Aluminum hydride, diethyl etherate

Solutions of lithium tellurolates were prepared by reacting a diaryl ditellurium or dibutyl ditellurium with lithium aluminum hydride. Diethyl ether , dioxane , or a mixture... 

Conditions for auxiliary removal have to be carefully chosen to avoid partial racemization of the newly formed stereogenic center. Such complications arise under reductive cleavage conditions (lithium aluminum hydride/diethyl ether) as well as basic hydrolysis employing potassium hydroxide in ethanol. However, treatment with lithium hydroxide in aqueous tetra-hydrofuran appears to effect clean cleavage whilst avoiding this complication713. 

Lithium aluminum hydride, diethyl ether, dichlorodiphenylsi-lane, hydrochloric acid. 

H. C. Brown and co-workers found that lithium aluminum hydride in ether solution reacts with 4 moles of methanol, ethanol, or isopropanol but with only 3 moles of t-butanol. Dropwise addition of 1 mole of /-butanol at room temperature to a stirred solution of 0.31 mole of LiAlH, in ether produces a white precipitate of lithium tri-/-butoxyaluminum hydride in essentially quantitative yield. The new reagent proved to be a milder reducing agent than LiAlH4, since it reduces aldehydes, ketones, and acid chlorides in diethyl ether or diglyme at 0° but fails to react with esters and nitriles. 

When the reduction of phenylboron dichloride is carried out with lithium aluminum hydride at the reflux temperature of dioxane (100 C) only the disproportionated products, triphenylborane and diborane, are found (7J). In contrast, a similar reduction of diethylphenylboronate in diethyl ether at room temperature gives the phenylborane (dimer) which is isolated as the pyridine adduct (74). Also, l-butoxy-3-methylboracyclopentane (VI) is reduced without difficulty by lithium aluminum hydride in ether solution to the corresponding tetrasubstituted diborane (VII) (75). 

Preparation. Commercial manufacture of LiAlH uses the original synthetic method (44), ie, addition of a diethyl ether solution of aluminum chloride to a slurry of lithium hydride (Fig. 2). 

Diethyl ether was dried by the submitters by refluxing over lithium aluminum hydride and was distilled immediately before use. The checkers distilled diethyl ether from the sodium ketyl of benzophenone before use. 

Lithium aluminum hydride reacts violently with water and alcohols, so it must be used in solvents such as anhydrous diethyl ether or tetrahydrofuran. Following reduction, a separate hydrolysis step is required to liberate the alcohol product ... 

The mixture is cooled and the excess of lithium aluminum hydride is decomposed with cracked ice. The water layer is separated and washed with diethyl ether. The combined ether extracts are dried over anhydrous magnesium sulfate and the solvent is removed by distillation under reduced pressure. Yield, 8.8 g boiling point, 160°C to 165°C/0.1 mm Hg. 

The synthesis of the right-wing sector, compound 4, commences with the prochiral diol 26 (see Scheme 4). The latter substance is known and can be conveniently prepared in two steps from diethyl malonate via C-allylation, followed by reduction of the two ethoxy-carbonyl functions. Exposure of 26 to benzaldehyde and a catalytic amount of camphorsulfonic acid (CSA) under dehydrating conditions accomplishes the simultaneous protection of both hydroxyl groups in the form of a benzylidene acetal (see intermediate 32, Scheme 4). Interestingly, when benzylidene acetal 32 is treated with lithium aluminum hydride and aluminum trichloride (1 4) in ether at 25 °C, a Lewis acid induced reduction takes place to give... 

Reduction of ethyl l//-azepine-l-carboxylate (1) with lithium aluminum hydride in diethyl ether at — 15°C yields l-(hydroxymethyl)-l//-azepine (2) as a thermally unstable, yellow oil, whereas reduction in refluxing diethyl ether yields the equally unstable 1-methyl-l//-azepine (3)-231... 

Dibenz[/>,e]azepines, e.g. 15, are reduced readily to the 5,6-dihydro derivatives, e.g. 16, with hydrogen and palladium on charcoal, or Raney nickel, at room temperature,28,104 with sodium in ethanol,104 with sodium borohydride in methanol,104 and with lithium aluminum hydride in diethyl ether.115... 

A 300 ml three-neck flask equipped with condenser, stirrer, dropping funnel, dry nitrogen inlet tube, and containing 5.5 g (0.145 mol) lithium aluminum hydride LAH suspension in 100 ml anhydrous diethyl ether, was placed in an ice bath. Over a period of 25 min 30 ml (0.123 mol) 1 was added dropwise into the stirred suspension. The mixture was stirred for an additional hour at 0 °C, then poured over a mixture of 50 ml ether, 100 g crushed ice, and 50 ml ice water with stirring. When necessary more crushed ice was added to cool the mixture. The layers were separated, and the organic layer was concentrated first by distillation over calcium hydride, then by vacuum distillation over calcium hydride. The yield of 4 was 22.5 g (86%). Bp. 78-9 °C, 0.4 mm. The product was stored in a freezer. The structure of 4 was confirmed by its H NMR spectrum as shown in Fig. 4. 

Remarkable solvent effects on the selective bond cleavage are observed in the reductive elimination of cis-stilbene episulfone by complex metal hydrides. When diethyl ether or [bis(2-methoxyethyl)]ether is used as the solvent, dibenzyl sulfone is formed along with cis-stilbene. However, no dibenzyl sulfone is produced when cis-stilbene episulfone is treated with lithium aluminum hydride in tetrahydrofuran at room temperature (equation 42). Elimination of phenylsulfonyl group by tri-n-butyltin hydride proceeds by a radical chain mechanism (equations 43 and 44). 

Some experimental evidences are in agreement with this proposed mechanism. For example, coordinating solvents like diethyl ether show a deactivating effect certainly due to competition with a Lewis base (149). For the same reason, poor reactivity has been observed for the substrates carrying heteroatoms when an aluminum-based Lewis acid is used. Less efficient hydrovinylation of electron-deficient vinylarenes can be explained by their weaker coordination to the nickel hydride 144, hence metal hydride addition to form key intermediate 146. Isomerization of the final product can be catalyzed by metal hydride through sequential addition/elimination, affording the more stable compound. Finally, chelating phosphines inhibit the hydrovinylation reaction. 

Prepare 6-methoxy-l-indanone (I) (JCS 1986(1962)) using polyphosphoric acid made by diluting 500 g of the commercial acid with 120 g 85% phosphoric acid. 2.5 g (I) in 176 ml ether and reflux one hour with 0.27 g lithium aluminum hydride. Cool and carefully add water and filter when bubbling stops (can use Celite filter aid). Dry and evaporate in vacuum and store twelve hours at -15° (under N2 if possible) to precipitate the white 6-methoxy-l-indanol (II) (recrystallize-n-hexane). 2.5 g (II) in 73 ml benzene and reflux one-half hour with 0.2 g p-toluenesulfonic acid. Cool, add water and separate the phases. Extract the aqueous phase with ether and combine with benzene phase and dry, evaporate in vacuum to get 5-methoxy-indene (III) (can distill 110-45/10). 1.53 g (III) and 1.39 g N.N-diethyl-aminoethyl-Cl.HCI in benzene (prepare the free base in benzene as described previously). Reflux four hours with 0.42 g sodamide, cool, wash with water and dry, evaporate in vacuum to get the indene analog of 6-methoxy DET as a dark liquid (can crystallize as oxalate). Alternatively, dissolve 2.51 g (III) in ether and treat (under N if possible) with 12 ml 1.6M buty-Li in hexane at 0-10°. After two hours cool to -30° and add 12 ml more of butyl-Li. Add ether suspension of 2.5 g N,N-diethylaminoethyl-CI. HCI over one-half hour and warm to room temperature. Filter, evaporate in vacuum to get the 6-methoxy-DET analog. 

The reduction of aminomethylenemalonates (1458) with lithium aluminum hydride (L AH) in diethyl ether or THF gave 2-aminomethy I-2-propen-1-ols (1459) in good yields (62JOC4137 64JMC68 66CB281). 

Reagent grades of diethyl ether and of tetrahydrofuran were distilled from lithium aluminum hydride immediately prior to use. 

Acetals of aldehydes are usually stable to lithium aluminum hydride but are reduced to ethers with alane prepared in situ from lithium aluminum hydride and aluminum chloride in ether. Butyraldehyde diethyl acetal gave 47% yield of butyl ethyl ether, and benzaldehyde dimethyl acetal and diethyl acetal afforded benzyl methyl ether and benzyl ethyl ether in 88% and 73% yields, respectively [792]. 

Diethyl ether was distilled from lithium aluminum hydride under argon before use. 

B. 2,3-Di-0 iaopropylidene-L-threitol (Note 13). In a dry, 2-L, threenecked, round-bottomed flask equipped with a 500-mL pressure-equalized addition funnel, reflux condenser, thermometer, and a large magnetic stirring bar. Is suspended lithium aluminum hydride (36 g, 0.95 mol) (Note 14) In diethyl ether (600 mL) (Note 15) under argon. The mixture Is stirred and heated to reflux for 30 min. Heating is discontinued while a solution of... 

---