
Cyclizations of Acyclic Esters with SmI(2) |
title_short | Diastereoselective
Radical 1,4-Ester Migration: Radical
Cyclizations of Acyclic Esters with SmI(2) |
title_sort | diastereoselective
radical 1,4-ester migration: radical
cyclizations of acyclic esters with smi(2) |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9377304/ https://www.ncbi.nlm.nih.gov/pubmed/35858251 http://dx.doi.org/10.1021/jacs.2c05972 |
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