Tailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative amination

Abstract Even though tuning electronic effect of chiral ligands has proven to be a promising method for designing efficient catalysts, the potential to achieve highly selective reactions by this strategy remains largely unexplored. Here, we report a palladium-catalyzed enantioselective ring-closing...

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Main Authors: Suchen Zou, Zeyu Zhao, Guoqing Yang, Hanmin Huang
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-024-54328-5
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author Suchen Zou
Zeyu Zhao
Guoqing Yang
Hanmin Huang
author_facet Suchen Zou
Zeyu Zhao
Guoqing Yang
Hanmin Huang
author_sort Suchen Zou
collection DOAJ
description Abstract Even though tuning electronic effect of chiral ligands has proven to be a promising method for designing efficient catalysts, the potential to achieve highly selective reactions by this strategy remains largely unexplored. Here, we report a palladium-catalyzed enantioselective ring-closing aminoalkylative amination of aminoenynes enabled by rationally tuning the remote electronic property of 1,1’-binaphthol-derived phosphoramidites. With a tailored 6,6’-CN-substituted 1,1’-binaphthol-derived phosphoramidite as a ligand, a broad range of aromatic amines are compatible with this reaction, allowing the efficient synthesis of a series of enantioenriched exocyclic allenylamines bearing saturated N-heterocycles with up to >99% enantiomeric excess. Remarkably, a one-pot aminoalkylative amination/hydroamination process for the rapid synthesis of chiral spirodiamines promoted by this catalytic system is also established. Detailed mechanistic studies provide solid evidence to support that the remote electronic character of these chiral ligands can efficiently tuning the enantioselectivity by altering the length of the allylic C-Pd bond of the key catalytic intermediate.
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spelling doaj-art-949df99f102c4ef8a3559cfdbffed44a2025-08-20T02:20:48ZengNature PortfolioNature Communications2041-17232024-12-0115111110.1038/s41467-024-54328-5Tailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative aminationSuchen Zou0Zeyu Zhao1Guoqing Yang2Hanmin Huang3Key Laboratory of Precision and Intelligent Chemistry and Department of Chemistry, University of Science and Technology of ChinaKey Laboratory of Precision and Intelligent Chemistry and Department of Chemistry, University of Science and Technology of ChinaKey Laboratory of Precision and Intelligent Chemistry and Department of Chemistry, University of Science and Technology of ChinaKey Laboratory of Precision and Intelligent Chemistry and Department of Chemistry, University of Science and Technology of ChinaAbstract Even though tuning electronic effect of chiral ligands has proven to be a promising method for designing efficient catalysts, the potential to achieve highly selective reactions by this strategy remains largely unexplored. Here, we report a palladium-catalyzed enantioselective ring-closing aminoalkylative amination of aminoenynes enabled by rationally tuning the remote electronic property of 1,1’-binaphthol-derived phosphoramidites. With a tailored 6,6’-CN-substituted 1,1’-binaphthol-derived phosphoramidite as a ligand, a broad range of aromatic amines are compatible with this reaction, allowing the efficient synthesis of a series of enantioenriched exocyclic allenylamines bearing saturated N-heterocycles with up to >99% enantiomeric excess. Remarkably, a one-pot aminoalkylative amination/hydroamination process for the rapid synthesis of chiral spirodiamines promoted by this catalytic system is also established. Detailed mechanistic studies provide solid evidence to support that the remote electronic character of these chiral ligands can efficiently tuning the enantioselectivity by altering the length of the allylic C-Pd bond of the key catalytic intermediate.https://doi.org/10.1038/s41467-024-54328-5
spellingShingle Suchen Zou
Zeyu Zhao
Guoqing Yang
Hanmin Huang
Tailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative amination
Nature Communications
title Tailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative amination
title_full Tailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative amination
title_fullStr Tailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative amination
title_full_unstemmed Tailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative amination
title_short Tailored chiral phosphoramidites support highly enantioselective Pd catalysts for asymmetric aminoalkylative amination
title_sort tailored chiral phosphoramidites support highly enantioselective pd catalysts for asymmetric aminoalkylative amination
url https://doi.org/10.1038/s41467-024-54328-5
work_keys_str_mv AT suchenzou tailoredchiralphosphoramiditessupporthighlyenantioselectivepdcatalystsforasymmetricaminoalkylativeamination
AT zeyuzhao tailoredchiralphosphoramiditessupporthighlyenantioselectivepdcatalystsforasymmetricaminoalkylativeamination
AT guoqingyang tailoredchiralphosphoramiditessupporthighlyenantioselectivepdcatalystsforasymmetricaminoalkylativeamination
AT hanminhuang tailoredchiralphosphoramiditessupporthighlyenantioselectivepdcatalystsforasymmetricaminoalkylativeamination