How Can Theory Predict the Selectivity of Palladium-Catalyzed Cross-Coupling of Pristine Aromatic Molecules?

Authors

  • Rinat Meir,

    1. Institute of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Hebrew University of Jerusalem, Givat Ram Campus, 91904 Jerusalem (Israel)
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  • Dr. Sebastian Kozuch,

    Corresponding author
    1. Department of Organic Chemistry, The Weizmann Institute of Science, 76100 Rehovot (Israel)
    • Department of Organic Chemistry, The Weizmann Institute of Science, 76100 Rehovot (Israel)
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  • Andreas Uhe,

    1. Institut für Technische und Makromolekulare Chemie, RWTH Aachen University, Worringerweg 1, 52074 Aachen (Germany)
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  • Prof. Sason Shaik

    Corresponding author
    1. Institute of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Hebrew University of Jerusalem, Givat Ram Campus, 91904 Jerusalem (Israel)
    • Institute of Chemistry and the Lise Meitner-Minerva Center for Computational Quantum Chemistry, Hebrew University of Jerusalem, Givat Ram Campus, 91904 Jerusalem (Israel)
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Abstract

The new approach for palladium-catalyzed cross-coupling of two non-activated aromatic compounds (D. R. Stuart, K. Fagnou, Science2007, 316, 1172) was studied theoretically. The energetic span model (S. Kozuch, S. Shaik, Acc. Chem. Res.2011, 44, 101, and references therein) was employed to analyze the kinetic behavior of the catalytic cycle. The computed energy profile, combined with the energetic span model, accounts for the experimental selectivity, which favors the hetero-coupling of benzene with indole. This selectivity is driven by a fine balance of the entropic contributions and the high ratio of concentrations used for benzene over indole. This analysis may allow future theoretical predictions of how different aromatic compounds can be effectively coupled.

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