Aldehydes, reduction with aluminum borohydride

Reduction to alcohols (Section 15.2) Aldehydes 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. 

Dihydroxylation of the stilbene double bond in the trans isomers of Combretastatin A-1 and A-4 produced diols which by treatment with boron trifluoride in ethyl ether [44] or with trifluoroacetic acid [17] resulted in pinacolic rearrangement to produce an aldehyde. The aldehyde was converted in a variety of derivatives, as illustrated in the Scheme 20, via the following reaction sequence reduction with sodium borohydride to primary alcohol which was derivatized to the corresponding mesylate or tosylate, substitution with sodium azide and final reduction to amine with lithium aluminum hydride. Alternatively the aldehyde was converted to oxime which was catalitically hydrogenated to amine [17]. 

Reduction Carbonyl groups in carbohydrates are reduced by the same methods used for aldehydes and ketones reduction with sodium borohydride or lithium aluminum hydride or by catalytic hydrogenation. 

Complex hydrides can be used for the selective reduction of the carbonyl group although some of them, especially lithium aluminum hydride, may reduce the a, -conjugated double bond as well. Crotonaldehyde was converted to crotyl alcohol by reduction with lithium aluminum hydride [55], magnesium aluminum hydride [577], lithium borohydride [750], sodium boro-hydride [751], sodium trimethoxyborohydride [99], diphenylstarmane [114] and 9-borabicyclo[3,3,l]nonane [764]. A dependable way to convert a, -un-saturated aldehydes to unsaturated alcohols is the Meerwein-Ponndorf reduction [765]. 

Usually alcohols accompany aldehydes in reductions with lithium aluminum hydride [1104] or sodium bis 2-methoxyethoxy)aluminum hydride [544], or in hydrogenolytic cleavage of trifluoroacetylated amines [7772]. Thus terr-butyl ester of. -(. -trifluoroacetylprolyl)leucine was cleaved on treatment with sodium borohydride in ethanol to rerr-butyl ester of A7-prolylleucine (92% yield) and trifluoroethanol [7772]. During catalytic hydrogenations over copper chromite, alcohols sometimes accompany amines that are the main products [7775]. 

Thioamides were converted to aldehydes by cautious desulfurization with Raney nickel [1137, 1138] or by treatment with iron and acetic acid [172]. More intensive desulfurization with Raney nickel [1139], electroreduction [172], and reduction with lithium aluminum hydride [1138], with sodium borohydride [1140] or with sodium cyanoborohydride [1140] gave amines in good to excellent yields. 

Ozonides are rarely isolated [75, 76, 77, 78, 79], These substances tend to decompose, sometimes violently, on heating and must, therefore, be handled with utmost safety precautions (safety goggles or face shield, protective shield, and work in the hood). In most instances, ozonides are worked up in the same solutions in which they have been prepared. Depending on the desired final products, ozonide cleavage is done by reductive or oxidative methods. Reductions of ozonides to aldehydes are performed by catalytic hydrogenation over palladium on carbon or other supports [80, 81, 82, S3], platinum oxide [84], or Raney nickel [S5] and often by reduction with zinc in acetic acid [72, 81, 86, 87], Other reducing agents are tri-phenylphosphine [SS], trimethyl phosphite [89], dimethyl sulfide (DMS) [90, 91, 92], and sodium iodide [93], Lithium aluminum hydride [94, 95] and sodium borohydride [95, 96] convert ozonides into alcohols. 

Reduction of the intermediate generated from a carboxylic acid and DMFCl provides aldehydes with Lithium Tri-tert-butoxy-aluminum Hydride, and alcohols with Sodium Borohydride both in high yield and chemoselectivity. 

Ketones and aldehydes are most commonly reduced by sodium borohydride (see Sections 10-11 and 18-12). Sodium borohydride (NaBH4) reduces ketones to secondary alcohols and aldehydes to primary alcohols. Lithium aluminum hydride (LiAlH4) also accomplishes these reductions, but it is a more powerful reducing agent, and it is much more difficult to work with. Sodium borohydride is preferred for simple reductions of ketones and aldehydes. 

Hydride reagents (lithium aluminum hydride, LiAlHt, and sodium borohy-dride, NaBHt) are a source of the nucleophilic hydride species Hr. Reaction of hydride with a suitable carbon electrophile results in a reduction of that carbon (by increasing the number of C-H bonds). Reactions of carbonyl compounds with lithium aluminum hydride (LAH) generally give an alcohol product (after workup), with the exception of amides, which give amine products. Sodium borohydride is less reactive than LAH. It does not react with esters, amides, or carboxylic acids, so it is described as being selective for aldehydes and ketones. Sodium borohydride also fails to reduce nitroalkanes or alkyl halides, so LAH must be used in those reactions. 

Carbonyl compounds are commonly reduced to alcohols by catalytic hydrogenation or with metal hydrides. When applied to aldehydes, reduction, represented by the symbol [H], provides a convenient route to primary alcohols (Eq. 17.15), whereas the reduction of ketones gives secondary alcohols (Eq. 17.16). Although catalytic hydrogenation of carbonyl groups is frequently the method of choice in industrial processes, lithium aluminum hydride, sodium borohydride, and their derivatives are generally used in the research laboratory. Sodium borohydride may be used in alcoholic and even aqueous solutions, because it reacts much more rapidly with the carbonyl group than with the solvent. On the other hand, lithium aluminum hydride reacts rapidly with protic solvents, so it must be used in anhi/-drous ethereal solvents such as diethyl ether or tetrahydrofuran. 

Similarly, reduction of both aromatic and aliphatic aldehydes and ketones where there is a chlorine (Cl) or bromine (Br) present elsewhere in the carbonyl-containing compound succeeds with sodium borohydride (NaBH,) and, occasionally, with lithium aluminum hydride (LiAIH,) at low temperatures. Catalytic reduction frequently leads to hydrogenolysis of the halogen, producing the halogen-free alcohol. 

Another method that has been used to produce hydroxyl-terminated HRs is the ozonolysis of butadiene copolymers followed by reduction of the aldehyde produced with lithium-aluminum hydride or sodium borohydride [295—297]. 

This was exercised with ester 266. The magnesium complex formed in the Grignard reaction was stereoselectively reduced with lithium borohydride while the aldehyde-aluminum complex formed in the low temperature DIBAL reduction is also stereoselectively attacked by the Grignard reagent [102]. 

What class of compounds results from the reduction of ketones with sodium borohydride What class of compounds results from the reduction of aldehydes by lithium aluminum hydride ... 

Sodium borohydride and lithium aluminum hydride react with carbonyl compounds in much the same way that Grignard reagents do except that they function as hydride donors rather than as carbanion sources Figure 15 2 outlines the general mechanism for the sodium borohydride reduction of an aldehyde or ketone (R2C=0) Two points are especially important about this process... 

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