Biomolecule-Compatible Dehydrogenative Chan–Lam Coupling of Free Sulfilimines

• DOI: 10.1021/jacs.2c04627
• Publication Date: 2022-06-29T19:21:12Z
• Authors: Tingting Meng; Lucille A. Wells; Tianxin Wang; Jinyu Wang; Shishuo Zhang; Jie Wang; Marisa C. Kozlowski; Tiezheng Jia
• Keywords: Biomolecule; Bioconjugation; Chemoselectivity

Inspired by the discovery of a S═N bond in collagen IV network and its essential role stabilizing basement membranes, sulfilimines have drawn much attention fields chemistry biology. However, their further uptake is hindered lack mild, efficient, environmentally benign protocols which can be constructed under biomolecule-compatible conditions. Here, we report terminal oxidant-free copper-catalyzed dehydrogenative Chan–Lam coupling free diaryl with arylboronic acids excellent chemoselectivity broad substrate compatibility. The mild reaction conditions nature allow employment this protocol late-stage functionalization complex peptides, more importantly, as an effective bioconjugation method showcased model protein. A combined experimental computational mechanistic investigation reveals that inner-sphere electron-transfer process circumvents sacrificial oxidant employed traditional reactions. An energetically viable concerted pathway was located wherein copper hydride facilitates hydrogen-atom abstraction from isopropanol solvent to produce dihydrogen via four-membered transition state.