The electrophilic halogenation of arenes is perhaps the
simplest
method to prepare aryl halides, which are important structural motifs
in agrochemicals, materials, and pharmaceuticals. However, the nucleophilicity
of arenes is weakened by the electron-withdrawing substituents, whose
electrophilic halogenation reactions usually require harsh conditions
and lead to limited substrate scopes and applications. Therefore,
the halogenation of arenes containing electron-withdrawing groups
(EWGs) and complex bioactive compounds under mild conditions has been
a long-standing challenge. Herein, we describe Brønsted acid-catalyzed
halogenation of arenes with electron-withdrawing substituents under
mild conditions, providing an efficient protocol for aryl halides.
The hydrogen bonding of Brønsted acid with the protic solvent
1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) enables this transformation
and thus solves this long-standing problem.
Direct substitution of alcohols has been a popular topic in organic chemistry. Deoxyhalogenation of alcohols represents one of the most important transformations for accessing organic halides. However, a practical catalytic protocol with readily available, inexpensive, and stable inorganic halides is still unknown. Herein, we report an organocatalytic deoxyhalogenation of alcohols with inorganic halides, which avoids the employment of stoichiometric activators and organic halogenating reagents. Various alcohols are transformed to the corresponding organic bromides and iodides in good yield.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.