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Electrosteric Activation by using Ion-Tagged Prolines: A Combined Experimental and Computational Investigation

Authors

  • Prof. Andrea Bottoni,

    1. Dipartimento di Chimica “G. Ciamician“, Università degli Studi di Bologna via Selmi 2, 40126, Bologna(Italy)
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  • Prof. Marco Lombardo,

    Corresponding author
    1. Dipartimento di Chimica “G. Ciamician“, Università degli Studi di Bologna via Selmi 2, 40126, Bologna(Italy)
    • Dipartimento di Chimica “G. Ciamician“, Università degli Studi di Bologna via Selmi 2, 40126, Bologna(Italy)
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  • Dr. Gian Pietro Miscione,

    Corresponding author
    1. Dipartimento di Chimica “G. Ciamician“, Università degli Studi di Bologna via Selmi 2, 40126, Bologna(Italy)
    • Dipartimento di Chimica “G. Ciamician“, Università degli Studi di Bologna via Selmi 2, 40126, Bologna(Italy)
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  • Dr. Elisa Montroni,

    1. Dipartimento di Chimica “G. Ciamician“, Università degli Studi di Bologna via Selmi 2, 40126, Bologna(Italy)
    2. Consorzio Interuniversitario “C.I.N.M.P.I.S.” via Orabona 4, 70125 Bari(Italy)
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  • Dr. Arianna Quintavalla,

    1. Dipartimento di Chimica “G. Ciamician“, Università degli Studi di Bologna via Selmi 2, 40126, Bologna(Italy)
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  • Prof. Claudio Trombini

    1. Dipartimento di Chimica “G. Ciamician“, Università degli Studi di Bologna via Selmi 2, 40126, Bologna(Italy)
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Abstract

We have recently proposed the empirical concept of electrosteric activation to explain the improved catalytic performances observed for a series of ion-tagged catalysts compared to the parent tag-free structures. Here, the results of a combined experimental and computational investigation on the asymmetric aldol reaction between cyclohexanone and benzaldehyde, catalyzed by a family of tag-free and ionic-tagged prolines, are presented. Whereas diastereo- and enantioselectivities remain very high in all cases examined, the ion-tagged catalyst cis-4-(2-(3-methyl-imidazol-3-ium-1-yl)acetoxy)-proline bistriflimide, cis-7, displays a remarkably high activity compared to its tagged trans analogue and to the tag-free catalysts cis and trans-4-(2-phenylacetoxy)-proline 8. A computational investigation of ion-tagged and tag-free model systems shows that the transition state involving cis-7 is stabilized by a complex interplay of hydrogen bonds (in particular, those involving the counter ion oxygen atoms and the hydrogen atoms of the ionic tag), π-stacking interactions involving the aldehyde phenyl ring, and similar π interactions between the proline carboxyl group and the imidazole ring. The overall effect of these interactions accounts for the observed enhanced activity.

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