Activation of polar organometallic reagents with alkali-metal alkoxides

The use of group 1 metal alkoxides as additives to activate s-block organometallics is an established phenomenon in polar organometallic chemistry. Typified by the Lochmann–Schlosser superbase, these reagents have proved to be exceptionally powerful bases for the deprotonative metallation of organic substrates. However, despite their long-standing importance in synthesis, the nature of this activating effect remains to be fully understood. Here we shed light on the origins of the special reactivities of which these reagents are capable, which generally cannot be replicated by their homometallic precursors. In addition, reactivity studies that have established the mixed-metal constitutions of these organometallic reagents are discussed. Opening up new directions in synthesis, the use of lithium alkoxides as additives to promote direct regioselective magnesium (or zinc)/halogen exchange processes to access highly functionalized organometallics is also discussed, with an emphasis on rationalizing the role of each metal in these transformations.