Lithium diisopropylamide-mediated ortholithiations: Lithium chloride catalysis

Ortholithiations of a range of arenes mediated by lithium diisopropylamide (LDA) in THF at -78 °C reveal substantial accelerations by as little as 0.5 mol % of LiCl (relative to LDA). Substrate dependencies suggest a specific range of reactivity within which the LiCl catalysis is optimal. Standard protocols with unpurified commercial samples of n-butyllithium to prepare LDA or commercially available LDA show marked batch-dependent rates-up to 100-fold-that could prove significant to the unwary practitioner. Other lithium salts elicit more modest accelerations. The mechanism is not discussed.