ORIGIN

Hypervalent bromine(III) reagents exhibit superior electrophilic reactivity compared with their iodine analogs. Recently, Wencel-Delord and coworkers described a strategy for the synthesis of cyclic bromonium salts and their utility as efficient arylating agents via aryne intermediates in the presence of a weak base.

REACTION MECHANISM

Aryl transfer reactions involving hypervalent halogen(III) reagents enable access to functionalized nucleophiles, and efficient methodology for arylations with diaryliodonium salts has been developed for a range of nucleophiles. Diarylbromonium salts are much less utilized, mainly due to instability and synthesis problems. However, transition metal-free C–O and C–N couplings involving cyclic bromonium(III) salts were recently reported under mild conditions. With carboxylates, exclusive meta- or ortho- selectivity was observed depending on the ring substitution pattern. The use of amine nucleophiles resulted in moderate to high regioselectivity in favor of the meta-substituted products.The reaction was found to proceed by deprotonation of bromonium salt A with simultaneous β-elimination of the excellent bromine(III) leaving group, leading to aryne B. Subsequent meta-selective nucleophilic attack by carboxylate C generates anionic intermediate D, which is either protonated by a new molecule of A in a possible autocatalytic process, or by the formed bicarbonate, releasing product E.Bromonium salts display greater reactivity and electrophilicity than the iodine analogs. Arylation of carboxylic acids with the latter proceeds regiospecifically at increased temperatures, whereas aryne formation is quite uncommon. Aryne intermediates have been utilized in cycloadditions and mechanistic studies from our group suggest that aryne formation also takes place in transition metal-free O-arylations of aliphatic alcohols with electron-rich diaryliodonium salts, resulting in regioisomeric product mixtures. Cyclic diaryliodonium salts are less reactive and their transformations generally require transition metal catalysis, as exemplified by the ortho-functionalization with carboxylic acids.