Photoredox-mediated hydroalkylation and hydroarylation of functionalized olefins for DNA-encoded library synthesis

DNA-encoded library (DEL) technology features a time- and cost-effective interrogation format for the discovery of therapeutic candidates in the pharmaceutical industry. To develop DEL platforms, the implementation of water-compatible transformations that facilitate the incorporation of multifunctio...

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Published inChemical science (Cambridge) Vol. 12; no. 36; pp. 1236 - 1245
Main Authors Badir, Shorouk O, Lipp, Alexander, Krumb, Matthias, Cabrera-Afonso, María Jesús, Kammer, Lisa Marie, Wu, Victoria E, Huang, Minxue, Csakai, Adam, Marcaurelle, Lisa A, Molander, Gary A
Format Journal Article
LanguageEnglish
Published England Royal Society of Chemistry 22.09.2021
The Royal Society of Chemistry
Subjects
Alkenes
Chemistry
Coordination compounds
Electron transfer
Functional groups
Industrial development
Interrogation
Libraries
Light irradiation
Photoredox catalysis
Single electrons
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Summary:DNA-encoded library (DEL) technology features a time- and cost-effective interrogation format for the discovery of therapeutic candidates in the pharmaceutical industry. To develop DEL platforms, the implementation of water-compatible transformations that facilitate the incorporation of multifunctional building blocks (BBs) with high C(sp 3 ) carbon counts is integral for success. In this report, a decarboxylative-based hydro alkylation of DNA-conjugated trifluoromethyl-substituted alkenes enabled by single-electron transfer (SET) and subsequent hydrogen atom termination through electron donor-acceptor (EDA) complex activation is detailed. In a further photoredox-catalyzed hydro arylation protocol, the coupling of functionalized, electronically unbiased olefins is achieved under air and within minutes of blue light irradiation through the intermediacy of reactive (hetero)aryl radical species with full retention of the DNA tag integrity. Notably, these processes operate under mild reaction conditions, furnishing complex structural scaffolds with a high density of pendant functional groups. DNA-encoded library (DEL) technology facilitates the rapid identification of therapeutic candidates in pharmaceutical settings. Herein, the development of photoredox-mediated hydrocarbofunctionalization protocols of olefins is described.
Bibliography:10.1039/d1sc03191k
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These authors contributed equally.
ISSN:2041-6520
2041-6539
DOI:10.1039/d1sc03191k