Julian Ilgen | Efficient Detection of 1H, 15N Correlations in Hydrogen Bonded Low Molecular

Julian Ilgen, Institute for Organic Chemistry, University Vienna, Austria Title: Efficient Detection of 1H, 15N Correlations in Hydrogen Bonded Low Molecular Catalyst-Substrate Intermediates Abstract: Nitrogen is a key element in a broad range of functional groups and thus, plays a crucial role in organic synthesis, biochemistry, pharmaceuticals and is further frequently present in reaction centers of catalyzed reactions. NMR spectroscopy is a powerful tool to characterize such systems as the mainly used NMR active isotope 15N is very sensitive to tiny variations of the chemical environment, a feature we applied to characterize hydrogen bonds in the heart of a catalytic center in ion pair catalysis with chiral phosphoric acids (CPAs).[1] However, NMR spectroscopy on 15N in small molecules applications is extremely challenging due to its very low natural abundance combined with a low and negative gyromagnetic ratio. Thus, at natural abundance excessive measurement times are required often exceeding the lifetime of intermediates. Selective 15N labelling as common in biochemistry is often laborious, expensive or even inaccessible due to the gigantesque variety of small to mid-size molecules. A solution to the sensitivity problem of 15N at natural abundance can be found in the emerging field of fast NMR methods.[2] In NMR applications on biomacromolecules the SOFAST[3] approach was highly successful, whereas it is quite underrepresented in studies of low molecular compounds and especially catalytic intermediates. On the example of intermediates from ion pair catalysis with CPAs we showed that SOFAST indeed offers an efficient technique for low molecular compounds.[4] Herein 1H and 15N chemical shifts as well as through hydrogen bond 1hJNH scalar coupling constants are detected within decent experimental times. This further allows a time- and cost-efficient characterization of hydrogen bonds for reactivity correlations by internal acidity scales without prior 15N substrate labeling. [5] We further expanded our approach to other catalyst-substrate interactions as well as other challenging 1H,X-correlations.