Integrated catalysis opens new arylation pathways via regiodivergent enzymatic C-H activation.
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.
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.|Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Jonathan
J
Latham
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.|Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Jean-Marc
JM
Henry
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.|Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Humera H
HH
Sharif
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.|Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Binuraj R K
BR
Menon
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.|Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Sarah A
SA
Shepherd
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Michael F
MF
Greaney
School of Chemistry, The University of Manchester, Oxford Road, Manchester M13 9PL, UK.|Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, UK.
Jason
J
Micklefield
D002384:Catalysis; D004129:Dimethylpolysiloxanes / Q000737:chemistry; D054879:Halogenation; D008024:Ligands; D010088:Oxidoreductases / Q000378:metabolism*; D010165:Palladium / Q000378:metabolism; D013237:Stereoisomerism
D004129:Dimethylpolysiloxanes; D008024:Ligands; D010165:Palladium; C013830:baysilon; D010088:Oxidoreductases