Hydrogenolysis aryl ketones

Die Reduktion polycyclischer Aryl-ketone gelingt bereits mit Lithiumalanat6, Na-trium-bis-[2-methoxy-athoxy]-dihydrido-aluminat7 und bei schwieriger hydrogenolysier-... 

Aryl acetonitriles.2 The aryl cyanophosphates obtained by reaction of aryl ketones or aldehydes (80-100% yield) are converted into aryl acetonitriles by hydrogenolysis using Pd/C. This method was used to convert the ketone 1 to ibuprofen (2) in 81% overall yield. 

As mentioned in Chapter 18, aryl ketones are hydrogenolyzed to the methylene over palladium catalysts under mild conditions. The addition of a little acid to the hydrogenation mixture facilitates the reaction. Since this reaction takes place under mild conditions few, if any, side reactions take place making this palladium catalyzed hydrogenolysis the preferred method for the removal of aryl carbonyl groups... 

Aryl ketones may be reduced to hydrocarbons by the Clemmensen reduction using zinc amalgam and HCI or by catalytic hydrogenolysis in the presence of palladium metal. Dissolving metal reduction of aromatic rings using an alkali metal in liquid ammonia gives 1,4-hexadienes. 

Reduction of aldehydes or ketones to hydrocarbons can be accomplished using the Clemmensen reaction (Zn/Hg/HCI), the Wolff-Kishner reaction (hydrazine, KOH), Raney nickel/Hj reduction of a dithioacetal, or palladium-catalyzed hydrogenolysis (aryl ketones only). 

In the reaction of Q,/3-unsaturated ketones and esters, sometimes simple Michael-type addition (insertion and hydrogenolysis, or hydroarylation, and hydroalkenylation) of alkenes is observed[53,54]. For example, a simple addition product 56 to methyl vinyl ketone was obtained by the reaction of the heteroaromatic iodide 55[S5]. The corresponding bromide affords the usual insertion-elimination product. Saturated ketones are obtained cleanly by hydroarylation of o,/3l-unsaturated ketones with aryl halides in the presence of sodium formate, which hydrogenolyses the R—Pd—I intermediate to R— Pd—H[56]. Intramolecular hydroarylation is a useful reaction. The diiodide 57 reacts smoothly with sodium formate to give a model compound for the afla-toxin 58. (see Section 1.1.6)[57]. Use of triethylammonium formate and BU4NCI gives better results. 

Aldehydes and ketones are similar in their response to hydrogenation catalysis, and an ordering of catalyst activities usually applies to both functions. But the difference between aliphatic and aromatic carbonyls is marked, and preferred catalysts differ. In hydrogenation of aliphatic carbonyls, hydrogenolysis seldom occurs, unless special structural features are present, but with aryl carbonyls either reduction to the alcohol or loss of the hydroxy group can be achieved at will. 

Cyclopropanes can be cleaved by catalytic hydrogenolysis. Among the catalysts used have been Ni, Pd, and Pt. The reaction can often be run under mild condi-tions." ° Certain cyclopropane rings, especially cyclopropyl ketones and aryl-substituted cyclopropanes," can be reductively cleaved by an alkali metal (generally Na or Li) in liquid anunonia." Similar reduction has been accomplished photo-chemically in the presence of LiC104." ... 

The hydrogenation of aryl aldehydes and ketones is complicated by the potential for the hydrogenolysis of the resulting benzyl alcohol as well as benzene ring hydrogenation (Eqn. 18.3). With the proper selection of reaction conditions... 

While the hydrogenation of unactivated aliphatic aldehydes and ketones does not generally take place over palladium, this catalyst readily promotes the hydrogenolysis of aryl aldehydes and ketones to the methylene at room temperature and 1-4 atmospheres pressure. The use of an acidic solvent facilitates this reaction2 -29 but is not essential for obtaining good to excellent yields of the desoxy product (Eqn. 18.8). 0 With a basic substrate such as a 2- or 4-acyl-pyridine, however, the alcohol product was obtained (Eqn. 18.9).31... 

Since aliphatic aldehydes and ketones are not hydrogenated over palladium, this reaction provides a means of selectively removing an aromatic carbonyl group in the presence of an aliphatic aldehyde or ketone (Eqn. 18.10).32 The palladium catalyzed hydrogenolysis of aryl aldehydes and ketones is preferable to any of the chemical reduction procedures such as the Wolff-Kishner or Clemmenson reactions for the removal of an aryl carbonyl group. 

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