A study on the metalation of alkoxydibromobenzenes

The metalation of (quasi)alkoxy-substituted dibromobenzenes C6H3(OR)Br2 with lithium diisopropylamide (LDA) has been investigated. For 1-(quasi)alkoxy-3,5-dibromobenzenes (R = Me, TMS), different selectivities were observed depending on reaction conditions and the size of the alkoxy group. The methoxy group was an effective ortho-director whereas this was not the case for the bulky trimethylsilyloxy group. The metalation of related 2,5-dibromoanisole was also examined showing a significant meta-directing effect by the methoxy group. The thermal stability of aryllithium intermediates is significantly lower when lithium is flanked by a bromine and a methoxy group, whereas 4-(quasi)alkoxy-2,6-dibromoaryllithiums are less labile.