C–H arylation of heterocyclic N oxides through in-situ diazotisation of anilines without added promoters: a green and selective coupling process

Aymeric P. Colleville, Richard A. J. Horan, Sandrine Olazabal, Nicholas C. O. Tomkinson

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Abstract

A green and selective method for the generation of bi-aryl compounds through C—H arylation of heterocyclic N-oxides is presented in which the addition of ascorbic acid as a promoter is not required for either the generation of an aryldiazonium species or the subsequent arylation. Reaction conditions were optimized through Multivariate Data Analysis, including Orthogonal Projections to Latent Structures (OPLS) and Design of Experiments (DoE) methodologies resulting in further sustainability improvements, and were then applied to a range of substrates to establish the scope and limitations of the process. The reaction was studied using in-situ infra-red spectroscopy and a mechanism is presented that accounts for the available data from this and previous studies. The reaction was also per-formed on a multigram scale, with calorimetry studies to support further scale-up of this promoter-free transformation.
Original languageEnglish
Pages (from-to)1283–1296
Number of pages14
JournalOrganic Process Research and Development
Volume20
Issue number7
DOIs
Publication statusPublished - 30 May 2016

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Keywords

  • radical arylation
  • aryldiazonium salts
  • green chemistry
  • n-oxide heterocycles
  • design of experiments
  • calorimetry

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