Probing long-range anisotropic interactions – A general and sign-sensitive strategy to measure 1H-1H residual dipolar couplings as a key advance for organic structure determination

Raw Bruker NMR data associated with the publication in Angewandte Chemie International Edition, 2020, DOI: 10.1002/anie.201915278

Residual dipolar couplings (RDCs) are amongst the most powerful NMR parameters for organic structure elucidation. In order to maximize their effectiveness in increasingly complex cases such as flexible compounds, a maximum of RDCs between nuclei sampling a large distribution of orientations is needed, including sign information. For this, the easily accessible one-bond 1H-13C RDCs alone often fall short. Long-range 1H-1H RDCs are both abundant and typically sample highly complementary orientations, but accessing them in a sign-sensitive way has been severely obstructed due to the overflow of 1H-1H couplings. Here, we present a generally applicable strategy that allows the measurement of a large number of 1H-1H RDCs, including the sign, that is based on a combination of the PSYCHEDELIC method and a new selective constant-time beta-COSY experiment. The potential of 1H-1H RDCs to better determine molecular alignment and to discriminate between enantiomers and diastereomers is demonstrated.