Enolate Anion Reactions

The problem of nitrogen alkylation of enamines, which one encounters with alkyl halides, is of no consequence in alkylations with positively activated olefins, since the generation of amonium salts can be expected to be reversible in these cases. Thus such enamine alkylations are obviously attractive to the synthetic chemist. Their particular importance, however, arises from avoidance of the serious obstacles often found with parallel enolate anion reactions. 

Enolate anion, reaction, 10 505 Enolate initiators, 14 258 Enolate reductases, 3 674 Enolboration, 13 671-672 Enol properties, of 1,3-diketones,... 

Problem 1 stresses the use of appropriate bases for generating enolate anions. Problems 2-4 deal with selectivity issues encountered in enolate anion reactions. The syntheses of TMs in Problems 5 and 6 require the selection of specific reagents to achieve chemo-, stereo-, or enantioselective carbon-carbon bond formations. 

With anions such as ester enolate anions, reaction occurs within minutes at -78 °C and the intermediate cyclohexadienyl complex can be observed spectroscopically [103]. The intermediates are exceedingly air sensitive and are generally quenched directly, without purification. In one case, from the addition of 2-lithio-l,3-dithiane, the adduct has been crystallized and fully characterized by X-ray diffraction analysis [103]. Oxidation with excess iodine (at least 2.5 mol-... 

Kuehne, M.E. and Nelson, J.A. (1970) Stereospecific s5mtheses of epimeric diterpenoid. Resin acids through enolate anion reactions. J. Org. Chem., 35, 161-70. 

This type of enolate anion reaction is particularly useful among reactions of aldehydes and ketones in the aldol reaction (Section 15.2). 

This type of enolate anion reaction occurs among esters in the Claisen (Section 15.3A) and Dieckmann condensations (Section 15.3B). 

The esters derived from dicarboxylic acids in Chapter 20 (Section 20.9) behave more or less like all other esters in enolate anion reactions. Dimethyl succinimide (87 dimethyl 1,4-butanedioate), for example, has a pK relatively close to that of ethyl butanoate (about 25) and it reacts similarly. Treatment of 87 with NaOMe will give 88 and this enolate anion reacts with aldehyde, ketones, or another ester. If 88 is treated with benzaldehyde in a second chemical step, the final product is 89, analogous to the conversion of 74 and 21 to 79 in Section 22.7.2. 

Compound 58 clearly offers more possibilities for disconnection. Disconnections are available at or near the carbon atom bearing the OH group, but also at or near both carbonyl carbons. The larger number of functional groups leads to more choices. Does the chemistry of the alcohol, the aldehyde, or the ketone offer the best choice for a disconnection The chemistry of alcohols is associated with oxidation and reduction (Chapter 17, Section 17.2 Chapter 19, Sections 19.2,19.3.4,19.4.1), formation and reactions of alkoxides as nucleophiles (Chapter 11, Section 11.3.2) and as bases (Chapter 12, Section 12.1), and formation of esters (Chapter 20, Section 20.5). Alcohols are converted to alkyl halides (Chapter 11, Section 11.7). Aldehydes and ketones are formed by the oxidation of alcohols (Chapter 17, Section 17.2), are reduced to alcohols (Chapter 19, Sections 19.2, 19.3.4, 19.4.1), undergo acyl addition (Chapter 18, Sections 18.1-18.7), and participate in enolate anion reactions (Chapter 22, Sections 22.2, 22.4, 22.6). Based on these reactions, several disconnections are shown, but several more are possible. 

The reactions discussed in section 4.1 obviously describe enolate anion reactions. The reactions in this section involve malonate derivatives that react with bases such as sodium hydride or lithium dialkylamides to generate the malonate anion, a highly stabilized enolate. This section also includes reactions of enolate anions derived from mono-esters and other acid derivatives. 

---