ja9b00669_si_001.pdf (44.19 MB)
Open-Air Alkylation Reactions in Photoredox-Catalyzed DNA-Encoded Library Synthesis
journal contribution
posted on 2019-02-12, 15:12 authored by James
P. Phelan, Simon B. Lang, Jaehoon Sim, Simon Berritt, Andrew J. Peat, Katelyn Billings, Lijun Fan, Gary A. MolanderDNA-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.