The lithiation of fluorinated benzenes and its dependence on solvent and temperature

Abstract

The formation of lithio derivatives from fluorinated benzenes and fluorinated bromobenzenes has been studied. The bases used were lithium diisopropylamide (LDA) in THF–hexane, butyllithium in diethyl ether–hexane and butyllithium in THF–hexane. The lithiated intermediates have been trapped using acetone, to form fluorinated 2-arylpropan-2-ols, or have been warmed to produce benzynes which have been trapped by furan in Diels–Alder additions. The use of LDA allows clean removal of the most acidic proton in the aromatic ring: butyllithium in ether–hexane brings about clean bromine–lithium exchange. In contrast, the use of butyllithium in THF–hexane at –78 °C results in autometallation and the formation of more complex product mixtures. For the formation of the benzynes involved in the Diels–Alder reactions it is necessary to warm the reaction mixtures. When ether–hexane is used as solvent the reactions remain fairly clean, but when THF is added the increasing autometallation again results in more complex reaction mixtures.