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Basicities and Nucleophilicities of Pyrrolidines and Imidazolidinones Used as Organocatalysts

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    Basicities and Nucleophilicities of Pyrrolidines and Imidazolidinones Used as Organocatalysts
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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2020, 142, 3, 1526–1547
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    https://doi.org/10.1021/jacs.9b11877
    Published January 8, 2020
    Copyright © 2020 American Chemical Society
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    Abstract

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    The Brønsted basicities pKaH (i.e., pKa of the conjugate acids) of 32 pyrrolidines and imidazolidinones, commonly used in organocatalytic reactions, have been determined photometrically in acetonitrile solution using CH acids as indicators. Most investigated pyrrolidines have basicities in the range 16 < pKaH < 20, while imidazolidinones are significantly less basic (10 < pKaH < 12). 2-(Trifluoromethyl)pyrrolidine (A14, pKaH 12.6) and the 2-imidazoliummethyl-substituted pyrrolidine A21 (pKaH 11.1) are outside the typical range for pyrrolidines with basicities comparable to those of imidazolidinones. Kinetics of the reactions of these 32 organocatalysts with benzhydrylium ions (Ar2CH+) and structurally related quinone methides, common reference electrophiles for quantifying nucleophilic reactivities, have been measured photometrically. Most reactions followed second-order kinetics, first order in amine and first order in electrophile. More complex kinetics were observed for the reactions of imidazolidinones and several pyrrolidines carrying bulky 2-substituents, due to reversibility of the initial attack of the amines at the electrophiles followed by rate-determining deprotonation of the intermediate ammonium ions. In the presence of 2,4,6-collidine or 2,6-di-tert-butyl-4-methyl-pyridine, the deprotonation of the initial adducts became faster, which allowed the rate of the attack of the amines at the electrophiles to be determined. The resulting second-order rate constants k2 followed the correlation log k2(20 °C) = sN(N + E), where electrophiles are characterized by one parameter (E) and nucleophiles are characterized by the two solvent-dependent parameters N and sN. In this way, the organocatalysts A1–A32 were integrated in our comprehensive nucleophilicity scale, which compares n-, π-, and σ-nucleophiles. The nucleophilic reactivities of the title compounds correlate only poorly with their Brønsted basicities.

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    The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.9b11877.

    • Procedures for the preparation of A1–A32 and C1H–C6H, details of the product studies, NMR and IR spectra of characterized compounds, details of kinetic experiments, and determinations of equilibrium constants (PDF)

    • Crystal structure for 4,4′-((2-tritylpyrrolidin-1-yl)methylene)bis(N,N-dimethylaniline) (CIF)

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    Journal of the American Chemical Society

    Cite this: J. Am. Chem. Soc. 2020, 142, 3, 1526–1547
    Click to copy citationCitation copied!
    https://doi.org/10.1021/jacs.9b11877
    Published January 8, 2020
    Copyright © 2020 American Chemical Society
    Request reuse permissions

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