Ketones, Wolff-Kishner reduction

Both the Wolff-Kishner and Clemmensen reductions of a, -unsaturated ketones give olefins. There has been considerable confusion concerning the exact product composition in the case of A -3-ketones. Wolff-Kishner reduction gives A" -, 5a-A - and 5 -A -olefins, and, depending on the substrate reaction conditions and work-up, any one or more of these may be isolated. (See ref. 287 for a recent review of the Wolff-Kishner reduction.)... 

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 ... 

Both the Clemmensen and the Wolff-Kishner reductions are designed to carry out a specific functional group transformation the reduction of an aldehyde or ketone carbonyl to a methylene group Neither one will reduce the carbonyl group of a carboxylic acid nor... 

Table 17 2 summarizes the reactions of aldehydes and ketones that you ve seen m ear her chapters All are valuable tools to the synthetic chemist Carbonyl groups provide access to hydrocarbons by Clemmensen or Wolff-Kishner reduction (Section 12 8) to alcohols by reduction (Section 15 2) or by reaction with Grignard or organolithmm reagents (Sections 14 6 and 14 7)... 

Wolff-Kishner reduction (Section 12 8) Method for reducing the carbonyl group of aldehydes and ketones to a methylene... 

Carbonyl deductions. The classical Wolff-Kishner reduction of ketones (qv) and aldehydes (qv) involves the intermediate formation of a hydrazone, which is then decomposed at high temperatures under basic conditions to give the methylene group, although sometimes alcohols may form (40). 

A third type of reduction of a-substituted ketones is typified by the expulsion of the substituent and the reduction of the keto function to form an olefin. Wolff-Kishner reductions of a-hydroxy, a-acetoxy, " a-halo, °° and a-epoxy (see below) ketones are the most frequently encountered steroid examples of this general class. ... 

The latter compound can be isolated from the reaction mixture by chromatography on acid-washed alumina. Similar treatment of the trans-ketone (117a) followed by isolation and chromatography on alumina gives the same equilibrium mixture. The structure of the thermodynamically more stable ketone (116a) was proved by its conversion by Wolff-Kishner reduction to the hydrocarbon (118) independently synthesized from the known... 

B-norketone (119) by enlarging ring A with diazomethane to give A-homo-B-norketone (120). Wolff-Kishner reduction of (120) gave hydrocarbon (118) identical to the product from ketone (116a). 

Another important synthetic method for the reduction of ketones and aldehydes to the corresponding methylene compounds is the Woljf-Kishner reduction. This reaction is carried out under basic conditions, and therefore can be applied for the reduction of acid-sensitive substrates it can thus be regarded as a complementary method. The experimental procedure for the Clemmensen reduction is simpler however for starting materials of high molecular weight the Wolff-Kishner reduction is more successful. 

An aldehyde or ketone 1 can react with hydrazine to give a hydrazone 2. The latter can be converted to a hydrocarbon—the methylene derivative 3—by loss of Na upon heating in the presence of base. This deoxygenation method is called the Wolff-Kishner reduction. ... 

The classical procedure for the Wolff-Kishner reduction—i.e. the decomposition of the hydrazone in an autoclave at 200 °C—has been replaced almost completely by the modified procedure after Huang-Minlon The isolation of the intermediate is not necessary with this variant instead the aldehyde or ketone is heated with excess hydrazine hydrate in diethyleneglycol as solvent and in the presence of alkali hydroxide for several hours under reflux. A further improvement of the reaction conditions is the use of potassium tcrt-butoxide as base and dimethyl sulfoxide (DMSO) as solvent the reaction can then proceed already at room temperature. ... 

Note that the Wolff-Kishner reduction accomplishes the same overall trans-fonnation as the catalytic hydrogenation of an acylbenzene to yield an alkyl-benzene (Section 16.10). The Wolff-Kishner reduction is more general and more useful than catalytic hydrogenation, however, because it works well with both alkyl and atyl ketones. 

Figure 19.11 MECHANISM Mechanism of the Wolff-Kishner reduction of an aldehyde or ketone to yield an alkane.

Reduction of aldehydes or ketones (Wolff-Kishner Clemmensen)... 

Wolff-Kishner reduction of ketones bearing other functional groups sometimes gives products other than the expected methylene reduction product. Several examples are given below. Indicate a mechanism for each reaction. 

The deoxygenation of aldehydes and ketones to the corresponding hydrocarbons via the hydrazones is known as the Wolff-Kishner reduction.28 Various modifications of the original protocols have been suggested. One of the most useful is the Huang-Minlon modification, which substituted hydrazine hydrate as a safer and less expensive replacement of anhydrous hydrazine. In addition, diethylene glycol together with sodium hydroxide was used to increase the reaction... 

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

Wolff-Kishner reduction of ketones that bear other functional groups sometimes give products other than the corresponding methylene compound. Some examples are... 

An important reduction reaction is Wolff-Kishner reduction of carbonyl group on aldehydes and ketones to form hydrazone ... 

Ganter has developed three different approaches to tricyclo[5.2.1.0 ]decane (403), yet another of the nineteen isomeric hydrocarbons of adamantaneland As seen in Scheme XXXIII, the routes involve intramolecular cyclization of keto tosylate 399 followed by Wolff-Kishner reduction of the resulting ketone, thermo-cyclization of 400 and subsequent dechlorination, hydrogenation, and photocycli-zation of aldehydes 401. Majerski s approach involved hypoiodite cleavage of alcohol 402... 

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