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Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy

Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine i...

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Autores principales: Mills, Mitchell D., Sonstrom, Reilly E., Vang, Zoua Pa, Neill, Justin L., Scolati, Haley N., West, Channing T., Pate, Brooks H., Clark, Joseph R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403034/
https://www.ncbi.nlm.nih.gov/pubmed/35700045
http://dx.doi.org/10.1002/anie.202207275
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author Mills, Mitchell D.
Sonstrom, Reilly E.
Vang, Zoua Pa
Neill, Justin L.
Scolati, Haley N.
West, Channing T.
Pate, Brooks H.
Clark, Joseph R.
author_facet Mills, Mitchell D.
Sonstrom, Reilly E.
Vang, Zoua Pa
Neill, Justin L.
Scolati, Haley N.
West, Channing T.
Pate, Brooks H.
Clark, Joseph R.
author_sort Mills, Mitchell D.
collection PubMed
description Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine in many facets of asymmetric synthesis, the same determinations for enantioisotopomers remains a formidable challenge. Here, we report the first highly enantioselective metal‐catalyzed synthesis of enantioisotopomers that are chiral by virtue of deuterium substitution along with the first general spectroscopic technique for assignment of the absolute configuration and quantitative determination of the enantiomeric excess of isotopically chiral molecules. Chiral tag rotational spectroscopy uses noncovalent chiral derivatization, which eliminates the possibility of racemization during derivatization, to perform the chiral analysis without the need of reference samples of the enantioisotopomer.
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spelling pubmed-94030342022-10-14 Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy Mills, Mitchell D. Sonstrom, Reilly E. Vang, Zoua Pa Neill, Justin L. Scolati, Haley N. West, Channing T. Pate, Brooks H. Clark, Joseph R. Angew Chem Int Ed Engl Research Articles Fundamental to the synthesis of enantioenriched chiral molecules is the ability to assign absolute configuration at each stereogenic center, and to determine the enantiomeric excess for each compound. While determination of enantiomeric excess and absolute configuration is often considered routine in many facets of asymmetric synthesis, the same determinations for enantioisotopomers remains a formidable challenge. Here, we report the first highly enantioselective metal‐catalyzed synthesis of enantioisotopomers that are chiral by virtue of deuterium substitution along with the first general spectroscopic technique for assignment of the absolute configuration and quantitative determination of the enantiomeric excess of isotopically chiral molecules. Chiral tag rotational spectroscopy uses noncovalent chiral derivatization, which eliminates the possibility of racemization during derivatization, to perform the chiral analysis without the need of reference samples of the enantioisotopomer. John Wiley and Sons Inc. 2022-07-08 2022-08-15 /pmc/articles/PMC9403034/ /pubmed/35700045 http://dx.doi.org/10.1002/anie.202207275 Text en © 2022 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Research Articles
Mills, Mitchell D.
Sonstrom, Reilly E.
Vang, Zoua Pa
Neill, Justin L.
Scolati, Haley N.
West, Channing T.
Pate, Brooks H.
Clark, Joseph R.
Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy
title Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy
title_full Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy
title_fullStr Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy
title_full_unstemmed Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy
title_short Enantioselective Synthesis of Enantioisotopomers with Quantitative Chiral Analysis by Chiral Tag Rotational Spectroscopy
title_sort enantioselective synthesis of enantioisotopomers with quantitative chiral analysis by chiral tag rotational spectroscopy
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9403034/
https://www.ncbi.nlm.nih.gov/pubmed/35700045
http://dx.doi.org/10.1002/anie.202207275
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