Abstract
Gaining an understanding of the conformational behavior of fluorinated compounds would allow for expansion of the current molecular design toolbox. In order to facilitate drug discovery efforts, a systematic survey of a series of diversely substituted and protected fluorinated piperidine derivatives has been carried out using NMR spectroscopy. Computational investigations reveal that, in addition to established delocalization forces such as charge–dipole interactions and hyperconjugation, solvation and solvent polarity play a major role. This work codifies a new design principle for conformationally rigid molecular scaffolds.
| Original language | American English |
|---|---|
| Pages (from-to) | 6141-6146 |
| Number of pages | 6 |
| Journal | Chemistry - A European Journal |
| Volume | 26 |
| Issue number | 28 |
| DOIs | |
| State | Published - 15 May 2020 |
| Externally published | Yes |
Bibliographical note
Funding Information:All computations were carried out on the high-performance computing system PALMA II (WWU Münster). We thank Prof. Ryan Gilmour (WWU Münster), Prof. Alexander Hillisch (Bayer Pharma AG) and Professor Peer Kirsch (Merck KGaA) for helpful discussions. Financial support by the European Research Council (ERC Advanced Grant Agreement no. 788558) and Deutsche Forschungsgemeinschaft (SPP2102) is gratefully acknowledged.
Funding Information:
All computations were carried out on the high‐performance computing system PALMA II (WWU Münster). We thank Prof. Ryan Gilmour (WWU Münster), Prof. Alexander Hillisch (Bayer Pharma AG) and Professor Peer Kirsch (Merck KGaA) for helpful discussions. Financial support by the European Research Council (ERC Advanced Grant Agreement no. 788558) and Deutsche Forschungsgemeinschaft (SPP2102) is gratefully acknowledged.
Publisher Copyright:
© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
Keywords
- NMR analysis
- conformational behavior
- fluorine
- piperidines
- solvation effect