Generality-oriented optimization of enantioselective aminoxyl radical catalysis
Jonas Rein, Soren D. Rozema, Olivia C. Langner, Samson B. Zacate, Melissa A. Hardy, Juno C. Siu, Brandon Q. Mercado, Matthew S. Sigman, Scott J. Miller, Song Lin
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 meso -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.