Amines 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... 

For the case of tri(o-tolyl)phosphine-ligated catalysts, the upper pathway appears to predominate. Oxidative addition occurs first via loss of a ligand from the bisphosphine precursor to form the oxidative adduct, which exists as a dimer bridged through the halogen atoms (equation 33). This dimer is broken up by amine, the coordination of which to palladium renders its proton acidic. Subsequent deprotonation by base leads to the amido complex, which can then reductively eliminate to form the product. When tert-butoxide is used as the base, the rate is limited by formation of and reductive elimination from the amido complex, while for the stronger hexamethyldisilazide, the rate-determining step appears to be oxidative addition. ... 

NPf) protected amine. The final ring formation was carried out by deprotonation of the benzylic methyl with potassium hexamethyldisilazide (KHMDS) which then added to the methyl ester to provide ketone 316. This compound was then carried on through a series of transformations to provide a common intermediate for every member of the FR900482 family. 

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). ... 

Carboxylic acid derivatives. Homologation of aryl and heteroaryl halides by the catalyzed carbonylation in the presence of amines leads to amides. For the preparation of primary amides, hexamethyldisilazide provides the amino group. ... 

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. 

Derivatization of amines and alcohols. Attachment of the Boc group to ary-lamines is achieved by reaction with sodium hexamethyldisilazide and B0C2O. Both nitrogen and oxygen atoms of hydroxylamine are derivatized in a biphasic system in the presence of EtjN as base. ... 

A number of interesting reactions have been carried out on ring systems of which the azepine ring is just one example of a number of cyclic amines. For example, treatment of (70) with potassium hexamethyldisilazide in THF at —78°C followed by trisyl azide gives a 65% yield of the /ru/ii-azide (71) <92TL6859>. A phenylseleno derivative is formed in 78% yield when trisyl azide is replaced by phenylselenylchloride. 

Both LHMDS and KHMDS have been successfully utilized as nitrogen sources in palladium(O) catalyzed aminations of allyl chlorides (eq 28). Up to 90% conversion and 55% isolated yield were obtained for the synthesis of allyl hexamethyldisilazide and no cyclization via deprotonation or significant hydrolysis during the work-up was observed. ... 

Potassium hexamethyldisilazide, KHMDS, has been used successfully in the past for a-deprotonation of sulfoxides. Aiming to probe the nature of the transition state in the reaction of a-metalated (i )-methyl //-tolyl sulfoxide with A -(benzylidene) aniline under kinetic conditions, the effect of the choice of the bases for the a-deprotonation on the reactivity and diastereoselectivity was studied, using LDA, LHMDS, NaHMDS, and KHMDS. Best yields anddiastereoselectivities (90%, 84 16) were achieved with LDA, whereas LHMDS showed diminished reactivity (50%) without a loss of diastereoselectivity (87 13). Improved yields and lower diastereoselectivities were recorded in reactions mediated by NaHMDS and KHMDS, providing the amine in 60% (dr 81 19) and 77% (dr 69 31) yields and diastereoselectivities, respectively (eq 64). 

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