Lithium tris aluminum hydride

This reducing agent is prepared in quantitative yield by the reaction of lithium tri-methoxyaluminum hydride (LTMA, 1, 625 2, 252-253) with the highly hindered tri-sec-butylborane in THF at 25°. Aluminum meihoxide is also formed, but since it is inert, the reaction mixture can be used directly. ... 

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. 

Wheeler and Mateos in a preliminary note reported that reduction of cholestane-3-one with either lithium tri-/-butoxyaluminum hydride or with lithium aluminum hydride-aluminum chloride affords 99% of the equatorial cholestane-3j8-ol, whereas reduction with lithium aluminum hydride alone was known to give only 88-91% ofthe3 -ol. ... 

Reducing agents Aluminum hydride. Bis-3-methyl-2-butylborane. n-Butyllithium-Pyridine. Calcium borohydride. Chloroiridic acid. Chromous acetate. Chromous chloride. Chromous sulfate. Copper chromite. Diborane. Diborane-Boron trifluoride. Diborane-Sodium borohydride. Diethyl phosphonate. Diimide. Diisobutylaluminum hydride. Dimethyl sulfide. Hexamethylphosphorous triamide. Iridium tetrachloride. Lead. Lithium alkyla-mines. Lithium aluminum hydride. Lithium aluminum hydride-Aluminum chloride. Lithium-Ammonia. Lithium diisobutylmethylaluminum hydride. Lithium-Diphenyl. Lithium ethylenediamine. Lithium-Hexamethylphosphoric triamide. Lithium hydride. Lithium triethoxyaluminum hydride. Lithium tri-/-butoxyaluminum hydride. Nickel-aluminum alloy. Pyridine-n-Butyllithium. Sodium amalgam. Sodium-Ammonia. Sodium borohydride. Sodium borohydride-BFs, see DDQ. Sodium dihydrobis-(2-methoxyethoxy) aluminate. Sodium hydrosulflte. Sodium telluride. Stannous chloride. Tin-HBr. Tri-n-butyltin hydride. Trimethyl phosphite, see Dinitrogen tetroxide. 

ENYNES Di-ji-carbonylhexacar-bonyldicobalt. Lithium diisobutyl-aluminum hydride. Tetrakis(tri-phenylphosphine)palladium(O). 

One of the more difficult partial reductions to accomplish is the conversion of a carboxylic acid derivative to an aldehyde without over-reduction to the alcohol. Aldehydes are inherently more reactive than acids or esters so the challenge is to stop the reduction at the aldehyde stage. Several approaches have been used to achieve this objective. One is to replace some of the hydrogens in a group III hydride with more bulky groups, thus modifying reactivity by steric factors. Lithium tri- -butoxyaluminum hydride is an example of this approach." Sodium tri- butoxyaluminum hydride can also be used to reduce acyl chlorides to aldehydes without over-reduction to the alcohol." The excellent solubility of sodium bis(2-methoxyethoxy)aluminum hydride makes it a useful reagent for selective... 

Other methods for the preparation of cyclohexanecarboxaldehyde include the catalytic hydrogenation of 3-cyclohexene-1-carboxaldehyde, available from the Diels-Alder reaction of butadiene and acrolein, the reduction of cyclohexanecarbonyl chloride by lithium tri-tcrt-butoxy-aluminum hydride,the reduction of iV,A -dimethylcyclohexane-carboxamide with lithium diethoxyaluminum hydride, and the oxidation of the methane-sulfonate of cyclohexylmethanol with dimethyl sulfoxide. The hydrolysis, with simultaneous decarboxylation and rearrangement, of glycidic esters derived from cyclohexanone gives cyclohexanecarboxaldehyde. 

The azido mesylate may also be reduced with lithium aluminum hydride in the same manner as previously described for iodo azide reductions. The sodium borohydride/cobalt(II)tris(a,a -dipyridyl)bromide reagent may be used, but it does not seem to offer any advantages over the more facile lithium aluminum hydride or hydrazine/Raney nickel procedures. 

The introduction of the l/, 2j5-methylene function into cortical hormones is best carried out by starting with the A -3)S-aIcohols (7) which are prepared by lithium aluminum hydride or lithium tri-t-butoxyaluminum hydride reduction of the corresponding A -3-ketones. 

Reduction of 3-methyl-4(3H)quinazolinone with lithium aluminum hydride is known to give 3-methyl-l,2,3,4-tetrahydroquinazoline. The most interesting tetrahydroquinazoline is Trbger s base ° since it has added to our knowledge of the stereochemistry of tri-... 

Bis(2-nitrophenyl)amine (la) is reduced by zinc/ sodium hydroxide to a mixture of 117/-dibenzo[r, /][l,2,5 triazcpine (2a) and the V-oxidc 3a.325 The reaction of Ar-methylbis(2-ni-trophenyl)amine with lithium aluminum hydride provides 11-methyl-1 l//-dibenzo[c,/][l,2,5]tri-azepine (2b).153... 

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). 

These reagents generally show increased solubility in organic solvents, particularly at low temperatures, and are useful in certain selective reductions.75 Lithium tri-r-butoxyaluminum hydride and sodium Mv-(2-meLhoxyethoxy)aluminum hydride (Red-Al)76 are examples of these types of reagents that have synthetic use. Their reactivity toward carbonyl groups is summarized in Table 5.3. 

The required working time is 3 to 4 hours. All equipment is thoroughly dried prior to use and is flushed with an inert gas (argon or nitrogen). Commercial sodium hydroborate is used without purification. The dimethyl ether of diethylene glycol (diglyme) is refluxed over calcium hydride for 8 hours and subsequently distilled over lithium tetrahydroaluminate (lithium aluminum hydride). Commercial tri-n-butylamine is refluxed with acetic anhydride and distilled at atmospheric pressure. 

Because direct glycosidation of 4 with phenols is not possible, indirect methods must be used for the preparation of aryl D-glucofuranosidurono-6,3-lactones (29). In addition, aryl 2,5-di-O-acetyl-D-glucofuranosidurono-6,3-lactones (30), obtained35-37 from the reaction of 1,2,5-tri-0-acetyl-D-glucofuranurono-6,3-lactones with phenols, can only be deacetylated by such multi-step procedures as (1) ammonolysis of 30 to afford aryl D-glucofuranosiduronamides (31), followed by amide hydrolysis and lactonization, 35,37 or (2) reduction of 30 with lithium aluminum hydride, and subsequent oxidation of the intermediate aryl D-glucofuranosides38 (32) (see Scheme 1). 

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... 

Purification. Two laboratories noted that commercial samples of KH12 and NaH2 are ineffective for conversion of hindered trialkylboranes into the corresponding borohydrides. Both groups find that treatment of the aged metal hydrides with lithium aluminum hydride in THF results in highly active hydrides that react readily even with such hindered trialkylboranes as tris(3-methyl-2-butyl)borane. 

In the fourth and final chapter, Howard Haubenstock discusses asymmetric reduction of organic molecules. Within this general topic of wide and continuing interest, Haubenstock s chapter deals with chiral derivatives of lithium aluminum hydride, their preparation from suitable amino or hydroxy compounds, and their use in reducing carbonyl groups. Related reactions of the Meerwein-Ponndorf-Verley type or involving tri-alkylaluminum reagents are also presented. 

Tertiary and aromatic nitroso compounds are not readily accessible consequently not many reductions have been tried. Nitrosobenzene was converted to azobenzene by lithium aluminum hydride (yield 69%) [592], and o-nitrosobiphenyl to carbazole, probably via a hydroxylamino intermediate, by treatment with triphenylphosphine or triethyl phosphite (yields 69% and 76%, respectively) [298]. Nitrosothymol was transformed to amino-thymol with ammonium sulfide (yield 73-80%) [245], and a-nitroso-/J-naphthol to a-amino-/J-naphthol with sodium hydrosulfite (yield 66-74%) [255]. 

Several reagents reduce aldehydes preferentially to ketones in mixtures of both. Very high selectivity was found in reductions using dehydrated aluminum oxide soaked with isopropyl alcohol and especially diisopropylcarbinol [755], or silica gel and tributylstamane [756]. The best selectivity was achieved with lithium trialkoxyalumimm hydrides at —78°. In the system hexanal/ cyclohexanone the ratio of primary to secondary alcohol was 87 13 at 0° and 91.5 8.5 at —78° with lithium tris(/er/-butoxy)aluminum hydride [752], and 93.6 6.4 at 0° and 99.6 0.4 at —78° with lithium tris(3-ethyl-3-pentyl-oxy)aluminum hydride [752],... 

Transformation of ketones to alcohols has been accomplished by many hydrides and complex hydrides by lithium aluminum hydride [55], by magnesium aluminum hydride [89], by lithium tris tert-butoxy)aluminum hydride [575], by dichloroalane prepared from lithium aluminum hydride and aluminum chloride [816], by lithium borohydride [750], by lithium triethylboro-hydride [100], by sodium borohydride [751,817], by sodium trimethoxyborohy-dride [99], by tetrabutylammonium borohydride [771] and cyanoborohydride [757], by chiral diisopinocampheylborane (yields 72-78%, optical purity 13-37%) [575], by dibutyl- and diphenylstannane [114], tributylstanrume [756] and others Procedure 21, p. 209). 

Reduction of unsaturated ketones to saturated alcohols is achieved by catalytic hydrogenation using a nickel catalyst [49], a copper chromite catalyst [50, 887] or by treatment with a nickel-aluminum alloy in sodium hydroxide [555]. If the double bond is conjugated, complete reduction can also be obtained with some hydrides. 2-Cyclopentenone was reduced to cyclopentanol in 83.5% yield with lithium aluminum hydride in tetrahydrofuran [764], with lithium tris tert-butoxy)aluminium hydride (88.8% yield) [764], and with sodium borohydride in ethanol at 78° (yield 100%) [764], Most frequently, however, only the carbonyl is reduced, especially with application of the inverse technique (p. 21). 

Esters are also reduced by sodium aluminum hydride (yields 95-97%) [<9<9] and by lithium trimethoxyaluminum hydride (2 mol per mol of the ester) [94] but not by lithium tris tert-butoxy)aluminum hydride [96], Another complex hydride, sodium bis(2-methoxyethoxy)aluminum hydride, reduces esters in benzene or toluene solutions (1.1 -1.2 mol per ester group) at 80° in 15-90 minutes in 66-98% yields [969], Magnesium aluminum hydride (in the form of its tetrakistetrahydrofuranate) reduced methyl benzoate to benzyl alcohol in 58% yield on refluxing for 2 hours in tetrahydrofuran [59]. 

Better reagents than lithium aluminum hydride alone are its alkoxy derivatives, especially di- and triethoxyaluminohydrides prepared in situ from lithium aluminum hydride and ethanol in ethereal solutions. The best of all, lithium triethoxyaluminohydride, gave higher yields than its trimethoxy and tris(/er/-butoxy) analogs. When an equimolar quantity of this reagent was added to an ethereal solution of a tertiary amide derived from dimethylamine, diethylamine, W-methylaniline, piperidine, pyrrolidine, aziridine or pyrrole, and the mixture was allowed to react at 0° for 1-1.5 hours aldehydes were isolated in 46-92% yields [95,1107], The reaction proved unsuccessful for the preparation of crotonaldehyde and cinnamaldehyde from the corresponding dimethyl amides [95]. 

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