Reductions of Carbonyl Compounds to Hydrocarbons

There are several methods of transforming C=Q to CH . In some cases, 

This route requires a hydrogen a to the carbonyl function and may give rearrangement in the dehydration step (Sections 8-9B and 15-5E). Alternatively, the hydroxyl can be converted to a better leaving group (halogen or sulfonate ester), which then may be displaced by H e (as LiAlH4 see Table 16-6)  

More direct methods may be used, depending on the character of the R groups of the carbonyl compound. If the R groups are stable to a variety of reagents there is no problem, but with sensitive R groups not all methods are equally applicable. When the R groups are stable to acid but unstable to base, the Clemmensen reduction with amalgamated zinc and hydrochloric acid is often very useful. 

The mechanism of the Clemmensen reduction is not well understood. It is clear that in most cases the alcohol is not an intermediate, because the Clemmensen conditions do not suffice to reduce most alcohols to hydrocarbons. 

16 Carbonyl Compounds I. Aldehydes and Ketones. Addition Reactions of the Carbonyl Group 

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The reduction of carbonyl compounds to hydrocarbons may be achieved under acidic conditions e.g. the Clemmensen reduction with zinc and concentrated hydrochloric acid), basic conditions (e.g. the Wolff-Kishner reduction of a hydrazone with alkali) or neutral conditions (e.g. the catalytic reduction of thioketals with Raney nickel). The carbonyl group may represent the residue from an earlier step in the synthesis of a compound. 

Two techniques, electrochemical reduction (section IIl-C) and Clem-mensen reduction (section ITI-D), have previously been recommended for the direct reduction of isolated ketones to hydrocarbons. Since the applicability of these methods is limited to compounds which can withstand strongly acidic reaction conditions or to cases where isotope scrambling is not a problem, it is desirable to provide milder alternative procedures. Two of the methods discussed in this section, desulfurization of mercaptal derivatives with deuterated Raney nickel (section IV-A) and metal deuteride reduction of tosylhydrazone derivatives (section IV-B), permit the replacement of a carbonyl oxygen by deuterium under neutral or alkaline conditions. 

Early work by Papa et al. indicated that reduction of carbonyl compounds with Raney nickel in alkaline solution gave the corresponding hydrocarbon or alcohol products, and formation of the hydrocarbon was only feasible in the case of aromatic carbonyl compounds at 80-90 C. Mitchell et al. reported an improved method under neutral conditions using W-7 Raney nickel in 50% aqueous ethanol, aryl aldehydes, alkyl aryl and diaryl ketones can be reduced to the methylene products in high yields. Aromatic substituents such as nitro, cyano and halogen also suffer reduction under these conditions. 

In situ reduction of tosylhydrazones by NaBHjCN provides an efficient method for the deoxygenation of carbonyl compounds to furnish the corresponding hydrocarbons (see also Section 3.4). In the case of tosylhydrazones derived from a,P-unsaturated carbonyl compounds, the reduction leads to a stereoselective migration of the double bond to give the corresponding tran -alkene. 

Similar to the Wolff-Kishner Reduction and Clemmensen Reduction, this reaction is also useful for the conversion of carbonyl compounds into hydrocarbons and olefins. 

Purely aromatic ketones generally do not give satisfactory results pinacols and resinous products often predominate. The reduction of ketonic compounds of high molecular weight and very slight solubility is facilitated by the addition of a solvent, such as ethanol, acetic acid or dioxan, which is miscible with aqueous hydrochloric acid. With some carbonyl compounds, notably keto acids, poor yields are obtained even in the presence of ethanol, etc., and the difficulty has been ascribed to the formation of insoluble polymolecular reduction products, which coat the surface of the zinc. The adffition of a hydrocarbon solvent, such as toluene, is beneficial because it keeps most of the material out of contact with the zinc and the reduction occurs in the aqueous layer at such high dilution that polymolecular reactions are largdy inhibited (see Section IV,143). 

Benzene hydrocarbons are known to undergo radical coupling reactions and the intramolecular reductive coupling of carbonyl compounds with a benzene ring has been achieved. Best conditions for this process are at a tin cathode with isopropanol solvent and tetaethylammonium tosylate as supporting electrolyte [102, 103], The reaction is performed at constant current in a divided cell. A single stereoiso-... 

Chapter 4 centers on two key transformations in organic synthesis (1) oxidation of alcohols and of unsaturated hydrocarbons (i.e., alkenes and alkynes) to carbonyl compounds (2) reduction of various carbonyl compounds to alcohols. 

Electrolysis of carbonyl compounds provides pinacols, alcohols or hydrocarbons, depending on the conditions, such as pH, the nature of the electrode, and its potential. Fundamental studies have been carried out on the mechanisms of hydrocarbon formation using acetone as a substrate. Although several electrodes, such as Cd, Pt, Pb or Zn, are recommended, carbonyl compounds, including aryl and alkyl derivatives, require strong aqueous acidic media for reduction to the hydrocarbons. The mechanism of the electrolytic reduction is probably similar to that of Clemmensen reduction, which starts from anion radical formation by one-electron transfer, as indicated in Scheme 3. The difference is that electrolytic reduction takes place in an electric double layer, rather than on the surface of the zinc metal. 

Although the reduction of carbonyls to alcohols or hydrocarbons is well documented, no general method was available for the reductive coupling of carbonyl compounds directly to alkenes prior to the use of low-valent transition metals. The reductive coupling of carbonyl compounds by low-valent transition metals is now an important method for C=C bond formation, and has been widely reviewed." ... 

These reagents are strong Lewis acids that cleave THF and acetals (Section 2.4). Nevertheless, they leave bromo- and chloroderivatives intact (Section 2.1). The regioselectivity of the opening of epoxides is opposite to that observed for LAH in THF (Section 2.3). Diarylcarbinols can be reduced to hydrocarbons (Section 2.4), and a,p-unsaturated carbonyl compounds to allylic alcohols (Section 3.2.9). The reduction of amides to amines is easier than with LAH (Section 3.2.8), especially in the case of a,p-ethylenic amides or of -lactams. These reagents do not reduce NO2 groups. 

Deoxygenation of carbonyl compounds. Hydrous Sn02 is prepared from SnCU by precipitation with aqueous ammonia then drying and calcination at 300°C for 5 h. The reduction of aliphatic carboxylic acids gives the corresponding alcohols, whereas aromatic acids are further reduced to the hydrocarbons. Aromatic ketones also give hydrocarbons. 

A method for the conversion of carbonyl compounds into the corresponding hydrocarbons involves reduction of the derived toluene-p-sulfonyl (tosyl) hydra-zones with sodium cyanoborohydride in acidic dimethylformamide (DMF). The reaction is specific for aliphatic carhonyl compounds aromatic compounds are normally unaffected. The tosyl hydrazone need not be isolated but can be prepared and reduced in situ. For example, the ketone 97 was reduced to the alkane 98 (7.89). 

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