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4. Conclusion and Future Research

\(\newcommand{\va}{V\cdot\AA^{-1}}\newcommand{\eh}{E_h}\newcommand{\dc}{^\circ C}\newcommand{\kcalmol}{Kcal\cdot mol^{-1}}\newcommand{\kjmol}{KJ\cdot mol^{-1}}\)Through the use of DFT based computational investigations, it was found that the non-catalysed pathway of the cyclisation of 2’-aminochalcone to aza-flavanone was a good candidate for further study into the effects of OEEF mediated stereocontrol.

When solvated in ethanol, which was identified as the optimal solvent choice, an OEEF oriented predominantly in-line with the newly forming \(\ce{N-C}\) bond resulted in stereoselection at the newly formed chiral centre, with an ee of 95.1% for \(|\vec F| = 0.1\:\va\) and 99.9% for \(|\vec F| = 0.2\:\va\). Derivatisation was able to influence the rate and stereoselection afforded by the OEEF, however the specific intricacies of each system need to be investigated individually, as few generalisations could be made from this particular study.

Catalysis of the formation of racemic aza-flavanone was also found to be achievable with an OEEF directed along the reaction axis from the newly forming \(\ce{N-C}\) bond up to the ketone, with in increase in \(\log(k)\) rate constant of 2.4 at \(|\vec F| = 0.1\:\va\) and 3.2 at \(|\vec F| = 0.2\:\va\).

This research focused on the use of optimal OEEF directions to obtain maximum stereoselective and catalytic results, however these effects were observed in non-optimal OEEF directions as well. Any deviation in OEEF direction from parallel with the reaction axis, in line with the newly forming \(\ce{N-C}\) bond caused a quantifiable amount of stereoselection.

It was found that the magnitude of the OEEF had to be kept relatively low for stereoselection to occur, as the rotational torque experienced by the molecule as \(\vec\mu\) would try to align with \(\vec F\), prevented the molecule from remaining in a stereoselective orientation. This is an important consideration when taking this research experimentally into the realm of freely rotating molecules in solution, as maintaining their orientation will likely come down to balancing the rotational torque with stabilising intermolecular interactions.

While this research was limited in what it could accomplish owing to time constraints, and resource limitations, it has provided valuable insights into the behaviour of the reaction, allowing for research to move forward with a more solid understanding of its behaviour within an OEEF.

Research by Xu et al. 1 has demonstrated that one way to overcome many off the limitations of conventional solvents within an electric field is to use EEFs to align a solvent composed of ionic liquids (IL), allowing them to generate an IEF that can act upon the solvated reaction. In doing so, this would overcome issues pertaining to competing electrochemical reactions, and would reduce the likelihood of an electronic double layer forming at the electrodes that would drastically attenuate the OEEF. Work by the Pas and Coote groups has shown that IEFs of \(>0.2\:\va\) can be formed and maintained for extended periods of time within an IL by aligning them with an OEEF before removing the field,2 and there is further evidence to show that ILs exhibit extensive hydrogen bonding within solution345 that could be utilised to align a solute in a particular orientation relative to the generated IEF. This hydrogen bonding could potentially provide enough rotational stabilisation to the overcome the rotational torque of the OEEF, allowing for stereoselection to occur.

In conjunction with research carried out by other members of the Pas group, the next steps for this research are to explore the reaction using polarisable molecular dynamics and ab initio molecular dynamics approaches to understand how different ILs will influence stereoselectivity, and to better understand the role of the generated IEF in translating this theoretical work into a more viable experimental protocol.

  1. Xu, L.; Izgorodina, E. I.; Coote, M. L. Ordered Solvents and Ionic Liquids Can Be Harnessed for Electrostatic Catalysis. J. Am. Chem. Soc. 2020, 142 (29), 12826–12833. https://doi.org/10.1021/jacs.0c05643. ↩

  2. Belotti, M.; Lyu, X.; Xu, L.; Halat, P.; Darwish, N.; Silvester, D. S.; Goh, C.; Izgorodina, E. I.; Coote, M. L.; Ciampi, S. Experimental Evidence of Long-Lived Electric Fields of Ionic Liquid Bilayers. J. Am. Chem. Soc. 2021, 143 (42), 17431–17440. https://doi.org/10.1021/jacs.1c06385. ↩

  3. Mohd, N.; Draman, S. F. S.; Salleh, M. S. N.; Yusof, N. B. Dissolution of Cellulose in Ionic Liquid: A Review. In AIP Conference Proceedings; 2017; Vol. 1809, p 020035. https://doi.org/10.1063/1.4975450. ↩

  4. Canongia Lopes, J. N. A.; Pádua, A. A. H. Nanostructural Organization in Ionic Liquids. J. Phys. Chem. B 2006, 110 (7), 3330–3335. https://doi.org/10.1021/jp056006y. ↩

  5. Brehm, M.; Weber, H.; Pensado, A. S.; Stark, A.; Kirchner, B. Liquid Structure and Cluster Formation in Ionic Liquid/Water Mixtures – An Extensive Ab Initio Molecular Dynamics Study on 1-Ethyl-3-Methylimidazolium Acetate/Water Mixtures – Part. Zeitschrift für Phys. Chemie 2013, 227 (2–3), 177–204. https://doi.org/10.1524/zpch.2012.0327. ↩