Lithium aluminum hydride reduction, alcohols

Which of the isomeric C5H12O alcohols can be prepared by lithium aluminum hydride reduction of... 

Epoxidation of an alkene followed by lithium aluminum hydride reduction of the result mg epoxide gives the same alcohol that would be obtained by acid catalyzed hydration (Section 610) of the alkene... 

Lithium aluminum hydride reduction (Sec tion 15 3) Carboxylic acids are reduced to primary alcohols by the powerful reducing agent lithium aluminum hydride... 

Neopentyl alcohol has been made by lithium aluminum hydride reduction of trimethylacetic acid and by treating ferf-butyl-magnesium chloride with methyl formate. ... 

In contrast to alcohols with their- rich chemical reactivity, ethers (compounds containing a C—O—C unit) undergo relatively few chemical reactions. As you saw when we discussed Grignaid reagents in Chapter 14 and lithium aluminum hydride reductions in Chapter 15, this lack of reactivity of ethers makes them valuable as solvents in a number of synthetically important transfonnations. In the present chapter you will leain of the conditions in which an ether linkage acts as a functional group, as well as the methods by which ethers are prepared. 

The chemical reduction of enamines by hydride again depends upon the prior generation of an imonium salt (111,225). Thus an equivalent of acid, such as perchloric acid, must be added to the enamine in reductions with lithium aluminum hydride. Studies of the steric course (537) of lithium aluminum hydride reductions of imonium salts indicate less stereoselectivity in comparison with the analogous carbonyl compounds, where an equatorial alcohol usually predominates in the reduction products of six-membered ring ketones. 

Butylcyclohexanol has been prepared from />-/-butylphenol by reduction under a variety of conditions.3 4 Winstein and Holness5 prepared the pure trans alcohol from the commercial alcohol by repeated crystallization of the acid phthalate followed by saponification of the pure trans ester. Eliel and Ro 6 obtained 4-f-butylcyclohexanol containing 91% of the trans isomer by lithium aluminum hydride reduction of the ketone. Iliickel and Kurz 7 reduced />-/-butylphenol with platinum oxide in acetic acid and then separated the isomers by column chromatography. 

From intermediate 28, the construction of aldehyde 8 only requires a few straightforward steps. Thus, alkylation of the newly introduced C-3 secondary hydroxyl with methyl iodide, followed by hydrogenolysis of the C-5 benzyl ether, furnishes primary alcohol ( )-29. With a free primary hydroxyl group, compound ( )-29 provides a convenient opportunity for optical resolution at this stage. Indeed, separation of the equimolar mixture of diastereo-meric urethanes (carbamates) resulting from the action of (S)-(-)-a-methylbenzylisocyanate on ( )-29, followed by lithium aluminum hydride reduction of the separated urethanes, provides both enantiomers of 29 in optically active form. Oxidation of the levorotatory alcohol (-)-29 with PCC furnishes enantiomerically pure aldehyde 8 (88 % yield). 

The homology between 22 and 21 is obviously very close. After lithium aluminum hydride reduction of the ethoxycarbonyl function in 22, oxidation of the resultant primary alcohol with PCC furnishes aldehyde 34. Subjection of 34 to sequential carbonyl addition, oxidation, and deprotection reactions then provides ketone 21 (31% overall yield from (—)-33). By virtue of its symmetry, the dextrorotatory monobenzyl ether, (/ )-(+)-33, can also be converted to compound 21, with the same absolute configuration as that derived from (S)-(-)-33, by using a synthetic route that differs only slightly from the one already described. 

The products are liberated by hydrolysis of the aluminum alkoxide at the end of the reaction. Lithium aluminum hydride reduction of esters to alcohols involves an elimination step in addition to hydride transfers. 

Direct hydrogenation of key intermediate 248 over the Adams catalyst and subsequent lithium aluminum hydride reduction yielded the two stereoisomeric alcohols 256 and 257, which were separately transformed to ( )-corynantheal (258) and ( )-3-epicorynantheal (259), respectively, by Moffatt oxidation, followed by Wittig reaction with methyltriphenylphosphonium bromide and, finally, by demasking the aldehyde function (151, 152). 

Lithium aluminum hydride reduction of tetrahydro-l,3-oxazin-2-ones 434 results in the corresponding A -methyl-substituted 1,3-amino alcohols 435 (60JA4656 87TL1623). 

Conversion of the keto ketoxime 1 to the exo-exo-amino alcohol 2 has been accomplished by hydrogenation over Adams catalyst and by reduction with lithium aluminum hydride. Amino alcohol 2 has also been prepared from 1 by a two-stage process in which selective reduction of the ketone is carried out with sodium borohydride, and the resultant hydroxy oxime is reduced with lithium aluminum hydride or by hydrogenation over Adams catalyst. ... 

Similarly, lipase-catalyzed kinetic resolution has also been applied to intermediate nitrile alcohol 46 (Scheme 14.14). Best results were obtained by using immobilized Pseudomonas cepacia (PS-D) in diisopropyl ether, leading to excellent yield and enantiomeric excess of the desired (5)-alcohol 46a, along with (/J)-nitrile ester 47. Reduction of 46a with borane-dimethylsulhde complex, followed by conversion to the corresponding carbamate and subsequent lithium aluminum hydride reduction gave rise to the desired (S)-aminoalcohol intermediate 36, a known precursor of duloxetine (3). 

Evans and co-workers synthesized bu-box 3 starting from commercially available (5)-ferf-leucine." Lithium aluminum hydride reduction of (iS)-tcrt-leucine afforded the amino alcohol 23 which, as shown in Figure 9.6, was acylated with dimethylmalonyl dichloride 24 to provide the corresponding bis(amidodiol) 25 in... 

An alternative cleavage procedure uses lithium aluminum hydride reduction, which furnishes the auxiliary along with the desired primary alcohol in high yield5. 

The iV-aminopyrrole - benzene ring methodology has been applied to a synthesis of the 9,10-dihydrophenanthrene juncusol (218) (81TL1775). Condensation of the tetralone (213) with pyrrolidine and reaction of the enamine with ethyl 3-methoxycarbonylazo-2-butenoate gave pyrrole (214). Diels-Alder reaction of (214) with methyl propiolate produced a 3 1 mixture of (215) and its isomer in 70% yield. Pure (215) was reduced selectively with DIBAL to the alcohol, reoxidized to aldehyde, and then treated with MCPBA to generate formate (216). Saponification to the phenol followed by O-methylation and lithium aluminum hydride reduction of the hindered ester afforded (217), an intermediate which had been converted previously to juncusol (Scheme 46). 

Thiochroman-4-ones are reduced to thiochroman-4-ols by sodium borohydride6 and lithium aluminum hydride.50 Lithium aluminum hydride reduction of thiofiavan-4-ones (27) forms the 2,4-ws-thiofiavan-4-ols (28) as in Eq. (8). By contrast, deamination of 2,4-cis-4-aminothio-flavans (29) with nitrous acid produced the trans- alcohol (30) as shown in Eq. (9).50 The alcohols obtained by the hydride reductions have... 

An important example of this type of reaction is the formation of esters, which was discussed previously in connection with the reactions of alcohols in Section 15-4D. Similar addition-elimination mechanisms occur in many reactions at the carbonyl groups of acid derivatives. A less obvious example of addition to carboxyl groups involves hydride ion (H 0) and takes place in lithium aluminum hydride reduction of carboxylic acids (Sections 16-4E and 18-3C). 

Reduction then proceeds by successive transfers of hydride ion, H e, from aluminum to carbon. The first such transfer reduces the acid salt to the oxidation level of the aldehyde reduction does not stop at this point, however, but continues rapidly to the alcohol. Insufficient information is available to permit very specific structures to be written for the intermediates in the lithium aluminum hydride reduction of carboxylic acids. However, the product is a complex aluminum alkoxide, from which the alcohol is freed by hydrolysis ... 

Most of the possible oxoindolizidines have been prepared by the application of the Dieckmann reaction to various piperidyl and pyrrol-idinyl diesters. Winterfeldt and Hoffstadt used it to convert 166 into 167 in good yield.227 Alkaline hydrolysis followed by lithium aluminum hydride reduction gave the alcohol 168 [Eq. (23)]. 

Reduction of isoxazolines, i-amino alcohols. Lithium aluminum hydride reduction of the ready available isoxazolines 1 is effected with unusually high 1,3-asymmetric induction (equation I). The stereoselectivity is not affected drastically by the presence of a hydroxyl group in the side chains at C3 or C5, but isoxazolines bearing a 4a-hydroxyl group are reduced almost entirely to the erythro ( fi)-diastereomer.1... 

Regio- and stereoselective reduction of the non-silylated triple bond, either by partial catalytic hydrogenation,13,14,15 or by lithium aluminum hydride reduction of the propargylic alcohols,11,16,17 afford (after desilylation), respectively, terminal (2)- and (E)-enynes. Furthermore, the remaining... 

Lithium aluminum hydride reduction of 4-protoadamantanone gives a 2 1 mixture of endo-4-protoadamantanol and its ejco-4-isomer 76> 78>79). This stereochemical assignment is consistent with the relative solvolytic reactivities of derivatives of these alcohols. xo-4-protoadamantyl 3,5-dinitrobenzoate solvolyses approximately 104 times faster than the corresponding endo iso-... 

Liquid injection molding, for silicone rubbers, 3, 674—675 Liquid ligands, in metal vapor synthesis, 1, 229 Liquid-phase catalysis, supported, for green olefin hydroformylation, 12, 855 Lithiacarbaboranes, preparation, 3, 114 Lithiation, arene chromium tricarbonyls, 5, 236 Lithium aluminum amides, reactions, 3, 282 Lithium aluminum hydride, for alcohol reductions, 3, 279 Lithium borohydride, in hydroborations, 9, 158 Lithium gallium hydride, in reduction reactions, 9, 738 Lithium indium hydride, in carbonyl reductions, 9, 713—714... 

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