Mechanistic Insights for Dimethyl Sulfoxide Catalyzed Aromatic Chlorination Reactions

Abstract

Recently, the dimethyl sulfoxide O=SMe2 catalyzed aromatic chlorination reaction using N-chlorosuccinimides (NsCl) under mild conditions has proven useful for bioactive compounds potentially containing various functional groups such as amide and hydroxyl. A novel catalytic mechanism is revealed by extensive DFT calculations using the anisole PhOMe as electron-rich model substrate. The Cl+ transfer from NsCl to O=SMe2 slowly reacts via the S-chloro sulfoxonium O=SClMe2+ to the S-chloro ylide O=SClMeCH2, followed by facile Cl+ transfer from NsCl to the ylide CH2 site to initialize efficient electrophilic Cl+ transfer to nucleophilic substrates. According to the new proposal, the polarizable S and electronegative O sites of O=SMe2 may act as efficient Cl+ and H+ shuttles, respectively, in catalytic aromatic chlorination. If O=SMe2 is present in high concentration, it can trap intermediate SMe2OH+ into a stable H+-bound dimer (SMe2O)2H+ to inhibit efficient protic NsCl activation. These mechanistic insights may be generally useful for the rational design of novel dual functional halonium transfer catalysts.