title: Aromatic Interactions in Organocatalyst Design: Augmenting Selectivity Reversal in Iminium Ion Activation.
abstract: Substituting N-methylpyrrole for N-methyindole in secondary-amine-catalysed Friedel-Crafts reactions leads to a curious erosion of enantioselectivity. In extreme cases, this substrate dependence can lead to an inversion in the sense of enantioinduction. Indeed, these closely similar transformations require two structurally distinct catalysts to obtain comparable selectivities. Herein a focussed molecular editing study is disclosed to illuminate the structural features responsible for this disparity, and thus identify lead catalyst structures to further exploit this selectivity reversal. Key to effective catalyst re-engineering was delineating the non-covalent interactions that manifest themselves in conformation. Herein we disclose preliminary validation that intermolecular aromatic (CH-π and cation-π) interactions between the incipient iminium cation and the indole ring system is key to rationalising selectivity reversal. This is absent in the N-methylpyrrole alkylation, thus forming the basis of two competing enantio-induction pathways. A simple L-valine catalyst has been developed that significantly augments this interaction.
authors.affiliation: Institut für Organische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster (Germany) http://www.uni-muenster.de/Chemie.oc/gilmour/|Current address: Department of Chemistry and Biochemistry, University of California Los Angeles, 607 Charles E. Young Drive East, Los Angeles 90095-1569 (USA).
authors.forename: Mareike C
authors.initials: MC
authors.lastname: Holland
authors.affiliation: Institut für Organische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster (Germany) http://www.uni-muenster.de/Chemie.oc/gilmour/
authors.forename: Jan Benedikt
authors.initials: JB
authors.lastname: Metternich
authors.affiliation: Institut für Organische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster (Germany) http://www.uni-muenster.de/Chemie.oc/gilmour/
authors.forename: Constantin
authors.initials: C
authors.lastname: Daniliuc
authors.affiliation: Laboratorium für Organische Chemie, ETH Zürich, Vladimir-Prelog-Weg 3, 8093 Zürich (Switzerland).
authors.forename: W Bernd
authors.initials: WB
authors.lastname: Schweizer
authors.affiliation: Institut für Organische Chemie, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster (Germany) http://www.uni-muenster.de/Chemie.oc/gilmour/. ryan.gilmour@uni-muenster.de.|Excellence Cluster EXC 1003 "Cells in Motion", Westfälische Wilhelms-Universität Münster, Münster (Germany). ryan.gilmour@uni-muenster.de.
authors.forename: Ryan
authors.initials: R
authors.lastname: Gilmour
mesh_terms: D000478:Alkylation; D002384:Catalysis; D002412:Cations / Q000737:chemistry*; D006860:Hydrogen Bonding; D007097:Imines / Q000737:chemistry*; D007211:Indoles / Q000737:chemistry*; D008958:Models, Molecular; D011758:Pyrroles / Q000737:chemistry*; D013237:Stereoisomerism; D014633:Valine / Q000737:chemistry*
chemical_list: D002412:Cations; D007097:Imines; D007211:Indoles; D011758:Pyrroles; C030374:indole; D014633:Valine
keywords: CH-π/cation-π interactions; imidazolidinone; molecular design; non-covalent interactions; selectivity reversal