Generality-oriented optimization of enantioselective aminoxyl radical catalysis

• 成果类型: Article
• 署名作者: Rein, Jonas; Rozema, Soren D.; Langner, Olivia C.; Zacate, Samson B.; Hardy, Melissa A.; Siu, Juno C.; Mercado, Brandon Q.; Sigman, Matthew S.; Miller, Scott J.; Lin, Song
• 署名单位: Cornell University; Yale University; Utah System of Higher Education; University of Utah
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11302
• DOI: 10.1126/science.adf6177
• 发表日期: 2023-05-19
• 页码: 706-712
• 关键词: oxidative kinetic resolution; mediated electrooxidation; meso-diols; desymmetrization; electrolysis; peptides

摘要

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 similar to 100,000 turnovers.