Ketones symmetrical, alkylation

Acylation of ketones with esters requires the presence of a strong base under anhydrous conditions. Ketones where only one unique mesomeric carbanion is formed (e.g. symmetrical ketones or alkyl aryl ketones) yield a single regio-isomer. The reaction is illustrated by the formation of benzoylacetone from acetophenone and ethyl acetate (Expt 5.103), and may be outlined mechanistically as follows ... 

The electrophile E+ can be an alkyl halide or sulfate, an aldehyde to give aldol products, or an a,P-unsatunited ester when conjugate addition is preferred. Examples from simple alkylation show that the alkyl halide can be primary alkyl, allylic 33, and even an a-bromoester or y-bromo-a,P-unsaturated ester 31. The original carbonyl compound that forms the chiral imine with SAMP or RAMP can be an aldehyde 27 or 29, a ketone (symmetrical 32 or blocked on one side 35), or an enone. Only the reagents and products are shown with oxidative [O] or hydrolytic [H20] workup. Notice that SAMP is used for the formation of either enantiomer of 28 by using different starting materials but that RAMP is used to enter the other enantiomeric series from 32. 

Symmetrical ketones can be prepared in good yields by the reaction of organo-mercuric halides with dicobalt octacarbonyl in THF, or with nickel carbonyl in DMF or certain other solvents. The R group may be aryl or alkyl. However, when R is alkyl, rearrangements may intervene in the C02(CO)g reaction, though the Ni(CO)4 reaction seems to be free from such rearrangements. Divinylic ketones... 

In addition to the Beckmann reaction, the Schmidt rearrangement is used to generate M-alkylated lactams, too. Alkyl azides 231 react with the cyclic ketones (and aldehydes) in the presence of proton or Lewis acids. On running the inter-molecular reactions, in most cases symmetric ketals 230 have been converted... 

When alkyl oxalyl chlorides were employed instead of acyl halides, symmetrical dibenzyl ketones were formed in good yields(44). Transition metal carbonyls or metal salts/carbon monoxide have generally been used for... 

Alternatively, CO2 can be used as source of CO. Indeed, it is well known that low-valent transition metal complexes can catalyze the chemical or electrochemical reduction of CO2 into CO. This approach was used to generate the mixed nickel complex Ni°bpy(CO)2 by the electrochemical reduction of Nibpy in NMP or DMF in the presence of CO2. The reduced complex can react with alkyl, benzyl, and allylhalides to give the symmetrical ketone along with the regeneration of Nibpy ". A two-step method alternating electroreduction and chemical coupling leading to the ketone has thus been set up (Scheme 9) [126,127]. 

Apart from the electrocarbonylation reactions of organic halides described in Sect. 6, other Ni-catalyzed reactions leading to ketones have been reported. Thus the electroreductive coupling between acylchlorides and alkyl halides, catalyzed by NiBr2bpy leads to unsymmetrical ketones [129]. Recently acylchlorides have been converted to symmetrical ketones in an undivided cell fitted with a nickel or stainless steel anode. In this reaction the active metallic species... 

The ready accessibility of 1,2-dioximes (glyoximes) and the ease with which they are dehydrated has ensured that this is the most common route to furazans. The starting materials are usually prepared by oximation of the appropriately substituted 1,2-diketone or, more often, by a-nitrosation of an alkyl ketone followed by oximation of the resulting 1,2-dione monooxime (Scheme 16). 1,2-Dioximes can also be prepared by reduction of furoxans (Section 4.05.5.2.4) and, in cases where the furoxan is more readily available than the furazan, for example, by nitrile oxide dimerization, this furoxan-> glyoxime-> furazan sequence represents a viable synthetic strategy for symmetrically substituted derivatives. 

Whereas branched ketimines are metalated at the less substituted carbon, metalation and alkylation of unsymmetric imines leads to regioisomers2,4,27. For this reason, only symmetrical ketones and unsymmctrical ketones with one substituent having no a-hydrogens have been applied in alkylation reactions via imines (see Table 4). 

Regioselectivity is not a problem in the metalation and alkylation of SAMP-hydrazones derived from aldehydes, symmetrical ketones and unsymmetrical ketones having one substituent without a-hydrogens. On the other hand, SAMP-hydrazones of unsymmetrical ketones react regioselectively at the less substituted carbon, regardless of the E/Z ratio of the starting hydrazone33. 

Symmetrical ethers are obtained from the dehydration of two molecules of alcohol with H2SO4 (see Section 5.5.3). Alcohols react with p-toluenesul-phonyl chloride (tosyl chloride, TsCl), also commonly known as sulphonyl chloride, in pyridine or EtsN to yield alkyl tosylates (see Section 5.5.3). Carboxylic acids, aldehydes and ketones are prepared by the oxidation of 1° and 2° alcohols (see Sections 5.7.9 and 5.7.10). Tertiary alcohols cannot undergo oxidation, because they have no hydrogen atoms attached to the oxygen bearing carbon atom. 

Treatment of the mercurio ketone with Ni(CO)4 results in a symmetrical coupling with incorporation of one molecule of carbon monoxide to give a triketone presumably via a 3-nickel substituted ketone Eq. (28) [34], This symmetrical coupling reaction is general for alkyl mercury compounds. 

Carboxylic acids can be converted to symmetrical ketones by pyrolysis in the presence of thorium oxide. In a mixed reaction, formic acid and another acid heated over thorium oxide give aldehydes. Mixed alkyl aryl ketones have been prepared by heating mixtures of ferrous salts.1717 When the R group is large, the methyl ester rather than the acid can be decarb-methoxylated over thorium oxide to give the symmetrical ketone. 

The direct a-alkylation of monoketones normally employs reaction of an alkyl halide or sulfonate with the enolate anion produced using a strong base. This method can be satisfactorily used with symmetrical ketones, which are to be dialkylated with a dihalide, and with intramolecular cyclization reactions, where the formation of five- and six-membered rings is often favored over the formation of three-, four-, seven-, and eight-membered rings (M. Mous-seron, 1937 W.S. Johnson, 1963). Regioselective alkylation of dianions according to Hauser s rule (see p. 9f.) is usually also a satisfactory procedure (F.W. Sum, 1979). 

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