Metal-free O–H/C–H difunctionalization of phenols by o-hydroxyarylsulfonium salts in water† †Electronic supplementary information (ESI) available. CCDC 1502491, 1502489 and 1502490. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6sc04504a Click here for additional data file. Click here for additional data file.

hemistry 2017 been widely used to construct important families of target molecules, aryl ethers, suldes and sulfoxides. Traditionally, these reactions are carried out in organic solvents (e.g., THF, CH3CN, DMSO, and DMF), which may cause potential health, safety, and waste disposal issues. Therefore, transition-metalfree C–O and C–S coupling reactions under greener conditions are desirable, especially in the pharmaceutical industry. Herein, we report our efforts toward a novel environmentally benign O–H/C–H difunctionalization of phenols by o-hydroxyarylsulfonium salts in water (Scheme 1). Our reaction design is detailed in Scheme 1. It is reasonable to hypothesize that sulfoxides 2 may be activated using a sulfonylating agent like triuoromethanesulfonic anhydride (Tf2O), inspired by the Pummerer reaction. The activated sulfoxide A could be attacked by phenols 1 at sulfur, giving rise to o-hydroxyarylsulfonium intermediates 3. Such intermediates might then undergo a Smiles-like rearrangement, thus affording versatile products o-(phenoxy)aryl suldes, 4, which could be readily converted to many important ligands and biologically active molecules (Scheme 1b). However, the following challenges in this strategy were anticipated: (1) the activated sulfoxide can be attacked by the phenolic hydroxyl group at the cationic sulfur, according to previous studies; (2) it may require one electron-withdrawing group (e.g., NO2) to activate the migration of the aromatic ring in the Smiles rearrangement; (3) such rearrangement of sulfonium salts has been seldom reported.