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Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines

[Image: see text] Cyclic triureas derived from 1,4,7-triazacyclononane (TACN) were synthesized; X-ray crystallography showed a chiral bowl-like conformation with each urea hydrogen-bonded to its neighbor with uniform directionality, forming a “cyclochiral” closed loop of hydrogen bonds. Variable-tem...

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Autores principales: Morris, David T. J., Wales, Steven M., Echavarren, Javier, Žabka, Matej, Marsico, Giulia, Ward, John W., Pridmore, Natalie E., Clayden, Jonathan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472504/
https://www.ncbi.nlm.nih.gov/pubmed/37594473
http://dx.doi.org/10.1021/jacs.3c06570
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author Morris, David T. J.
Wales, Steven M.
Echavarren, Javier
Žabka, Matej
Marsico, Giulia
Ward, John W.
Pridmore, Natalie E.
Clayden, Jonathan
author_facet Morris, David T. J.
Wales, Steven M.
Echavarren, Javier
Žabka, Matej
Marsico, Giulia
Ward, John W.
Pridmore, Natalie E.
Clayden, Jonathan
author_sort Morris, David T. J.
collection PubMed
description [Image: see text] Cyclic triureas derived from 1,4,7-triazacyclononane (TACN) were synthesized; X-ray crystallography showed a chiral bowl-like conformation with each urea hydrogen-bonded to its neighbor with uniform directionality, forming a “cyclochiral” closed loop of hydrogen bonds. Variable-temperature (1)H NMR, (1)H-(1)H exchange spectroscopy, Eyring analysis, computational modeling, and studies in various solvents revealed that cyclochirality is dynamic (ΔG(‡)(25°C) = 63–71 kJ mol(–1) in noncoordinating solvents), exchanging between enantiomers by two mechanisms: bowl inversion and directionality reversal, with the former subject to a slightly smaller enantiomerization barrier. The enantiomerization rate substantially increased in the presence of hydrogen-bonding solvents. Population of only one of the two cyclochiral hydrogen-bond directionalities could be induced by annulating one ethylene bridge with a trans-cyclohexane. Alternatively, enantiomerization could be inhibited by annulating one ethylene bridge with a cis-cyclohexane (preventing bowl inversion) and replacing one urea function with a formamide (preventing directionality reversal). Combining these structural modifications resulted in an enantiomerization barrier of ΔG(‡)(25°C) = 93 kJ mol(–1), furnishing a planar-chiral, atropisomeric bowl-shaped structure whose stereochemical stability arises solely from its hydrogen-bonding network.
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spelling pubmed-104725042023-09-02 Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines Morris, David T. J. Wales, Steven M. Echavarren, Javier Žabka, Matej Marsico, Giulia Ward, John W. Pridmore, Natalie E. Clayden, Jonathan J Am Chem Soc [Image: see text] Cyclic triureas derived from 1,4,7-triazacyclononane (TACN) were synthesized; X-ray crystallography showed a chiral bowl-like conformation with each urea hydrogen-bonded to its neighbor with uniform directionality, forming a “cyclochiral” closed loop of hydrogen bonds. Variable-temperature (1)H NMR, (1)H-(1)H exchange spectroscopy, Eyring analysis, computational modeling, and studies in various solvents revealed that cyclochirality is dynamic (ΔG(‡)(25°C) = 63–71 kJ mol(–1) in noncoordinating solvents), exchanging between enantiomers by two mechanisms: bowl inversion and directionality reversal, with the former subject to a slightly smaller enantiomerization barrier. The enantiomerization rate substantially increased in the presence of hydrogen-bonding solvents. Population of only one of the two cyclochiral hydrogen-bond directionalities could be induced by annulating one ethylene bridge with a trans-cyclohexane. Alternatively, enantiomerization could be inhibited by annulating one ethylene bridge with a cis-cyclohexane (preventing bowl inversion) and replacing one urea function with a formamide (preventing directionality reversal). Combining these structural modifications resulted in an enantiomerization barrier of ΔG(‡)(25°C) = 93 kJ mol(–1), furnishing a planar-chiral, atropisomeric bowl-shaped structure whose stereochemical stability arises solely from its hydrogen-bonding network. American Chemical Society 2023-08-18 /pmc/articles/PMC10472504/ /pubmed/37594473 http://dx.doi.org/10.1021/jacs.3c06570 Text en © 2023 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 Morris, David T. J.
Wales, Steven M.
Echavarren, Javier
Žabka, Matej
Marsico, Giulia
Ward, John W.
Pridmore, Natalie E.
Clayden, Jonathan
Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines
title Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines
title_full Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines
title_fullStr Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines
title_full_unstemmed Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines
title_short Dynamic and Persistent Cyclochirality in Hydrogen-Bonded Derivatives of Medium-Ring Triamines
title_sort dynamic and persistent cyclochirality in hydrogen-bonded derivatives of medium-ring triamines
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10472504/
https://www.ncbi.nlm.nih.gov/pubmed/37594473
http://dx.doi.org/10.1021/jacs.3c06570
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