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Controlling the Regio- and Enantioselectivity of Iridium-Catalysed Arene Borylation Using Sulfonated Bipyridine Ligands



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Non-covalent interactions are commonly used in nature to control the selectivity of chemical transformations. Inspired by this, synthetic chemists have begun to use them to control selectivity in small molecule catalysis. Two types of interaction that are frequently exploited are hydrogen bonding and ion-pairing. This thesis details efforts to use these interactions to control both the regio- and enantioselectivity of iridium-catalysed arene borylation, an incredibly synthetically useful transformation that commonly suffers from a lack of regioselectivity, and for which enantioselective variants are very few. The strategy followed involved the design and synthesis of novel bipyridine ligands containing a distal anionic sulfonate group, that when bound to iridium can interact with substrates, either through ion-pairing or hydrogen bonding interactions, controlling the selectivity of the transformation.

Building on previous work in which a sulfonated bipyridine ligand was developed to promote the meta-selective borylation of aromatic ammonium salts and amides through ion-pairing and hydrogen bonding respectively, the first part of this thesis explores the design and synthesis of larger bipyridine ligands with a more remote sulfonate functionality, with the aim of promoting para-selective borylation. Through exploring various ligand scaffolds some promising outcomes were obtained, relative to the control, although selectivities were still only moderate.

Despite their often-privileged nature, chiral cations have generally found limited use in transition metal catalysis. The second part of this thesis explores a strategy in which a chiral cation, derived from the privileged class of cinchona alkaloids, is associated with an anionic sulfonated bipyridine ligand through ion-pairing. This chiral ligand enables a long-range, desymmetrising arene borylation to occur, forming new carbon or phosphorus stereocentres with high levels of enantiocontrol. The optimisation and scope exploration of this reaction is documented, as well as attempts to expand this methodology to kinetic resolution, although this was met with limited success. Additionally, mechanistic investigations identified both ion-pairing and hydrogen bonding interactions to be key for enantioinduction.

Overall, this work aims to demonstrate that non-covalent interactions are an incredibly useful tool for controlling the selectivity of transition metal catalysis, particularly in achieving remote enantioselective functionalisation.





Phipps, Robert


Organic Chemistry, Non-Covalent Catalysis, Synthesis, Chiral Cation, Transition Metal Catalysis, Ion-Pairing, Hydrogen-Bonding, C-H Activation


Doctor of Philosophy (PhD)

Awarding Institution

University of Cambridge
Engineering and Physical Sciences Research Council (1918558)