Amines lithium hexamethyldisilazide

Many organic syntheses requHe the use of stericaHy hindered and less nucleophilic bases than //-butyUithium. Lithium diisopropylamide (LDA) and lithium hexamethyldisilazide (LHS) are often used (140—142). Both compounds are soluble in a wide variety of aprotic solvents. Presence of a Lewis base, most commonly tetrahydrofuran, is requHed for LDA solubdity in hydrocarbons. A 30% solution of LHS can be prepared in hexane. Although these compounds may be prepared by reaction of the amine with //-butyUithium in the approprite medium just prior to use, they are also available commercially in hydrocarbon or mixed hydrocarbon—THF solvents as 1.0—2.0 M solutions. 

Lithium hexamethyldisilazide, 165 Potassium permanganate, 258 Trialkylaluminums, 21 Tris[2-(2-methoxyethoxy)ethyl]amine, 336... 

Owing to the importance of the amine, probably acting as a ligand of lithium or a proton carrier [ammonium salt of (2R,3R)-DPTA], a process was proposed allowing the introduction of different amines and consequently a modification of the selectivity of the protonation after deprotonation of a Schiff base of methyl valinate with Lithium Hexamethyldisilazide (LHMDS), the liberated HMDS was replaced by a more basic primary, secondary, or tertiary amine prior to the addition of (2R,3R)-DPTA (eq 5) (Table 3). In some cases, higher ee were observed compared to the classical procedure with LHMDS (34% ee) or LDA (47% ee). ... 

What is needed for the alkylation is rapid conversion of the ester into a reasonably stable enolate, so rapid in fact that there is no unenolised ester left. In other words the rate of proton removal must be faster than the rate of combination of enolate and ester. These conditions are met when lithium enolates are made from esters with lithium amide bases at low temperature, often 78 °C. Hindered bases must be used as otherwise nucleophilic displacement will occur at the ester carbonyl group to give an amide. Popular bases are LDA (Lithium Di-isopropyl Amide, 66), lithium hexamethyldisilazide 67, and lithium tetramethylpiperidide 68, the most hindered of all. These bases are conveniently prepared from the amine, e.g. 65 for LDA, and BuLi in dry THF solution. 

Amines. In situ transformation of the Grignard reaction products of carbonyl compounds into amines is accomplished by the addition of lithium hexamethyldisilazide and LiC104. 

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