Directed metalation superbases

The lithiation of anisylpyridines has been studied.80 Whereas usual reagents did not react or gave addition products on the pyridine ring, the BuLi-LiDMAE superbase has induced exclusive pyridino-directed metallation. The latter selectivity has been attributed to an internal cooperating lithium complexation by both the pyridine nitrogen and methoxy group. 

DIRECTED METALATION OF ARENES WITH ORGANOLITHIUMS, LITHIUM AMIDES, AND SUPERBASES... 

Alkali metal alkyls, particularly n-butyl lithium, are the most frequently used reagents to form metallated intermediates.246 247 In certain cases (di- and triphenyl-methane, acetylene and 1-alkynes, cyclopentadiene) alkali metals can be directly applied. Grignard reagents are used to form magnesium acetylides and cyclopenta-dienyl complexes.248 Organolithium compounds with a bulky alkoxide, most notably M-BuLi-ferf-BuOK in THF/hexane mixture, known as the Lochmann-Schlosser reagent or LICKOR superbase, are more active and versatile reagents.249-252... 

Tuning of selectivity in the metallation of m-anisic acid has been realized by an appropriate choice of base.67 The results obtained with LTMP have indicated that the regiochemistry of the lithiation of m-anisic acid is thermodynamically controlled. Resonance and inductive effects favour removal of the H(2) proton. In contrast, superbases such as n-BuLi-r-BuOK are not significantly influenced by or//m-directing groups and preferentially attack H(4), the inductively activated aromatic position next to the most electronegative heteroatom and/or the most acidic position available. 

To further examine the nucleophilic side of the CH activation continuum, the our group and the Cundari group undertook a computational study [59] of alkali metal amide and alkaline earth metal amide CH activation reactions with alkanes. This study is directly related to classic superbase chemistry using cesium cyclohexylamide-type reagents to induce CH bond deprotonation of alkanes [60]. 

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