Reduction by Metal Hydrides

The carbonyl group is highly polar. The carbonyl carbon atom has a partial positive charge that reacts with nucleophiles. 

Although hydride anion is an excellent nucleophile, it is also an extremely strong base, which reacts with far too many other functional groups to be a useful reagent for the reduction of carbonyl compounds. However, the basicity of the hydride ion is greatly diminished in sodium borohydride (NaBH ) and hthium aluminum hydride (LiAIH ). Borohydride and aluminum hydride are excellent sources of hydride anions for the reduction of carbonyl compounds. 

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For a review of reductions by metal hydride-Lewis acid combinations, see Rerick, M.N. in Augustine Reduction, Marcel Dekker NY, 1968, p. 1. 

Crown ethers have also been found to lower the rate of reduction by metal hydrides. Wiegers and Smith (1978) reported that the rate of reduction of camphor by LiAlH4 in tetrahydrofuran was depressed by a factor of 6 on addition of one equivalent of crown ether [201]. They also concluded that, although the free cation shows a catalytic effect in metal hydride reduction, it is not indispensable. Dibenzo-18-crown-6 [11] was also found to lower the rate of... 

Reduction of dienes and polyenes 3. Reduction by metal hydrides and dissolving metals... 

Twccdie Barron J. Org. Chem. 1960,25, 2023. See also Hutchins Learn J. Org. Chem. 1982, 47, 4380. ""For a review of reductions by metal hydride-Lcwis acid combinations, see Rerick, in Augustine Reduction-, Marcel Dekker New York, 1968, pp. 1-94. 

The reduction of unsaturated-ketohexosyl purines has been thoroughly studied.52 53 In particular, in the case of the unsaturated 2 -keto-nucleosides 61a, 61b, and 63, a mechanism of the reduction by metal hydride was established53 by study of the n.m.r. spectra of the different deoxynucleosides obtained by the action of sodium borohydride in deu-terated solvents and of sodium borodeuteride in nondeuterated solvents. The reduction of both 7-(3-0-acetyl-4,6-dideoxy-L-g(i/cm>-hex-3-eno-pyranosyl-2-ulose)theophylline (61a) and its 6-chloropurine relative 61b in methanol led, respectively, to 7-(2-0-acetyl-4,6-dideoxy-/ -L-xi/fo-hexopyranosyl)theophylline (90a) and (2-0-acetyl-4,6-dideoxy-/ -L-xi/fo-hexopyranosyl)-6-chloropurine (90b) having OH-2 equatorial,... 

Reduction by metal hydrides (LiAlH4, NaBH4) of these benzofuran-ones gives 3-hydroxy-2,3-dihydrobenzofurans which are dehydrated by distillation or by treatment with an acid or with P205 or treating the 3-acetoxy derivative with trifluoroacetic acid.39 The intermediates are more or less stable depending on their structures or their degree of purity 3-hydroxy-2,3-dihydrobenzofuran, described by Stoermer as... 

The nicotinamide ring of nicotinamide adenine dinucleotide can exist in both oxidized (NAD+) and reduced (NADH) forms, where the reduced form can be viewed as a double vinylogous amine, i.e. a double enamine. The hydrogen transfer from the C4 atom is widely believed to proceed by a hydride transfer mechanism, reminiscent of the mechanism of carbonyl reduction by metal hydrides. 

Let us look a little more closely at reduction by metal hydrides. Alcohols are formed from carbonyl compounds, smoothly and in high yield, by the action of such compounds as lithium aluminum hydride, LiAlH4. Here again, we see... 

There are three main processes for direct replacement of carbonyl-oxygen by hydrogen Clemmensen reduction, catalytic hydrogenation, and reduction by metal hydrides. 

Reduction of nitriles is an important method of preparing amines. It is, however, not always easy to carry out in spite of the unsaturated character of the nitrile group three methods are available (i) catalytic reduction, (ii) reduction by metal hydrides, and (iii) reduction by sodium in an alcohol. 

Stereoselective reduction of terpene ketones via hydrosilylation [36] exhibited significant difference in stereochemistry from other reduction by metal hydrides. Results of the reduction of camphor and menthone via hydrosilylation are listed in Table 6. Included also in the Table are reported selectivities obtained by using conventional reducing agents. It is seen in the Table that the bulkiness of silanes exerts remarkable influence on the stereochemical course of the reduction, i.e., a bulky hydrosilane favors the production of the more stable alcohols. This trend is quite... 

The mechanism of this reaction is complex and may vary with the number of alkyl groups on the amide nitrogen. However, the first step is certainly the same as in the other reductions by metal hydrides the hydride adds to the carbonyl to give an alkoxide that is coordinated to a metal (Fig. 18.43). Now, the metal oxide is lost with formation of an iminium ion. There are several possible ways to describe the formation of the iminium ion, but once it is produced, reduction by the metal hydride to give the amine is sure to be rapid. 

The hydrolysis is applied for preparation of aldehydes [55] and ketones [56]. The reductive decomposition is carried out in the presence of Zn/AcOH, SO3 2, HSO3-, LiAlH, SnCl, ArP PhjP, SO, (CHjj S, HJ catalyst. The reduction by metal hydrides leads to alcohol formation in the decomposition products mixture while the use of other reductors yields carbonyl compounds. Actually there are no clear requirements for selection of the most appropriate redactor, but it turned out that dimethylsulf-oxide is probably [57] the most preferable redactor in methanol solution. The ozonolysis in the presence of tetracyanoethylene yields directly carbonyl moieties omitting the reduction step [58]. A novel modification of... 

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