Clemmensen-type reduction

Because of the many examples of such activation of metal powders by TCS 14 only a limited and arbitrary number will be discussed here. The Clemmensen-type reduction of ketones such as cyclohexanone with Zn powder in the presence of TCS 14 affords, via 2082, 2084, and 2085, cyclohexene and, via 2082, O-silylated pinacol 2083 [19, 20]. Ketones such as 5a-cholestan-3-one 2086 are reduced by Zn dust-TCS 14 in TFIF, in ca 65-70% yield, to give 5a-cholest-2-ene 2087 and ca 5% 5a-cholest-3-ene [21] (Scheme 13.8). 

Clemmensen-type reduction.1 Aromatic ketones can be reduced to the corresponding methylene compounds with ammonium formate on transfer hydrogenation in acetic acid catalyzed by 10% Pd/C. The reduction is usually complete in 10-30 minutes at 110°. Halo and nitro substituents can be reduced under these conditions, and a,p-unsaturated carbonyl groups are reduced to saturated carbonyl groups. 

It was also suggested that the relationship of the two forms (A) and (B) might be that of stereoisomerides of the cis-trans decalin type and a good deal of work was done to provide experimental evidence for this view or the alternative that they are structural isomerides. It was also found that of the methods used to synthesise the pyridocoline system all but one gave norlupinane (A) on reduetion, the exceptional formation of uorlupinane (B) being limited to reduction of the 1-keto compound by the Clemmensen method. 

Mossy zinc is activated by conversion to zinc amalgam by brief immersion in a dilute aqueous solution of mercuric chloride and decantation of the solution before the reaction proper (40 g of mossy zinc, 4g of mercuric chloride, 4 ml of concentrated hydrochloric acid and 40 ml of water [759]). This type of activation is especially used in the Clemmensen reduction which converts carbonyl groups to methylene groups [160 Procedure 31, p. 213). 

Clemmensen reduction can be effected either using amalgamated zinc or cadmium and hydrochloric acid, or in the equivalent electrochemical reaction at cathodes of cadmium or lead in 30 % sulphuric acid (see p. 344). Where the amino function is associated with a ring system, Clemmensen reduction of a-aminoketones gives rise to three types of product ... 

Both methods are fairly specific for aldehydes and ketones and can be carried out with many other functional groups present. However, certain types of aldehydes and ketones do not give normal reduction products. Under Clemmensen conditions,508 a-hydroxy ketones give either ketones (hydrogenolysis of the OH, 0-78) or olefins, and 1,3-diones usually... 

The Clemmensen reduction of saturated steroid ketones (zinc amalgam and hydrochloric acid) has not been examined in detail, although it was frequently used in early steroid chemistry to reduce a C==0 group to CH2 [37J. The mechanism inferred from studies on other ketones involves ratedetermining addition of zinc to the carbonyl group, and subsequent transformations of the type indicated (Fig. 28) [38]. 

This type of compound is called a hydrazone, and is the first intermediate in a very important reaction called the Wolff-Kishner reduction. This reaction, along with the Clemmensen reduction (which we will discuss in more detail in the chapter on redox reactions), is one of the principal methods for reducing a carbonyl compound to the corresponding alkane, i.e. R2C=0 to R2CH2. In... 

Similarly, nitro groups are not so easily reduced as with lithium aluminium hydride itself, and 4-nitrobenzaldehyde can be converted into 4-nitrobenzyl alcohol in 75% yield. Aldehydes and ketones are reduced to alcohols and there is no advantage in the use of mixed hydrides in these cases (although the stereoselectivity may vary if reduction leads to diastereomeric alcohols). With diaryl ketones and with aryl alkyl ketones, however, the carbonyl group is reduced to the methylene group, and this procedure offers a useful alternative to the Clemmensen or other methods for reduction of this type of ketone. 

This method involves formation of the thioacetal followed by desulfurization with Raney nickel. It is the third method we have encountered for achieving this type of transformation. The other two methods are the Clemmensen reduction (Section 19.6) and the WoUF-Kishner reduction (Section 20.6). 

The Clemmensen reduction of 1,4-diketones has been investigated by two groups. Alcohols with unchanged carbon skeletons are obtained when conformational mobility allows the two carbonyl groups to approach each other for example, hexane-2,5-dione gives a mixture of hexan-2-ol and cis- and /ra/z5-hex-4-en-2-ol the participation of the carbonyl oxygen in the solvolysis of intermediates such as (165) is proposed (Scheme 92). Pinacol-type prod-... 

Examples of the Wolff-Kishner reduction are given in Figure 14.46. In the first example, notice that the ester group is not reduced—esters don t form hydrazones. In the second example, the acetal group survives the conditions of the Wolff Kishner a Clemmensen reduction would not have succeeded here because of the sensitivity of the acetal to acid conditions. Neither the Clemmensen nor the Wolff-Kishner reductions are generally successful for enones. One final method that may be employed involves the formation of a dithioacetal, followed by treatment with hydrogen/Raney nickel (Figure 14.47). We will explore the affinity for this specially prepared type of nickel for sulfur in Chapter 23. 

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