Generality-oriented optimization of enantioselective aminoxyl radical catalysis.

Rein, Jonas; Rozema, Soren D; Langner, Olivia C; Zacate, Samson B; Hardy, Melissa A; Siu, Juno C; Mercado, Brandon Q; Sigman, Matthew S et al. · Science · 2023

basic_science · Level V

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Abstract

Catalytic enantioselective methods that are generally applicable to a broad range of substrates are rare. We report a strategy for the oxidative desymmetrization of <i>meso</i>-diols predicated on a nontraditional catalyst optimization protocol by using a panel of screening substrates rather than a singular model substrate. Critical to this approach was rational modulation of a peptide sequence in the catalyst incorporating a distinct aminoxyl-based active residue. A general catalyst emerged, providing high selectivity in the delivery of enantioenriched lactones across a broad range of diols, while also achieving up to ~100,000 turnovers.