Sodium diisopropylamide

Interactions between sodium atoms and C = CH2 units (Na-C 270-2 287.3 pm) are apparent in the crystal structure of the enolate Li2Na4(0-C(=CH2)tBu)6.2 Pr2NH obtained from the reaction between lithium and sodium diisopropylamides and 3,3-dimethyl-2-butanone.119... 

Acylation (see also Acetylation, Cathylation) Acyl fluorides. Benzoylchloride (see Hippuric acid, preparation). N-Carbonylsulfamic acid chloride. Chloroacetic anhydride. Chloroacetyl chloride. Magnesium. Mesyl chloride. Methanesulfonic anhydride. 1-Morpholinocyclo-hexene. Pyridine. Sodium diisopropylamide. Sodium hydride. Trifluoroacetic anhydride. 

Sodium dihydrobis-(2-methoxyethoxy)alaminate, NaH2Al(OCH2CH2OCH3)2 [1, 1064, before Sodium diisopropylamide]. Mol. wt. 202.17. Suppher Chemapol,... 

Because carbonyl compounds are only weakly acidic, a strong base is needed for enolate ion formation. If an alkoxide such as sodium ethoxide is used as base, deprotonation takes place only to the extent of about 0. l% because acetone is a weaker acid than ethanol (pKa - 16). If, however, a more powerful base such as sodium hydride (NaH) or lithium diisopropylamide ILiNO -CjHy ] is used, a carbonyl compound can be completely converted into its enolate ion. Lithium diisopropylamide (LDA), which is easily prepared by reaction of the strong base butyllithium with diisopropylamine, is widely used in the laboratory as a base for preparing enolate ions from carbonyl compounds. 

GABA HMG-CoA HMPA HT LDA LHMDS LTMP NADH NBH NBS NCS NIS NK NMP PMB PPA RaNi Red-Al RNA SEM SnAt TBAF TBDMS TBS Tf TFA TFP THF TIPS TMEDA TMG TMP TMS Tol-BINAP TTF y-aminobutyric acid hydroxymethylglutaryl coenzyme A hexamethylphosphoric triamide hydroxytryptamine (serotonin) lithium diisopropylamide lithium hexamethyldisilazane lithium 2,2,6,6-tetramethylpiperidine reduced nicotinamide adenine dinucleotide l,3-dibromo-5,5-dimethylhydantoin A-bromosuccinimide A-chlorosuccinimide A-iodosuccinimide neurokinin 1 -methyl-2-pyrrolidinone para-methoxybenzyl polyphosphoric acid Raney Nickel sodium bis(2-methoxyethoxy)aluminum hydride ribonucleic acid 2-(trimethylsilyl)ethoxymethyl nucleophilic substitution on an aromatic ring tetrabutylammonium fluoride tert-butyldimcthyisilyl fert-butyldimethylsilyl trifluoromethanesulfonyl (triflyl) trifluoroacetic acid tri-o-furylphosphine tetrahydrofuran triisopropylsilyl A, N,N ,N -tetramethy lethylenediamine tetramethyl guanidine tetramethylpiperidine trimethylsilyl 2,2 -bis(di-p-tolylphosphino)-l,r-binaphthyl tetrathiafulvalene... 

Triethylamine in THF can be used as the external base to deprotonate triazolium salts. The resulting NHCs were complexed in situ, e.g., to [(/7 -cymene)RuCl2]2, [(/ -cod)RhCl]2, and [(/ -C5Me5)RhCl2]2. Sodium carbonate in water/ DMSO deprotonates imidazolium iodides in the presence of mercury(II) dichloride to give [Hg(NHC)2][Hgl3Cl]. " A pyridine-functionalized imidazolium salt was deprotonated by lithium diisopropylamide (LDA) in THF and attached in situ to [(p -cod)Pd(Me)Br] [Eq.(17)]. After abstraction of the bromide anion with silver(I) a tetranuclear ring is formed. 

Kinetic control can be achieved by slow addition of the ketone to an excess of strong base in an aprotic solvent. Kinetic control requires a rapid, quantitative and irreversible deprotonation reaction 2-6. The use of a very strong, sterically hindered base, such as lithium diisopropylamide or triphenylmethyllithium (trityllithium), at low temperature (— 78 °C) in an aprotic solvent in the absence of excess ketone has become a general tool for kinetic control in selective enolate formation. It is important to note that the nature of the counterion is sometimes important for the regioselectivity. Thus, lithium is usually better than sodium and potassium for the selective generation of enolates by kinetic control. 

The key reagents for the deprotonation of esters, acids and carbonyl compounds in general are the hindered metal amides, such as lithium diisopropylamide (1), lithium cyclohexyliso-propylamide (2) and lithium, sodium and potassium hexamethyldisilazanides (3). 

This important synthetic problem has been satisfactorily solved with the introduction of lithium dialkylamide bases. Lithium diisopropylamide (LDA, Creger s base ) has already been mentioned for the a-alkylation of acids by means of their dianions1. This method has been further improved through the use of hexamethylphosphoric triamide (HMPA)2 and then extended to the a-alkylation of esters3. Generally, LDA became the most widely used base for the preparation of lactone enolates. In some cases lithium amides of other secondary amines like cyclo-hexylisopropylamine, diethylamine or hexamethyldisilazane have been used. The sodium or potassium salts of the latter have also been used but only as exceptions (vide infra). Other methods for the preparation of y-Iactone enolates. e.g., in a tetrahydrofuran solution of potassium, containing K anions and K+ cations complexed by 18-crown-6, and their alkylation have been successfully demonstrated (yields 80 95 %)4 but they probably cannot compete with the simplicity and proven reliability of the lithium amide method. 

This section deals with the alkylation reactions of such enolates. In the presence of strong bases, amides carrying at least one a-hydrogen 1 can be deprotonated to form enolate ions which, on subsequent alkylation, give alkylated amides. Further reaction, e g., hydrolysis or reduction, furnishes the corresponding acids or primary alcohols, respectively. The pKa values for deprotonation are typically around 35 (extrapolated value DMSO3 7) unless electron-withdrawing substituents are present in the a-position. Thus, deprotonation usually requires non-nucleophilic bases such as lithium diisopropylamide (extrapolated 8 pKa for the amine in DMSO is around 44) or sodium hexamethyldisilazanide. 

In the alkylation reactions of the chiral 3-acyl-2-oxazolidinones, deprotonation to the lithium or sodium enolate is by treatment with lithium diisopropylamide or lithium or sodium hexamethyldisilazanide in tetrahydrofuran at low temperature (usually — 78 °C). The haloalka-ne, usually in excess, is then added to the enolate solution at low temperature (usually — 78 °C) for the sodium enolates and at higher temperatures (between —78 and 0CC) for the lithium enolates. When small, less sterically demanding halides, such as iodomethane, are used the sodium enolate is usually preferred 2 24 and in these cases up to five equivalents2,6- 24,26,27 of the halide are necessary in order to obtain good yields of the alkylation products. Conventional extractive workup provides the crude product as a diastereomeric mixture (d.r. usually > 90 10) which is relatively easy to separate by silica gel chromatography and/or by recrystallization (for crystalline products). Thus, it is possible to obtain one diastereomer in very high diastereomeric purity. 

The chiral complex 2 also requires the use of strong bases to achieve deprotonation no exchange is observed upon treatment with sodium hydroxide-rf/water-dicarbonyl complex 1, monophosphane complexes, such as 2, undergo clean a-deprotonation at — 78 °C with butyllithium or lithium diisopropylamide to generate the enolate 7, which under-... 

Mayer and co-workers improved the amide bond formation of TenBrink s method using unprotected amino alcohols and active esters of bromoalkyl carboxylic acids.[5] More recently, Anthony et al.,[6] and Norman and Kroin[7l reported stereospecific alkylation of acylmorpholinone (Schemes 3 and 4) using sodium hexamethyldisilazanide and lithium diisopropylamide, respectively. 

A convenient procedure for preparing dialkylphosphinic acids 62 involves addition of H-phosphinic acids and esters to conjugated double bonds via the silyl 87-89 or metal phos-phonite 61,[90 94] as illustrated in Scheme 21. The silyl phosphonite intermediates 61 (M = TMS) are typically formed either from phosphinic acids or esters using chlorotri-methylsilane or bis(trimethylsilyl)acetamide. The metal phosphonite intermediates 61 (Y = Li, Na, etc.) are prepared by deprotonation of the acids with a base such as sodium hydride, sodium methoxide, or lithium diisopropylamide. The conjugated double bonds are typically acrylic acids and esters substituted in the a-position with the appropriate amino acid side chain. After appropriate protecting group manipulations, additional amino acids... 

A study investigated the use of various bases, such as potassium hydroxide, potassium tert-butoxide, sodium methoxide, methyllithium, rrrf-butyllithium, sec-butyllithium, phenyllithium, lithium diisopropylamide, and lithium hcxamethyldisila/anidc over a temperature range of — 78 to 80°C in the dehydrofluorination of 2-(fluoromethoxy)-l,l,l,3,3,3-hexafluoropropane to give 2-(fluoromethoxy)pentafluoropropene.28... 

Lithium diisopropylamide, 163 Sodium hydroxide-N-(p-Trifluoro-methylbenzyl)cinchoninium bromide, 325... 

Lithium diisopropylamide, 163 Phenyl azide-Aluminum chloride, 240 Halo carbonyl compounds (see also Unsaturated carbonyl compounds) a-Chloro acids Sodium nitrite, 282 a-Halo aldehydes and ketones... 

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