Ketones synthesis from halides

TABLE 1. Unsymmetrical Ketone Synthesis from Aryl Iodide and Alkyl Halide... 

The catalytic performance of 1 was examined for hydroformylation of alkyne (as a catalyst additive) and methoxycarbonylation of alkyl halide, and 1 is also used as a stoichiometric reagent for an Ni-catalyzed ketone synthesis from alkyl halide. " Heterogeneous catalysts derived from 1 are used for hydrogenation of GO and coal tar pitch, crude oil upgrading, and coal liquefaction (preparation of the pyrrhotite catalyst). An Fe-Ru-Se catalyst dispersed on a glassy carbon-supported Nafion film prepared from 1 is reported to be effective for electro-catalytic oxygen reduction. ... 

No overaddition of the organometallic reagent, a side reaction that is typical for ketone synthesis from acid halides, was observed. 

The a-alkylation of enolates derived from ketones with alkyl halides is a very important and frequently used method for forming new carbon-carbon bonds in organic synthesis [40]. Yet, if the a-alkylation of enolates derived from ketones with alkyl halides can be replaced by the direct reaction of ketones with alcohols, this method would provide a very useful waste-free, green route to a-alkylation, producing no side products other than water. 

Ring synthesis from non-heterocycles by closure y to the heteroatom are reported. Sulfonium ylides (135) with active methylene compounds such as malononitrile give a C-phenacyl product (136) however, when reacted with /3-diketones and /3-ketonic esters they produce furans quantitatively (74CL101). In these cases O-phenacylation takes place followed by cyclization to give the 3-hydroxydihydrofuran (137), which is dehydrated to the furan (138) (Scheme 30). These furans differ from those formed by the reaction of the diketone or ketonic esters with phenacyl halides. The latter reaction takes place by C-phenacylation, yielding the isomeric furans (139). 

For the ketone synthesis via the present protocol, acid chlorides are useful precursors, in deed. Nevertheless, carbonylative cross coupling with organic halides is strategically the most simple and direct way to this purpose. The palladium-catalyzed carbonylative cross-coupling reaction with various organic halides has been extensively investigated, because of its merits from synthetic as well as phenomenal point of view. Acid chlorides are not always readily available, and their preparation is not always compatible with many sensitive functionalities. Therefore the development of this type of reaction widens the scope of the ketone synthesis in the present protocol because of the ready availability and storability of organic halides and pseudohalides. 

Until recently, a-substitution of carbonyl compounds was largely restricted to those cases where alkyl groups, such as Me, allyl, and benzyl, were introduced via classical enolate alkylation. a-Aiylation of ketones with aryl halides can be effected using K in NH3 [120-123]. However, this reaction does not appear to be satisfactory for selective -alkenylation and a-alkynylation. -Arylation of ketones has also been catalyzed by Ni [124] and Pd [125,126]. The Pd-catalyzed version employed enolstannanes. This reaction has also been applied to a-alkenylation [127]. However, these reactions appear to be of very limited scope. Thus, the Pd-catalyzed procedures appear to be satisfactory mainly for a-substitution of methyl ketones. Furthermore, none of them addresses the critical question of how to control the regiochemistry of c-substitution, i.e., a vs. a. Critically needed from the viewpoint of selective synthesis were... 

By far the most important method of preparing alcohols is the Grignard synthesis. This is an example of the second approach, since it leads to the formation of carbon-carbon bonds. In the laboratory a chemist is chiefly concerned with preparing the more complicated alcohols that he cannot buy these are prepared by the Grignard synthesis from rather simple starting materials. The alkyl halides from which the Grignard reagents are made, as well as the aldehydes and ketones themselves, are most conveniently prepared from alcohols thus the method ultimately involves the synthesis of alcohols from less complicated alcohols. 

The alkylation of protected cyanohydrin anions constitutes an excellent method for ketone synthesis. Generally the anions are generated from aliphatic or aromatic aldehyde protected cyanohyd with LDA under nitrogen at -78 C. The addition of an alkyl halide produces the protected ketone cyanohydrin. The carbonyl group is then liberated by successive treatment with dilute acid and dilute aqueous base. This method is applicable for the synthesis of buflomedil. ... 

Lithium derivatives of these sulfones can be alkylated with alkyl halides or epoxides,28 and acylated with esters to give the ketones 95 from which the sulfonyl group can be removed with aluminium amalgam Deprotection and cyclisation provides a synthesis of cyclopentenones 98 (cf. chapter 6).26... 

It is important to distinguish this synthesis from the alkylation of a 1,3-dicarbonyl enolate with a 2-halo-ketone, with displacement of halide, producing a 1,4-dicarbonyl unit for subsequent ring closure " presumably the difference lies in the greater reactivity of the carbonyl group (aldehyde in the example) in the Feist-Benary sequence. 

The use of an acyl chloride in the presence of aluminum chloride constitutes the most frequently used type of Friedel-Crafts ketone synthesis. Many examples from the earlier literature are reported in the reviews mentioned at the beginning of this chapter.The reactivity of acyl halides in reactions of acyl halides with aluminum halides decreases in the order I > Br > Cl > F, but a different order was report for reactions catalyzed by boron halides. In the latter case the order was acyl fluoride > acyl bromide > acyl chloride. We shall concentrate our attention on recently reported examples. 

The only difference between the acetoacetic ester synthesis and the malonic ester synthesis is the use of acetoacetic ester rather than malonic ester as the starting material. The difference in starting material causes the product of the acetoacetic ester synthesis to be a methyl ketone rather than a carboxylic acid. The carbonyl group of the methyl ketone and the carbon atoms on either side of it come from acetoacetic ester, and the rest of the ketone comes from the alkyl halide used in the second step of the reaction. 

Ketone Synthesis. The monoalkylated MT-sulfone undergoes further alkylation by action of alkyl halide and NaH or n-BuLi to give a dialkylated product. Since the dialkylated product can be hydrolyzed easily, MT-sulfone has proven to be very useful for synthesizing ketones (eq 5). Symmetrical ketones are prepared by direct dialkylation with NaH and alkyl hahde in DMF and hydrolysis (eq 6). Cyclic ketones are also synthesized from a,a>-dihaloalkanes. An efficient synthesis of a-hydroxy ketones is also achieved by the addition of the monoalkyl derivative to an aldehyde to give an adduct and subsequent hydrolysis (eq 7). ... 

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