Ketone Wolff-Kishner reaction

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.)... 

A useful variant of the imine-forming reaction just discussed involves the treatment of an aldehyde or ketone with hydrazine, H2NNH2, in the presence of KOH. Called the Wolff-Kishner reaction, the process is a useful and genera method for converting an aldehyde or ketone into an alkane, r2c=o —> R2CH2. 

Wolff-Kishner reaction (Section 19.9) The conversion of an aldehyde or ketone into an alkane by reaction with hydrazine and base. 

Hydrogenolysis of an aldehyde or ketone carbonyl to >CH2 is an important organic transformation, and classical procedures such as the Clemmenson and Wolff-Kishner reactions have limitations (24, 25) heterogeneous catalytic systems and several two-step procedures are also known (1, 24, 26). Our observation of this conversion in what is essentially a 2-phase medium... 

Alkanes, RH (Sec. 7.7) (Sec. 10.7) (Sec. 10.8) (Sec. 19.9) from alkenes by catalytic hydrogenation from alkyl halides by protonolysis of Grignard reagents from alkyl halides by coupling with Gilman reagents from ketones and aldehydes by Wolff-Kishner reaction... 

Hydrazine, H2NNH2 Reacts with ketones or aldehydes in the presence of KOH to yield the corresponding alkanes (Wolff-Kishner reaction Section 19.10). 

Direct transition from level 2 to level 0 can be achieved by way of the Wolff-Kishner reaction (treatment of the respective hydrazones with alkali), a classical pathway for the reduction of carbonyl compounds. At the same time, a direct conversion of aldehydes and ketones into alkenes is also feasible via reductive cleavage of their tosylhydrazones under the action of MeLi, the Shapiro reaction (Scheme 2.63). "... 

As is the case with Wolff-Kishner reactions, the application of tosylhydrazone reductions relies on the successful conversion of carbonyls to the requisite hydrazone derivatives (58). This usually presents no problem except with relatively hindered or deactivated ketones and, in fact, several failures of the methodology are traced to unsuccessful tosylhydrazone formation (i.e. for examples with 62, 63, -- diketone (9) in equation 4, and the substrate of entry 3, Table 2). 

Bicycloannelation.2 The a -enolate of an a,/J-cyclohexenone reacts with this phosphonium salt to form a tricyclo[3.2.1.02 7]octane in low to moderate yield. This reaction was used in a short synthesis of the pentacyclic diterpene trachyloban-19-oic acid (4). Reaction of the lithium enolate of 2, prepared from podocarpic acid, with I provided the pentacyclic ketone 3, which was reduced by the Wolff-Kishner reaction to 4. 

For the preparation of hydrazones, Schonberg " recommends that equivalent amounts of the ketone and hydrazine be refluxed in -butanol (b.p. 117.7°) for 2 hrs. Use of ethanol requires a longer reflux period and use of ethylene or propylene glycol may lead to side reactions. Thus on applying the glycol procedure for conversion of fluorenone to the hydrazone, Baltzly et al. observed formation of considerable fluorene (interference by an unusually facile Wolff-Kishner reaction). On refluxing the reactants in n-butanol for 4 hrs., the hydrazone was obtained in 67% yield. However, a superior method for the preparation of hydrazones involves reaction of the ketone with N,N-dimethylhydrazine which see) followed by an exchange reaction with hydrazine. 

Wolff-Kishner reaction. This reduction reaction was discovered independently in Germany (Wolff, 1912) and in Russia (Kishner, 1911). A ketone (or aldehyde) is converted into the hydra-zone, and this derivative is heated in a sealed tube or an autoclave with sodium ethoxide in absolute ethanol. 

The reaction of hydrazine with a,/S-unsaturated aldehydes and ketones (the anomalous Wolff-Kishner reaction, Houben-Weyl, Vol. 4/3, p71) sometimes provides a one-pot procedure in which the cyclopropane is formed directly, but often the intermediate 2,3-dihydro-l//-pyrazole is isolated and heated either alone or with a basic catalyst to effect elimination of nitrogen. Hence in the conversion of chalcone to 1,2-diphenylcyclopropane the intermediate 3,5-diphenyl-2,3-dihydro-l//-pyrazole (10) was isolated and heated with potassium hydroxide. 

The Wolff-Kishner reaction is a classical reduction method of ketones to alkanes. This method involves converting the ketone to its corresponding hydrazine treatment of the resulting hydrazine with base affords the alkane and nitrogen gas. Because elevated temperatures (> 200 °C) and strong base are required, this method is harsh when sensitive functionality is present. However, milder methods have been developed including the Myers modification where the reaction temperatures are much lower (s 100 °C). 

Yamamoto et al. have been trying to synthesize limonene by a biomimetic cyclization of nerol (37) derivatives. The principle is to use the chiral derivative 523 and an alkylaluminum. After much experimentation,the best conditions were with the reagent 524 in CCI3F, when 77% ee of (-I-)-limonene (285) was obtained.It is widely believed still that the Wolff-Kishner reduction of optically active carvone (281) will yield optically active limonene (e.g., see Ref. 16, p. 152), a reaction reported by Friedman and Miller." This was already doubtful (Friedman and Miller gave no experimental evidence), since Jeger et al. had shown in 1950 that the Wolff-Kishner reaction with a,p-unsaturated ketones displaces the double bond, but Akhila and Banthorpe have now shown conclusively that (-)-carvone (281) yields ( )-limonene [( -285] by the Wolff-Kishner reaction. ... 

A method of almost universal applicability for the deoxygenation of carbonyl compounds is the Wolff-Kishner reduction While the earlier reductions were carried out in two steps on the derived hydrazone or semicarbazone derivatives, the Huang-Minlon modification is a single-pot operation. In this procedure, the carbonyl compound and hydrazine (hydrate or anhydrous) are heated (180-220 °C) in the presence of a base and a proton source. Sodium or potassium hydroxide, potassium-t-butoxide and other alkoxides are the frequently used bases and ethylene glycol or its oligomers are used as the solvent and proton source. Over the years, several modifications of this procedure have been used to cater to the specific needs of a given substrate. The Wolff-Kishner reaction works well with both aldehydes and ketones and remains the most routinely used procedure for the preparation of alkanes from carbonyl compounds (Table 9). This method is equally suitable for the synthesis of polycyclic and hindered alkanes. 

The third example in Table 9.4, that is, 3a-c, where G = NH2, describes the addition of hydrazine (H2NNH2) and substituted hydrazines (ArNHNH2) to the carbonyl (C=0) to produce the corresponding hydrazones ( hydrazine derivatives ) of the aldehyde or ketone with which the reaction began. It will be remembered that the hydrazone derived from hydrazine (H2NNH2) itself has already been encountered during the discussion of the reduction of ketones to alkanes (Scheme 9.12) as part of the Wolff-Kishner reaction sequence vide supra). 

The Wharton reaction converts an epoxy ketone to an allylic alcohol by reaction with hydrazine. Propose a mechanism. (Hint Review the Wolff-Kishner reaction in Section 19.9.)... 

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