Lithium diisopropylamide, formation reaction with esters

Metallation of TTF (5) has been accomplished at — 78°C by either lithium diisopropylamide or by -butyllithium (Scheme 82) <77CC161,79JOC1476>. It has been found that strict temperature control is essential for the success of these reactions, since at — 20°C a redistribution of product formation is observed <79J0C1476>. 1-Lithio-TTF (426) reacts at —70°C with a series of electrophiles to afford the corresponding alcohols, aldehydes, ketones, carboxylic acids, and esters as well as monoalkylated TTF <77CCi6i, 79JOCi476>. Improvement of this procedure allowed the synthesis of carboxy-TTF (427), formyl-TTF (428), and hydroxymethyl-TTF in 80-92% yield (Scheme 83) <94S489>. 

Another related method uses the anion of nitroalkanes in a reaction with halo-esters. Nitromethane reacted with lithium diisopropylamide to form the nitro enolate and then with methyl 3-chloropentanoatc to give 4.110. Reduction of the nitro group with ammonium formate gave methyl 2-phenyl-3-aminopropanoate, 4.111. 

Base-catalyzed alkylations of simple esters require strongly basic catalysts. Relatively weak bases such as alkoxides promote condensation reactions (Chapter 2). The techniques for successful formation of ester enolates which have been developed typically involve amide bases, most commonly lithium diisopropylamide, at low temperature. The resulting enolates can be successfully alkylated with alkyl bromides or iodides. Some examples of the alkylation of enolates of esters and lactones are presented in Scheme 1.8. 

---