An Exploration of Ion Pairing Interactions as a Tool to Control Regioselectivity in Iridium-Catalysed C–H Borylation

Inspired by their use in nature, non-covalent interactions have recently started being used in small molecule catalysis for control of selectivity. To date, this has been particularly fruitful in the area of enantioselective catalysis when using ion pairing or hydrogen bonding. Despite the success seen by ion pairing in enantioselective organocatalysis, this interaction has rarely been used for other types of selectivity, such as positional selectivity. This thesis explores the possibility of implementing ion pairing in transition metal catalysis for control of regioselectivity. Specifically, ion pairing was investigated for achieving meta and para selectivity in iridium catalysed C–H borylation. An ion pairing interaction between a functionalised ligand and matching functionality on a substrate was initially explored for achieving meta C–H selectivity. By using an anionic sulfonate group on the ligand and cationic quaternary ammonium salt substrates, good to excellent meta selectivity was obtained with four classes of substrates, with various tether lengths between the arene and the ammonium functionality. Further functionalisation of the products was demonstrated and a similar strategy was attempted on protonated pyridines as cationic substrates, with limited success. Para selectivity was next achieved by using ion pairing in a different context; sulfonate salt substrates were ion paired with bulky tetrabutylammonium counterions, which were proposed to sterically disfavour borylation at the meta position, leading to selective para borylation. Remarkably, this selectivity was obtained with standard bipyridine ligands. Six classes of substrates were amenable to this methodology: derivatives of aniline and benzylamines, phenol and benzylalcohols, as well as benzenesulfonate and benzylsulfonate salts. Following borylation, the sulfamate and sulfate salts were deprotected to reveal the parent free aniline, benzylamine, phenol or benzylalcohol, borylated at the para position. Overall this work shows that ion pairing is a viable interaction for control of positional selectivity, and two different operating modes have been demonstrated. It is hoped that the findings presented herein will encourage further exploration of this interaction for control of positional selectivity in catalysis.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2020

Author dc:creator

• Mihai, Madalina Teodora

Advisor dc:contributor.advisor

• Phipps, Robert

• C-H borylation
• meta C-H borylation
• para C-H borylation
• ion-pairing
• non-covalent interactions

Licence

• https://apollo8-f-pro.lib.cam.ac.uk/bitstreams/06dc7e0c-5537-4e08-8e7d-c5f58985470e/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.50095

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/303019