Organocatalysis by halogen bonding donors: A promising complement to hydrogen bond-based catalysis.

Abstract

Catalytic transformations, previously dominated by metal catalysts, have seen exponential growth in the use of organocatalysts over the last two decades. The emergence of small organic molecules employed to facilitate chemical reactions has played a significant role in a more economical and sustainable synthetic approach. Examples of such molecules include the well-established hydrogen bond catalysts and their analogous halogen bond catalysts. While halogen bond catalysts are known to have more desirable features than their predecessor, such as a higher degree of directionality and tunability, there have only been a handful of reports on the use of halogen bond-based catalysts in organocatalysis. Herein, in this project, theoretical investigations have been carried out in rela- tion to non-covalent interactions within organocatalysis. The first study involved hydrogen bond interactions to analyse the type of binding modes that can simul- taneously form and the influences cooperativity and secondary interactions have on them. In the second part of this research project, halogen bond-based catalysis was studied and for that two different reactions were theoretically investigated. The first reaction involved a halide abstraction reaction between a benzyl bromide and acetonitrile, catalysed by two catalysts to reveal the reaction mechanism and to determine the binding modes of each catalyst. The second reaction carried out was a Michael addition reaction between a trans-crotonophenone and an indole, catalysed by five different catalysts, in order to establish the effects produced when different halogen atoms are used and to study the substituent effects on the halogen bond strength by modifying the catalytic scaffolds. A successful redesign of two new catalysts was established based on the results obtained.