Reductive 1,2-Arylation of Isatins
Amrah Nasim1, Gilian T Thomas1, Jeffrey S Ovens1
1Centre for Catalysis Research and Innovation, Department of Chemistry and Biomolecular Sciences, University of Ottawa, 10 Marie Curie, Ottawa, Ontario K1N 6N5, Canada.
Organic Letters
|September 28, 2022
Summary
This study introduces a new nickel-catalyzed reaction coupling aryl iodides and isatins. It uses a greener alcohol reductant, producing 3-hydroxyoxindoles with minimal waste.
Area of Science:
- Organic Chemistry
- Catalysis
- Green Chemistry
Background:
- Metal-mediated coupling reactions are crucial in organic synthesis.
- Existing methods often involve harsh reductants and generate hazardous waste.
- Developing sustainable alternatives for synthesizing valuable organic compounds is essential.
Purpose of the Study:
- To develop a novel intermolecular nickel-catalyzed reductive coupling reaction.
- To synthesize 3-hydroxyoxindoles from aryl iodides and isatins using a mild reductant.
- To explore a greener catalytic system with benign byproducts.
Main Methods:
- Nickel-catalyzed reductive coupling of aryl iodides and isatins.
- Utilized *sec*-butanol as a stoichiometric reductant.
- Employed a 1,5-diaza-3,7-diphosphacyclooctane (P2N2) ligand for catalysis.
- Characterized active Ni(0)-P2N2 species.
Main Results:
- Successfully synthesized 3-hydroxyoxindoles via a formal 1,2-addition reaction.
- Demonstrated the efficacy of *sec*-butanol as a mild and green reductant.
- Identified active Ni(0)-P2N2 catalytic species.
- Proposed a modified carbonyl-Heck-type mechanism.
Conclusions:
- A novel and sustainable Ni-catalyzed reductive coupling method for 3-hydroxyoxindole synthesis has been established.
- The use of *sec*-butanol offers a greener alternative to traditional reductants.
- The developed catalytic system and mechanistic insights advance the field of sustainable organic synthesis.
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