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Mechanistic Insights for Dimethyl Sulfoxide Catalyzed Aromatic Chlorination Reactions
Author(s) -
Qu ZhengWang,
Zhu Hui,
Grimme Stefan
Publication year - 2021
Publication title -
chemcatchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.497
H-Index - 106
eISSN - 1867-3899
pISSN - 1867-3880
DOI - 10.1002/cctc.202001396
Subject(s) - chemistry , catalysis , ylide , dimethyl sulfoxide , nucleophile , electrophile , anisole , medicinal chemistry , density functional theory , combinatorial chemistry , organic chemistry , computational chemistry
Recently, the dimethyl sulfoxide O=SMe 2 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=SMe 2 slowly reacts via the S ‐chloro sulfoxonium O=SClMe 2 + to the S ‐chloro ylide O=SClMeCH 2 , followed by facile Cl + transfer from NsCl to the ylide CH 2 site to initialize efficient electrophilic Cl + transfer to nucleophilic substrates. According to the new proposal, the polarizable S and electronegative O sites of O=SMe 2 may act as efficient Cl + and H + shuttles, respectively, in catalytic aromatic chlorination. If O=SMe 2 is present in high concentration, it can trap intermediate SMe 2 OH + into a stable H + ‐bound dimer (SMe 2 O) 2 H + to inhibit efficient protic NsCl activation. These mechanistic insights may be generally useful for the rational design of novel dual functional halonium transfer catalysts.