Deoxygenative Suzuki–Miyaura arylation of tertiary alcohols through silyl ethers

Conventional Suzuki–Miyaura arylations use halogenated compounds as electrophilic coupling partners. Although the catalytic activation of organohalides is well established, these substrates are seldom naturally abundant and questions exist as to their metabolic and environmental friendliness. Owing to their existence as readily available chemical feedstocks, alcohols are highly desirable cross-coupling partners, although pathways to activate the strong C–O bond are rarer. Here the coupling of tertiary alcohols with boronic esters through in situ alcohol silylation is described, providing access to quaternary carbon scaffolds without needing to proceed by an activated alkyl halide or pseudohalide intermediate. A dual catalyst system is used with both Ni(0) and Bi(III) components playing a critical role, along with a mild chlorosilane reactant. This method was found to tolerate diverse functional groups including chloro, nitro, olefin, ketone, ester and phenol moieties, while also being applicable to the derivatization of heterocyclic scaffolds. Mechanistic studies suggest the combination of a Lewis acid catalyst and organosilane promote the heterolytic cleavage of the substrate C–O bond to generate an electrophilic intermediate, providing a powerful strategy for derivatizing readily available alcohols. Alkyl alcohols are attractive surrogates for alkyl halides in the Suzuki–Miyaura cross-coupling reactions, but methods to activate the C–O bond are underdeveloped. Now a Ni-catalysed arylation is reported that uses aryl boronic esters and tertiary alcohols, through in situ alcohol silylation.