Halogen-lithium exchange between substituted dihalobenzenes and butyllithium: application to the regioselective synthesis of functionalized bromobenzaldehydes

Halogen-lithium interconversion reactions between unsymmetrically substituted mono-and bifunctional dihalobenzenes C(6)H(3)XHal(2), and C(6)H(2)XYHal(2) (Hal = Br, I; X, Y = F, OR, CF3, CH(OMe)(2)) and butyllithium were investigated. The resultant organolithium intermediates were converted into the corresponding benzaldehydes in moderate to good yields. As a rule, bromine atoms in the position ortho to the functional group were replaced preferentially with lithium. Intramolecular competition experiments with bifunctional systems revealed that fluorine is capable of activating the neighboring bromine atom more strongly than methoxy and dimethoxymethyl groups. On the replacement of the non-activated bromine with iodine a complete reversal of this reactivity pattern can be accomplished due to the preferred iodine-lithium exchange. (c) 2005 Elsevier Ltd. All rights reserved.