DMSO: A Magic Chemical for Bromination and Chlorination

Abstract

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.

Keywords

Dimethyl sulfoxide / Halogenation / Bromination / Hydrobromic acid / Chlorination / N-Chlorosuccinimide / Lewis base catalysis / Late-stage modification

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