Multiple Atropo Selectivity by κ2‐N,O‐Oxazoline Urea Ligands in Cobaltaelectro‐Catalyzed C─H Activations: Decoding Selectivity with Data Science Integration

Enantioselective catalysis is one of the most prominent strategies in organic synthesis to access chiral bioactive compounds and advanced organic materials. Particularly, the development of chiral ligands has significantly advanced the efficiency and selectivity of transition metal‐catalyzed enantio...

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Main Authors: Philipp Boos, Neeraj Kumar Pandit, Suman Dana, Tristan von Münchow, Airu Hashidoko, Laura Haberstock, Regine Herbst‐Irmer, Dietmar Stalke, Lutz Ackermann
Format: Article
Language:English
Published: Wiley-VCH 2025-05-01
Series:ChemistryEurope
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Online Access:https://doi.org/10.1002/ceur.202500071
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author Philipp Boos
Neeraj Kumar Pandit
Suman Dana
Tristan von Münchow
Airu Hashidoko
Laura Haberstock
Regine Herbst‐Irmer
Dietmar Stalke
Lutz Ackermann
author_facet Philipp Boos
Neeraj Kumar Pandit
Suman Dana
Tristan von Münchow
Airu Hashidoko
Laura Haberstock
Regine Herbst‐Irmer
Dietmar Stalke
Lutz Ackermann
author_sort Philipp Boos
collection DOAJ
description Enantioselective catalysis is one of the most prominent strategies in organic synthesis to access chiral bioactive compounds and advanced organic materials. Particularly, the development of chiral ligands has significantly advanced the efficiency and selectivity of transition metal‐catalyzed enantioselective transformations. Over recent decades, numerous chiral ligand classes with distinct geometrical and electronic properties have been established. Despite these advances, the demand for novel, tunable, and highly effective chiral ligands persists, driven by the need for structurally diverse chiral molecules and the pursuit of greener, more sustainable catalytic processes. Herein, a novel class of chiral oxazoline ureas is introduced and their potential as κ2‐N,O‐preligands in enantioselective transition metal catalysis is demonstrated. The chiral oxazoline urea ligands are featurized and compared with amide and enol derivatives using the physical organic descriptors. A multivariate linear regression model is constructed to quantitatively describe the effect of the quinoline fragment from the substrate and the ligand on enantioselectivity. Moreover, the model is effectively applied to atropo‐enantioselective cobaltaelectro‐catalyzed C─H annulations of 1‐alkynyl indoles.
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spelling doaj-art-a815a96447e54b2fa16dc3f9e8edd1022025-08-20T01:50:13ZengWiley-VCHChemistryEurope2751-47652025-05-0133n/an/a10.1002/ceur.202500071Multiple Atropo Selectivity by κ2‐N,O‐Oxazoline Urea Ligands in Cobaltaelectro‐Catalyzed C─H Activations: Decoding Selectivity with Data Science IntegrationPhilipp Boos0Neeraj Kumar Pandit1Suman Dana2Tristan von Münchow3Airu Hashidoko4Laura Haberstock5Regine Herbst‐Irmer6Dietmar Stalke7Lutz Ackermann8Wöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyWöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyWöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyWöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyWöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyWöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyWöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyWöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyWöhler‐Research Institute for Sustainable Chemistry (WISCh) Georg‐August‐Universität Göttingen Tammannstraße 2 37077 Göttingen GermanyEnantioselective catalysis is one of the most prominent strategies in organic synthesis to access chiral bioactive compounds and advanced organic materials. Particularly, the development of chiral ligands has significantly advanced the efficiency and selectivity of transition metal‐catalyzed enantioselective transformations. Over recent decades, numerous chiral ligand classes with distinct geometrical and electronic properties have been established. Despite these advances, the demand for novel, tunable, and highly effective chiral ligands persists, driven by the need for structurally diverse chiral molecules and the pursuit of greener, more sustainable catalytic processes. Herein, a novel class of chiral oxazoline ureas is introduced and their potential as κ2‐N,O‐preligands in enantioselective transition metal catalysis is demonstrated. The chiral oxazoline urea ligands are featurized and compared with amide and enol derivatives using the physical organic descriptors. A multivariate linear regression model is constructed to quantitatively describe the effect of the quinoline fragment from the substrate and the ligand on enantioselectivity. Moreover, the model is effectively applied to atropo‐enantioselective cobaltaelectro‐catalyzed C─H annulations of 1‐alkynyl indoles.https://doi.org/10.1002/ceur.202500071C─H activationC─N atropoisomerscobalt catalysiselectrocatalysisligand design
spellingShingle Philipp Boos
Neeraj Kumar Pandit
Suman Dana
Tristan von Münchow
Airu Hashidoko
Laura Haberstock
Regine Herbst‐Irmer
Dietmar Stalke
Lutz Ackermann
Multiple Atropo Selectivity by κ2‐N,O‐Oxazoline Urea Ligands in Cobaltaelectro‐Catalyzed C─H Activations: Decoding Selectivity with Data Science Integration
ChemistryEurope
C─H activation
C─N atropoisomers
cobalt catalysis
electrocatalysis
ligand design
title Multiple Atropo Selectivity by κ2‐N,O‐Oxazoline Urea Ligands in Cobaltaelectro‐Catalyzed C─H Activations: Decoding Selectivity with Data Science Integration
title_full Multiple Atropo Selectivity by κ2‐N,O‐Oxazoline Urea Ligands in Cobaltaelectro‐Catalyzed C─H Activations: Decoding Selectivity with Data Science Integration
title_fullStr Multiple Atropo Selectivity by κ2‐N,O‐Oxazoline Urea Ligands in Cobaltaelectro‐Catalyzed C─H Activations: Decoding Selectivity with Data Science Integration
title_full_unstemmed Multiple Atropo Selectivity by κ2‐N,O‐Oxazoline Urea Ligands in Cobaltaelectro‐Catalyzed C─H Activations: Decoding Selectivity with Data Science Integration
title_short Multiple Atropo Selectivity by κ2‐N,O‐Oxazoline Urea Ligands in Cobaltaelectro‐Catalyzed C─H Activations: Decoding Selectivity with Data Science Integration
title_sort multiple atropo selectivity by κ2 n o oxazoline urea ligands in cobaltaelectro catalyzed c─h activations decoding selectivity with data science integration
topic C─H activation
C─N atropoisomers
cobalt catalysis
electrocatalysis
ligand design
url https://doi.org/10.1002/ceur.202500071
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