HMPA lithium complexes with

Ketene dithioacetals are deprotonated with LDA-HMPA and complexed with copper(l) iodide (Scheme 36). This reagent reacts with allylic halides exclusively at the y-position with allylic rearrangement (5n20. The reaction of the lithium reagent with simple alkylating reagents gives mostly a-attack. Ketene dithioacetals can be converted to esters by aqueous mercury(II) chloride. 

Lithium diisopropylamide complexed with HMPA will give the lithium derivative of 3-picoline and of 3-methylquinoline, and the products have been condensed with a variety of electrophiles (e.g. Scheme 58) (76JOC716, 75S705). 

Butadiyne has also been alkylated through the lithium alkynide. Thus, Holmes and Jones treated bis(trimethylsilyl)buta-l,3-diyne with MeLi in the presence of lithium bromide and obtained the monolithium alkynide, which was then alkylated in HMPA (Scheme 30). If the lithium alkynide was complexed with ethylenediamine then DMSO could be used as solvent. In addition, Himbert and Feustel prepared the lithium derivative of l-A A(-dialkylbuta-l,3-diyne by treatment of 4- -dialkyl-l,l,2-trichlorobut-l-en-3-yne with butyllithium. The lithium salt was not isolated but was alkylated to the l-alkyl-4-lV-di-alkylbuta-l,3-diyne (Scheme 31). 

Solid complexes of defined stoichiometry have been prepared for all the lithium halides with HMPA. For LiBr, both [LiBr(HMPA)2] and [LiBr(HMPA)4] have been obtained as solids of defined m.p., but the 1 1 complex, the kinetically active species for epoxide rearrangement, has not been isolated. The rate of epoxide loss and solubility of LiBr increased proportionately with added solubilizer (HMPA), to a maximum rate at a 1 1 ratio of addend LiBr. Additional HMPA beyond this ratio caused the rate to decrease even though all the LiBr remained in solution. At an addend LiBr ratio of 2 1, the reaction effectively ceased. These observations allow the conclusions that [LiBr(HMPA)2] is more stable than the reactive 1 1 complex in benzene, and that only the latter is kinetically competent. 

Carbanion Reactivity. An increase in reaction rate is observed for the reaction of alkynyllithium reagents with alkyl halides and oxiranes (eq 10). The strongly coordinating HMPA probably complexes the lithium cation, thereby increasing the negative charge density on the carbon and creating a much more nucleophilic alkynyl anion. A similar effect is observed for (Trimethyl-stannylmethyl)Uthium, which does not react with oxiranes in THF but in THF-HMPA the reaction proceeds readily. ... 

To a solution of hexamethyldisilane (2.5 mmol) in HMPA (CAUTION— CANCER SUSPECT AGENT) (3 ml) at 0-5 °C was added methyl lithium (2.5 mmol, 1.5 m MeLi.LiBr complex in ether) dropwise. After being stirred for 3 min, the red solution was treated with Cul (2.5 mmol) in Me2S (1 ml), the resulting black reaction mixture was stirred for 3 min. and 2,3-dibromo-propene (1 mmol) was added rapidly via a syringe. The reaction mixture was allowed to warm to room temperature, and was stirred for 1.5 h. It was then poured into pentane (25 ml) and saturated ammonium chloride solution (25 ml, buffered to pH 8 by the addition of ammonium hydroxide), and the mixture was stirred vigorously for 1 h. The aqueous phase was re-extracted with pentane, and the combined organic extracts were dried. Removal of... 

To a solution of hexamethyldisilane (2.5 mmol) in HMPA (CAUTION— CANCER SUSPECT AGENT) (3 ml) at 0-5 °C was added methyl lithium (2.5 mmol, 1.5 m MeLi.LiBr complex in ether) dropwise. After being stirred for 3 min, the red solution was treated with Cul (2.5 mmol) in Me2S (1 ml), and the resulting black reaction mixture was stirred for 3 min. Ether (6 ml)... 

As a contrast to this, when 5-phenylamino-l,2,3,4-thiatriazole (42) and an equimolar amount of HMPA in toluene at — 78°C is treated with 1 equivalent of solid lithium bases, LiOH, MeOLi, LiNH2, /-PrjNLi or BuLi dissolved in hexane, extrusion of nitrogen and sulfur is observed on heating to room temperature, resulting in formation of PhNCNLi, HMPA complex (101) (Equation (11)) <93AG1801>. 

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. 

The general intransigence of the crystalline iminolithium hexamers toward further interaction with Lewis bases is not shown by the amorphous diaryliminolithiums. This may reflect their extensively stacked nature (Section II,A Fig. 10), which, while raising the lithium coordination number to four in all but the outer rings of the polymer, will presumably weaken individual N—Li bonds. These materials dissolve quite readily in several polar solvents, e.g., THF (66), pyridine (66, 78, 85), and HMPA (86). Crystalline complexes can be recovered from these solutions. Two of these, both derivatives of (Ph2C=NLi) , have been characterized structurally in the solid state. The tetrameric cubane (Ph2C=NLipyridine)4 (7) is depicted in Fig. 14 (78, 85). 

Analogous lithium ate complexes 53 are detected by NMR when solutions of PhLi are treated with HMPA,65 and the formation of an intensely yellow solution in the halogen-metal exchange of the diiodide 54 with BuLi suggests the intermediacy of the ate complex 55.66... 

Enolates may be converted directly into a-hydroxy-ketones by reaction with the molybdenum peroxide complex MoOs,py,HMPA. The 17-ketone (188), transformed into its enolate with lithium di-isopropylamide at —70°C, gives the 16a-hydroxy-17-ketone (189) in 75% yield.172 Carbonyl transposition to the vicinal position can be effected in high yield by a new five-step process.173 A 17-oxo-steroid (188) was transformed into the 16-ketone (193) via the phenylthioketone (190) and the 16-phenylthio-16-ene (192) by the route illustrated in Scheme 5. 

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