Title:	The halogen bonding of halonium ions
DNr:	NAISS 2024/5-583
Project Type:	NAISS Medium Compute
Principal Investigator:	Mate Erdelyi <mate.erdelyi@kemi.uu.se>
Affiliation:	Uppsala universitet
Duration:	2024-11-27 – 2025-12-01
Classification:	10405 10407
Homepage:	http://halogenbond.weebly.com/
Keywords:

Abstract

In the last decade, my group has investigated the nature of halogen bonds. This has resulted in a number of publications unraveling, for instance, their directionality, their binding strength and their importance in halofunctionalization reactions (for example ChemComm 2012, 48, 1458, J. Am. Chem. Soc. 2012, 134, 5706, Cryst Eng Comm 2013, 15, 3087, Chem. Sci. 2014, 5, 3226-3233, Chem. Sci. 2015, 6, 3746-3756, J. Am. Chem. Soc. 2016, 138, 9853, J. Am Chem. Soc. 2018, 140, 13503, J. Am. Chem. Soc. 2018, 140, 17571, Angew. Chem. Int. Ed. 2019, 58, 9012, Chem. Commun. 2020, 56, 14431; J. Chem. Theory Comput. 2020, 16, 7690; Chem. Commun. 2020, 56, 9671; Chem. Sci. 2020, 11, 7979; Chem. Soc. Rev. 2020, 49, 2688, Chem. Eur. J. 2021, 27, 13748 – 13756; J. Am. Chem. Soc. 2021,143, 10695; Bull. Chem. Soc. Jpn. 2021, 94, 191, ChemComm 2022, 58, 4977; ACS Catalysis 2022, 12, 7210, J. Am. Chem. Soc. 2024, 146, 3, etc). Our spectroscopic studies used computations for prediction, design and data interpretation. We have developed computational methodologies for evaluating properties of molecules that cannot be measured through NMR-spectroscopy (e.g. minor changes in bond length, electron distribution, or nature of the chemical bonds). In this proposal we wish to apply, and expand, the computational methodologies we have developed previously to both new, and ongoing projects. First, we wish to study a set of substrates halogenated at strategic positions to gain understanding of the weakest halogen bonds in solution in an intramolecular setup. These compounds are flexible and determination of their ensembles is a true challenge. We will predict the conformational ensemble of these molecules using a Monte Carlo-based molecular mechanics screening, followed by DFT-refinement of the geometries. The computational data will then used in combination with NMR spectroscopic data to gain knowledge of the weak halogen bonds by evaluating their influence on the ensemble populations. Secondly, we will investigate the enantioselectivity of halofunctionalization reactions. These reactions are crucial for the generation of enantiopure synthetic intermediates. However, currently no general applicable methodologies exist. To address this, we will computationally design continuously chiral ligands and organic frameworks, and investigate their potential for applicability in asymmetric halogenation reactions. To design the ligands, we will compute the relative energies of possible conformers, in order to estimate to which degree the ligands are monochiral in solution. Furthermore, we will investigate their potential for asymmetric halogenation reactions, by computing the potential energy surfaces towards both enantiomeric products of a model iodo-lactonization reaction. The physical factors responsible for the relative barrier height towards either products will be investigated using the activation strain model of reactivity and energy decomposition analysis. This projects is related to our previous work in the projects HPC2N-2013-019, HPCN-2014-2-21, SNIC 2020/5-435, SNIC 20215-359, SNIC 2022/5-431 and NAISS 2023/5-392. We wish to build on the previous work and reach a new level of understanding as well as explore applications.