Ether Cleavage Re-Investigated: Elucidating the Mechanism of BBr₃-Facilitated Demethylation of Aryl Methyl Ethers

One of the most well-known, highly utilized reagents for ether cleavage is boron tribromide (BBr₃), and this reagent is frequently employed in a 1:1 stoichiometric ratio with ethers. Density functional theory calculations predict a new mechanistic pathway involving charged intermediates for ether cleavage in aryl methyl ethers. Moreover, these calculations predict that one equivalent of BBr₃ can cleave up to three equivalents of anisole, producing triphenoxyborane [B(OPh)₃] prior to hydrolysis. These predictions were validated by gas chromatography analysis of reactions where the BBr₃:anisole ratio was varied. Not only do we confirm that sub-stoichiometric equivalents may be used for ether demethylation, but the findings also support our newly proposed three cycle mechanism for cleavage of aryl methyl ethers.