Developing and Understanding Iridium-Catalysed Arene Borylation

Abstract

Iridium catalysed C-H borylation has moved from an interesting observation to an efficient catalytic reaction. This work has developed and improved upon some of the key issues associated with the methodology.
The one-pot conversion of aryl boronates, generated by C-H borylation, to other functionality has been one area of interest. However, reactions typically require a change in reaction solvent to make this possible. This thesis describes a one-pot, single solvent C-H borylation/Suzuki-Miyaura cross-coupling sequence. The key to this transformation is the use of methyl tert-butyl ether (MTBE). This procedure allows efficient synthesis of biaryls by initial C-H borylation of aromatic substrates followed by addition of water, subsequent reagents and aryl halide to complete the Suzuki-Miyaura cross-coupling without the need for change in reaction solvent.
Another issue associated with the C-H borylation reaction is the extended reaction times required for some substrates. This issue was tackled by development of a microwave accelerated C-H borylation reaction. Microwave reactions are conducted at the same temperature as standard heated reactions with accelerations of 2 - 24 times affording comparable product yields. Typically reaction times were reduced from hours to minutes. A microwave accelerated one-pot, single solvent C-H borylation/Suzuki-Miyaura cross-coupling sequence allowed synthesis of biaryls from arene plus aryl halides in reaction times of minutes.
Subsequent work focussed on the borylation of novel substrates classes, in particular quinolines. The borylation of substituted quinolines highlighted interesting electronic selectivity of the reaction. The site of borylation can be directed by changing the nature of the substituent on the ring. DFT calculations have been conducted to gain understanding into the causes of selectivity. A link between C-H acidity, calculated by DFT methods, and the borylation site was observed. Preliminary studies into the borylation of azaindoles are discussed. Studies towards a procedure to convert aryl boronates to trifluoromethyl groups are also been introduced.