BBr3-Assisted Cleavage of Most Ethers Does Not Follow the Commonly Assumed Mechanism

Density-functional computations were used to probe the reaction mechanism of BBr3-assisted ether cleavage. After the initial formation of an ether-BBr3 adduct, secondary and tertiary alkyl ethers are cleaved through Br- transfer from the activated BBr3 to the alkyl moiety, as postulated in the literature. In contrast, all other ethers studied react through a novel pathway involving two ether-BBr3 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 BBr3-assisted ether cleavage may become impossible if the ether is surrounded by bulky portions of the molecule that prevent the approach of the attacking BBr3 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.