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meta-Selective C–H arylation of phenols via regiodiversion of electrophilic aromatic substitution

Senior, Aaron; Ruffell, Katie; Ball, Liam T.


Aaron Senior

Katie Ruffell

Associate Professor


Electrophilic aromatic substitution is among the most widely used mechanistic manifolds in organic chemistry. Access to certain substitution patterns is, however, precluded by intrinsic and immutable substituent effects that ultimately restrict the diversity of the benzenoid chemical space. Here we demonstrate that the established regioselectivity of electrophilic aromatic substitution can be overcome simply by diverting the key σ-complex intermediate towards otherwise inaccessible substitution products. This ‘regiodiversion’ strategy is realized through the development of a general and concise method for the meta-selective C–H arylation of sterically congested phenols. Consisting of a Bi(V)-mediated electrophilic arylation and a subsequent aryl migration/rearomatization, our process is orthogonal to conventional C–H activation and cross-coupling approaches, and does not require prefunctionalization of the substrate. Mechanistically informed applications in synthesis showcase its utility as a versatile and enabling route to highly functionalized, contiguously substituted aromatic building blocks that defy synthesis via existing methods.


Senior, A., Ruffell, K., & Ball, L. T. (2022). meta-Selective C–H arylation of phenols via regiodiversion of electrophilic aromatic substitution. Nature Chemistry,

Journal Article Type Article
Acceptance Date Oct 27, 2022
Online Publication Date Dec 12, 2022
Publication Date Dec 12, 2022
Deposit Date Dec 13, 2022
Publicly Available Date Jun 13, 2023
Journal Nature Chemistry
Print ISSN 1755-4330
Electronic ISSN 1755-4349
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Keywords General Chemical Engineering; General Chemistry
Public URL
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Additional Information This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: