Alkali lithium diisopropylamide

N-Alkylations, especially of oxo-di- and tetra-hydro derivatives, e.g. (28)->(29), have been carried out readily using a variety of reagents such as (usual) alkyl halide/alkali, alkyl sulfate/alkali, alkyl halide, tosylate or sulfate/NaH, trialkyloxonium fluoroborate and other Meerwein-type reagents, alcohols/DCCI, diazoalkanes, alkyl carbonates, oxalates or malon-ates, oxosulfonium ylides, DMF dimethyl acetal, and triethyl orthoformate/AcjO. Also used have been alkyl halide/lithium diisopropylamide and in one case benzyl chloride on the thallium derivative. In neutral conditions 8-alkylation is observed and preparation of some 8-nucleosides has also been reported (78JOC828, 77JOC997, 72JOC3975, 72JOC3980). 

A reported procedure based on lithium diisopropylamide induced double elimination of ethanol from bromoacetaldehyde diethyl acetal also was not very effective for the large scale preparation of phenylthioacetylene.8 Another more recent synthesis of the title compound relies on the reaction of dimethyl(chloroethynyl)carbinol with an alkali metal phenylthiolate, followed by... 

A few comments concerning the crystallization of carbanions are in order. These comments are based upon the personal experience developed in our own laboratory and also upon observations noted in the literature in the course of crystallizing enolate anions. Although alkali metal enolate anions are relatively unstable compounds, they have been prepared in the solid state, isolated, and characterized by IR and UV spectroscopy in the 1970s. Thus the ot-lithiated esters of a number of simple esters of isobutyric acid are prepared by metallation of the esters with lithium diisopropylamide in benzene or toluene solution. The soluble lithiated esters are quite stable at room temperature in aliphatic or aromatic hydrocarbon solvents and are crystallized out of solution at low temperature (e.g. -70 °C.). Alternatively the less soluble enolates tend to precipitate out of solution and are isolated by centrifugation and subsequent removal of the solvent. Recrystallization from a suitable solvent can then be attempted. The thermal stability of the lithiated ester enolates is dramatically decreased in the presence of a solvent with a donor atom such as tetrahydrofuran. 

Deprotonation of carbonyl compounds by lithium dialkylamide bases is the single most common method of forming alkali enolates. Four excellent reviews have already been published. " Sterically hindered amide bases are employed to retard nucleophilic attack on the carbonyl group. The most common and generally useful bases are (i) lithium diisopropylamide (LDA 5) (ii) lithium isopropylcyclo-hexylamide (LICA 6) (iii) lithium 2,2,6,6-tetramethylpiperidide (LITMP 7) (iv) lithium hexamethyldisilylamide (LHMDS 8) and (v) lithium tetramethyldiphenyldisilylamide (LTDDS 9). Bases that are not amides include sodium hydride, potassium hydride and triphenylmethyllithium. 

When the preparation of alkali metal enolates derived from alkanoylphosphonates was attempted by treatment with strong anhydrous bases such as lithium diisopropylamide or sodium hydride, the formation of phosphate phosphonate-type products was observed. This was interpreted in terms of fragmentation of the enolate formed in the first step to ketene and dialkyl phosphite anion (equation 75), and addition of the latter to the carbonyl group of an unreacted acylphosphonate molecules to form a bisphosphonate. Such molecules are known to rearrange to phosphate phosphonates ... 

Introduction. Potassium f-butoxide is intermediate in power among the bases which are commonly employed in modem organic synthesis. It is a stronger base than the alkali metal hydroxides and primary and secondary alkali metal alkoxides, but it is a weaker base than the alkali metal amides and their alkyl derivatives, e.g. the versatile strong base Lithium Diisopropylamide. ... 

The values for alkene and alkane hydrogens are so large (they are so weakly acidic) that neither the commonly used alkali metal hydroxides nor sodium hydride, sodium amide, or lithium diisopropylamide are strong enough bases to remove a proton from alkanes or alkenes. 

To remove a proton from the OH group of an alcohol (Figure 9-1, cleavage of bond a), we must use a base stronger than the alkoxide. Examples include lithium diisopropylamide (Section 7-8), butyllithium (Section 8-7), and alkali metal hydrides (Section 8-6, Exercise 8-4), such as potassium hydride, KH. Such hydrides are particularly useful because the only byproduct of the reaction is hydrogen gas. 

Synthetically important alkali—metal amides Lithium, sodium, and potassium hexamethyldisilazides, diisopropylamides, and tetramethylpiper-idides 13AG(E)11470. 

Garcia-AlvarezJ, Graham DV, Hevia E, Kennedy AR, Mulvey RE. Synthesis and characterisation of new bimetallic alkali metal-magnesium mixed diisopropylamide-acetyhdes structural variations in bimetallic lithium- and sodium-heteroleptic magnesiates. Dalton Trans. 2008 (11) 1481—1486. 

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