Repository logo

Ortho -Selective amination of arene carboxylic acids via rearrangement of acyl O -hydroxylamines †

Published version

Repository DOI

Change log


Gillespie, James E. 


Direct amination of arene C–H bonds is an attractive disconnection to form aniline-derived building blocks. This transformation presents significant practical challenges; classical methods for ortho-selective amination require strongly acidic or forcing conditions, while contemporary catalytic processes often require bespoke directing groups and/or precious metal catalysis. We report a mild and procedurally straightforward ortho-selective amination of arene carboxylic acids, arising from a facile rearrangement of acyl O-hydroxylamines without requiring precious metal catalysts. A broad scope of benzoic acid substrates are compatible and the reaction can be applied to longer chain arene carboxylic acids. Mechanistic studies probe the specific requirement for trifluoroacetic acid in generating the active aminating agent, and suggest that two separate mechanisms may be operating in parallel in the presence of an iron catalyst: (i) an iron-nitrenoid intermediate and (ii) a radical chain pathway. Regardless of which mechanism is followed, high ortho selectivity is obtained, proposed to arise from the directivity (first) or attractive interactions (second) arising with the carboxylic acid motif.


Acknowledgements: We are grateful to the Royal Society for a PhD studentship (J. E. G.) and a University Research Fellowship (R. J. P.; URF\R\191003)). We also thank Trinity Hall, Cambridge for a Research Fellowship (N. Y. S. L.) and the ERC (Starting Grant NonCovRegioSiteCat, 757381) for funding.


Journal Title

Chemical Science

Conference Name

Journal ISSN


Volume Title


The Royal Society of Chemistry
H2020 European Research Council (NonCovRegioSiteCat, 757381)
Royal Society (PhD Studentship, University Research Fellowship URF\R\191003)