Lithium aluminum hydride method

The condensation is usually carried out by adding a solution containing equimolar amounts of the allyl halide and the aldehyde or ketone to a solution of at least two equivalents of chromium-(II) chloride in THF at 0 5°C. Frequently, the less precious component is used in 50-100% excess. Although commercially available anhydrous chromium(II) chloride can be utilized (Method B), its in situ preparation from chromium(III) chloride and lithium aluminum hydride (Method A) is often preferred. The removal of chromium and aluminum hydroxide, which are formed on aqueous workup, can be accomplished by filtration in the presence of a filtration aid. 

A wide variety of methods have been described for the synthesis of variously substituted phenethylamines. Some frequently used procedures are presented in Scheme 1. Most of these have been discussed in previous reviews (305, 306). Condensation of an appropriately substituted benzaldehyde with nitromethane followed by reduction of the nitrostyrene (Method A) has proved to be a versatile method which has been employed by numerous workers (cf. 306, 358). Another common method (Method B) affords the amines by reduction of substituted phenylacetonitriles obtained via benzylchlorides (cf.. 306) or benzylamines (307). Reduction of phenylacetamides with lithium aluminum hydride (Method C) has also been applied successfully (308, 309). The substituted phenylacetamides were obtained either via diazoketones by an Amdt-Eistert synthesis (308) or by transformation of the corresponding acetophenones (310). 

Table 3. anti-, 2-Diols by Selective Reduction of a-Hydroxy Ketones with Zinc Borohydride (Method A)15 16 or Lithium Aluminum Hydride (Method B)13 14... 

For most laboratory scale reductions of aldehydes and ketones catalytic hydro genation has been replaced by methods based on metal hydride reducing agents The two most common reagents are sodium borohydride and lithium aluminum hydride... 

In contrast to alcohols with their nch chemical reactivity ethers (compounds contain mg a C—O—C unit) undergo relatively few chemical reactions As you saw when we discussed Grignard reagents m Chapter 14 and lithium aluminum hydride reduc tions m Chapter 15 this lack of reactivity of ethers makes them valuable as solvents m a number of synthetically important transformations In the present chapter you will learn of the conditions m which an ether linkage acts as a functional group as well as the methods by which ethers are prepared... 

Reduction to alcohols (Section 15 2) Aide hydes are reduced to primary alcohols and ketones are reduced to secondary alcohols by a variety of reducing agents Catalytic hydrogenation over a metal catalyst and reduction with sodium borohydride or lithium aluminum hydride are general methods... 

Reduction of an azide a nitrile or a nitro compound furnishes a primary amine A method that provides access to primary secondary or tertiary amines is reduction of the carbonyl group of an amide by lithium aluminum hydride... 

Trifluoroethanol was first prepared by the catalytic reduction of trifluoroacetic anhydride [407-25-0] (58). Other methods iaclude the catalytic hydrogeaatioa of trifluoroacetamide [354-38-1] (59), the lithium aluminum hydride reductioa of trifluoroacetyl chloride [354-32-5] (60) or of trifluoroacetic acid or its esters (61,62), and the acetolysis of 2-chloro-l,l,l-trifluoroethane [75-88-7] followed by hydrolysis (60). More recently, the hydrogenation of... 

In general, if the desired carbon—phosphoms skeleton is available in an oxidi2ed form, reduction with lithium aluminum hydride is a powerful technique for the production of primary and secondary phosphines. The method is appHcable to halophosphines, phosphonic and phosphinic acids as well as thein esters, and acid chlorides. Tertiary and secondary phosphine oxides can be reduced to the phosphines. 

AletalHydrides. Metal hydrides can sometimes be used to prepare amines by reduction of various functional groups, but they are seldom the preferred method. Most metal hydrides do not reduce nitro compounds at all (64), although aUphatic nitro compounds can be reduced to amines with lithium aluminum hydride. When aromatic amines are reduced with this reagent, a2o compounds are produced. Nitriles, on the other hand, can be reduced to amines with lithium aluminum hydride or sodium borohydride under certain conditions. Other functional groups which can be reduced to amines using metal hydrides include amides, oximes, isocyanates, isothiocyanates, and a2ides (64). 

Hydroisoquinolines. In addition to the ring-closure reactions previously cited, a variety of reduction methods are available for the synthesis of these important ring systems. Lithium aluminum hydride or sodium in Hquid ammonia convert isoquinoline to 1,2-dihydroisoquinoline (175). Further reduction of this intermediate or reduction of isoquinoline with tin and hydrochloric acid, sodium and alcohol, or catalyticaHy using platinum produces... 

Good yields of phenylarsine [822-65-17, C H As, have been obtained by the reaction of phenylarsenic tetrachloride [29181-03-17, C H AsCl, or phenyldichloroarsine [696-28-6], C3H3ASCI25 with lithium aluminum hydride or lithium borohydride (41). Electrolytic reduction has also been used to convert arsonic acids to primary arsines (42). Another method for preparing primary arsines involves the reaction of arsine with calcium and subsequent addition of an alkyl haUde. Thus methylarsine [593-52-2], CH As, is obtained in 80% yield (43) ... 

Hydroxymethylferrocene has been made by condensing ferrocene with N-methylformanilide to give ferrocenecarboxalde-hyde, and reducing the latter with lithium aluminum hydride, sodium borohydride, or formaldehyde and alkali. The present procedure is based on the method of Lindsay and Hauser. A similar procedure has been used to convert gramine methiodide to 3-hydroxymethylindole, and the method could probably be used to prepare other hydroxymethyl aromatic compounds. 

The treatment of ketoximes with lithium aluminum hydride is usually a facile method for the conversion of ketones into primary amines, although in certain cases secondary amine side products are also obtained. Application of this reaction to steroidal ketoximes, by using lithium aluminum deuteride and anhydrous ether as solvent, leads to epimeric mixtures of monodeuterated primary amines the ratio of the epimers depends on the position of the oxime function. An illustrative example is the preparation of the 3(x-dj- and 3j5-di-aminoandrostane epimers (113 and 114, R = H) in isotopic purities equal to that of the reagent. 

A facile method for the stereospecific labeling of carbon atoms adjacent to an oxygenated position is the reductive opening of oxides. The stereospecificity of this reaction is due to virtually exclusive diaxial opening of steroidal oxides when treated with lithium aluminum hydride or deuteride. The resulting /ra/w-diaxial labeled alcohols are of high stereochemical and isotopic purity, with the latter property depending almost solely on the quality of the metal deuteride used. (For the preparation of m-labeled alcohols, see section V-D.)... 

A direct reduction of the A" -3-keto system can be effected with lithium aluminum hydride-aluminum chloride. The last two methods are unsatisfactory with A -3-ketones (ref. 185, p. 253 ref. 255, but cf. ref. 229). 

An alternate method of producing the 21-hydroxy-20-ketone consists in lithium aluminum hydride reduction of the dimethyl acetal, hydrolysis to the 20-hydroxy-21-aldehyde and rearrangement, preferably via the bisulfite addition product... 

The reduction of iminium salts can be achieved by a variety of methods. Some of the methods have been studied primarily on quaternary salts of aromatic bases, but the results can be extrapolated to simple iminium salts in most cases. The reagents available for reduction of iminium salts are sodium amalgam (52), sodium hydrosulfite (5i), potassium borohydride (54,55), sodium borohydride (56,57), lithium aluminum hydride (5 ), formic acid (59-63), H, and platinum oxide (47). The scope and mechanism of reduction of nitrogen heterocycles with complex metal hydrides has been recently reviewed (5,64), and will be presented here only briefly. 

The Meerwein-Ponndorf-Verley procedure has largely been replaced by reduction procedures that use lithium aluminum hydride, sodium borohydride or derivatives thereof. The Meerwein-Ponndorf-Verley reduction however has the advantage to be a mild and selective method, that does not affect carbon-carbon double or triple bonds present in the substrate molecule. 

The procedure employs a readily available starting material and produces the pure trans isomer in high yield. The method described is an improvement on that used by Eliel and Rerick2 in that it is not necessary to use a clear solution of lithium aluminum hydride in ether for the preparation of the mixed hydride. It is not necessary to know the precise amount of lithium aluminum hydride used so long as a slight excess is present. The excess hydride is destroyed by adding /-butanol the excess /-butanol has no effect on the subsequent equilibration and purification. The equilibration of the 4 / butylcyclohexanol is effected by adding a small amount of 4-/-butylcyclohexanone. 

Since double bonds may be considered as masked carbonyl, carboxyl or hydroxymethylene groups, depending on whether oxidative or reductive methods are applied after cleavage of the double bond, the addition products from (E)-2 and carbonyl compounds can be further transformed into a variety of chiral compounds. Thus, performing a second bromine/lithium exchange on compound 4, and subsequent protonation, afforded the olefin 5. Ozonolysis followed by reduction with lithium aluminum hydride gave (S)-l-phenyl-l,2-ethanediol in >98% ee. 

In a more general sense, this reduction method provides a convenient pathway for converting an aromatic carboxyl group to a methyl group (see Table I).7 Previously, this transformation has been achieved by reduction of the acid to the alcohol with lithium aluminum hydride, conversion of the alcohol to the tosylate, and a second reduction either with lithium aluminum hydride [Aluminate(l —), tetrahydro, lithium,... 

Although catalytic hydrogenation is the method most often used, double bonds can be reduced by other reagents, as well. Among these are sodium in ethanol, sodium and rerr-butyl alcohol in HMPA, lithium and aliphatic amines (see also 15-14), " zinc and acids, sodium hypophosphate and Pd-C, (EtO)3SiH—Pd(OAc)2, trifluoroacetic acid and triethylsilane (EtsSiH), and hydroxylamine and ethyl acetate.However, metallic hydrides, such as lithium aluminum hydride and sodium borohydride, do not in general reduce carbon-carbon double bonds, although this can be done in special cases where the double bond is polar, as in 1,1-diarylethenes and in enamines. " °... 

The preparation of Pans-1,2-cyclohexanediol by oxidation of cyclohexene with peroxyformic acid and subsequent hydrolysis of the diol monoformate has been described, and other methods for the preparation of both cis- and trans-l,2-cyclohexanediols were cited. Subsequently the trans diol has been prepared by oxidation of cyclohexene with various peroxy acids, with hydrogen peroxide and selenium dioxide, and with iodine and silver acetate by the Prevost reaction. Alternative methods for preparing the trans isomer are hydroboration of various enol derivatives of cyclohexanone and reduction of Pans-2-cyclohexen-l-ol epoxide with lithium aluminum hydride. cis-1,2-Cyclohexanediol has been prepared by cis hydroxylation of cyclohexene with various reagents or catalysts derived from osmium tetroxide, by solvolysis of Pans-2-halocyclohexanol esters in a manner similar to the Woodward-Prevost reaction, by reduction of cis-2-cyclohexen-l-ol epoxide with lithium aluminum hydride, and by oxymercuration of 2-cyclohexen-l-ol with mercury(II) trifluoro-acetate in the presence of ehloral and subsequent reduction. ... 

The tetrahydrofuran was freshly distilled from lithium aluminum hydride. For a warning regarding this method of purifying tetrahydrofuran, see Org. Syre., Coll. Vol. 5, 976 (1973). 

A second method is the replacement of a chiral leaving group of an (optically unstable) organotin compound (a triorganotin menthoxide for instance) by a more nucleophilic reagent (a Grignard reagent or lithium aluminum hydride for instance). 

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