Iron-Catalyzed Kumada Arylation of Aliphatic Alcohol-Derived Electrophiles via Sulfonate-to-Halide Substitution

Abstract

Iron-catalyzed Kumada cross-coupling was explored for C(sp³)–O arylation of activated cyclohexanol derivatives, revealing cyclohexyl tosylate as a competent substrate. Investigation of the effect of bromide additives indicated that cyclohexyl tosylate underwent bromide substitution in a reaction with MgBr₂─the salt byproduct generated during cross-coupling. The single-turnover reaction of 1 equivalent of cyclohexyl tosylate with 1 equivalent of 4-fluorophenylmagnesium bromide in the presence of bis(diphenylphosphino)benzene (dppbz)iron(II) dichloride showed no conversion to arylated product, indicating that cyclohexyl tosylate was not activated by catalytically relevant iron intermediates and that tosylate-to-bromide substitution was necessary for productive cross-coupling. A two-step method was developed, which involved in situ bromide substitution of alkyl tosylate substrates using MgBr₂·OEt₂, followed by (dppbz)iron(II)-catalyzed Kumada arylation, which was used to convert 16 C(sp³)–OTs substrates to the corresponding C(sp²)–C(sp³) arylated products in 31–84% yield.