Enolate anions, esters, reaction with nitriles

Many types of carbonyl compounds, including aldehydes, ketones, esters, thioesters, acids, and amides, can be converted into enolate ions by reaction with LDA. Table 22.1 lists the approximate pKa values of different types of carbonyl compounds and shows how these values compare to other acidic substances we ve seen. Note that nitriles, too, are acidic and can be converted into enolate-like anions. 

The synthesis begins with an Sn2 reaction (Chapter 10, Section 10.2) of bromide 141 with potassium cyanide to give 144. Note the use of the aprotic solvent DMF to facilitate the 8 2 reaction. A Grignard reaction of the nitrile with methylmagnesium bromide followed by hydrolysis leads to the requisite ketone (see Chapter 20, Section 20.9.3). The final step simply reacts the methyl ketone with LDA under kinetic control conditions to give the enolate anion (143), which is condensed with the ester (142) to give the diketone target, 140 (Section 22.7.2). 

Selenenyl halides are relatively stable, though moisture sensitive, compounds that are generally prepared by the reactions shown in Scheme 7 and behave as electrophihc selenium species. " They react with ketones and aldehydes via their enols or enolates to afford a-seleno derivatives (e.g. (17) in equation 11). Similar a-selenenylations of /3-dicarbonyl compounds, esters, and lactones can be performed, although the latter two types of compounds require prior formation of their enolates. Moreover, the a-selenenylation of anions stabilized by nitrile, nifro, sulfone, or various types of phosphorus substituents has also been reported (equation 12). In many such cases, the selenenylation step is followed by oxidation to the selenoxide and spontaneous syn elimination to provide a convenient method for the preparation of the corresponding a ,/3-unsaturated compound (e.g. 18 in equation 11). Enones react with benzeneselenenyl chloride (PhSeCl) and pyridine to afford a-phenylselenoenones (equation 13). 

The previous sections have dealt primarily with reactions in which the new carbon-carbon bond is formed in an Sn2 reaction between the nucleophilic species and the alkylating reagent. There is another important method for alkylation of carbon. This reaction involves the addition of a nucleophilic carbon species to an electrophilic multiple bond. The reaction is applicable to a wide variety of enolates and enamines. The electrophilic reaction partner is typically an a,jS-unsaturated ketone, aldehyde, ester, or nitrile, but other electron-withdrawing substituents such as nitro or sulfonyl also activate carbon-carbon double and triple bonds to nucleophilic attack. The reaction is called conjugate addition or the Michael reaction. Other kinds of nucleophiles such as amines, alkoxides, and sulfide anions also react similarly, but we will focus on the carbon-carbon bond-forming reactions. 

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