Aggregates lithium amide/halide

Scheme 2.17 Mixed aggregates of lithium amide bases and lithium halides.

Scheme 2.23 Dimeric structures of chiral lithium amide bases and their mixed aggregates with lithium halides.

The low reactivity of glycine enolate with unactivated alkyl halides to form a-amino acids could be overcome by stabilizing the nucleophile using m-aminoindanol-derived hippuric acid 53. This key substrate was readily prepared from commercially available azalactone 54 by a one-pot operation (85% yield, 2 steps). The lithium enolate of amide acetonide 53 with a wide range of alkyl halides proceeded in moderate yields (>60%) and excellent diastereoselectivities (>95% de). Assuming that lithium halide would facilitate the dissociation of the amide enolate from the aggregated state and thus enhance its reactivity, 4 equivalents of lithium chloride were used as additive and resulted in a 25% increase in yield (Scheme 24.11). Reactions with secondary halides... 

As most organometallic compounds, lithium enolates are highly polar entities susceptible to combine in various types of (eventually solvated) aggregates that undergo dynamic equilibria in solution. This phenomenon explains why enolate solutions are difficult to describe by the classical spectroscopic, physicochemical or theoretical methods, a difficulty enhanced by the sensitivity of these equilibria to many physicochemical factors such as the concentration, the temperature or the presence of complexing additives (lithium halides, amides, amines, HMPA,. ..). The problems due to dynamics are avoided in the solid state where many clusters of lithium enolates, alone or co-crystallized with exogenous partners, have been identified by X-ray crystallography. 

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