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Stereoselectivity Predictions for the Pd-Catalyzed 1,4-Conjugate Addition Using Quantum-Guided Molecular Mechanics.
Wahlers, Jessica; Maloney, Michael; Salahi, Farbod; Rosales, Anthony R; Helquist, Paul; Norrby, Per-Ola; Wiest, Olaf.
Afiliación
  • Wahlers J; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
  • Maloney M; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
  • Salahi F; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
  • Rosales AR; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
  • Helquist P; Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, Indiana 46556, United States.
  • Norrby PO; Data Science and Modelling, Pharmaceutical Sciences, R&D, AstraZeneca Gothenburg, Pepparedsleden 1, SE-431 83 Mölndal, Sweden.
  • Wiest O; Department of Chemistry and Molecular Biology, University of Gothenburg, SE-412 96 Gothenburg, Sweden.
J Org Chem ; 86(8): 5660-5667, 2021 04 16.
Article en En | MEDLINE | ID: mdl-33769065
The conjugate addition of aryl boronic acids to enones is a powerful synthetic tool to introduce quaternary chiral centers, but the experimentally observed stereoselectivities vary widely, and the identification of suitable substrate-ligand combinations requires significant effort. We describe the development and application of a transition-state force field (TSFF) by the quantum-guided molecular mechanics (Q2MM) method that is validated using an automated screen of 9 ligands, 38 aryl boronic acids, and 22 enones, leading to a MUE of 1.8 kJ/mol and a R2 value of 0.877 over 82 examples. A detailed error analysis identified the structural origin for the deviations in the small group of outliers. The TSFF was then used to predict the stereoselectivity for 27 ligands and 59 enones. The vast majority of the virtual screening results are in line with the expected results. Selected results for 6-substituted pyrox ligands, which were not part of the training set, were followed up by density functional theory and experimental studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paladio / Ácidos Borónicos Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Org Chem Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Paladio / Ácidos Borónicos Tipo de estudio: Prognostic_studies / Risk_factors_studies Idioma: En Revista: J Org Chem Año: 2021 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos