Reductions of Aldehydes and Ketones

The three most useful oxidation and reduction reactions of carbonyl starting materials can be summarized as follows  

The Su i carSol li aci andtli rcie t iTOs gives a variety of products, depending on the identity of Z and the nature of the reducing agent. The usual products are aldehydes or 1 alcohols. 

The most useful oxidation reaction of carbonyl compounds is the oxidation of aldehydes to carboxylic acids. 

We begin with reduction, because the mechanisms of reduction reactions follow directly from the general mechanisms for nucleophilic addition and substimtion. 

LIAIH4 and NaBH4 serve as a source of H , but there are no free H ions present in reactions with these reagents. 

Treating an aldehyde or a ketone with NaBH4 or LiAlH4, followed by water or some other proton source, affords an alcohol. This is an addition reaction because the elements of H2 are added across the n bond, but it is also a reduction because the product alcohol has fewer C-0 bonds than the starting carbonyl compound. 

Both alkanes and alcohols can be produced by the reduction of aldehydes and ketones. However, reactions that produce alcohols generally do not produce alkanes and vice versa. This means that the alcohols do not lie on the reductive pathway to alkanes. Of course, as noted in Chapter 8, alcohols produced by the reduction of aldehydes or ketones can be subsequently converted to alkanes, but the reductive methods for alkanes from the aldehydes and ketones are different from those for alcohols to alkanes. 

Second, the variety of conditions applied to the reduction of the carbonyl groups of aldehydes and ketones, both in the presence and in the absence of other substituents, is immense. Further, many studies involving the reduction of the carbonyl 

Finally, it is clear that under almost every set of conditions examined for the reduction of aldehydes and ketones, aldehydes are more easily reduced than ketones. 

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Clemmensen reduction of aldehydes and ketones. Upon reducing aldehydes or ketones with amalgamated zinc and concentrated hydrochloric acid, the main products are the hydrocarbons (>C=0 —> >CHj), but variable quantities of the secondary alcohols (in the case of ketones) and unsaturated substances are also formed. Examples are ... 

Wolff - Kishner reduction of aldehydes and ketones. Upon heating the hydrazoiie or semicarbazone of an aldehyde or ketone with potassium hydroxide or with sodium ethoxide solution (sealed tube), the corresponding hydrocarbon is obtained ... 

We will begin with the reduction of aldehydes and ketones... 

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... 

The mechanism of lithium aluminum hydride reduction of aldehydes and ketones IS analogous to that of sodium borohydride except that the reduction and hydrolysis... 

Sodium cyanoborohydride is remarkably chemoselective. Reduction of aldehydes and ketones are, unlike those with NaBH pH-dependent, and practical reduction rates are achieved at pH 3 to 4. At pH 5—7, imines (>C=N—) are reduced more rapidly than carbonyls. This reactivity permits reductive amination of aldehydes and ketones under very mild conditions (42). 

Addition of sodium dithionite to formaldehyde yields the sodium salt of hydroxymethanesulfinic acid [79-25-4] H0CH2S02Na, which retains the useful reducing character of the sodium dithionite although somewhat attenuated in reactivity. The most important organic chemistry of sodium dithionite involves its use in reducing dyes, eg, anthraquinone vat dyes, sulfur dyes, and indigo, to their soluble leuco forms (see Dyes, anthraquinone). Dithionite can reduce various chromophores that are not reduced by sulfite. Dithionite can be used for the reduction of aldehydes and ketones to alcohols (348). Quantitative studies have been made of the reduction potential of dithionite as a function of pH and the concentration of other salts (349,350). 

The aromatic primary and secondary stibines are readily oxidized by air, but they are considerably more stable than their aHphatic counterparts. Diphenylstibine is a powerful reducing agent, reacting with many acids to Hberate hydrogen (79). It has also been used for the selective reduction of aldehydes and ketones to the corresponding alcohols (80). At low temperatures, diphenylstibine undergoes an addition reaction with ketene (81) ... 

Reduction of Aldehydes and Ketones to Hydrocarbons. Deep hydrogenation of aldehydes and ketones removes the oxygen functionahty and produces the parent hydrocarbons. 

Table 8.3. Rates of Reduction of Aldehydes and Ketones by Sodium Borohydride...

Section 15.2 Alcohols can be prepared from car bonyl compounds by reduction of aldehydes and ketones. See Table 15.3. 

Reduction of aldehydes and ketones with aluminum isopropoxide... 

Lithium aluminum hydride, LiAIH4/ is another reducing agent often used for reduction of aldehydes and ketones. A grayish powder that is soluble in ether and tetrabydrofuran, LiAlH4 is much more reactive than NaBH4 but also more dangerous. It reacts violently with water and decomposes explosively when heated above 120 °C. 

Formation of an Alcohol The simplest reaction of a tetrahedral alkoxide intermediate is protonation to yield an alcohol. We ve already seen two examples of this kind of process during reduction of aldehydes and ketones with hydride reagents such as NaBH4 and LiAlH4 (Section 17.4) and during Grignard reactions (Section 17.5). During a reduction, the nucleophile that adds to the carbonyl... 

There are other stereochemical aspects to the reduction of aldehydes and ketones. If there is a chiral center to the carbonyl group, even an achiral reducing agent can give more of one diastereomer than of the other. Such diastereoselective reductions have been carried out with considerable success. In most such cases Cram s rule (p. 147) is followed, but exceptions are known. ... 

As with the reduction of aldehydes and ketones (16-23), the addition of organometallic compounds to these substrates can be carried out enantioselectively and diastereoselectively. Chiral secondary alcohols have been obtained with high ee values by addition to aromatic aldehydes of Grignard and organolithium compounds in the presence of optically active amino alcohols as ligands. ... 

Diols (pinacols) can be synthesized by reduction of aldehydes and ketones with active metals such as sodium, magnesium, or aluminum. Aromatic ketones give better yields than aliphatic ones. The use of a Mg—Mgl2 mixture has been called the Gomberg-Bachmann pinacol synthesis. As with a number of other reactions involving sodium, there is a direct electron transfer here, converting the ketone or aldehyde to a ketyl, which dimerizes. 

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