Aryl ketones, reductive coupling

Catalytic processes based on the use of electrogenerated nickel(O) bipyridine complexes have been a prominent theme in the laboratories of Nedelec, Perichon, and Troupel some of the more recent work has involved the following (1) cross-coupling of aryl halides with ethyl chloroacetate [143], with activated olefins [144], and with activated alkyl halides [145], (2) coupling of organic halides with carbon monoxide to form ketones [146], (3) coupling of a-chloroketones with aryl halides to give O -arylated ketones [147], and (4) formation of ketones via reduction of a mixture of a benzyl or alkyl halide with a metal carbonyl [148]. 

The synthesis of the right-hand fragment of ziprasidone started with a Wolff-Kishner reduction of isatin 43 to give the oxmdole 44 (Scheme 14). Friedel-Crafts acylation with chloroacetyl chloride afforded aryl ketone 45, which was reduced with triethylsilane in trifluoroacetic acid to the phenethyl chloride 46. The two fragments were joined by alkylation of 40 with 46 in the presence of Nal and Na2CO3 to give ziprasidone (4) in low yield. The yield of the coupling step was improved dramatically when the reaction was conducted in water (Scheme 15). 

Reductive coupling benzyl ketones.1 Benzyl bromides and acyl chlorides undergo reductive coupling when treated with zinc (2 equiv.) and catalytic amounts of Pd[P(Cr,H5)3]4 or Cl2Pd[P(C6H5)3]2 to form benzyl ketones. The highest yields are obtained with aryl acyl chlorides. ArCHzZnBr is considered to be an intermediate. 

Sml2 can effectively promote the intermolecular reductive dimerisation of aldehydes or ketones giving rise to symmetrical diols.7 9 Generally, arylalde-hydes and aryl ketones couple within seconds in THF at room temperature. Aliphatic aldehydes and ketones react considerably more slowly several hours are required for the aldehydes, whereas for ketones reaction times of 24 h are usually needed. Nevertheless, these slower couplings can be greatly accelerated by the addition of additives such as HMPA.10... 

Aryl pinacols are readily obtained from the photolysis of substituted benzophenones in isopropyl alcohol. Photochemical coupling of benzophenones in isopropyl alcohol has even been reported to occur in direct sunlight.7 It is known however, that some aryl ketones do not give the pinacol from photolysis in isopropyl alcohol.8 Nevertheless, aryl pinacols have also been prepared from electrochemical reduction,9 hydroxylation of olefins,10 photoreduction of ketones by amines,11 metal reduction,12 and by other routes.13 The phenanthrene ring system has often been... 

As with the aryl compounds the reaction scheme is simplified for the sake of clarity. The reactions observed are various and include reductive coupling (ketones, nitriles), insertion (diphenylacetylene, isocyanate, isonitrile, CO2 and CO), and disproportionation (diphenylacetylene, CS2). The course of the reactions and the complexity of the product mixtures strongly depend on the nature of the alkyl groups and the substituents on the substrate molecule. As examples we will discuss reactions with ketones, acetylenes and CO. The reaction with ketones strongly resembles the coupling of nitriles R C=N on Cp2TiR (R = aryl). The coupling proceeds more slowly when R, R and R" increase in size. 

To date, no report has appeared using manganese metal. We wish to report a mild method for reductive coupling reactions of aryl aldehydes, aryl ketones, andaldimines [100]. 

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