During the course of several syntheses, we have had occasion to face the tactical necessity of alkylating ester residues.
This type of transformation has classically been accomplished using malonic esters but experience has shown the yields of these reactions to be quite variable.' Rathke and coworkers have recently reported what appeared to us to be a promising approach to the problem of ester alkylation.' These authors described the generation in THF solution of some simple lithium ester enolates using lithium isopropylcyclohexylamide as the base. Alkylation was then carried out at 0 o by adding the enolate solution to a 50% excess of the alkylating agent dissolved in DMSO. Although ingenious, Rathke's method struck us as having some potential preparative drawbacks. For example, the apparent requirement of adding the ester enolate to the alkylating solution could become critical when dealing with a temperature sensitive enolate, especially on a large scale. Furthermore, the use of a 50% excess of alkylating agent might be disadvantageous if the alkylating species were the valuable reaction component.
We now wish to report a significantly more convenient one-flask experimental procedure for the high yield alkylation of ester enolates at low temperature using a wide variety of alkylating agents under nearly theoretical stoichiometric conditions. This procedure consists simply of adding a given ester (1 equivalent, neat or as a solid) to a 1 molar THF solution containing 1