Lithium reagents, standardization

The titration consists of addition of a few milliliters of distilled water and an excess of standard HCl (0.1 N), followed by back-titration with standard NaOH solution (0.1 N). The lithium stoichiometry is calculated on the basis of the titration results. It has been shown that this total base titration gives the same results as are obtained with active lithium reagent and atomic absorption analysis. 

Aryl bromide TFVE-Br is easily prepared on the multi-pound per batch scale and is isolated pure by vacuum distillation. The corresponding Grignard reagent is generated by standard methods and is remarkably stable in THF solution, even at elevated temperatures. Recently discovered arly lithium reagents, on the other hand, are much more reactive and their formation is more specific (vide infra)P (Caution When warmed above solutions of TFVE-Li react very exothermically with... 

Several reviews cover hetero-substituted allyllic anion reagents48-56. For the preparation of allylic anions, stabilized by M-substituents, potassium tm-butoxide57 in THF is recommended, since the liberated alcohol does not interfere with many metal exchange reagents. For the preparation of allylic anions from functionalized olefins of medium acidity (pKa 20-35) lithium diisopropylamide, dicyclohexylamide or bis(trimethylsilyl)amide applied in THF or diethyl ether are the standard bases with which to begin. Butyllithium may be applied advantageously after addition of one mole equivalent of TMEDA or 1,2-dimethoxyethane for activation when the functional groups permit it, and when the presence of secondary amines should be avoided. 

Excellent selectivities are also observed with (CH,)2CuZnCl, Bti2CiiTi[OCH(CH3)2], and BnCu BF3. The reaction of a standard cuprate reagent, e.g., lithium dibutylcuprate, with ( )-l in tetrahydrofuran gives predominantly the SN2 product. 

A pentane solution of terf-butyllithium (purchased from either Alfa Inorganics, Inc. or Lithium Corporation of America, Inc.) was standardized by one of the previously described titration procedures (Note 1). If possible, it is desirable to use a freshly opened bottle of lert-butyllithium since previously used bottles of this reagent often contain lithium ferf-butoxide which will lead to formation of a contaminant in the final product (Note 10). 

A method based on equation 21 may be performed, where the organic residue of an organometallic compound becomes derivatized with excess dimethylphenylchlorosUane (67) and determined by GC, using cumene (i -PrPh) as internal standard. Although lithium alkoxide impurities also react with 67, the product appears at a different retention time. The method is also suitable for Grignard reagents. ... 

In brief, a 200-pl sample will be deproteinized with 20 pi 5% SSA containing internal standard. Following precipitation and centrifugation, 150 pi supernatant is diluted with 150 pi of the lithium citrate buffer and placed in the autosampler. The derivatization step takes 40 pi of sample and 20 pi of the OPA reagent, which are mixed and left to react for 30 s. A 20-pl aliquot is injected. 

In a closely related asymmetric reaction, the required absolute stereochemistry at C-4 was established via a Michael addition of a cuprate reagent to a dihydropiperidinone (Scheme 12). The stereochemistry at C-3 was introduced in the form of piperidinone 61, a compound readily available from (5)-glutamic acid. Protection of both the amino and alcohol functionalities was achieved using standard reaction conditions to give 62. Introduction of the A -double bond was accomplished via phenylselenation of the lithium... 

In the course of oxidation of the sulfonyl group in 32, lithium di isopropyl ami do is used to form the a-sulfonyl carbanion 33 This anion reacts with MOPH via complex 34 to give natural product 1. The MOPH complex utilized here is crystalline and stable to air over brief periods of time, so it is relatively convenient to employ. It has become a standard reagent tor a-hydroxylation of CH-acidic compounds.1 ... 

Merck has used the L-phenylalanine-derived Evans oxazolidinone to make matrix metalloproteinase inhibitors such as 45 (Scheme 23.14) (see also Chapter 2).62 The mixed anhydride of 4-butyric acid was reacted with the lithium anion of the oxazolidinone. This was enolized with the standard titanium reagents. An enantioselective Michael addition was then carried out by the addition of t-butyl acrylate at low temperature. The auxiliary was removed with LiOH/peroxides to give the acid, which was further derivatized over multiple steps to yield the desired drug. 

Standard Solution Transfer 399.3 mg of reagent-grade lithium carbonate to a 1000-mL volumetric flask, dissolve in a minimal amount of 1 1 hydrochloric acid water, dilute to volume with water, and mix. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, dilute to volume with water, and mix. Finally, transfer 10.0 mL of this solution to a second 100-mL volumetric flask, add 1.0 mL of hydrochloric acid, dilute to volume with water, and mix. This solution contains 75 xg of lithium per 100 mL. 

The reaction of metals with alkyl halide to form alkylmetal compounds is typical for lithium and magnesium. This so-called direct synthesis was applied to the preparation of both cyclopropyllithium" and derivatives and cyclopropylmagnesium halides under the standard preparative conditions of Grignard reagents without ring cleavage (equation 1). 

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