Comprehensive Summary Halogenation plays a crucial role in organic synthesis. Over the past century, numerous reaction systems have been developed for the synthesis of halogen‐containing molecules. However, traditional halogenation reactions rely on highly reactive halogenating reagents, suffer from poor regioselectivity and limited functional group tolerance. In 2015, Jiao et al. from Peking University achieved the efficient oxidative bromination of (hetero)arenes and alkenes using a mild reaction system consisting of stoichiometric amounts of dimethyl sulfoxide (DMSO) and aqueous hydrobromic acid (Jiao Bromination). Following in‐depth research on Lewis base activation systems, Jiao and coworkers further developed a DMSO‐catalyzed chlorination of (hetero)arenes using N ‐chlorosuccinimide (NCS), which enables the late‐stage modification of complex molecules (Jiao Chlorination). Their works clarify that DMSO plays distinct roles at different loadings: stoichiometric DMSO acts as a mild oxidant to drive oxidative bromination with hydrobromic acid, catalytic DMSO serves as a Lewis base catalyst to activate NCS for selective chlorination, and excess DMSO forms an inert (DMSO) n •X + adduct to inhibit reaction activity. The theoretical framework promotes the innovation of halogenation strategies. Jiao halogenation has been widely applied to various fields of organic synthesis, including late‐stage modification of bioactive compounds, total synthesis of natural products, and preparation of material molecules. Key Scientists In 1866, Alexander Zaytsev first synthesized dimethyl sulfoxide (DMSO). 1 In 1957, Kornblum's group discovered that alkyl halides could be efficiently oxidized by simply dissolving the substrates in DMSO. 2 Later, in 1963, Moffatt and his student Pfitzner observed that primary and secondary alcohols could be oxidized to aldehydes and ketones, respectively, when DMSO was activated by dicyclohexyl carbodiimide (DCC) in the presence of catalytic anhydrous phosphoric acid. 3 In 1976, Swern and colleagues showed that activation of DMSO with trifluoroacetic anhydride (TFAA) also enabled the rapid oxidation of primary and secondary alcohols. 4 Subsequently, Megyeri, 5 Majetich, 6 and Dai, 7 independently reported the oxidative bromination of arenes using DMSO as the oxidant in 1989, 1997, and 2014, respectively. In 2013, Yoshida and co‐workers demonstrated through experiments and density functional theory calculations that DMSO could stabilize halogen cations (Br + , I + ) via coordination. 8 In 2015, Jiao's group achieved an efficient halogenation of arenes using stoichiometric combination of DMSO/HX (rather than as a solvent). 9 This approach avoided the significant reduction in reactivity of X + species caused by excess DMSO, enabling highly efficient oxidative halogenation of arenes. The system was subsequently extended to the halogenation of various substrates, including alkenes, alkynes, ketones, benzyl bromides, and benzylic alcohols. 10‐13 In 2019, the same group further showed that DMSO could also act as a catalyst to activate electrophilic halogenating reagents, enabling late‐stage chlorination of various bioactive molecules and pharmaceuticals. 14
He et al. (Mon,) studied this question.