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Control of stereogenic oxygen in a helically chiral oxonium ion

The control of tetrahedral carbon stereocentres remains a focus of modern synthetic chemistry and is enabled by their configurational stability. By contrast, trisubstituted nitrogen(1), phosphorus(2) and sulfur compounds(3) undergo pyramidal inversion, a fundamental and well-recognized stereochemica...

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Autores principales: Smith, Owen, Popescu, Mihai V., Hindson, Madeleine J., Paton, Robert S., Burton, Jonathan W., Smith, Martin D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017494/
https://www.ncbi.nlm.nih.gov/pubmed/36922609
http://dx.doi.org/10.1038/s41586-023-05719-z
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author Smith, Owen
Popescu, Mihai V.
Hindson, Madeleine J.
Paton, Robert S.
Burton, Jonathan W.
Smith, Martin D.
author_facet Smith, Owen
Popescu, Mihai V.
Hindson, Madeleine J.
Paton, Robert S.
Burton, Jonathan W.
Smith, Martin D.
author_sort Smith, Owen
collection PubMed
description The control of tetrahedral carbon stereocentres remains a focus of modern synthetic chemistry and is enabled by their configurational stability. By contrast, trisubstituted nitrogen(1), phosphorus(2) and sulfur compounds(3) undergo pyramidal inversion, a fundamental and well-recognized stereochemical phenomenon that is widely exploited(4). However, the stereochemistry of oxonium ions—compounds bearing three substituents on a positively charged oxygen atom—is poorly developed and there are few applications of oxonium ions in synthesis beyond their existence as reactive intermediates(5,6). There are no examples of configurationally stable oxonium ions in which the oxygen atom is the sole stereogenic centre, probably owing to the low barrier to oxygen pyramidal inversion(7) and the perception that all oxonium ions are highly reactive. Here we describe the design, synthesis and characterization of a helically chiral triaryloxonium ion in which inversion of the oxygen lone pair is prevented through geometric restriction to enable it to function as a determinant of configuration. A combined synthesis and quantum calculation approach delineates design principles that enable configurationally stable and room-temperature isolable salts to be generated. We show that the barrier to inversion is greater than 110 kJ mol(−1) and outline processes for resolution. This constitutes, to our knowledge, the only example of a chiral non-racemic and configurationally stable molecule in which the oxygen atom is the sole stereogenic centre.
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spelling pubmed-100174942023-03-17 Control of stereogenic oxygen in a helically chiral oxonium ion Smith, Owen Popescu, Mihai V. Hindson, Madeleine J. Paton, Robert S. Burton, Jonathan W. Smith, Martin D. Nature Article The control of tetrahedral carbon stereocentres remains a focus of modern synthetic chemistry and is enabled by their configurational stability. By contrast, trisubstituted nitrogen(1), phosphorus(2) and sulfur compounds(3) undergo pyramidal inversion, a fundamental and well-recognized stereochemical phenomenon that is widely exploited(4). However, the stereochemistry of oxonium ions—compounds bearing three substituents on a positively charged oxygen atom—is poorly developed and there are few applications of oxonium ions in synthesis beyond their existence as reactive intermediates(5,6). There are no examples of configurationally stable oxonium ions in which the oxygen atom is the sole stereogenic centre, probably owing to the low barrier to oxygen pyramidal inversion(7) and the perception that all oxonium ions are highly reactive. Here we describe the design, synthesis and characterization of a helically chiral triaryloxonium ion in which inversion of the oxygen lone pair is prevented through geometric restriction to enable it to function as a determinant of configuration. A combined synthesis and quantum calculation approach delineates design principles that enable configurationally stable and room-temperature isolable salts to be generated. We show that the barrier to inversion is greater than 110 kJ mol(−1) and outline processes for resolution. This constitutes, to our knowledge, the only example of a chiral non-racemic and configurationally stable molecule in which the oxygen atom is the sole stereogenic centre. Nature Publishing Group UK 2023-03-15 2023 /pmc/articles/PMC10017494/ /pubmed/36922609 http://dx.doi.org/10.1038/s41586-023-05719-z Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Smith, Owen
Popescu, Mihai V.
Hindson, Madeleine J.
Paton, Robert S.
Burton, Jonathan W.
Smith, Martin D.
Control of stereogenic oxygen in a helically chiral oxonium ion
title Control of stereogenic oxygen in a helically chiral oxonium ion
title_full Control of stereogenic oxygen in a helically chiral oxonium ion
title_fullStr Control of stereogenic oxygen in a helically chiral oxonium ion
title_full_unstemmed Control of stereogenic oxygen in a helically chiral oxonium ion
title_short Control of stereogenic oxygen in a helically chiral oxonium ion
title_sort control of stereogenic oxygen in a helically chiral oxonium ion
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10017494/
https://www.ncbi.nlm.nih.gov/pubmed/36922609
http://dx.doi.org/10.1038/s41586-023-05719-z
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