Lithium aluminum hydride, reducing epoxides

SCHEME 6.73 Lithium aluminum hydride reduces epoxides producing products consistent with the Fiirst-Plattner rule. 

Lithium aluminum hydride reduces the carboxylic acid to the corresponding primary alcohol, compound E. Treatment of the vicinal chlorohydrin with base results in formation of an epoxide, compound F. 

Epoxides are reduced to alcohols on treatment with lithium aluminum hydride Hydride is transferred to the less substituted carbon... 

Lithium aluminum hydride (LiAlH4) is the most powerful of the hydride reagents. It reduces acid chlorides, esters, lactones, acids, anhydrides, aldehydes, ketones and epoxides to alcohols amides, nitriles, imines and oximes to amines primary and secondary alkyl halides and toluenesulfonates to... 

To overcome this, the A -acetyl group is reduced with lithium aluminum hydride. The resulting basic enamine then reacts extremely rapidly and selectively with peracid. The derived epoxide is hydrolyzed very easily with alkali during the workup. 

Epoxides are reduced by treatment with lithium aluminum hydride to yield alcohols. Propose a mechanism for this reaction. 

The synthesis of isomeric DL-allitol succeeded when the hydroxyl groups in cts,cis-2,4-hexadiene-l,6-diol were protected with benzoyl or mesyl groups. Epoxidation gave the appropriate derivatives of 2,3 4,5-dianhydro-DL-allitol (16%), which were then reduced with lithium aluminum hydride to DL-crt/f/iro-2,5-hexanediol. 

Several alioyclio epoxides substituted with polar atoms have been reduced with lithium aluminum hydride, largely by Moueesron and eo-workers, although subsequent investigators3 -1,70 have expressed disagreement with certain of their results. Experimental difficulties in... 

Reduction of oxetanes. Oxetanes, like epoxides (1, 598), are reduced by lithium aluminum hydride -aluminum chloride (ratio 3 1) in refluxing ether. Thus oxctanc (1) is... 

Sodium borohydride is a mild and selective reducing reagent. In ethanol solution it reduces aldehydes and ketones rapidly at 25°C, esters very slowly, and is inert toward functional groups that are readily reduced by lithium aluminum hydride carboxylic acids, epoxides, lactones, nitro groups, nitriles, azides, amides, and acid chlorides. 

Hofmann degradation, styrene 468 was formed. Epoxidation of 468 with m-chloroperbenzoic acid from the less hindered side and lithium aluminum hydride reduction gave ( )-epicorynoline (469). Moreover, slow addition of the a-methoxystyrene 471 to isoquinolinium salt 470 gave cycloadduct 472 in 90% yield. The adduct was hydrolyzed by acid and the resultant aldehyde oxidized to naphthoic acid by Jones oxidation. Modified Curtius rearrangement of 473 with added benzyl alcohol afforded benzyl urethane 474, which was reduced by lithium aluminum hydride and formylated with chloral to give 0-methylarnottiamide (475) (Scheme 60). 

Whitesell and Minton have synthesized (- )-xylomollin (408), the only trans-fiised iridoid, from the racemic bicyclic diene 409. Control of the stereochemistry was effected in the first step by addition of the glyoxylate 410. The two products were separated and the major one, 411, was reduced with lithium aluminum hydride. Conversion of the primary alcohol to a methyl group, with concomitant inversion of stereochemistry at the secondary alcohol carbon atom was carried out by protection of the primary alcohol function (fert-butyldimethylsilyl), tosylation of the secondary hydroxyl, then removal of the silyl group with formation of an epoxide with inversion, and reduction (LiEtaBH) of the epoxide. The remaining steps are shown in Scheme 36. It remains to point out that isoxylomoUin (412) was produced preferentially, and is indeed formed from xylomollin (408) slowly in methanolic solution. ... 

Reduction of epoxides. Hallsworth and Henbest (1,579,refs. 12 and 13)found that some steroidal epoxides, which were unreactive to lithium aluminum hydride, are easily reduced with a large excess of lithium in ethylamine. However, some olefin is also formed in some cases. Brown et al.1 now report that the combination of lithium and ethylenediamine at 50° is excellent for reduction of labile epoxides of bicyclic ketones, which are reduced only slowly by lithium aluminum hydride and usually with some extensive rearrangement. They chose ethylenediamine rather than ethylamine because the reduction is less vigorous in ethylenediamine than in ethylamine and thus easier to control. Also isolation of the alcohol is simplified because ethylenediamine is very soluble in water and only slightly soluble in ether, whereas ethylamine is miscible both in water and in ether. By this procedure, norbomene oxide (1) is reduced to pure ejco-norbomanol (2) in 87% yield (isolation). Analysis by glpc indicated that two rearranged alcohols (3, 4) are formed to a minor extent and that (2) is formed in 99.3% yield. 

Even the very labile 2-methylene-7,7-dimethylnorbornane epoxide (5) is reduced in this way to the tertiary alcohol (6) in 89% yield. Reduction with lithium aluminum hydride gives chiefly a primary alcohol. 

A slight modification of Corey synthesis (see Scheme 3.16) affords an estrane that bears a hydroxyl at C14. The 14-dehydroestrone intermediate from that synthesis is first reduced to give the corresponding 17[3-hydroxy analogue. This, in turn, is converted to its tert-butyldimethylsilyl ether (TBDMS) (32-1) by reaction with the silyl chloride (Scheme 3.32). Oxidation by means of w-chloroperbenzoic acid (mCPBA) affords the 14—15 epoxide 32-2 as a 3 1 mixture of a- and p-epimers. Treatment of the former with lithium aluminum hydride leads to the alcohol... 

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