Application of Iridium-Catalysed C–H Borylation to the Functionalisation of Indoles

This thesis describes several novel applications of the iridium-catalysed C–H borylation of indoles. Research commenced with the development of a general procedure for the conversion of indoles 242 to 7-hydroxyindoles 245 and indolequinones 243. This was achieved by a three-step procedure – an initial C7–H borylation was followed by hydrogen peroxide-mediated oxidative hydrolysis affording the 7-hydroxyindoles 245. Upon oxidation with salcomine/O2 these 7-hydroxyindoles 245 were converted to the indolequinones 243. This is the first general procedure that can be used to convert indoles to indolequinones. We developed a general procedure for the triborylation of indoles, and subjected a variety of indoles to this transformation. In the absence of a substituent at C3, the triborylation was directed to C2 and C7 by the indole N–H, followed by a sterically-governed C–H borylation, which gave a mixture of C4–H and C5–H borylated products, favouring the former. In the case of 3-substituted indoles, the sterically-governed C–H borylation was selective for C5–H, affording 2,3,5,7-tetrasubstituted indoles 246. A selection of these triborylated indoles were synthesised, demonstrating that this procedure is general and can be used to selectively functionalise three C–H bonds in a single operation. We subsequently developed several new applications of the aforementioned C–H triborylation. A one-pot triborylation-protodeborylation procedure delivered 5,7- diborylindoles 500. Further functionalisation of these 5,7-diborylindoles 500 enabled access to rare 3,5,7-trisubstituted indoles 247, such as the natural product plakohypaphorine C 536 and those that are differentially substituted at C5 and C7. Finally, we developed a novel indole to benzoxazole rearrangement enabled by C–H borylation. 2,3-Dimethylindole 349 was converted to the 7-borylindole 350. Upon treatment with mCPBA under basic conditions, concomitant oxidative hydrolysis of the arylboronate and oxidative cleavage of the indole C2–C3 bond occurred, giving the amidophenol 581. Cyclisation to give the benzoxazole 582 was achieved with TFA.

Name thesis:degree_name

PhD

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Chemical Sciences

Grantor dc:publisher

ResearchSpace@Auckland

Year dc:date.issued

2018

Author dc:creator

• Eastabrook, Andrew

Advisor dc:contributor.advisor

• Sperry, J

Statement dc:rights

• Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher.

Licence dc:rights.uri

• https://researchspace.auckland.ac.nz/docs/uoa-docs/rights.htm

Handle dc:identifier.uri

https://hdl.handle.net/2292/37255

OAI identifier oai:identifier

oai:researchspace.auckland.ac.nz:2292/37255