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. 2019 Feb 27;141(8):3723-3732.
doi: 10.1021/jacs.9b00669. Epub 2019 Feb 12.

Open-Air Alkylation Reactions in Photoredox-Catalyzed DNA-Encoded Library Synthesis

James P Phelan  1 , Simon B Lang  1 , Jaehoon Sim  1 , Simon Berritt  1 , Andrew J Peat  2 , Katelyn Billings  3 , Lijun Fan  3 , Gary A Molander  1
Affiliations

Open-Air Alkylation Reactions in Photoredox-Catalyzed DNA-Encoded Library Synthesis

James P Phelan et al. J Am Chem Soc. .

Abstract

DNA-encoded library (DEL) technology is a powerful tool commonly used by the pharmaceutical industry for the identification of compounds with affinity to biomolecular targets. Success in this endeavor lies in sampling diverse chemical libraries. However, current DELs tend to be deficient in C(sp3) carbon counts. We report unique solutions to the challenge of increasing both the chemical diversity of these libraries and their C(sp3) carbon counts by merging Ni/photoredox dual catalytic C(sp2)-C(sp3) cross-coupling as well as photoredox-catalyzed radical/polar crossover alkylation protocols with DELs. The successful integration of multiple classes of radical sources enables the rapid incorporation of a diverse set of alkyl fragments.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Workflow in generating and utilizing DELs.
Figure 2.
Figure 2.
Mechanistic view of Ni/photoredox dual catalytic C(sp2)–C(sp3) cross-coupling.
Figure 3.
Figure 3.
Major DNA-containing side products from the cross-coupling.
Figure 4.
Figure 4.
Radical/polar crossover defluorinative alkylation of trifluoromethyl alkenes.
See this image and copyright information in PMC

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