Late-Stage Functionalization of Biologically Active Heterocycles Through Photoredox Catalysis

The direct CH functionalization of heterocycles has become an increasingly valuable tool in modern drug discovery. However, the introduction of small alkyl groups, such as methyl, by this method has not been realized in the context of complex molecule synthesis since existing methods rely on the us...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2014-05, Vol.53 (19), p.4802-4806
Main Authors: DiRocco, Daniel A., Dykstra, Kevin, Krska, Shane, Vachal, Petr, Conway, Donald V., Tudge, Matthew
Format: Article
Language:English
Subjects:
Activated
Catalysis
Drugs
Experimentation
Heterocyclic Compounds - chemistry
homogeneous catalysis
Organic peroxides
Oxidation-Reduction
Pharmaceutical industry
Photochemistry
photoredox catalysis
radical reactions
Radicals
Searching
Synthesis
visible light
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Summary:The direct CH functionalization of heterocycles has become an increasingly valuable tool in modern drug discovery. However, the introduction of small alkyl groups, such as methyl, by this method has not been realized in the context of complex molecule synthesis since existing methods rely on the use of strong oxidants and elevated temperatures to generate the requisite radical species. Herein, we report the use of stable organic peroxides activated by visible‐light photoredox catalysis to achieve the direct methyl‐, ethyl‐, and cyclopropylation of a variety of biologically active heterocycles. The simple protocol, mild reaction conditions, and unique tolerability of this method make it an important tool for drug discovery. Search and find: A method has been developed for the direct methyl‐, ethyl‐, and cyclopropylation of biologically active heterocycles using visible‐light photoredox catalysis. High‐throughput experimentation was used to discover the best catalyst. The simple protocol, mild reaction conditions, and unique tolerability make this method a valuable tool for drug discovery.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201402023