BBr 3 ‐Assisted Cleavage of Most Ethers Does Not Follow the Commonly Assumed Mechanism

Density‐functional computations were used to probe the reaction mechanism of BBr 3 ‐assisted ether cleavage. After the initial formation of an ether–BBr 3 adduct, secondary and tertiary alkyl ethers are cleaved through Br – transfer from the activated BBr 3 to the alkyl moiety, as postulated in the literature. In contrast, all other ethers studied react through a novel pathway involving two ether–BBr 3 adducts, one of which acts as Br – donor, and the second as the reaction substrate. The identification of the novel bimolecular mechanism for this classical reaction has further applications, because it implies that BBr 3 ‐assisted ether cleavage may become impossible if the ether is surrounded by bulky portions of the molecule that prevent the approach of the attacking BBr 3 adduct. Our data also allow the construction of an order of reactivity of alkyl ether deprotection: isopropyl, benzyl, tertiary alkyl, allyl, isobutyl and ethyl can be removed sequentially as their bromo derivatives; phenyl, cyanomethyl and chloromethyl groups can be sequentially removed as their corresponding alcohols.