Integrated catalysis opens new arylation pathways via regiodivergent enzymatic C-H activation

Research output: Research - peer-reviewArticle

  • External authors:
  • Jonathan Latham
  • Jean-Marc Henry
  • Humera Sharif
  • Binuraj Menon
  • Sarah Shepherd

Abstract

Despite major recent advances in C-H activation, discrimination between two similar, unactivated C-H positions is beyond the scope of current chemocatalytic methods. Here we demonstrate that integration of regioselective halogenase enzymes with Pd-catalysed cross-coupling chemistry, in one-pot reactions, successfully addresses this problem for the indole heterocycle. The resultant 'chemobio-transformation' delivers a range of functionally diverse arylated products that are impossible to access using separate enzymatic or chemocatalytic C-H activation, under mild, aqueous conditions. This use of different biocatalysts to select different C-H positions contrasts with the prevailing substrate-control approach to the area, and presents opportunities for new pathways in C-H activation chemistry. The issues of enzyme and transition metal compatibility are overcome through membrane compartmentalization, with the optimized process requiring no intermediate work-up or purification steps.

Bibliographical metadata

Original languageEnglish
Article number11873
JournalNature communications
Volume7
DOIs
StatePublished - 10 Jun 2016