Alkylation of carboxylic esters

Alkylation of carboxylic esters 0-97 Alkylation of aryl esters 0-98 Alkylation and alcoholysis of oxazines... 

The classical example of alkylation of stabilized carbanion is the alkylation of diethyl malonate. Double alkylation followed by hydrolysis and decarboxylation affords a-substituted carboxylic acids. The same target molecules are available by a-alkylation of carboxylic esters, which requires much stronger bases since the p Ta of the a-CU.2 group is about 25. 

The protocols for the utilization of ketone-derived silyl enol ethers in Tsuji-Trost reactions were preceded by a report of Morimoto and coworkers on the enantioselective allylation of sUyl ketene acetals 88. Without external activation, they reacted with the allylic substrate 19d in the presence of the palladium complex derived from the amidine ligand 89 to give y,5-unsaturated esters 90 in moderate chemical yield but high enantiomeric excess (Scheme 5.29) [46]. Presumably, the pivalate anion hberated during the oxidative addition functions as an activator of the silyl ketene acetal. The protocol is remarkable in view of the fact that asymmetric allylic alkylations of carboxylic esters are rare. Interestingly, the asymmetric induction originates from a ligand with an uncomplicated structure. The protocol seems however rather restricted with respect to the substitution pattern of allylic component and sUyl ketene acetal. 

Trost and coworkers extended their protocol to 2-acylimidazoles after accomplished enantioselective decarboxylative allylation of this type of ketones, the heterocycle was cleaved under formation of y,8-unsaturated esters. Thus, this protocol can be considered an equivalent of the enantioselective allylic alkylation of carboxylic esters [55a]. For the same purpose, the decarboxylative allylation of Af-acyloxazolinones was developed. The allylation products were converted, under cleavage of the heterocycle, into carboxylic acids, esters, and thioesters in high enantiomeric purity [55b]. 

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